Ganoderma lucidum total triterpenes prevent γ-radiation induced oxidative stress in Swiss albino mice in vivo.

PubMed

Smina, T P; Joseph, Jini; Janardhanan, K K

2016-11-01

The in vivo radio-protective effect of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst was evaluated using Swiss albino mice, by pre-treatment with total triterpenes for 14 days, followed by a whole body exposure to γ-radiation. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) were analysed in liver and brain homogenates. The extent of lipid and protein peroxidation was also estimated in liver and brain homogenates after irradiation. Protection of radiation-induced DNA strand breaks in peripheral blood lymphocytes and bone marrow cells was assessed using the comet assay. Total triterpenes were highly effective in reducing the levels of lipid peroxidation and protein oxidation to near normal values in both liver and brain tissues. Total triterpenes, when administered in vivo, were also found to be successful in restoring the antioxidant enzyme activities and GSH level in liver and brain of irradiated mice. Administration of total triterpenes, prior to radiation exposure, significantly decreased the DNA strand breaks. The results of the present study thus revealed the potential therapeutic use of Ganoderma total triterpenes as an adjuvant in radiation therapy.

Evaluation of in vivo anti-hyperglycemic and antioxidant potentials of α-santalol and sandalwood oil.

PubMed

Misra, Biswapriya B; Dey, Satyahari

2013-03-15

Sandalwood finds numerous mentions across diverse traditional medicinal systems in use worldwide. The objective of this study was to evaluate the in vivo anti-hyperglycemic and antioxidant potential of sandalwood oil and its major constituent α-santalol. The in vivo anti-hyperglycemic experiment was conducted in alloxan-induced diabetic male Swiss albino mice models. The in vivo antioxidant experiment was performed in d-galactose mediated oxidative stress induced male Swiss albino mice models. Intraperitoneal administration of α-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for an week modulated parameters such as body weight, blood glucose, serum bilirubin, liver glycogen, and lipid peroxides contents to normoglycemic levels in the alloxan-induced diabetic mice. Similarly, intraperitoneal administration of α-santalol (100mg/kg BW) and sandalwood oil (1g/kg BW) for two weeks modulated parameters such as serum aminotransferases, alkaline phosphatase, bilirubin, superoxide dismutase, catalase, free sulfhydryl, protein carbonyl, nitric oxide, liver lipid peroxide contents, and antioxidant capacity in d-galactose mediated oxidative stress induced mice. Besides, it was observed that the beneficial effects of α-santalol were well complimented, differentially by other constituents present in sandalwood oil, thus indicating synergism in biological activity of this traditionally used bioresource. Copyright © 2012 Elsevier GmbH. All rights reserved.

Zoledronic acid induces cytogenetic toxicity in male germline cells of Swiss albino mice.

PubMed

Dasari, Ramakrishna; Misra, Sunil

2018-04-12

This study mainly focuses on the cytogenetic toxicity induction by zoledronic acid (ZA), a nitrogen containing bisphosphonate (N-BPs) in the male germline cells of Swiss albino mice. A single intraperitoneal exposure with three different doses of ZA (2, 4, and 8 mg/kg body weight), toxicity was assessed by analyzing spermatogonial metaphase chromosome aberrations at 24 h, aberrant primary spermatocytes at week 4, and abnormal spermatozoa at week 8 posttreatment. Cyclophosphamide (40 mg/kg) and 0.9% NaCl were used as positive and vehicle controls respectively in the study. The results showed that there was a significant induction in the number of chromosomal aberrations especially at two doses of ZA (4 and 8 mg/kg) after 24 h in the spermatogonial cells (p < 0.001) compared to vehicle control. The transmission genetic damages were noticed as aberrant spermatocytes with atypical bivalents (X-Y/autosomal asynapsis) at 4 mg/kg of ZA (p < 0.01) and at 8 mg/kg of ZA (p < 0.001) at week 4 posttreatment. A statistically significant higher number of abnormal spermatozoa (sperm) were also noticed at week 8 posttreatment of both at 4 and 8 mg/kg of ZA (p < 0.001). Hence, from these genotoxicity studies, it can be concluded that ZA is genotoxic in male germline cells and has the potential of transmitting the genotoxic effects from spermatogonial cells to sperm in male Swiss mice.

Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

PubMed

Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

2016-09-01

Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

Evaluation of antitumour activity of Calotropis gigantea L. root bark against Ehrlich ascites carcinoma in Swiss albino mice.

PubMed

Habib, M Rowshahul; Karim, M Rezaul

2011-10-01

To investigate experimentally the possible antitumor effect of methanol extract (ME) of Calotropis gigantea L. (C. gigantean) root bark and its petroleum ether (PEF) and chloroform (CF) soluble fractions against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. The effects of ME (10 and 20 mg/kg), PEF (40 and 80 mg/kg) and CF (20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied. Hematological profile and biochemical parameters (SALP, SGPT and SGOT) were also estimated. Results of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one. The life span of ME and CF treated animals was significantly (P<0.05) increased by 43.90% (20 mg ME/kg) and 57.07% (40 mg CF/kg). ME and CF brought back the hematological parameter more or less normal level. ME and CF also restored the altered levels of serum alkaline phosphatase (SALP) and serum glutamate oxaloacetate transaminase (SGOT). Methanol extract (ME) of C. gigantea root bark and its chloroform soluble fraction (CF) possesses significant antitumor activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Long-term exposure to a butter-rich diet induces mild-to-moderate steatosis in Chang liver cells and Swiss albino mice models.

PubMed

Nalloor, Thomas John Philip; Kumar, Nitesh; Narayanan, Kasinathan; Palanimuthu, Vasanth Raj

2017-05-01

Butter is one of the widely used fats present in the diet. However, there is no satisfactory study available that evaluates the effect of a high-fat diet containing butter as the principal fat on the development of non-alcoholic fatty liver disease (NAFLD). In the present study, butter was used for the development of steatosis in Chang liver cells in an in vitro study and Swiss albino mice in an in vivo study. In vitro steatosis was established, and butter was compared with oleic acid in Chang liver cells using an oil red O (ORO)-based colorimetric assay. In the in vivo study, a butter-rich special diet was fed for 15 weeks to mice, who showed no significant change in body weight. The expression pattern of phosphatase and tensin homolog (PTEN) and miR-21 was compared by reverse transcriptase-PCR. Special diet-fed animals showed downregulated PTEN compared to normal diet-fed animals, while levels of miR-21 remained the same. Elevations in biochemical parameters, viz., triglycerides and liver function tests showed symptoms of onset of NAFLD. Histophathological study of livers of test animals confirmed mild-to-moderate degree of NAFLD.

Protective effect of Withania somnifera roots extract on hematoserological profiles against lead nitrate-induced toxicity in mice.

PubMed

Sharma, Veena; Sharma, Sadhana; Pracheta

2012-12-01

The in vivo protective role of hydro-methanolic root extract of Withania somnifera (WS) was evaluated in alleviating lead nitrate (LN)-induced toxicity in male Swiss albino mice by measuring hematoserological profiles. The lead-treated (20 mg/kg body wt, p.o.) albino mice (25-30 g) concurrently received the root extract (200 and 500 mg/kg body wt, p.o.) once daily for the duration of six weeks. Animals exposed to LN showed significant (P < 0.001) decline in haemoglobin content, red blood cell count, white blood cell count, packed cell volume and insignificant decrease in mean corpuscular haemoglobin and mean corpuscular haemoglobin content, while mean corpuscular volume and platelet count were increased. A significant elevation (P < 0.001) in serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, acid phosphatase and total cholesterol were also observed, when compared with control mice. Thus, the study demonstrated that the concurrent daily administration of root extract of WS protected the adverse effects of LN intoxication in mice.

Anti-Alzheimer activity of isolated karanjin from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f.

PubMed

Saini, Prachi; Lakshmayya, L; Bisht, Vinod Singh

2017-01-01

The aim of this study is to find out the anti-Alzheimer's activity of isolated karanjin and embelin. Karanjin isolated from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f. and their purity was confirmed by ultraviolet spectrophotometric and Thin layer chromatography based study. Anti-Alzheimer's activity of isolated compounds were evaluated through elevated plus maze and Morris water maze model on Swiss albino mice. Diazepam (1 mg/kg body weight, intraperitoneally) was used for the induction of Alzheimer's like effects (amnesia) on Swiss albino mice and piracetam (200 mg/kg body weight, oral) used as a standard treatment. In EPM, embelin and karanjin decrease the transfer latency time in dose dependent manner and escape latency time in MWM method. A significant ( P < 0.01) reduction in amnesia with an anti-Alzheimer's effect found when results of isolated compounds were compared with standard and vehicle control. Diazepam (1 mg/kg) treated group showed significant increase in escape latency and transfer latency when compared with vehicle control; which indicates impairment in learning and memory. Both isolated compounds and standard significantly reversed the amnesia induced by diazepam and improved learning and memory of mice in dose and time dependent manner. This study supports the ethnobotanical use of these two plants in India for the management of nerve or brain related problems.

Infrared spectroscopic analysis of skin tumor of mice treated with several medicinal plants

PubMed Central

Ali, Huma; Dixit, Savita

2013-01-01

Objective To evaluate the differences between cancerous tissue, drug treated tissue and its corresponding normal tissue by infrared spectroscopic analysis. Methods Methanolic extracts of Azadirachta indica, Ocimum sanctum, Aloe barbandesis, Tinospora cordifolia and Triticum aestivum were assessed for the isolation and purification of active compound. After that, combine crude and combine isolated samples were prepared. Skin tumor was induced by topical application of 7, 12-dimethyl benz (a) anthracene and promoted by croton oil in Swiss albino mice. To assess the chemopreventive potential of different drugs, it was administered at a concentration of 400 mg/kg body weight daily up to 16 weeks. Fourier transform infrared spectroscopy analysis was used to differentiate the drug treated tissues with the normal and cancerous tissue. In the present study, spectra of different tissues were recorded in the range of 400-4 000 cm−1. Results The results of the present study have shown that the remarkable difference exists between the IR spectra of normal, drugs treated and cancerous tissue in terms of frequencies and intensities of prominent bands of cellular biomolecules. Conclusions Fourier transform infrared spectroscopy analysis suggests the chemopreventive effect of above treated drugs and the best result was observed in combine crude sample and in combine isolated sample or synergistic effect of individual crude and isolated extract in 7, 12-dimethyl benz (a) anthracene croton oil induced skin carcinogenesis in Swiss albino mice.

A study of the toxicology of pyrolysis gases from synthetic polymers

NASA Technical Reports Server (NTRS)

Young, W.; Hilado, C. J.; Kourtides, D. A.; Parker, J. A.

1976-01-01

An apparatus and procedure for evaluating the toxicity of pyrolysis gases from synthetic polymers are described. In each test, four Swiss albino mice are exposed in a 5-liter chamber to the gases from materials pyrolyzed at 700 C. The apparatus is simple in design, easy to clean, inexpensive and gives reproducible results. Data on several fluorine-containing and polyamide polymers are presented.

Nanoparticle mediated brain targeted delivery of gallic acid: in vivo behavioral and biochemical studies for improved antioxidant and antidepressant-like activity.

PubMed

Nagpal, Kalpana; Singh, Shailendra Kumar; Mishra, Dina Nath

2012-11-01

Gallic acid had been reported to possess antidepressant like activity, which may be attributed to its CNS effects like increase in reduced glutathione levels, increased catalase activity and decreased malonaldehyde levels in brain. This study was designed to enhance the antidepressant-like activity of gallic acid (GA) using nanoparticulate delivery system in swiss male albino mice and to explore the possible underlying mechanisms for this activity. GA loaded chitosan nanoparticles (GANP) and corresponding tween 80 coated batch (cGANP) were formulated for brain targeting of GA and characterized for physicochemical parameters, morphology, differential scanning calorimetry and in vitro drug release. GA, GANP, cGANP (dose equivalent to GA 10 mg/kg, i.p.) and positive control drug, Fluoxetine (10 mg/kg, i.p.) were administered for successive seven days to male swiss albino mice. Then, the in vivo antidepressant-like activity was evaluated using Despair Swim Test (DST) and Tail Suspension Test (TST); along with the evaluation of MAO-A activity, reduced glutathione, malonaldehyde level, catalase and locomotor activity in mice. KEYFINDINGS: cGANP (equivalent to 10 mg/kg, i.p.) significantly decreased immobility period of mice in DST and TST, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by GA and its nanoparticle formulations. cGANP (10 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in mice. GA possess significant antidepressant like activity and ligand coated nanoparticle approach with improved brain targeting may serve as an effective approach to enhance such effect.

The protective effect of royal jelly on chronic lambda-cyhalothrin toxicity: serum biochemical parameters, lipid peroxidation, and genotoxic and histopathological alterations in swiss albino mice.

PubMed

Cavuşoğlu, Kültiğin; Yapar, Kürşad; Oruç, Ertan; Yalçın, Emine

2011-10-01

The present study was undertaken to investigate the protective effect of royal jelly (RJ) against toxicity induced by a synthetic pyrethroid insecticide, lambda-cyhalothrin (LCT), in Swiss albino mice. Animals were randomly divided into six groups of six animals each. The control group received distilled water alone, whereas mice in the treatment groups received RJ alone (100 or 250 mg/kg of body weight), LCT alone (668 ppm), or RJ+LCT for 21 days. All mice (100%) survived until the end of experiment and were sacrificed at the end of 24 hours. Blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and reduced glutathione (GSH) levels and micronucleus (MN) frequency, chromosomal aberrations (CAs), and pathological damages. Serum AST, ALT, BUN, and creatinine levels were elevated in mice treated with LCT alone compared with the other tested groups (P<.05). LCT-induced oxidative damage caused a significant decrease in GSH levels and a significant rise in MDA levels of liver and kidney tissues. LCT alone-treated mice presented higher frequencies (P<.05) of MNs, CAs, and abnormal metaphases compared with the controls; moreover, the mitotic index was lower than in controls (P<.05). Oral treatment with RJ significantly ameliorated the indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity induced by LCT. Both doses of RJ tested provided significant protection against LCT-induced toxicity, and its strongest effect was observed at the dose level of 250 mg/kg of body weight. In vivo results suggest that RJ is a potent antioxidant against LCT-induced toxicity, and its protective effect is dose dependent.

Chemoprotective and chemosensitizing properties of selenium nanoparticle (Nano-Se) during adjuvant therapy with cyclophosphamide in tumor-bearing mice.

PubMed

Bhattacharjee, Arin; Basu, Abhishek; Biswas, Jaydip; Sen, Tuhinadri; Bhattacharya, Sudin

2017-01-01

Cyclophosphamide (CP) is one of the widely used anticancer agents; however, it has serious deleterious effects on normal host cells due to its nonspecific action. The essential trace element Selenium (Se) is suggested to have chemopreventive and chemotherapeutic efficacy and currently used in pharmaceutical formulations. Previous report had shown Nano-Se could protect CP-induced hepatotoxicity and genotoxicity in normal Swiss albino mice; however, its role in cancer management is still not clear. The aim of present study is to investigate the chemoprotective efficacy of Nano-Se against CP-induced toxicity as well as its chemoenhancing capability when used along with CP in Swiss albino mice against Ehrlich's ascites carcinoma (EAC) cells. CP was administered (25 mg/kg b.w., i.p.) and Nano-Se was given (2 mg Se/kg b.w., p.o.) in concomitant and pretreatment schedule. Increase levels of serum hepatic marker, hepatic lipid peroxidation, DNA damage, and chromosomal aberration in CP-treated mice were significantly (P < 0.05) reversed by Nano-Se. The lowered status of various antioxidant enzymes in tumor-bearing mice after CP treatment was also effectively increased by Nano-Se. Administration of Nano-Se along with CP caused a significant reduction in tumor volume, packed cell volume, viable tumor cell count, and increased the survivability of the tumor-bearing hosts. The results suggest that Nano-Se exhibits significant antitumor and antioxidant effects in EAC-bearing mice. The potential for Nano-Se to ameliorate the CP-evoked toxicity as well as to improve the chemotherapeutic effect could have beneficial implications for patients undergoing chemotherapy with CP.

Toxicity of tomato red, a popular food dye blend on male albino mice.

PubMed

Sharma, Shipra; Goyal, Rajendra P; Chakravarty, Geetanjali; Sharma, Anjali

2008-06-01

Colour in food is an integral part of our culture and is also indispensable to the modern day consumer. During the past several decades, the technology of food processing has changed dramatically and the growth in the use of synthetic food colours as an individual dye or in the form of blends has increased enormously. In the present investigation, an attempt has been made to evaluate the toxic effects of a commonly used dye blend, tomato red on male Swiss albino mice. The mice were treated orally with 2 and 6g/kg body weight/day for 42 days. The present study revealed an increase in the body weight and liver weight. However, a decrease was recorded in the weights of kidneys and testes. Histopathological study revealed severe degenerative changes in the liver, kidney and testes. In conclusion, the use of the dye blend in various food items has adverse effect on the vital organs.

Prophylactic Role of Averrhoa carambola (Star Fruit) Extract against Chemically Induced Hepatocellular Carcinoma in Swiss Albino Mice.

PubMed

Singh, Ritu; Sharma, Jyoti; Goyal, P K

2014-01-01

Liver cancer remains one of the severe lethal malignancies worldwide and hepatocellular carcinoma (HCC) is the most common form. The current study was designed to evaluate the prophylactic role of the fruit of Averrhoa carambola (star fruit or Kamrak) on diethylnitrosamine- (DENA-) induced (15 mg/kg b.wt.; single i.p. injection) and CCl4-promoted (1.6 g/kg b.wt. in corn oil thrice a week for 24 weeks) liver cancer in Swiss albino mice. Administration of ACE was made orally at a dose of 25 mg/kg b.wt/day for 5 consecutive days and it was withdrawn 48 hrs before the first administration of DENA (preinitiational stage). CCl4 was given after 2 weeks of DENA administration. A cent percent tumor incidence was noted in carcinogen treated animals while ACE administration resulted in a considerable reduction in tumor incidence, tumor yield, and tumor burden. Further, ACE treatment brings out a significant reduction in lipid peroxidation (P < 0.001) along with an elevation in the activities of enzymatic antioxidants (superoxide dismutase, P < 0.001, and catalase, P < 0.001), nonenzymatic antioxidant (reduced glutathione, P < 0.001), and total proteins (P < 0.001) when compared to the carcinogen treated control. These results demonstrate that ACE prevents the DENA/CCl4 induced adverse physical and biochemical alterations during hepatic carcinogenesis in mice. This study suggests the prophylactic role of Averrhoa carambola against hepatocellular carcinoma in mice; therefore, it could be employed for the further screening as a good chemopreventive natural supplement against cancer.

Prophylactic Role of Averrhoa carambola (Star Fruit) Extract against Chemically Induced Hepatocellular Carcinoma in Swiss Albino Mice

PubMed Central

Singh, Ritu; Sharma, Jyoti; Goyal, P. K.

2014-01-01

Liver cancer remains one of the severe lethal malignancies worldwide and hepatocellular carcinoma (HCC) is the most common form. The current study was designed to evaluate the prophylactic role of the fruit of Averrhoa carambola (star fruit or Kamrak) on diethylnitrosamine- (DENA-) induced (15 mg/kg b.wt.; single i.p. injection) and CCl4-promoted (1.6 g/kg b.wt. in corn oil thrice a week for 24 weeks) liver cancer in Swiss albino mice. Administration of ACE was made orally at a dose of 25 mg/kg b.wt/day for 5 consecutive days and it was withdrawn 48 hrs before the first administration of DENA (preinitiational stage). CCl4 was given after 2 weeks of DENA administration. A cent percent tumor incidence was noted in carcinogen treated animals while ACE administration resulted in a considerable reduction in tumor incidence, tumor yield, and tumor burden. Further, ACE treatment brings out a significant reduction in lipid peroxidation (P < 0.001) along with an elevation in the activities of enzymatic antioxidants (superoxide dismutase, P < 0.001, and catalase, P < 0.001), nonenzymatic antioxidant (reduced glutathione, P < 0.001), and total proteins (P < 0.001) when compared to the carcinogen treated control. These results demonstrate that ACE prevents the DENA/CCl4 induced adverse physical and biochemical alterations during hepatic carcinogenesis in mice. This study suggests the prophylactic role of Averrhoa carambola against hepatocellular carcinoma in mice; therefore, it could be employed for the further screening as a good chemopreventive natural supplement against cancer. PMID:24696677

Ameliorating Role of Lycopene, Tomato Puree, and Spirulina + Tomato Puree on the Hematology of Fluoride-Exposed Swiss Albino Mice.

PubMed

Sharma, Shweta; Parashar, Puneet; Sharma, Subhasini; Sharma, Kanta Prasad

2018-01-16

Plant species rich in antioxidants (vitamins, flavonoids, lignans, and carotenoids) have been explored for complementary therapy of chronic diseases (cancers, coronary heart disease) and mitigation of pollutant toxicity. This article investigates their ameliorative role on selective hematological and serum biochemical parameters in fluoride-exposed (190 mg/kg body weight) Swiss albino mice pretreated with the antioxidant-rich diet supplements tomato puree (with and without peels), spirulina (cyanobacteria), and lycopene (present in tomato) for 45 days prior to entry into experimental protocol. Compared with standard feed control, diet-modulated controls had more hairy and lustrous white fur, hemodilution, increase in platelet counts (2- to 5-fold), red blood cell (RBC) size (11%-14%), mean corpuscular hemoglobin (Hb) concentration (MCHC; 5%-14%), and serum albumin (23%-27%). Fluoride-exposed mice reared on standard feed had less hairy, pale white, lusterless fur and black nails, reduction in RBC and white blood cell (WBC) counts and Hb content, and morphological abnormalities in RBCs (poikilocytosis). By contrast, fur quality of fluoride-treated diet-modulated groups was similar to standard feed control; counts and morphology of their RBCs and Hb content similar to the respective controls, and increase in WBC counts greater than controls. In comparison to the fluoride-treated standard feed group, platelet counts were higher in the treated mice of the diet-modulated groups. This study thus revealed the hemoprotective role of diet supplements in fluoride-treated mice. Considering the prevalence of fluoride-induced chronic toxicity in developing countries, our findings have relevance in minimizing hematological disorders among people residing in the fluoride-affected areas, because indigenously cultivated low-price tomato fruits are easily available for consumption.

Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice.

PubMed

Sengupta, Mahuya; Sharma, Gauri Dutta; Chakraborty, Biswajit

2011-06-01

To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl4 intoxicated Swiss albino mice. First group of mice (n=5) received CCl4 treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl4 (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups. The result of present study suggested that CCl4 administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl4 intoxicated mice. Apart from damaging the liver system, CCl4 also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of CCl4 intoxicated mice. In conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice

PubMed Central

Sengupta, Mahuya; Sharma, Gauri Dutta; Chakraborty, Biswajit

2011-01-01

Objective To evaluate the hepatoprotective and immunotherapeutic effects of aqueous extract of turmeric rhizome in CCl4 intoxicated Swiss albino mice. Methods First group of mice (n=5) received CCl4 treatment at a dose of 0.5 mL/kg bw (i.p.) for 7 days. Second group was fed orally the aqueous extract of turmeric at a dose of 50 mg/kg bw for 15 days. The third group was given both the turmeric extract (for 15 days, orally) and CCl4 (for last 7 days, i.p.). The fourth group was kept as a control. To study the liver function, the transaminase enzymes (SGOT and SGPT) and bilirubin level were measured in the serum of respective groups. For assaying the immunotherapeutic action of Curcuma longa (C. longa), non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages were studied from the respective groups. Results The result of present study suggested that CCl4 administration increased the level of SGOT and SGPT and bilirubin level in serum. However, the aqueous extract of turmeric reduced the level of SGOT, SGPT and bilirubin in CCl4 intoxicated mice. Apart from damaging the liver system, CCl4 also reduced non specific host response parameters like morphological alteration, phagocytosis, nitric oxide release, myeloperoxidase release and intracellular killing capacity of peritoneal macrophages. Administration of aqueous extract of C. longa offered significant protection from these damaging actions of CCl4 on the non specific host response in the peritoneal macrophages of CCl4 intoxicated mice. Conclusions In conclusion, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity. PMID:23569758

Anti-Alzheimer activity of isolated karanjin from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f.

PubMed Central

Saini, Prachi; Lakshmayya, L.; Bisht, Vinod Singh

2017-01-01

Aim: The aim of this study is to find out the anti-Alzheimer’s activity of isolated karanjin and embelin. Materials and Methods: Karanjin isolated from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f. and their purity was confirmed by ultraviolet spectrophotometric and Thin layer chromatography based study. Anti-Alzheimer’s activity of isolated compounds were evaluated through elevated plus maze and Morris water maze model on Swiss albino mice. Diazepam (1 mg/kg body weight, intraperitoneally) was used for the induction of Alzheimer’s like effects (amnesia) on Swiss albino mice and piracetam (200 mg/kg body weight, oral) used as a standard treatment. Results: In EPM, embelin and karanjin decrease the transfer latency time in dose dependent manner and escape latency time in MWM method. A significant (P < 0.01) reduction in amnesia with an anti-Alzheimer’s effect found when results of isolated compounds were compared with standard and vehicle control. Diazepam (1 mg/kg) treated group showed significant increase in escape latency and transfer latency when compared with vehicle control; which indicates impairment in learning and memory. Conclusion: Both isolated compounds and standard significantly reversed the amnesia induced by diazepam and improved learning and memory of mice in dose and time dependent manner. This study supports the ethnobotanical use of these two plants in India for the management of nerve or brain related problems. PMID:29861598

Number and Distribution of Mouse Retinal Cone Photoreceptors: Differences between an Albino (Swiss) and a Pigmented (C57/BL6) Strain

PubMed Central

Jiménez-López, Manuel; Alburquerque-Béjar, Juan J.; Nieto-López, Leticia; García-Ayuso, Diego; Villegas-Pérez, Maria P.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

2014-01-01

We purpose here to analyze and compare the population and topography of cone photoreceptors in two mouse strains using automated routines, and to design a method of retinal sampling for their accurate manual quantification. In whole-mounted retinas from pigmented C57/BL6 and albino Swiss mice, the longwave-sensitive (L) and the shortwave-sensitive (S) opsins were immunodetected to analyze the population of each cone type. In another group of retinas both opsins were detected with the same fluorophore to quantify all cones. In a third set of retinas, L-opsin and Brn3a were immunodetected to determine whether L-opsin+cones and retinal ganglion cells (RGCs) have a parallel distribution. Cones and RGCs were automatically quantified and their topography illustrated with isodensity maps. Our results show that pigmented mice have a significantly higher number of total cones (all-cones) and of L-opsin+cones than albinos which, in turn, have a higher population of S-opsin+cones. In pigmented animals 40% of cones are dual (cones that express both opsins), 34% genuine-L (cones that only express the L-opsin), and 26% genuine-S (cones that only express the S-opsin). In albinos, 23% of cones are genuine-S and the proportion of dual cones increases to 76% at the expense of genuine-L cones. In both strains, L-opsin+cones are denser in the central than peripheral retina, and all-cones density increases dorso-ventrally. In pigmented animals S-opsin+cones are scarce in the dorsal retina and very numerous in the ventral retina, being densest in its nasal aspect. In albinos, S-opsin+cones are abundant in the dorsal retina, although their highest densities are also ventral. Based on the densities of each cone population, we propose a sampling method to manually quantify and infer their total population. In conclusion, these data provide the basis to study cone degeneration and its prevention in pathologic conditions. PMID:25029531

Stimulatory effects of Cuminum cyminum and flavonoid glycoside on Cyclosporine-A and restraint stress induced immune-suppression in Swiss albino mice.

PubMed

Chauhan, Prashant Singh; Satti, Naresh Kumar; Suri, Krishan Avtar; Amina, Musarat; Bani, Sarang

2010-04-15

Many herbs and spices are known to modulate the immune system and have been shown to restore the immunity in immuno-compromised individuals. Spices generally used to increase the taste and flavor of food also has the history of usage as an ayurvedic medicine. Therefore to explore the health modulating effects of Cuminum cyminum and to identify the active compound, immunomodulatory properties were evaluated using flowcytometry and ELISA in normal and immune-suppressed animals. C. cyminum and compound 1 stimulated the T cells and Th1 cytokines expression in normal animals. Swiss albino mice subjected to Cyclosporine-A induced immune-suppression were dosed orally with C. cyminum (25, 50, 100 and 200 mg/kg) on consecutive days. The results showed that administration significantly increased T cells (CD4 and CD8) count and Th1 predominant immune response in a dose dependent manner thereby suggesting immunomodulatory activity through modulation of T lymphocytes expression. In restraint stress induced immune-suppressed animals, compound 1 countered the depleted T lymphocytes, decreased the elevated corticosterone levels and size of adrenal glands and increased the weight of thymus and spleen. Based on the data we may conclude that C. cyminum is a potent immunomodulator and may develop as a lead to recover the immunity of immuno-compromised individuals. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Ganoderma lucidum total triterpenes attenuate DLA induced ascites and EAC induced solid tumours in Swiss albino mice.

PubMed

Smina, T P; Mathew, J; Janardhanan, K K

2016-04-30

G. lucidum total triterpenes were assessed for its apoptosis-inducing and anti-tumour activities. The ability of the total triterpenes to induce apoptosis was evaluated in Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. Total triterpenes were found to be highly cytotoxic to DLA and EAC cell lines with IC50 values 5 ± 0.32 and 7.9 ± 0.2 µg/ml respectively. Total triterpenes induced apoptosis in both cell lines which is evident from the DNA fragmentation assay. Anti-tumour activity was accessed using DLA induced solid and EAC induced ascites tumour models in Swiss albino mice. Administration of 10, 50 and 100 mg/kg b. wt. total triterpenes showed 11.86, 27.27 and 40.57% increase in life span of animals in ascites tumour model. Treatment with 10, 50 and 100 mg/kg b. wt. total triterpenes exhibited 76.86, 85.01 and 91.03% inhibition in tumour volume and 67.96, 72.38 and 77.90% inhibition in tumour weight respectively in the solid tumour model. The study reveals the significant dose-dependent anti-tumour activity of total triterpenes in both models. Total triterpenes were more active against the solid tumour than the ascites tumour. The anti-oxidant potential and ability to induce cell-specific apoptosis could be contributing to its anti-tumour activities.

Vitis vinifera peel and seed gold nanoparticles exhibit chemopreventive potential, antioxidant activity and induce apoptosis through mutant p53, Bcl-2 and pan cytokeratin down-regulation in experimental animals.

PubMed

Nirmala, J Grace; Narendhirakannan, R T

2017-05-01

Several studies suggest surface modifications of gold nanoparticles (AuNPs) by capping agents or surface coatings could play an important role in biological systems, and site directed delivery. The present study was carried out to assess the antioxidant and apoptotic activities of the Vitis vinifera peel and seed gold nanoparticles in experimentally induced cancer in Swiss albino mice. 12-dimethylbenz [a] anthracene (DMBA) (single application) and 12-O-tetradecanoylphorbol 13-acetate (TPA) (thrice a week) were applied on the dorsal area of the skin to induce skin papillomagenesis in Swiss albino mice for 16 weeks. Gold nanoparticles were synthesized using Vitis vinifera peel and seed aqueous extracts and characterized by Transmission electron microscopic (TEM) analyses. On topical application, peel and seed gold nanoparticles demonstrated chemopreventive potential by significantly (p<0.05) reducing the cumulative number of tumors while increasing the antioxidant enzyme activities in the gold nanoparticles treated mice. The down-regulated expression of mutant p53, Bcl-2 and the levels of pan-cytokeratins might have facilitated the process of apoptosis in the chemical carcinogenesis process. The results were supported by the histopathological evaluation which exhibited mild dysplasia and acanthosis in the skin tissues of Vitis vinifera peel and seed AuNPs treated mice. Based on the present study, the chemopreventive action of Vitis vinifera peel and seed AuNPs is probably due to its ability to stimulate the antioxidant enzymes within the cells and suppressed abnormal skin cell proliferation that occurred during DMBA-induced skin papillomagenesis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Influence of enriched environment on viral encephalitis outcomes: behavioral and neuropathological changes in albino Swiss mice.

PubMed

de Sousa, Aline Andrade; Reis, Renata; Bento-Torres, João; Trévia, Nonata; Lins, Nara Alves de Almeida; Passos, Aline; Santos, Zaire; Diniz, José Antonio Picanço; Vasconcelos, Pedro Fernando da Costa; Cunningham, Colm; Perry, Victor Hugh; Diniz, Cristovam Wanderley Picanço

2011-01-11

An enriched environment has previously been described as enhancing natural killer cell activity of recognizing and killing virally infected cells. However, the effects of environmental enrichment on behavioral changes in relation to virus clearance and the neuropathology of encephalitis have not been studied in detail. We tested the hypothesis that environmental enrichment leads to less CNS neuroinvasion and/or more rapid viral clearance in association with T cells without neuronal damage. Stereology-based estimates of activated microglia perineuronal nets and neurons in CA3 were correlated with behavioral changes in the Piry rhabdovirus model of encephalitis in the albino Swiss mouse. Two-month-old female mice maintained in impoverished (IE) or enriched environments (EE) for 3 months were behaviorally tested. After the tests, an equal volume of Piry virus (IEPy, EEPy)-infected or normal brain homogenates were nasally instilled. Eight days post-instillation (dpi), when behavioral changes became apparent, brains were fixed and processed to detect viral antigens, activated microglia, perineuronal nets, and T lymphocytes by immuno- or histochemical reactions. At 20 or 40 dpi, the remaining animals were behaviorally tested and processed for the same markers. In IEPy mice, burrowing activity decreased and recovered earlier (8-10 dpi) than open field (20-40 dpi) but remained unaltered in the EEPy group. EEPy mice presented higher T-cell infiltration, less CNS cell infection by the virus and/or faster virus clearance, less microgliosis, and less damage to the extracellular matrix than IEPy. In both EEPy and IEPy animals, CA3 neuronal number remained unaltered. The results suggest that an enriched environment promotes a more effective immune response to clear CNS virus and not at the cost of CNS damage.

The Relationship Between Fusobacterium Species and Other Flora in Mixed Infection

DTIC Science & Technology

1986-01-01

inhibition with antibiotics and by quanti- tative cultures of abscess contents. 1-_4r (X) Animals d Male Swiss Alb*ino mice, 20-25 g, were obtained from...of the length and width is zole. Antibiotic levels were determined in serum tr’,, proportional to the outer surface of the abscess. This abscess fluid...at -70 C comparative measure. By this criterion, after 5 days until they were assayed. without antibiotic therapy the abscesses caused by a single

Gastric tumorigenesis by a single dose of 4-(hydroxymethyl)benzenediazonium ion of Agaricus bisporus.

PubMed Central

Toth, B.; Nagel, D.; Ross, A.

1982-01-01

4-(Hydroxymethyl-benzenediazonium tetrafluoroborate was administered as a single intragastric instillation at 400 micrograms/g to Swiss albino mice. The treatment gave rise to glandular stomach tumours in incidences of 30% in females and 32% in males. Histopathologically, the tumours were classified as polypoid adenomas and adenocarcinomas. This diazonium ion is an ingredient of the cultivated mushroom of commerce, Agaricus bisporus. The implications are self-evident. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6889885

Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice.

PubMed

Brosnan-Watters, G; Ogimi, T; Ford, D; Tatekawa, L; Gilliam, D; Bilsky, E J; Nash, D

2000-08-01

1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA receptor antagonists, a finding which may be important given the NMDA receptor hypofunction hypothesis for the etiology of schizophrenic symptoms.

Effect of clozapine and molindone on plasma and brain levels of mescaline in mice.

PubMed

Shah, N S; Gulati, O D

1984-01-01

Levels of unchanged mescaline were examined in the plasma and brain of albino Swiss-Webster mice pretreated with various doses of either clozapine or molindone. In clozapine treated mice, the mescaline levels were statistically significantly higher at 2 and 3 h with 7.5 and 15.0 mg/kg and at 1, 2 and 3 h with 30 mg/kg. Molindone at 4.0 and 8.0 mg/kg produced no significant effect; at 16.0 and 48.0 mg/kg, the levels were significantly higher at 1 and 2 h. Elevated brain levels of mescaline by clozapine and molindone indicate an adverse metabolic interaction between a hallucinogen and drugs that are commonly used to treat mescaline-induced psychosis.

Antimutagenic effects of garlic extract on chromosomal aberrations.

PubMed

Shukla, Yogeshwer; Taneja, Pankaj

2002-02-08

Garlic (Allium sativum) has been used since ancient times, as a spice and also for its medicinal properties. In present set of investigations antimutagenic effect of garlic extract (GE) has been evaluated using 'in vivo chromosomal aberration assay' in Swiss albino mice. Cyclophosphamide (CP), a well-known mutagen, was given at a single dose of 25 mg/kg b.w. intraperitoneally. Pretreatment with 1, 2.5 and 5% of freshly prepared GE was given through oral intubation for 5 days prior to CP administration. Animals from all the groups were sacrificed at sampling times of 24 and 48 h and their bone marrow tissue was analyzed for chromosomal damage. The animals of the positive control group (CP alone) shows a significant increase in chromosomal aberrations both at 24 and 48 h sampling time. GE, alone did not significantly induced aberrations at either sampling time, confirming its non-mutagenicity. However in the GE pre-treated and CP post-treated groups, a dose dependent decrease in cytogenetic damage was recorded. A significant suppression in the chromosomal aberrations was recorded following pretreatment with 2.5 and 5% GE administration. The anticytotoxic effects of GE were also evident, as observed by significant increase in mitotic index, when compared to positive control group. Reduction in CP induced clastogenicity by GE was evident at 24 h and to a much greater extent at 48 h of cell cycle. Thus results of the present investigations revealed that GE has chemopreventive potential against CP induced chromosomal mutations in Swiss albino mice.

Influence of environmental enrichment vs. time-of-day on behavioral repertoire of male albino Swiss mice.

PubMed

Loss, Cássio Morais; Binder, Luisa Bandeira; Muccini, Eduarda; Martins, Wagner Carbolin; de Oliveira, Paulo Alexandre; Vandresen-Filho, Samuel; Prediger, Rui Daniel; Tasca, Carla Inês; Zimmer, Eduardo R; Costa-Schmidt, Luiz Ernesto; de Oliveira, Diogo Losch; Viola, Giordano Gubert

2015-11-01

Environmental enrichment (EE) is a non-pharmacological manipulation that promotes diverse forms of benefits in the central nervous system of captive animals. It is thought that EE influences animal behavior in a specie-(strain)-specific manner. Since rodents in general present different behaviors during distinct periods of the day, in this study we aimed to investigate the influence of time-of-day on behavioral repertoire of Swiss mice that reared in EE. Forty male Swiss mice (21days old) were housed in standard (SC) or enriched conditions (EC) for 60days. Behavioral assessments were conducted during the light phase (in presence of light) or dark phase (in absence of light) in the following tasks: open field, object recognition and elevated plus maze. First, we observed that the locomotor and exploratory activities are distinct between SC and EC groups only during the light phase. Second, we observed that "self-protective behaviors" were increased in EC group only when mice were tested during the light phase. However, "less defensive behaviors" were not affected by both housing conditions and time-of-day. Third, we showed that the performance of EE animals in object recognition task was improved in both light and dark conditions. Our findings highlight that EE-induced alterations in exploratory and emotional behaviors are just evident during light conditions. However, EE-induced cognitive benefits are remarkable even during dark conditions, when exploratory and emotional behaviors were similar between groups. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of Ratnaprash for its effect on strength, stamina and fatigue using swim endurance test and biochemical estimation in swiss albino mice

PubMed Central

Gupta, Arun; Kumar, Satyendra; Rajput, Rashmi; Srivastava, Ruchi; Rai, Rajiv K.; Sastry, J. L. N.

2015-01-01

Context: Traditional medicines have been considered as important resources for postponing fatigue, accelerating elimination of fatigue related metabolites and improving physical ability. Rasāyanās or rejuvenative therapies are mentioned as one of the eight clinical specialties in Ayurveda for attaining longevity, healthy life and regulation of bodily balance. Eventhough more detailed studies are needed to confirm the claims of benefits in the light of evidence based research, Ratnaprash, a herbo-mineral rasāyana formulation, is proposed here to be an antifatigue supplement that is good in promoting strength and stamina. Materials and Methods: In the present study, anti fatigue, strength and stamina enhancing properties of Ratnaprash were examined based on swim endurance capacity and the change in biochemical parameters in Swiss Albino mice. Treatment groups were orally administered Ratnaprash at various test doses (500, 1000, 2000 mg/Kg per day), while the control group received distilled water at similar dose volumes. Effect of therapy was evaluated after 28 days of treatment. Results: At the end of study period, the swimming times to exhaustion were longer in the treated groups than in the control group. Plasma lactate levels of treated groups were lower than those of the control group (P < 0.05) while tissue ATP levels were higher. These effects were dose dependent and the strongest effect was seen in groups treated at 1000 mg/Kg. Conclusion: Ratnaprash enhanced the forced swimming capacity of mice and exhibited elevated anti-fatigue activity, reduced blood lactate levels and increased tissue ATP levels in preclinical models in comparison to vehicle control, exhibiting possible role in increasing strength and stamina and contributing anti-fatigue activity. PMID:26600664

Evaluation of Ratnaprash for its effect on strength, stamina and fatigue using swim endurance test and biochemical estimation in swiss albino mice.

PubMed

Gupta, Arun; Kumar, Satyendra; Rajput, Rashmi; Srivastava, Ruchi; Rai, Rajiv K; Sastry, J L N

2015-01-01

Traditional medicines have been considered as important resources for postponing fatigue, accelerating elimination of fatigue related metabolites and improving physical ability. Rasāyanās or rejuvenative therapies are mentioned as one of the eight clinical specialties in Ayurveda for attaining longevity, healthy life and regulation of bodily balance. Eventhough more detailed studies are needed to confirm the claims of benefits in the light of evidence based research, Ratnaprash, a herbo-mineral rasāyana formulation, is proposed here to be an antifatigue supplement that is good in promoting strength and stamina. In the present study, anti fatigue, strength and stamina enhancing properties of Ratnaprash were examined based on swim endurance capacity and the change in biochemical parameters in Swiss Albino mice. Treatment groups were orally administered Ratnaprash at various test doses (500, 1000, 2000 mg/Kg per day), while the control group received distilled water at similar dose volumes. Effect of therapy was evaluated after 28 days of treatment. At the end of study period, the swimming times to exhaustion were longer in the treated groups than in the control group. Plasma lactate levels of treated groups were lower than those of the control group (P < 0.05) while tissue ATP levels were higher. These effects were dose dependent and the strongest effect was seen in groups treated at 1000 mg/Kg. Ratnaprash enhanced the forced swimming capacity of mice and exhibited elevated anti-fatigue activity, reduced blood lactate levels and increased tissue ATP levels in preclinical models in comparison to vehicle control, exhibiting possible role in increasing strength and stamina and contributing anti-fatigue activity.

An Indian Desert Shrub 'Hiran Chabba', Farsetia Hamiltonii Royle, Exhibits Potent Antioxidant and Hepatoprotective Effect Against Iron-Overload Induced Liver Toxicity in Swiss Albino Mice.

PubMed

Basu, Tapasree; Kumar, Bipul; Shendge, Anil Khushalrao; Panja, Sourav; Chugh, Heerak; Gautam, Hemant K; Mandal, Nripendranath

2018-04-18

Farsetia hamiltonii Royle, also known as Hiran Chabba grows in desert regions. It is widely used as folk medicine to treat joint pains, diarrhea and diabetes. However, its antioxidant and iron chelation abilities both in vitro and in vivo have not yet been investigated. The 70% methanolic extract of F.hamiltonii (FHME) was investigated for its free radical scavenging and iron chelation potential, in vitro. An iron-overload situation was established by intraperitoneal injection of iron-dextran in Swiss albino mice, followed by oral administration of FHME. Liver damage and serum parameters due to iron-overload were measured biochemically and histopathologically to test iron-overload remediation and hepatoprotective potential of FHME. Phytochemical analyses were performed to determine its probable bioactive components. FHME showed promising antioxidant activity, scavenged various reactive oxygen and nitrogen species and chelated iron in vitro. FHME reduced liver iron, serum ferritin, normalized serum parameters, reduced oxidative stress in liver, serum and improved liver antioxidant status in iron-overloaded mice. It also alleviated liver damage and fibrosis as evident from biochemical parameters and morphological analysis of liver sections. The phytochemical analyses of FHME reflected the presence of alkaloids, phenols, flavonoids and tannins. HPLC analysis indicated presence of tannic acid, quercetin, methyl gallate, catechin, reserpine, ascorbic acid and gallic acid. Based on the experimental outcome, FHME, an ethnologically important plant can be envisaged as excellent antioxidant and iron chelator drug capable of remediating iron-overload induced hepatotoxicity and the bioactive compounds present in FHME might be responsible for its efficacy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cathinone, an active principle of Catha edulis, accelerates oxidative stress in the limbic area of swiss albino mice.

PubMed

Safhi, Mohammed M; Alam, Mohammad Firoz; Hussain, Sohail; Hakeem Siddiqui, Mohammed Abdul; Khuwaja, Gulrana; Jubran Khardali, Ibrahim Abdu; Al-Sanosi, Rashad Mohammed; Islam, Fakhrul

2014-10-28

Cathinone hydrochloride is an active principle of the khat plant (Catha edulis) that produces pleasurable and stimulating effects in khat chewers. To the best of our knowledge no data of cathinone on oxidative stress in limbic areas of mice is available. This is the first study of cathinone on oxidative stress in limbic areas of the brain in Swiss albino male mice. The animals were divided into four groups. Group-I was the control group and received vehicle, while groups-II to IV received (-)-cathinone hydrochloride (0.125, 0.25 and 0.5 mg/kg body wt., i.p.) once daily for 15 days. The level of lipid peroxidation (LPO) was elevated dose-dependently and was significant (p<0.05, p<0.01) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. In contrast, the content of reduced glutathione (GSH) was decreased significantly (p<0.01, p<0.001) with doses of 0.25 and 0.5mg/kg body wt. of cathinone as compared to control group. The activity of antioxidant enzymes (GPx, GR, GST, CAT, and SOD) was also decreased dose-dependently: the decreased activity of GPx, GR, catalase and SOD was significant with doses of 0.25 and 0.5 mg of cathinone as compared to control group, while the activity of GST was decreased dose-dependently and was significant with 0.5mg of cathinone as compared to control group. The results indicate that the cathinone generated oxidative stress hampered antioxidant enzymes, glutathione and lipid peroxidation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

PRIMARY AND SECONDARY ANTITOXIN RESPONSES IN THYMECTOMIZED MICE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hess, M.W.; Cottier, H.; Stoner, R.D.

1963-04-11

A total of 68 Swiss albino mice of either sex were thy; mectoraized at the following time intervals after birth: 22 during day one, 21 during day two, 17 on day four and 8 on day eight. Sixty-one nonoperated litter-rnates served as controls. All mice were given primary andtigenic stimulation with adsorbed tetanus toxoids when four weeks of age. Three weeks later a booster injection of fluid tetanus tokoid was given. With these time intervals thymectomized mice showed only slightly impaired primary responses but severely repressed secondary responses as compared to nonoperated litter-mates. This uncommon finding is difficult to explainmore » at present and results are discussed with regard to other reports on the effect of postnatal thymectoniy on immune responses. Special emphasis is placed on the unknown effect of postthymectomy wasting syndrome. (auth)« less

ANTI – TUMOUR EFFECT OF BERBERIS ASIATICA ROXB. EX. DC. ON DALTON'S LYMPHOMA ASCITE

PubMed Central

Kumar, E.P.; Elshurafa, Allam Ahmed; Elango, K.; Subburaju, T.; Suresh, B.

1998-01-01

Berberis asiatica Roxb. Ex. Dc., non Griff. Belongs to the family berberidaceae commonly occurring in the dry outer Himalaya, Assam etc. Roots along with stem bark s a reputed drug in Ayurvedic medicine contain several alkaloids. 50% Ethaolnic extract of roots reported to posses anti-cancer activity. The present study examines the antitumour effect of ethanolic root extract (BRE) against Dalton's lymphoma ascites tumour cells and solid tumour in swiss albino mice, A significant enhancement of mean survival time of BRE treated tumour bearing mice was found. Oral administration of BRE reduced the solid tumour induced by DLE and restored the altered haematological parameters to normal. PMID:22556858

The exposure to water with cigarette residue changes the anti-predator response in female Swiss albino mice.

PubMed

Cardoso, Letícia Silva; Estrela, Fernanda Neves; Chagas, Thales Quintão; da Silva, Wellington Alves Mizael; Costa, Denys Ribeiro de Oliveira; Pereira, Igor; Vaz, Boniek Gontijo; Rodrigues, Aline Sueli de Lima; Malafaia, Guilherme

2018-03-01

Recent studies have shown that cigarette consumption affects much more than human health. Smoked cigarette butt (SCB) disposal into the environment can bring little-known negative biological consequences to mammals, since it contains many organic and inorganic toxic chemical constituents. Thus, we aim at assessing whether the ingestion of water with leached SCB for 60 days by female Swiss mice changes their defensive behavioral response to potential predators (cats and snakes). We worked with the following groups of animals: control (pollutant-free water), water with environmental concentration of SCB (1.9 μg/L of nicotine), and concentration 1000 times higher (EC1000×). Our data show that the treatments did not cause locomotor, visual, auditory, and olfactory deficit in the animals. However, we observed that the animals exposed to the pollutants did not present behavioral differences in the test session with or without the snake. On the other hand, animals in all groups showed defensive behavior when the test was conducted with the cat in the apparatus. However, female mice presented weaker response than the control. Thus, our data point towards the potential neurotoxic damage caused to mice who have ingested water with SCB residues, even at low concentrations.

A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

PubMed

Basu, Tapasree; Panja, Sourav; Shendge, Anil Khushalrao; Das, Abhishek; Mandal, Nripendranath

2018-05-01

Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation. © 2018 Wiley Periodicals, Inc.

Effect of Cuscuta reflexa stem and Calotropis procera leaf extracts on glucose tolerance in glucose-induced hyperglycemic rats and mice.

PubMed

Rahmatullah, Mohammed; Sultan, Shamsuddin; Toma, Tanzila Taher; Lucky, Sayeda-A-Safa; Chowdhury, Majeedul H; Haque, Wahid Mozammel; Annay, Eashmat Ara; Jahan, Rownak

2009-12-30

Cuscuta reflexa (whole plant) and Calotropis procera (leaves) are used in folk medicine of Bangladesh to control blood sugar in patients suffering from diabetes mellitus. The hypoglycemic effects of methanol and chloroform extracts of whole plants of Cuscuta reflexa, and methanol extract of leaves of Calotropis procera were investigated in oral glucose tolerance tests in Long Evans rats and Swiss albino mice, respectively. Both methanol and chloroform extracts of Cuscuta reflexa whole plant demonstrated significant oral hypoglycemic activity in glucose-loaded rats at doses of 50, 100 and 200 mg/kg body weight. The methanol extract of leaves of Calotropis procera, when tested at doses of 100 and 250 mg/kg body weight did not demonstrate any oral hypoglycemic effect when tested in glucose-loaded mice.

Antitumour evaluation of di-(2-ethylhexyl) phthalate (DEHP) isolated from Calotropis gigantea L. flower.

PubMed

Habib, Muhammad Rowshanul; Karim, Muhammad Rezaul

2012-12-01

The objective of the study is to explore the anticancer activity of di-(2-ethylhexyl) phthalate (DEHP) isolated from Calotropis gigantea flower against Ehrlich ascites carcinoma cells (EAC) in Swiss albino mice. The activity of DEHP was evaluated at doses of 10, 20 and 40 mg kg-1 body mass applied intraperitoneally. DEHP showed a significant decrease in viable cell count (p < 0.05), mass gain (due to tumour burden) and elevated the life span of EAC cell bearing mice. Altered hematological profiles such as RBC, hemoglobin, WBC and differential count were reverted to normal levels in DEHP-treated mice. DEHP also brought back altered biochemical parameters (glucose, cholesterol, triglycerides, blood urea, SALP and SGOT) to normal level. Results of this study indicate that DEHP show potent dose dependent antitumour activity against EAC in vivo.

Mutagenicity of the Musa paradisiaca (Musaceae) fruit peel extract in mouse peripheral blood cells in vivo.

PubMed

Andrade, C U B; Perazzo, F F; Maistro, E L

2008-01-01

Plants are a source of many biologically active products and nowadays they are of great interest to the pharmaceutical industry. In the present study, the mutagenic potential of the Musa paradisiaca fruit peel extract was assessed by the single-cell gel electrophoresis (SCGE) and micronucleus assays. Animals were treated orally with three different concentrations of the extract (1000, 1500, and 2000 mg/kg body weight). Peripheral blood cells of Swiss mice were collected 24 h after treatment for the SCGE assay and 48 and 72 h for the micronucleus test. The results showed that the two higher doses of the extract of M. paradisiaca induced statistically significant increases in the average numbers of DNA damage in peripheral blood leukocytes for the two higher doses and a significant increase in the mean of micronucleated polychromatic erythrocytes in the three doses tested. The polychromatic/normochromatic erythrocyte ratio scored in the treated groups was not statistically different from the negative control. The data obtained indicate that fruit peel extract from M. paradisiaca showed mutagenic effect in the peripheral blood cells of Swiss albino mice.

Relative toxicity of pyrolysis products of some polyurethane and polychloroprene foams

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Slattengren, C. L.; Kourtides, D. A.; Parker, J. A.

1977-01-01

Results of toxicity screening tests on some polyurethane and polychloroprene flexible foams are presented. The test method involves the exposure of four Swiss albino male mice in a 4.2-liter hemispherical chamber to the pyrolysis effluents from 1 g of sample exposed to temperatures rising from 200 to 800 C at a rate of 40 C/min. Mortality and times to incapacitation and to death are recorded. Comparisons indicate that flexible polyurethane foams without fire retardant are more toxic than the corresponding foams containing fire retardant, and polychloroprene foams are least toxic.

Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophinmore » (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA damage.« less

Influence of heat, wind, and humidity on ultraviolet radiation injury.

PubMed

Owens, D W; Knox, J M

1978-12-01

We investigated the influence of heat, wind, and humidity on UVR-induced acute and chronic skin damage of experimental animals housed in environmental chambers and irradiated under controlled conditions. Hairless mice (strain HRS/J) irradiated after an increase of 10 degrees F in skin temperature had more skin damage than irradiated controls. Significantly more Swiss albino mice irradiated for 400 days while maintained at 90 degrees F developed tumors than did those receiving the same amount of UVR but maintained at room temperature. Mice exposed to UVR daily for 4 weeks while kept in wind of 7 mph had greater damage and slower recovery than animals irradiated but protected from wind. Wind also accelerated tumorigenesis in mice than received chronic UVR. Mice kept at 80% relative humidity and given a single dose of UVR had greater skin injury than animals irradiated while at 5% relative humidity. High midity also appears to accelerate skin cancer formation in animals that were exposed to chronic UVR.

Protective effects of the dietary supplementation of turmeric (Curcuma longa L.) on sodium arsenite-induced biochemical perturbation in mice.

PubMed

Karim, Md Rezaul; Haque, Abedul; Islam, Khairul; Ali, Nurshad; Salam, Kazi Abdus; Saud, Zahangir Alam; Hossain, Ekhtear; Fajol, Abul; Akhand, Anwarul Azim; Himeno, Seiichiro; Hossain, Khaled

2010-12-01

The present study was undertaken to evaluate the protective effect of turmeric powder on arsenic toxicity through mice model. Swiss albino male mice were divided into four groups. The first group was used as control, while groups 2, 3, and 4 were treated with turmeric powder (T, 50 mg/kg body weight/day), sodium arsenite (Sa, 10 mg/kg body weight/day) and turmeric plus Sa (T+Sa), respectively. Results showed that oral administration of Sa reduced the weight gain of the mice compared to the control group and food supplementation of turmeric prevented the reduction of weight gain. Turmeric abrogated the Sa-induced elevation of serum urea, glucose, triglyceride (TG) level and alanine aminotransferase (ALT) activity except the activity of alkaline phosphatase (ALP). Turmeric also prevented the Sa-induced perturbation of serum butyryl cholinesterase activity (BChE). Therefore, ameliorating effect of turmeric on Sa-treated mice suggested the future application of turmeric to reduce or to prevent arsenic toxicity in human.

Evaluation of antidepressant like property of amisulpride per se and its comparison with fluoxetine and olanzapine using forced swimming test in albino mice.

PubMed

Pawar, Ganesh R; Agrawal, Rajendra P; Phadnis, Pradeep; Paliwal, Abhay; Vyas, Savita; Solanki, Pooja

2009-01-01

Amisulpride, an atypical antipsychotic was evaluated for antidepressant like activity in forced swimming test in Swiss albino mice. The effect of amisulpride was compared with that of fluoxetine, the standard antidepressant and olanzapine, another atypical antipsychotic claimed to have antidepressant like activity. Both acute and chronic studies were carried out. In both the studies, animals were divided into four groups (n = 8 each) and subjected to oral drug interventions as follows -- Group 1- control (distilled water, 1 mL/kg); Group 2- fluoxetine in a dose of 10 mg/kg 23.5, 5 and 1 h before the test; Group 3-amisulpride in a dose of 70 mg/kg 23.5, 5 and 1 h before the test; Group 4- olanzapine in a dose of 2 mg/kg 23.5, 5 and 1 h before the study. In the chronic study, the treatment was given daily for 28 days with last dose being given 2 h prior to the test. A time sampling method was used to score the behavioral activity in each group. Results of both the studies indicated that animals given amisulpride displayed significant improvement in swimming behavior (p < 0.01), while markedly reducing immobility as compared to control group (p <0.01). Fluoxetine also showed significant difference in activity as compared to amisulpride and olanzapine (p < 0.01). There was no statistically significant difference between amisulpride and olanzapine in terms of effect on immobility and swimming phases in albino mice (p > 0.05). We conclude that amisulpride per se has an antidepressant like activity comparable to that of olanzapine though the activity was significantly less than that of fluoxetine.

Baicalein abrogates reactive oxygen species (ROS)-mediated mitochondrial dysfunction during experimental pulmonary carcinogenesis in vivo.

PubMed

Naveenkumar, Chandrashekar; Raghunandhakumar, Subramanian; Asokkumar, Selvamani; Devaki, Thiruvengadam

2013-04-01

Our current study aimed to evaluate the chemotherapeutic efficacy of baicalein (BE) in Swiss albino mice, which is exposed to benzo(a)pyrene [B(a)P] for its ability to alleviate mitochondrial dysfunction and systolic failure. Here, we report that oral administration of B(a)P (50 mg/kg body weight)-induced pulmonary genotoxicities in mice was assessed in terms of elevation in reactive oxygen species (ROS) generation and DNA damage in lung mitochondria. MDA-DNA adducts were formed in immunohistochemical analysis, which confirmed nuclear DNA damage. mRNA expression levels studied by RT-PCR analysis of voltage-dependent anion channel (VDAC) and adenine nucleotide translocase (ANT) were found to be significantly decreased and showed a marked increase in membrane permeability transition pore (MPTP) opening. Accompanied by up-regulated Bcl-xL and down-regulated Bid, Bim and Cyt-c proteins studied by immunoblot were observed in B(a)P-induced lung cancer-bearing animals. Administration of BE (12 mg/kg body weight) significantly reversed all the above deleterious changes. Moreover, assessment of mitochondrial enzyme system revealed that BE treatment effectively counteracts B(a)P-induced down-regulated levels/activities of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase, cytochrome-C-oxidase and ATP levels. Restoration of mitochondria from oxidative damage was further confirmed by transmission electron microscopic examination. Further analysis of lipid peroxidation, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, reduced glutathione, vitamin E and vitamin C in lung mitochondria was carried out to substantiate the antioxidant effect of BE. The overall data conclude that chemotherapeutic efficacy of BE might have strong mitochondria protective and restoration capacity in sub-cellular level against lung carcinogenesis in Swiss albino mice. © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

The Role of Musk in Relieving the Neurodegenerative Changes Induced After Exposure to Chronic Stress.

PubMed

Abd El Wahab, Manal Galal; Ali, Soad Shaker; Ayuob, Nasra Naeim

2018-06-01

This study aimed to evaluate the effect induced by musk on Alzheimer's disease-such as neurodegenerative changes in mice exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice were divided into 4 groups (n = 10); control, CUMS, CUMS + fluoxetine, CUMS + musk. At the end of the experiment, behavior of the mice was assessed. Serum corticosterone level, hippocampal protein level of the glucocorticoid receptors, and brain-derived neurotropic factor were also assessed. Hippocampus was histopathologically examined. Musk improved depressive status induced after exposure to CUMS as evidenced by the forced swimming and open field tests and improved the short-term memory as evidenced by the elevated plus maze test. Musk reduced both corticosterone levels and the hippocampal neurodegenerative changes observed after exposure to CUMS. These improvements were comparable to those induced by fluoxetine. Musk alleviated the memory impairment and neurodegenerative changes induced after exposure to the chronic stress.

Enhancement of Neuromuscular Activity by Natural Specimens and Cultured Mycelia of Cordyceps sinensis in Mice

PubMed Central

Singh, K. P.; Meena, H. S.; Negi, P. S.

2014-01-01

The present study was aimed to evaluate the effect of natural specimen and laboratory cultured mycelia of Cordyceps sinensis on neuromuscular activity in mice. The powder of natural specimen and laboratory cultured Cordyceps sinensis was orally administered at the dose rate of 100, 300 and 500 mg/kg for 30 days. Natural specimen and in vitro propagated Cordyceps sinensis showed significant (P<0.05) enhancement in neuromuscular endurance and antidepressant activity at 300 and 500 mg/kg as compared to the control group. However, the fungus did not proved to be as effective as fluoxetine in exhibiting antidepressant action. Muscular endurance was determined on a Rota rod apparatus while antidepressant (mood elevating) activity was measured on a photoactometer in Swiss albino mice. The effects produced by both natural specimens and laboratory cultured Cordyceps sinensis were comparable and showed almost equal potency. PMID:25425763

Enhancement of Neuromuscular Activity by Natural Specimens and Cultured Mycelia of Cordyceps sinensis in Mice.

PubMed

Singh, K P; Meena, H S; Negi, P S

2014-09-01

The present study was aimed to evaluate the effect of natural specimen and laboratory cultured mycelia of Cordyceps sinensis on neuromuscular activity in mice. The powder of natural specimen and laboratory cultured Cordyceps sinensis was orally administered at the dose rate of 100, 300 and 500 mg/kg for 30 days. Natural specimen and in vitro propagated Cordyceps sinensis showed significant (P<0.05) enhancement in neuromuscular endurance and antidepressant activity at 300 and 500 mg/kg as compared to the control group. However, the fungus did not proved to be as effective as fluoxetine in exhibiting antidepressant action. Muscular endurance was determined on a Rota rod apparatus while antidepressant (mood elevating) activity was measured on a photoactometer in Swiss albino mice. The effects produced by both natural specimens and laboratory cultured Cordyceps sinensis were comparable and showed almost equal potency.

Oxidative stress due to (R)-styrene oxide exposure and the role of antioxidants in non-Swiss albino (NSA) mice.

PubMed

Meszka-Jordan, Anna; Mahlapuu, Riina; Soomets, Ursel; Carlson, Gary P

2009-01-01

Styrene produces lung and liver damage that may be related to oxidative stress. The purpose of this study was to investigate the toxicity of (R)-styrene oxide (R-SO), the more active enantiomeric metabolite of styrene, and the protective properties of the antioxidants glutathione (GSH), N-acetylcysteine (NAC), and 4-methoxy-L-tyrosinyl-gamma-L-glutamyl-L-cysteinyl-glycine (UPF1) against R-SO-induced toxicity in non-Swiss Albino (NSA) mice. UPF1 is a synthetic GSH analog that was shown to have 60 times the ability to scavenge reactive oxygen species (ROS) in comparison to GSH. R-SO toxicity to the lung was measured by elevations in the activity of lactate dehydrogenase (LDH), protein concentration, and number of cells in bronchoalveolar lavage fluid (BALF). Toxicity to the liver was measured by increases in serum sorbitol dehydrogenase (SDH) activity. Antioxidants were not able to decrease the adverse effects of R-SO on lung. However, NAC (200 mg/kg) ip and GSH (600 mg/kg), administered orally prior to R-SO (300 mg/kg) ip, showed significant protection against liver toxicity as measured by SDH activity. Unexpectedly, a synthetic GSH analog, UPF1 (0.8 mg/kg), administered intravenously (iv) prior to R-SO, produced a synergistic effect with regard to liver and lung toxicity. Treatment with UPF1 (0.8 mg/kg) iv every other day for 1 wk for preconditioning prior to R-SO ip did not result in any protection against liver and lung toxicity, but rather enhanced the toxicity when administered prior R-SO. The results of the present study demonstrated protection against R-SO toxicity in liver but not lung by the administration of the antioxidants NAC and GSH.

Anti-neoplastic activities of sepia officinalis ink and coelatura aegyptiaca extracts against Ehrlich ascites carcinoma in Swiss albino mice

PubMed Central

Soliman, Amel M; Fahmy, Sohair R; El-Abied, Salma A

2015-01-01

Objectives: With the development of sophisticated instruments for the isolation and elucidation of natural products structures from marine and freshwater organisms, major advances have been made in the discovery of aquatic derived therapeutics. Present investigations were carried out to evaluate cuttlefish (Sepia officinalis) ink extract (IE) and freshwater clam (Coelatura aegyptiaca) extract (CE) for their anticancer and antioxidant activities as compared to 5-flurouracil (5-Fu), in Ehrlich ascites carcinoma (EAC). Methods: Sixty female Swiss albino mice were divided into five groups (n = 12). All groups except group I received EAC cells (5 × 106 cells/mouse i.p.) and this was taken as the 0th day. Group I served as saline control (5 ml/kg 0.9% NaCl w/v p.o). Group II served as EAC control. Rats of groups III, IV and V received IE, CE (200 mg/kg body weight i.p.), and reference drug (5-Fu, 20 mg/kg body weight i.p.), respectively. Results: The reduction in tumor volume, packed cell volume, tumor cell counts and increase in median survival time and percentage increase in life span in treated animals were observed. There was a significant increase in RBC count; Hb content in treated animals and reduction in total WBC count. There was a significant decrease in AST, ALT, ALP and liver MDA levels and increase in GSH, SOD and NO levels were observed in all treated animals. Conclusion: Both IE and CE were effective in inhibiting the tumor growth in ascitic tumor models. The biochemical, antioxidants and histopathological studies were also supported their antitumor properties. PMID:26097537

Protective effect of Selenium nanoparticle against cyclophosphamide induced hepatotoxicity and genotoxicity in Swiss albino mice.

PubMed

Bhattacharjee, Arin; Basu, Abhishek; Ghosh, Prosenjit; Biswas, Jaydip; Bhattacharya, Sudin

2014-08-01

Cyclophosphamide (CP) is the most commonly used chemotherapeutic drug for various types of cancer. However, its use causes severe cytotoxicity to normal cells in human. It is well known that the undesirable side effects are caused due to the formation of reactive oxygen species. Selenium is an essential micronutrient for both animals and humans and has antioxidant and membrane stabilizing property, but selenium is also toxic above certain level. Nano selenium has been well proved to be less toxic than inorganic selenium as well as certain organoselenium compounds. The objective of the study is to evaluate the protective role of Nano-Se against CP-induced hepatotoxicity and genotoxicity in Swiss albino mice. CP was administered intraperitoneally (25 mg/kg b.w.) and Nano-Se was given by oral gavages (2 mg Se/kg b.w.) in concomitant and pretreatment scheme. Intraperitoneal administration of CP induced hepatic damage as indicated by the serum marker enzymes aspartate and alanine transaminases and increased the malonaldehyde level, depleted the glutathione content and antioxidant enzyme activity (glutathione peroxidase, glutathione-s-transferase, superoxide dismutase and catalase), and induced DNA damage and chromosomal aberration. Oral administration of Nano-Se caused a significant reduction in malonaldehyde, ROS level and glutathione levels, restoration of antioxidant enzyme activity, reduction in chromosomal aberration in bone marrow, and DNA damage in lymphocytes and also in bone marrow. Moreover, the chemoprotective efficiency of Nano-Se against CP induced toxicity was confirmed by histopathological evaluation. The results support the protective effect of Nano-Se against CP-induced hepatotoxicity and genotoxicity. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Altered host resistance to Listeria monocytogenes in mice exposed to 1-chloroacetophenone (CN) vapours

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, P.; Kumar, P.; Zachariah, K.

1992-06-01

Short term repeated exposure of 1-chloroacetophenone (CN) vapours at a concentration of 0.153 mg per litre for 15 minutes daily on 10 consecutive days in Swiss albino male mice resulted in increased mortality to Listeria monocytogenes. Significantly elevated bacterial growth was observed in the spleen and liver of the CN exposed animals. The increased bacterial count in these organs was evident within 4-6 days post challenge as compared to vehicle exposed infected and unexposed infected animals. Increased susceptibility to infection has been considered to be the function of immune alteration due to cumulative short term effects of CN vapour inhalation.more » This may be attributed to immunotoxic effects of CN on T-cells mediated macrophage functions.« less

Fourier transform-infrared spectroscopy as a diagnostic tool for mosquito coil smoke inhalation toxicity in Swiss Albino mice

NASA Astrophysics Data System (ADS)

Anusha, Chidambaram; Sankar, Renu; Varunkumar, Krishnamoorthy; Sivasindhuja, Gnanasambantham; Ravikumar, Vilwanathan

2017-12-01

The goal of this study is to establish Fourier transform-infrared (FTIR) spectroscopy as a diagnostic tool for allethrin-based mosquito coil smoke inhalation induced toxicity in mice. Primarily, we confirmed mosquito coil smoke inhalation toxicity in mice via reduced the body, organ weight and major vital organ tissue morphological structure changes. Furthermore, FTIR spectra was collected from control and mosquito coil smoke inhalation (8 h per day for 30 days) mice various tissues like liver, kidney, lung, heart and brain, to investigate the functional groups and their corresponding biochemical content variations. The FTIR spectra result shown major bio macromolecules such as protein and lipid functional peaks were shifted (decreased) in the mosquito coil smoke inhalation group as compared to control. The drastic peak shift was noticed in the liver, kidney followed by lung and brain. It is therefore concluded that the FTIR spectroscopy can be a successful detection tool in mosquito coil smoke inhalation toxicity.

Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells.

PubMed

Ozkan, L; Ozuysal, S; Egeli, U; Adim, S B; Tunca, B; Aydemir, N; Ceçener, G; Ergül, E; Akpinar, G; Cimen, C; Engin, K; Ahmed, M M

2001-07-01

In this study we investigated the effect of Taxol, radiation, or Taxol plus radiation on highly proliferative normal tissue--the intestinal crypt cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered by bolus intravenously through the tail vein. Radiation was given using a linear accelerator. There were four treatment categories, which comprised a total of 34 groups. Each group consisted of five animals. The first category was a control category which comprised one group (n = 5). The second treatment category was Taxol alone which comprised three groups (n = 15). The third treatment category was radiation alone which comprised three groups (n = 15). The fourth treatment category was Taxol plus radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol or radiation or combined administration using ether anesthesia. Using a light microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of mice that were stained with hematoxylin-eosin. Differences between groups were statistically evaluated with Student's t-test. Taxol caused a dose-dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P = 0.006) at high doses. Similarly, radiation caused a dose-dependent increase in apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher radiation doses. Compared to radiation alone, Taxol caused a significant induction of apoptosis (P = 0.010). In combination, no significant radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when compared to radiation alone. However, an increase in apoptosis was observed after 24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001 and P = 0.0001). These findings suggest that Taxol did not cause a radiosensitizing effect in intestinal crypt cells. However, a 24-hour pretreatment of Taxol exposure followed by radiation caused significant induction of apoptosis and reduction of the mitotic index when compared to other Taxol timing sequences. Thus, the lack of a radiosensitizing effect of Taxol in these proliferative cells may be due to enhanced mitotic death rather than apoptotic death.

RADIATION EFFECTS ON IMMUNE MECHANISMS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoner, R.D.; Hale, W.M.

1963-03-01

Experiments were performed on pathogen-free Swiss albino mice to determine the repressive effect of ionizing radiation on immune mechanisms. In animals given sublethal doses of Co/sup 60/ gamma radiation by acute short-term exposure or by chronic long-term exposure at a low dose rate, ability to produce antibody was inhibited or abolished, and natural resistance and active and passive immunity to pneumococcal and Trichinella infections were severely depressed. It appears that the repression resulted from damage to the cellular defensive mechanisms of the host. Active immunity and natural resistance to influenza virus infections were not altered significantly by radiation. Exposure tomore » radiation enhanced the severity of anaphylactic shock markedly in mice previously sensitized to tetanus toxoid and challenged with tetanus toxoid after radiation. Chronic exposure to radiation caused immediate increased sensitivity to fatal anaphylaxis. (auth)« less

Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice.

PubMed

Cavuşoğlu, Kültiğin; Yapar, Kürşad; Oruç, Ertan; Yalçın, Emine

2011-10-01

The aim of the present study was to investigate the protective role of Ginkgo biloba L. leaf extract against the active agent of Roundup® herbicide (Monsanto, Creve Coeur, MO, USA). The Swiss Albino mice were randomly divided into six groups, with each group consisting of six animals: Group I (control) received an intraperitoneal injection of dimethyl sulfoxide (0.2 mL, once only), Group II received glyphosate at a dose of 50 mg/kg of body weight, Group III received G. biloba at a dose of 50 mg/kg of body weight, Group IV received G. biloba at a dose of 150 mg/kg of body weight, Group V received G. biloba (50 mg/kg of body weight) and glyphosate (50 mg/kg of body weight), and Group VI received G. biloba (150 mg/kg of body weight) and glyphosate (50 mg/kg of body weight). The single dose of glyphosate was given intraperitoneally. Animals from all the groups were sacrificed at the end of 72 hours, and their blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and glutathione (GSH) levels and the presence of micronucleus (MN), chromosomal aberrations (CAs), and pathological damages. The results indicated that serum AST, ALT, BUN, and creatinine levels significantly increased in mice treated with glyphosate alone compared with the other groups (P<.05). Besides, glyphosate-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels of the liver and kidney tissues. Moreover, glyphosate alone-treated mice presented higher frequencies of CAs, MNs, and abnormal metaphases compared with the controls (P<.05). These mice also displayed a lower mean mitotic index than the controls (P<.05). Treatment with G. biloba produced amelioration in indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity relative to Group II. Each dose of G. biloba provided significant protection against glyphosate-induced toxicity, and the strongest effect was observed at a dose of 150 mg/kg of body weight. Thus, in vivo results showed that G. biloba extract is a potent protector against glyphosate-induced toxicity, and its protective role is dose-dependent.

Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway.

PubMed

De, Soumita; Maroo, Niteeka; Saha, Piu; Hazra, Samik; Chatterjee, Mitali

2013-01-01

The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action. Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA) and generation of reactive oxygen species (ROS) was measured by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate. PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001). In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01. The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration.

Photocarcinogenesis by methoxypsoralen, neutral red, proflavine, and long UV radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santamaria, L.; Bianchi, A.; Arnaboldi, A.

1985-01-01

A study of the photosensitizing effects of 8-methoxypsoralen (MOP), neutral red (NR), and proflavine (PF) on the skin of female Swiss albino mice, strain 955, was carried out using fractionated exposure to long ultraviolet light (300-400 nm) and visible light (tungsten emission). The results (1) confirmed MOP photocarcinogenicity, (2) demonstrated that both NR and PF are photocarcinogens, and, further, (3) showed that the above UV light with 2.6% of fluence at 313 nm is a long-term carcinogenic agent even though the total dose of 313 nm was 100 times less than the minimal UV tumorigenic dose in mice. The tumorsmore » were mammary adenocarcinomas, carcinomas of skin appendages, carcino-mixo-sarcomas, lymphomas, and one case of thyroid adenocarcinoma. The implications of the above data regarding the controversy about oncogenic risks in photochemotherapy are discussed.« less

In vivo anticancer activity of vanillin semicarbazone

PubMed Central

Ali, Shaikh M Mohsin; Azad, M Abul Kalam; Jesmin, Mele; Ahsan, Shamim; Rahman, M Mijanur; Khanam, Jahan Ara; Islam, M Nazrul; Shahriar, Sha M Shahan

2012-01-01

Objective To evaluate the anticancer activity of vanillin semicarbazone (VSC) against Ehrlich ascites carcinoma (EAC) cells in Swiss albino mice. Methods The compound VSC at three doses (5, 7.5 and 10 mg/kg i.p.) was administered into the intraperitoneal cavity of the EAC inoculated mice to observe its efficiency by studying the cell growth inhibition, reduction of tumour weight, enhancement of survival time as well as the changes in depleted hematological parameters. All such parameters were also studied with a known standard drug bleomycin at the dose of 0.3 mg/kg (i.p.). Results Among the doses studied, 10 mg/kg (i.p.) was found to be quite comparable in potency to that of bleomycin at the dose of 0.3 mg/kg (i.p.). The host toxic effects of VSC was found to be negligible. Conclusions It can be concluded that VSC can therefore be considered as potent anticancer agent. PMID:23569946

Light intensity and the oestrous cycle in albino and normally pigmented mice.

PubMed

Donnelly, H; Saibaba, P

1993-10-01

The effects of light intensity (15-20 lux & 220-290 lux) on the oestrous cycle of albino and normally pigmented mice were examined. The oestrous cycle of both types of mice was shorter at the lower intensity but the difference was significant only with the black mice. The proportion of albino mice from which embryos were recovered was significantly smaller than the proportion of black mice at 15-20 lux but not at 220-290 lux. No significant differences due to strain or light intensity were found in the number of embryos recovered. We conclude that pigmented mice respond in the same way as albino mice to changes in light intensity within the range normally found in laboratory animal accommodation. That is, increased light intensity prolongs the oestrous cycle and the period of vaginal cornification.

Anti-tumor activity of Aloe vera against DMBA/croton oil-induced skin papillomagenesis in Swiss albino mice.

PubMed

Saini, M; Goyal, Pradeep Kumar; Chaudhary, Geeta

2010-01-01

Human populations are increasingly exposed to various carcinogens such as chemicals, radiation, and viruses in the environment. Chemopreventive drugs of plant origin are a promising strategy for cancer control because they are generally nontoxic or less toxic than synthetic che-mopreventive agents, and can be effective at different stages of carcinogenesis. The present investigation was undertaken to explore the antitumor activity of topical treatment with aloe vera (Aloe vera) gel, oral treatment with aloe vera extract, and topical and oral treatment with both gel and extract in stage-2 skin carcinogenesis in Swiss albino mice induced by 7,12-dim ethylbenz(a)anthracene (DMBA) and promoted croton (Croton tiglium) oil. The animals were randomly divided into 4 groups and treated as follows: Group I, DMBA + croton oil only (controls); Group II, DMBA + croton oil + topical aloe vera gel; Group III, DMBA + croton oil + oral aloe vera extract; Group I V, DMBA + croton oil + topical aloe vera gel + oral aloe vera extract. Results showed that body weight was significantly increased from 78.6% in the control group (Group I) to 92.5%, 87.5%, and 90.0% in Groups II, III, and I V, respectively. A 100% incidence of tumor development was noted in Group I, which was decreased to 50%, 60%, and 40% in Groups II, III, and I V, respectively. Also in Groups II, III, and IV, the cumulative number of papillomas was reduced significantly from 36 to 12, 15, and 11; tumor yield from 3.6 to 1.2, 1.5, and 1.1; and tumor burden from 3.6 to 2.4, 2.50, and 2.75, respectively, after treatment with aloe vera. Conversely, the average latent period increased significantly from 4.9 (Group I) to 5.23, 5.0, and 6.01 weeks in Groups II, III, and I V, respectively. We conclude that aloe vera protects mice against DMBA/croton oil-induced skin papillomagenesis, likely due to the chemopreventive activity of high concentrations of antioxidants such as vitamins A, C, and E; glutathione peroxidase; several isozymes of superoxide dismutase; the minerals selenium and zinc; and polysaccharides in aloe vera.

Protective effects of Moringa oleifera Lam. leaves against arsenic-induced toxicity in mice

PubMed Central

Sheikh, Afzal; Yeasmin, Fouzia; Agarwal, Smita; Rahman, Mashiur; Islam, Khairul; Hossain, Ekhtear; Hossain, Shakhawoat; Karim, Md Rezaul; Nikkon, Farjana; Saud, Zahangir Alam; Hossain, Khaled

2014-01-01

Objective To evaluate the protective role of leaves of Moringa oleifera (M. oleifera) Lam. against arsenic-induced toxicity in mice. Methods Swiss albino male mice were divided into four groups. The first group was used as non-treated control group while, the second, third, and fourth groups were treated with M. oleifera leaves (50 mg/kg body weight per day), sodium arsenite (10 mg/kg body weight per day) and sodium arsenite plus M. oleifera leaves, respectively. Serum indices related to cardiac, liver and renal functions were analyzed to evaluate the protective effect of Moringa leaves on arsenic-induced effects in mice. Results It revealed that food supplementation of M. oleifera leaves abrogated the arsenic-induced elevation of triglyceride, glucose, urea and the activities of alkaline phospatase, aspartate aminotransferase and alanine aminotransferase in serum. M. oleifera leaves also prevented the arsenic-induced perturbation of serum butyryl cholinesterase activity, total cholesterol and high density lipoprotein cholesterol. Conclusions The results indicate that the leaves of M. oleifera may be useful in reducing the effects of arsenic-induced toxicity. PMID:25183111

Metabolic rate and thermal insulation in albino and hairless mice

PubMed Central

Mount, L. E.

1971-01-01

1. Rates of oxygen consumption of albino and hairless mice were measured in a metabolism chamber during periods of approximately 5 or 24 hr. Rectal temperature was measured before and after each period. The chamber temperatures used were 22, 30 and 32° C for both albino and hairless, and in addition 34 and 36° C for the hairless mice. 2. The mean age and body weight of the albino mice were 102 days and 34·6 g; the corresponding values for the hairless mice were 87 days and 32·8 g. 3. The mean minimum rates of oxygen consumption (ml./kg.min) were 31·0 for the albino and 38·8 for the hairless mouse; the corresponding estimated critical temperatures were in the ranges 30-32° C for the albino mouse and 32-34° C for the hairless mouse. 4. The mean values for core-ambient thermal insulation (° C.m2.hr/kcal) were 0·418 and 0·328 for the albino mouse, and 0·275 and 0·221 for the hairless mouse, at 22 and 30° C respectively in each case. PMID:5097602

Quercetin ameliorates chronic unpredicted stress-induced behavioral dysfunction in male Swiss albino mice by modulating hippocampal insulin signaling pathway.

PubMed

Mehta, Vineet; Singh, Tiratha Raj; Udayabanu, Malairaman

2017-12-01

Chronic stress is associated with impaired neurogenesis, neurodegeneration and behavioral dysfunction, whereas the mechanism underlying stress-mediated neurological complications is still not clear. In the present study, we aimed to investigate whether chronic unpredicted stress (CUS) mediated neurological alterations are associated with impaired hippocampal insulin signaling or not, and studied the effect of quercetin in this scenario. Male Swiss albino mice were subjected to 21day CUS, during which 30mg/kg quercetin treatment was given orally. After 21days, behavioral functions were evaluated in terms of locomotor activity (Actophotometer), muscle coordination (Rota-rod), depression (Tail Suspension Test (TST), Forced Swim Test (FST)) and memory performance (Passive-avoidance step-down task (PASD)). Further, hippocampal insulin signaling was evaluated in terms of protein expression of insulin, insulin receptor (IR) and glucose transporter 4 (GLUT-4) and neurogenesis was evaluated in terms of doublecortin (DCX) expression. 21day CUS significantly impaired locomotion and had no effect on muscle coordination. Stressed animals were depressed and showed markedly impaired memory functions. Quercetin treatment significantly improvement stress-mediated behavior dysfunction as indicated by improved locomotion, lesser immobility time and greater frequency of upward turning in TST and FST and increased transfer latency on the day 2 (short-term memory) and day 5 (long-term memory) in PASD test. We observed significantly higher IR expression and significantly lower GLUT-4 expression in the hippocampus of stressed animals, despite of nonsignificant difference in insulin levels. Further, chronic stress impaired hippocampal neurogenesis, as indicated by the significantly reduced levels of hippocampal DCX expression. Quercetin treatment significantly lowered insulin and IR expression and significantly enhanced GLUT-4 and DCX expression in the hippocampus, when compared to CUS. In conclusion, quercetin treatment efficiently alleviated stress mediated behavioral dysfunction by modulating hippocampal insulin signaling and neurogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of genotoxic effect of taxol plus radiation on mice bone marrow cells.

PubMed

Ozkan, Lütfi; Egeli, Unal; Tunca, Berrin; Aydemir, Nilüfer; Ceçener, Gülşah; Akpinar, Gürler; Ergül, Emel; Cimen, Ciğdem; Ozuysal, Sema; Kahraman-Cetintaş, Sibel; Engin, Kayihan; Ahmed, Mansoor M

2002-01-01

In this study, we investigated the genotoxic effect of taxol, radiation, or taxol plus radiation on highly proliferative normal tissue-bone marrow cells of Swiss albino mice. Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered bolus intravenously through the tail vein. Radiation was given by using a linear accelerator. There were four treatment categories, which had a total of 34 groups. Each group consisted of five animals. The first was the control category that had one group (n = 5). The second treatment category was taxol alone, which had three groups as per taxol dose alone (n = 15). The third treatment category was radiation alone, which had three groups as per the radiation dose (n = 15). The fourth treatment category was taxol plus radiation, which had 27 groups as per combined radiation dose plus taxol dose concentration and as per pre-treatment timing sequence of taxol before radiation (n = 135). Mice were sacrificed 24 h after taxol or radiation or combined administration using ether anesthesia. The cells were then dropped on two labeled slides, flamed, air dried, and stained in 7% Giemsa; 20-30 well-spread mitotic metaphases were analyzed for each animal; the cells with chromosome breaks, acentric fragments, and rearrangements were evaluated on x1,000 magnification with light microscope (Zeiss axioplan). The mitotic index was determined by counting the number of mitotic cells among 1,000 cells per animal. Differences between groups were evaluated with Student's t-test statistically. Taxol caused a dose-dependent increase in chromosomal aberrations (P = 0.027). Similarly, radiation caused a dose-dependent increase in chromosomal aberrations (P = 0.003) and decreased mitotic index (P = 0.002). In combination, there were a small enhancements at the 40 mg/kg taxol dose level and at 0.25 and 0.5 Gy radiation doses in the 48 h group. However, an increase in chromosomal aberrations was observed after 48 hours of taxol exposure when compared 12 or 24 h of taxol exposure (P = 0.001 and P = 0.019). These findings suggest that taxol at the high doses with low dose radiation caused radiosensitizing effect in bone marrow cells. Forty-eight-hour pretreatment of taxol exposure followed by radiation caused significant induction of chromosomal aberrations and a reduction of mitotic index when compared to other taxol timing sequence. Copyright 2002 Wiley-Liss, Inc.

Attenuation of hepatotoxicity and oxidative stress in diabetes STZ-induced type 1 by biotin in Swiss albino mice

PubMed Central

Aldahmash, Badr Abdullah; El-Nagar, Doaa Mohamed; Ibrahim, Khalid Elfakki

2015-01-01

Diabetes mellitus is one of the major health problems. This study was designed to investigate the effect of biotin to regulate blood glucose level, reduced toxicity and oxidative stress in liver of diabetic mice STZ-induced type 1. Male mice were divided into three groups, the first one served as the control group, the second and the third groups received single ip dose of 150 mg/kg of STZ, the second group served as the untreated diabetic group, the third group received daily oral dose of 15 mg/kg of biotin, livers and liver index showed insignificant difference among groups. Blood glucose level showed a significant decrease in treated diabetic mice compared to untreated diabetic mice. Biochemical analysis showed a significant decrease in liver enzymes AST and ALT compared to the control group. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and moderate to severe histopathological score, whereas, treated diabetic mice with biotin showed reduction in hepatotoxicity represented by appearance of relative healthy hepatocytes and normal histopathological score. Immunohistochemistry of acrolein showed intense immunoreactions in liver section of untreated diabetic mice and faint immunoreactions in treated diabetic mice with biotin as evidence to oxidative stress reduction. PMID:26981014

Cognitive and biochemical effects of monosodium glutamate and aspartame, administered individually and in combination in male albino mice.

PubMed

Abu-Taweel, Gasem M; A, Zyadah M; Ajarem, Jamaan S; Ahmad, Mohammad

2014-01-01

The present study was designed to investigate the in vivo effects of monosodium glutamate (MSG) and aspartame (ASM) individually and in combination on the cognitive behavior and biochemical parameters like neurotransmitters and oxidative stress indices in the brain tissue of mice. Forty male Swiss albino mice were randomly divided into four groups of ten each and were exposed to MSG and ASM through drinking water for one month. Group I was the control and was given normal tap water. Groups II and III received MSG (8 mg/kg) and ASM (32 mg/kg) respectively dissolved in tap water. Group IV received MSG and ASM together in the same doses. After the exposure period, the animals were subjected to cognitive behavioral tests in a shuttle box and a water maze. Thereafter, the animals were sacrificed and the neurotransmitters and oxidative stress indices were estimated in their forebrain tissue. Both MSG and ASM individually as well as in combination had significant disruptive effects on the cognitive responses, memory retention and learning capabilities of the mice in the order (MSG+ASM)>ASM>MSG. Furthermore, while MSG and ASM individually were unable to alter the brain neurotransmitters and the oxidative stress indices, their combination dose (MSG+ASM) decreased significantly the levels of neurotransmitters (dopamine and serotonin) and it also caused oxidative stress by increasing the lipid peroxides measured in the form of thiobarbituric acid-reactive substances (TBARS) and decreasing the level of total glutathione (GSH). Further studies are required to evaluate the synergistic effects of MSG and ASM on the neurotransmitters and oxidative stress indices and their involvement in cognitive dysfunctions. Copyright © 2014 Elsevier Inc. All rights reserved.

Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice

PubMed Central

Islam, Farhadul; Ali, Shaikh Mohummad Mohsin; Khanam, Jahan Ara

2013-01-01

Objective To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice. Methods Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed. Results The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC. Conclusions ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice. PMID:23593588

Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice.

PubMed

Thakare, Vishnu N; Dhakane, Valmik D; Patel, Bhoomika M

2017-04-01

Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro-/anti-oxidative homeostasis.

Effect of GABAB receptor antagonists (CGP 35348 and CGP 55845) on serum interleukin 6 and 18 concentrations in albino mice following neonatal hypoxia ischemia insult.

PubMed

Gillani, Quratulane; Ali, Muhammad; Iqbal, Furhan

2016-09-01

Interleukin (IL) 6 and 18 plays an important role in inflammatory response following hypoxia ischemia encephalopathy (HIE). Present study was designed to demonstrate the effect of two GABAB receptor antagonists (CGP 35348 and 55845), respectively, on the serum IL6 and IL 18 concentrations in albino mice. Albino mice pups (of both genders) were subjected to Murine model of hypoxia-ischemia encephalopathy on postnatal day 10 (right common carotid artery was ligated followed by 8% hypoxia for 25 minutes). After neonatal brain damage and following weaning, mice were divided in three groups, in gender specific manner, and fed on normal rodent diet till they were 13 week old. At this time point, group 1 received intraperitonial saline solution (control group), group 2 was supplemented with CGP 35348 (1mg/ml solvent/Kg body weight) and group 3 with CGP 55845 (1mg/ml solvent/Kg body weight), intraperitonially, for 12 days and IL 6 and 18 concentrations were determined in serum by ELISA. It was observed that CGP 35348 supplementation resulted in reduced interlukin-6 and interlukin-18 concentrations in male albino mice. While CGP 55845 supplementation increased IL-6 and IL-18 concentrations in female albino mice following HIE. Our results are indicating that GABAB receptor antagonist's supplementation affects IL concentrations in albino mice in a gender specific manner following neonatal brain damage and can be further explored for the treatments of hypoxia ischemia associated neurological ailments.

Antimalarial and hepatoprotective effects of crude ethanolic extract of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.)P.Karst. (higher Basidiomycetes), in Plasmodium berghei-infected mice.

PubMed

Oluba, Olarewaju M; Olusola, Augustine O; Fagbohunka, Bamidele S; Onyeneke, E

2012-01-01

This study was aimed at investigating the in vivo antimalarial activity (using some biochemical indices) of crude aqueous extracts of the fruiting bodies of Ganoderma lucidum, a mushroom with well-established medicinal properties. A rodent malaria parasite, Plasmodium berghei (1 × 107), was inoculated intraperitoneally into Swiss albino mice. The test groups were administered G. lucidum extract and chloroquine (CQ, as standard drug), while the control groups were administered the same amount of distilled water by an intragastric tube once daily. The antimalarial activity of the extract was investigated from the suppressive, curative, and prophylactic effects of the extract on parasite growth. Serum aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma glutamine transpeptidase (γ-GT) levels monitored following the 4-day suppressive test were significantly reduced, with a corresponding significant increase in the livers of mice treated with the extract compared with infected untreated mice. The results obtained from this study provide scientific justification in an animal model of malaria that an ethanolic extract of G. lucidum possesses potent antimalarial activity and also could help ameliorate the attendant Plasmodium-induced liver damage due to malarial infection.

Evaluation of protective effect of cactus pear seed oil (Opuntia ficus-indica L. MILL.) against alloxan-induced diabetes in mice.

PubMed

Berraaouan, Ali; Abderrahim, Ziyyat; Hassane, Mekhfi; Abdelkhaleq, Legssyer; Mohammed, Aziz; Mohamed, Bnouham

2015-07-01

To evaluate the in vitro antioxidant power of cactus pear seed oil [Opuntia ficus-indica L. MILL. (CPSO)] and its protective effect against chemically induced diabetes mellitus in mice. The in vitro antioxidant effect of CPSO was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay. The preventive effect was conducted on Swiss albino mice treated with CPSO (2 mL/kg, per os), before and after a single intraperitoneal alloxan administration (100 mg/kg). Survival rate, body weight and fasting blood glucose were measured and histopathological analysis of pancreas was performed to evaluate alloxan-induced tissue injuries. CPSO exhibited an antioxidant effect in DPPH scavenging assay. Moreover, the administration of CPSO (2 mL/kg) significantly attenuated alloxan-induced death and hyperglycemia (P < 0.001) in treated mice. Morphometric study of pancreas revealed that CPSO significantly protected islets of langerhans against alloxan induced-tissue alterations. Based on theses results, CPSO can prevente alloxan-induced-diabetes by quenching free radicals produced by alloxan and inhibiting tissue injuries in pancreatic β-cells. Copyright © 2015 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Quercetin attenuates the development of 7, 12-dimethyl benz (a) anthracene (DMBA) and croton oil-induced skin cancer in mice

PubMed Central

Ali, Huma; Dixit, Savita

2015-01-01

Abstract To evaluate the chemopreventive potential of quercetin in an experimental skin carcinogenesis mouse model. Skin tumor was induced by topical application of 7, 12-dimethyl Benz (a) anthracene (DMBA) and Croton oil in Swiss albino mouse. Quercetin was orally administered at a concentration of 200 mg/kg and 400 mg/kg body weight daily for 16 weeks in mouse to evaluate chemopreventive potential. Skin cancer was assessed by histopathological analysis. We found that quercetin reduced the tumor size and the cumulative number of papillomas. The mean latent period was significantly increased as compared to carcinogen treated controls. Quercetin significantly decreased the serum levels of glutamate oxalate transaminase, glutamate pyruvate transaminase, alkaline phosphatase and bilirubin. It significantly increased the levels of glutathione, superoxide dismutase and catalase. The elevated level of lipid peroxides in the control group was significantly inhibited by quercetin. Futhermore, DNA damage was significantly decreased in quercetin treated mice as compared to DMBA and croton oil treated mice. The results suggest that quercetin exerts chemopreventive effect on DMBA and croton oil induced skin cancer in mice by increasing antioxidant activities. PMID:25859269

Evaluation of anxiolytic activity of aqueous extract of Coriandrum sativum Linn. in mice: A preliminary experimental study

PubMed Central

Latha, K.; Rammohan, B.; Sunanda, B. P. V.; Maheswari, M. S. Uma; Mohan, Surapaneni Krishna

2015-01-01

Objectives: To evaluate the anxiolytic effect of Coriandrum sativum (CS) aqueous extract in mice. To compare the antianxiety activity of CS against standard drug diazepam (3 mg/kg). Materials and Methods: After obtaining Institutional Animal Ethics Committee approval, Swiss albino mice (18–25 g) of either sex were randomly divided into five groups of six animals each. Dried powder of CS leaves was boiled with distilled water, cooled, filtered, placed on a hotplate for complete evaporation, finally weighed and stored. The control group, test group, and standard drugs group received saline, CS extract (50, 100, and 200 mg/kg), diazepam (3 mg/kg), respectively, by oral feeding. The antianxiety effect was assessed by elevated plus maze (EPM) in mice. Results: In EPM, it implied that CS 50 mg/kg (Group III), 100 mg/kg (Group IV), and 200 mg/kg (Group V) significantly (P < 0.001) increases the number of entries in open arms compared to control. The time spent in open arms also increased in all the doses of CS extract significantly. Conclusion: The current study demonstrates statistically significant dose-dependent antianxiety activity of CS leaves. PMID:26109787

Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway

PubMed Central

De, Soumita; Maroo, Niteeka; Saha, Piu; Hazra, Samik; Chatterjee, Mitali

2013-01-01

Objectives: The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE) along with establishing its putative mechanism of action. Materials and Methods: Male Swiss albino mice after pre-treatment (1 h) with different doses of PBE were injected 0.8% (v/v) acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA) and generation of reactive oxygen species (ROS) was measured by flow cytometry using 2’,7’-dichlorodihydrofluorescein diacetate. Results: PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001). In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01. Conclusions: The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration. PMID:24130383

Modulation of antioxidant potential in liver of mice by kernel oil of cashew nut (Anacardium occidentale) and its lack of tumour promoting ability in DMBA induced skin papillomagenesis.

PubMed

Singh, Bimala; Kale, R K; Rao, A R

2004-04-01

Cashew nut shell oil has been reported to possess tumour promoting property. Therefore an attempt has been made to study the modulatory effect of cashew nut (Anlacardium occidentale) kernel oil on antioxidant potential in liver of Swiss albino mice and also to see whether it has tumour promoting ability like the shell oil. The animals were treated orally with two doses (50 and 100 microl/animal/day) of kernel oil of cashew nut for 10 days. The kernel oil was found to enhance the specific activities of SOD, catalase, GST, methylglyoxalase I and levels of GSH. These results suggested that cashew nut kernel oil had an ability to increase the antioxidant status of animals. The decreased level of lipid peroxidation supported this possibility. The tumour promoting property of the kernel oil was also examined and found that cashew nut kernel oil did not exhibit any solitary carcinogenic activity.

Three further triterpenoid saponins from Gleditsia caspica fruits and protective effect of the total saponin fraction on cyclophosphamide-induced genotoxicity in mice.

PubMed

Melek, Farouk R; Aly, Fawzia A; Kassem, Iman A A; Abo-Zeid, Mona A M; Farghaly, Ayman A; Hassan, Zeinab M

2015-01-01

Three triterpenoidal saponins were isolated from the saponin fraction derived from a Gleditsia caspica Desf. methanolic fruit extract. The isolated saponins were identified as gleditsiosides B, C, and Q based on spectral data. The saponin-containing fraction was evaluated in vivo for genotoxic and antigenotoxic activities. The fraction caused no DNA damage in Swiss albino male mice treated with a dose of 45 mg/kg body weight for 24 h, although it significantly inhibited the number of chromosomal aberrations induced by cyclophosphamide (CP) in bone marrow and germ cells when applied before or after CP administration. The inhibitory indices in chromosomal aberrations were 59% and 41% for bone marrow and 48% and 43% for germ cells, respectively. In addition, the saponin fraction was found to reduce the viability of the human tumor cell line MCF-7 in a dose-dependent manner with an extrapolated IC50 value in the range of 220 μg/mL.

Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.

PubMed

Dwivedi, Gaurav Raj; Tiwari, Nimisha; Singh, Aastha; Kumar, Akhil; Roy, Sudeep; Negi, Arvind Singh; Pal, Anirban; Chanda, Debabrata; Sharma, Ashok; Darokar, Mahendra P

2016-03-01

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

Chemopreventive effects of cardamom (Elettaria cardamomum L.) on chemically induced skin carcinogenesis in Swiss albino mice.

PubMed

Qiblawi, Samir; Al-Hazimi, Awdah; Al-Mogbel, Mohammed; Hossain, Ashfaque; Bagchi, Debasis

2012-06-01

The chemopreventive potential of cardamom was evaluated on 7,12-dimethylbenz[a]anthracene-initiated and croton oil-promoted mouse skin papillomagenesis. A significant reduction in the values of tumor incidence, tumor burden, and tumor yield and the cumulative number of papillomas was observed in mice treated orally with 0.5 mg of cardamom powder in suspension continuously at pre-, peri-, and post-initiational stages of papillomagenesis compared with the control group. The average weight and diameter of tumors recorded were also comparatively lower in the cardamom-treated mouse group. Treatment of cardamom suspension by oral gavage for 15 days resulted in a significant decrease in the lipid peroxidation level of the liver (P < .01). In addition, the reduced glutathione level was significantly elevated in comparison with the control group (P < .05) following cardamom suspension treatment. Taken together, these findings indicate the potential of cardamom as a chemopreventive agent against two-stage skin cancer.

Antidepressant-like effects of methanol extract of Hibiscus tiliaceus flowers in mice

PubMed Central

2012-01-01

Background Hibiscus tiliaceus L. (Malvaceae) is used in postpartum disorders. Our purpose was to examine the antidepressant, anxiolytic and sedative actions of the methanol extract of H. tiliaceus flowers using animal models. Methods Adult male Swiss albino mice were treated with saline, standard drugs or methanol extract of H. tiliaceus and then subjected to behavioral tests. The forced swimming and tail suspension tests were used as predictive animal models of antidepressant activity, where the time of immobility was considered. The animals were submitted to the elevated plus-maze and ketamine-induced sleeping time to assess anxiolytic and sedative activities, respectively. Results Methanol extract of H. tiliaceus significantly decreased the duration of immobility in both animal models of antidepressant activity, forced swimming and tail suspension tests. This extract did not potentiate the effect of ketamine-induced hypnosis, as determined by the time to onset and duration of sleeping time. Conclusion Our results indicate an antidepressant-like profile of action for the extract of Hibiscus tiliaceus without sedative side effect. PMID:22494845

Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

PubMed

C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

2014-12-01

3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions.

Generating Chimeric Mice by Using Embryos from Nonsuperovulated BALB/c Mice Compared with Superovulated BALB/c and Albino C57BL/6 Mice.

PubMed

Esmail, Michael Y; Qi, Peimin; Connor, Aurora Burds; Fox, James G; García, Alexis

2016-01-01

The reliable generation of high-percentage chimeras from gene-targeted C57BL/6 embryonic stem cells has proven challenging, despite optimization of cell culture and microinjection techniques. To improve the efficiency of this procedure, we compared the generation of chimeras by using 3 different inbred, albino host, embryo-generating protocols: BALB/cAnNTac (BALB/c) donor mice superovulated at 4 wk of age, 12-wk-old BALB/c donor mice without superovulation, and C57BL/6NTac-Tyr(tm1Arte) (albino B6) mice superovulated at 4 wk of age. Key parameters measured included the average number of injectable embryos per donor, the percentage of live pups born from the total number of embryos transferred to recipients, and the number of chimeric pups with high embryonic-stem-cell contribution by coat color. Although albino B6 donors produced significantly more injectable embryos than did BALB/c donors, 12-wk-old BALB/c donor produced high-percentage (at least 70%) chimeras more than 2.5 times as often as did albino B6 mice and 20 times more efficiently than did 4-wk-old BALB/c donors. These findings clearly suggest that 12-wk-old BALB/c mice be used as blastocyst donors to reduce the number of mice used to generate each chimera, reduce the production of low-percentage chimeras, and maximize the generation of high-percentage chimeras from C57BL/6 embryonic stem cells.

Immunopathological Changes in the Brain of Immunosuppressed Mice Experimentally Infected with Toxocara canis

PubMed Central

Eid, Mohamed M.; El-Kowrany, Samy I.; Othman, Ahmad A.; Gendy, Dina I. El; Saied, Eman M.

2015-01-01

Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection. PMID:25748709

Does vitamin E prevent tubal damage caused by smoking? A light microscopy and animal study.

PubMed

Duran, Muzeyyen; Ustunyurt, Emin; Kosus, Aydin; Kosus, Nermin; Turhan, Nilgun; Hızlı, Deniz; Sarac, Gulce Naz; Erdogan, Deniz

2014-04-01

To assess the histomorphological effects of smoking on the cilia of fallopian tubes in mice and the effect of vitamin E on the negative effects of smoke. Eighteen 12-14 week-old Swiss albino type female mice were randomly divided into three groups, each consisting of six mice: Group A: control group; Group B: mice exposed to cigarette smoke; Group C: mice exposed to cigarette smoke together with vitamin E. Groups B and C were exposed to cigarette smoke for 10 weeks. After 10 weeks, tubal excision was performed in all animals. Histopathologic examination of excised tubal tissue was conducted under light microscopy. The number of cilia was significantly lower in Group B. Although not statistically significant, the median number of cilia in Group C was measured to be higher than in Group B but lower than in Group A. Based on the results, it can be concluded that smoking decreases tubal cilia numbers. Supplementation by vitamin E may treat or at least help to slow down the decrease in number of cilia caused by smoking; therefore it could be used therapeutically in the treatment of smoking-related tubal damage. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

Spatiotemporal features of early neuronogenesis differ in wild-type and albino mouse retina

NASA Technical Reports Server (NTRS)

Rachel, Rivka A.; Dolen, Gul; Hayes, Nancy L.; Lu, Alice; Erskine, Lynda; Nowakowski, Richard S.; Mason, Carol A.

2002-01-01

In albino mammals, lack of pigment in the retinal pigment epithelium is associated with retinal defects, including poor visual acuity from a photoreceptor deficit in the central retina and poor depth perception from a decrease in ipsilaterally projecting retinal fibers. Possible contributors to these abnormalities are reported delays in neuronogenesis (Ilia and Jeffery, 1996) and retinal maturation (Webster and Rowe, 1991). To further determine possible perturbations in neuronogenesis and/or differentiation, we used cell-specific markers and refined birth dating methods to examine these events during retinal ganglion cell (RGC) genesis in albino and pigmented mice from embryonic day 11 (E11) to E18. Our data indicate that relative to pigmented mice, more ganglion cells are born in the early stages of neuronogenesis in the albino retina, although the initiation of RGC genesis in the albino is unchanged. The cellular organization of the albino retina is perturbed as early as E12. In addition, cell cycle kinetics and output along the nasotemporal axis differ in retinas of albino and pigmented mice, both absolutely, with the temporal aspect of the retina expanded in albino, and relative to the position of the optic nerve head. Finally, blocking melanin synthesis in pigmented eyecups in culture leads to an increase in RGC differentiation, consistent with a role for melanin formation in regulating RGC neuronogenesis. These results point to spatiotemporal defects in neuronal production in the albino retina, which could perturb expression of genes that specify cell fate, number, and/or projection phenotype.

Anxiety-like behaviour in mice exposed to tannery wastewater: The effect of photoelectrooxidation treatment.

PubMed

Siqueira, Ionara Rodrigues; Vanzella, Cláudia; Bianchetti, Paula; Rodrigues, Marco Antonio Siqueira; Stülp, Simone

2011-01-01

The leather industry is a major producer of wastewaters and releases large quantities of many different chemical agents used in hide processing into the environment. Since the central nervous system is sensitive to many different contaminants, our aim was to investigate the neurobehavioral effects of exposure of mice to tannery effluents using animal models of depression and anxiety, namely forced swim and elevated plus-maze. In order to propose a clean technology for the treatment of this effluent, we also investigated the exposure of mice to effluents treated by photoelectrooxidation process (PEO). Adult male Swiss albino mice (CF1 strain) were given free access to water bottles containing an effluent treated by a tannery (non-PEO) or PEO-treated tannery wastewater (0.1 and 1% in drinking water). Exposure to tannery wastewater induced behavioural changes in the mice in elevated plus-maze. Exposure to non-PEO 1% decreased the percentage of time spent in the open arms, indicating anxiety-like behaviour. Exposure to tannery wastewater did not alter immobility time in the forced swim test, suggesting that tannery effluents did not induce depression-like behaviour in the mice. These behavioural data suggest that non-PEO tannery effluent has an anxiogenic effect, whereas PEO-treated tannery effluents do not alter anxiety levels. Copyright © 2011 Elsevier Inc. All rights reserved.

Design and synthesis of novel diphenyl oxalamide and diphenyl acetamide derivatives as anticonvulsants.

PubMed

Nikalje, Anna Pratima G; Ghodke, Mangesh; Girbane, Amol

2012-01-01

A series of novel N(1) -substituted-N(2) ,N(2) -diphenyl oxalamides 3a-l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF and K(2) CO(3) . Also 2-substituted amino-N,N-diphenylacetamides 5a-m were designed by pharmacophore generation and synthesized by stirring 2-chloro-N,N-diphenylacetamide (4) and various substituted amines in acetone using triethyl amine as a catalyst. All the synthesized compounds were screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Neurotoxicity screening and behavioral testing was also carried out. Some of the synthesized test compounds were found to be more potent than the standard drug. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protective effect of Heliotropium eichwaldi against cisplatin-induced nephrotoxicity in mice.

PubMed

Sharma, Surendra Kr; Goyal, Naveen

2012-05-01

The aim of the present study was to evaluate the nephroprotective effect of methanolic extract of Heliotropium eichwaldii (MHE) in mice with cisplatin-induced acute renal damage. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin (16mg/kg). Swiss albino mice were injected with vehicle, cisplatin, cisplatin plus MHE 200 mg/kg and cisplatin plus MHE 400mg/kg, respectively. MHE was administered for 7 d at a dose of 200 and 400 mg/kg per day orally starting 4 d before cisplatin injection. Animals were sacrificed 3d after treatment and blood as well as kidney tissue was isolated and analyzed. The various parameters such as blood urea nitrogen (BUN), serum creatinine (CRE), malondialdehyde (MDA), and catalase (CAT) and superoxide dismutase (SOD) activities were analyzed. MHE treatment significantly reduced BUN and serum CRE levels elevated by cisplatin administration (P<0.05). Also, it significantly attenuated cisplatin-induced increase in MDA level and improved the decreased CAT and SOD activities in renal cortical homogenates (P<0.05). Additionally, histopathological examination and scoring showed that MHE markedly ameliorated cisplatin-induced renal tubular necrosis. MHE can be considered a potential candidate for protection of nephrotoxicity induced by cisplatin.

Effect of helium-neon laser irradiation on hair follicle growth cycle of Swiss albino mice.

PubMed

Shukla, S; Sahu, K; Verma, Y; Rao, K D; Dube, A; Gupta, P K

2010-01-01

We report the results of a study carried out to investigate the effect of helium-neon (He-Ne) laser (632.8 nm) irradiation on the hair follicle growth cycle of testosterone-treated and untreated mice. Both histology and optical coherence tomography (OCT) were used for the measurement of hair follicle length and the relative percentage of hair follicles in different growth phases. A positive correlation (R = 0.96) was observed for the lengths of hair follicles measured by both methods. Further, the ratios of the lengths of hair follicles in the anagen and catagen phases obtained by both methods were nearly the same. However, the length of the hair follicles measured by both methods differed by a factor of 1.6, with histology showing smaller lengths. He-Ne laser irradiation (at approximately 1 J/cm(2)) of the skin of both the control and the testosterone-treated mice was observed to lead to a significant increase (p < 0.05) in % anagen, indicating stimulation of hair growth. The study also demonstrates that OCT can be used to monitor the hair follicle growth cycle, and thus hair follicle disorders or treatment efficacy during alopecia. (c) 2009 S. Karger AG, Basel.

Regulation of cellular marker modulated upon irradiation of low power laser light in burn injured mice

NASA Astrophysics Data System (ADS)

Rathnakar, Bharath; Prabhu, Vijendra; Rao, Bola Sadashiva Satish; Chandra, Subhash; Rai, Sharada; Mahato, Krishna Kishore

2016-12-01

The present study intends to understand the importance of cellular marker in tissue regeneration regulated upon irradiation of low power laser light in burn inflicted mice. Under anesthetic conditions, the thermal injury was induced on Swiss albino mice of either sex. Following injury, the animals were randomly divided into three groups; i. e., un-illuminated control, the group treated with 5% Povidone iodine (reference standard) and single exposure of 3 J/cm2 (830 nm). Burn tissue samples from each group were excised at day 6 post burn injury upon euthanization and used for histological and immunohistochemical analysis. Haematoxylin and Eosin (H and E) staining was performed on the selected sections to asses proliferation and angiogenesis at day 6 post-injury. For immunohistochemical analysis, tissue sections from all the three treatment groups on day 6 were stained using specific antibody against Proliferating cell nuclear antigen (PCNA). The results of the histological and immunohistochemical analysis showed improved tissue restoration in animals treated with optimal laser influence as compared to un-illuminated controls. The findings of present study clearly demonstrated the beneficial effects of 830 nm laser in burn wound healing and its influence in regulating the cellular marker.

Biochemical changes after subchronic and chronic interaction of Schistosoma mansoni infection in Swiss albino mice with two specific compounds.

PubMed

Hanna, Laila S; Medhat, Amina M; Abdel-Menem, Hanan A

2003-04-01

In Egypt, infection with Schistosoma mansoni (S.m.) and residues of pesticides have been considered as major environmental pollutants that adversely affect health. Effects of diazinon (DZN) and/or praziquantel (PZQ) on the levels of plasma triiodothyronine (T3), thyroxine (T4), activities of brain acetylcholinesterase (AchE) and liver alanine aminotransferase (ALT) in addition to blood reduced glutathione (GSH) in healthy and S.m. infected mice were investigated after 9 and 17 weeks of either infection or intoxication with DZN. Triiodothyronine showed significant differences among the different treatments. The group of mice treated with PZQ showed the highest levels of T3 at both time intervals. Thyroxine level showed significant differences between the two time intervals. The lowest levels of T4 were observed in the infected-PZQ group at week 17. The maximum inhibition of brain AchE activity was noticed in DZN-PZQ treated group after 9 and 17 weeks. The different treatments significantly reduced the activities of liver ALT. The highest decrease was recorded in the infected-DZN-PZQ group at week 9. All treatments significantly lowered the levels of blood GSH after 9 weeks.

Effects of Cecropia pachystachya and Larrea divaricata aqueous extracts in mice.

PubMed

Bigliani, M C; Grondona, E; Zunino, P M; Ponce, A A

2010-07-01

Our studies were performed to investigate the effects of the aqueous extracts of Cecropia pachystachya and Larrea divaricata. These plants are used in folkloric medicine in infusion and were administered orally (0.76 g/kg) to male Albino Swiss mice for 16 days, on drink intake, organ weight/body weight (OW/BW x 100) ratio, histology, broqueoalveolar fluid (BALF) and elevated plus-maze (EPM). Feeding as well as body weight were unaffected by the consumption of these extracts. There were no signs of toxicity in BALF, morbidity or mortality during the study. C. pachystachya caused an increase in relative kidney OW/BW (p

Effect of pretreatment with chromium picolinate on haematological parameters during dengue virus infection in mice.

PubMed

Shrivastava, Richa; Nagar, R; Ravishankar, G A; Upreti, R K; Chaturvedi, U C

2007-11-01

Dengue virus (DV) has caused severe epidemics of dengue fever (DF) and dengue haemorrhagic fever (DHF) and is endemic all over India. We have earlier reported that exposure of mice to hexavalent chromium [Cr(VI)] compounds increased the severity of dengue virus infection. Trivalent chromium picolinate (CrP) is used worldwide as micronutrient and nutritional supplement. The present study was therefore, carried out to investigate the effects of CrP on various haematological parameters during DV infection of mice. The Swiss Albino smice were inoculated with dengue virus (1000 LD50, intracerebrally) and fed with chromium picolinate (CrP) in drinking water (100 and 250 mg/l) for 24 wk. Peripheral blood leucocytes and other haematological parameters, and spleens were studied on days 4 and 8 after virus inoculations and the findings were compared with those given only CrP and the normal control age matched mice. CrP in drinking water for 24 wk had no significant effects on peripheral blood cells of mice. On the other hand, there was significant decrease in different haematological parameters following inoculation of normal mice with DV. In CrP fed mice the effects of DV infection were abolished on most of the haematological parameters. The findings of present study showed that the adverse effects of DV infection, specially on platelets and leucocytes, were abrogated by pretreatment of mice with CrP. The therapeutic utility of CrP in viral infections including dengue needs to be studied in depth.

Protective effects of agmatine against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.

PubMed

El-Agamy, Dina S; Makled, Mirhan N; Gamil, Nareman M

2014-06-01

Fulminant hepatic failure (FHF) is a life-threatening syndrome characterized by massive hepatic necrosis and high mortality. There is no effective therapy for the disease other than liver transplantation. This study aimed to investigate the effect of agmatine, inducible nitric oxide synthase (iNOS) inhibitor, on D-galactosamine and lipopolysaccharide (GalN/LPS)-induced FHF in mice and explore its possible mechanism(s). Male Swiss albino mice were injected with a single dose agmatine (14 mg/kg, IP) 8 h prior to challenge with a single intraperitoneal injection of both GalN (800 mg/kg) and LPS (50 μg/kg). Agmatine significantly attenuated all GalN/LPS-induced biochemical and pathological changes in liver. It prevented the increase of serum transaminases and alkaline phosphatase (ALP). In addition, agmatine markedly attenuated GalN/LPS-induced necrosis and inflammation. Agmatine significantly reduced oxidative stress and enhanced antioxidant enzymes. Importantly, agmatine decreased total nitric oxide (NO) and pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-α). These findings reveal that agmatine has hepatoprotective effects against GalN/LPS-induced FHF in mice that may be related to its ability to suppress oxidative stress, NO synthesis and TNF-α production. Therefore, agmatine may serve as a novel therapeutic strategy for hepatic inflammatory diseases.

Oxidative impairment and histopathological alterations in kidney and brain of mice following subacute lambda-cyhalothrin exposure.

PubMed

Pawar, Nitin Nanasaheb; Badgujar, Prarabdh Chandrakant; Sharma, Laxman Prasad; Telang, Avinash Gopal; Singh, Karam P

2017-03-01

Lambda cyhalothrin (LCT), a broad-spectrum type II (α-cyano) synthetic pyrethroid pesticide, is widely employed in various agricultural and animal husbandry practices for the control of pests. Acute and chronic exposure to LCT can elicit several adverse effects including oxidative stress. With the objective to investigate nephrotoxicity and neurotoxicity of LCT in mice, we evaluated oxidative stress parameters and histological changes in the kidney and brain of LCT exposed mice. Swiss albino mice were divided randomly into four groups ( n = 6 per group) as: (A) corn oil/vehicle control; (B) 0.5 mg/kg body weight (b.w.) LCT; (C) 1 mg/kg b.w. LCT; (D) 2 mg/kg b.w. LCT. Mice were treated orally for 28 days. LCT exposure significantly increased serum urea nitrogen, creatinine and urea levels. LCT exposure also increased lipid peroxidation, superoxide anion generation, nitrite level and decreased the level of reduced glutathione. The activities of superoxide dismutase, catalase and glutathione- S-transferase were depleted significantly in both kidney and brain. Histological examination revealed marked histopathological changes in the kidney and brain of mice that were more pronounced at high dose of LCT. Thus, results of the present study indicate that 28 days oral exposure of LCT causes oxidative damage to the kidney and brain of mice which in turn could be responsible for nephrotoxicity and neurotoxicity. Nevertheless, further detailed studies are required to prove these effects especially after long-term exposure.

The utility of direct agglutination (DAT) and fast agglutination screening (FAST) tests in serodiagnosis of experimental microsporidiosis.

PubMed

Abou El Naga, Iman F; Gaafar, Maha R; El-Zawawy, Lobna A; El-Said, Doaa; Mossallam, Sherin F

2008-12-01

The present study was designed to evaluate the efficiency of two serodiagnostic tests; the direct agglutination test (DAT) and the fast agglutination screening test (FAST) in the diagnosis of Microsporidia in experimentally infected mice and to differentiate between different species of the parasite. The swiss albino mice were divided into non infected control and infected experimental groups which were further subdivided into ten subgroups. Ten samples of microsporidial spores were isolated from ten human stools and each one was used to infect each subgroup of mice. Stool and sera were collected weekly from each subgroup from the 1st to the 4th week post infection (PI). DAT & FAST tests, using antigen prepared from the different species of microsporidial spores were used to detect antibodies in sera of different mice subgroups. The cross reactivity of microsporidial spores with the antibodies of Cyclospora cyatenensis and Cryptosporidium parvum was investigated by DAT & FAST. The results proved that DAT & FAST were effective in detecting microsporidial antibodies in sera of experimentally infected mice from the 2nd week PI till the end of the study, without cross reactivity with C. cyatenensis or C. parvum. They failed to differentiate between different Microspoiridia species used but, they gave good interpretation and they were specific and sensitive, and did not need sophisticated equipments.

Plumbagin, a vitamin K3 analogue ameliorate malaria pathogenesis by inhibiting oxidative stress and inflammation.

PubMed

Gupta, Amit Chand; Mohanty, Shilpa; Saxena, Archana; Maurya, Anil Kumar; Bawankule, Dnyaneshwar U

2018-03-22

Plumbagin, a vitamin K3 analogue is the major active constituent in several plants including root of Plumbago indica Linn. This compound has been shown to exhibit a wide spectrum of pharmacological activities. The present investigation was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria pathogenesis due to involvement of oxidative stress and inflammatory response in Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by intra-peritoneal injection of P. berghei infected red blood cells into the Swiss albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day following Peter's 4 day suppression test. Oral administration of PL showed significant reduction of parasitaemia and increase in mean survival time. PL treatment is also attributed to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. Significant inhibition in level of oxidative stress and pro-inflammation related markers were observed in PL treated group. The trend of inhibition in oxidative stress markers level after oral treatment of PL was MPO > LPO > ROS in organ injury in P. berghei infected mice. This study showed that plumbagin is able to ameliorate malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism apart from its effect on reducing parasitaemia and increasing mean survival time of malaria-induced mice.

Antidepressant-like activity of plumbagin in unstressed and stressed mice.

PubMed

Dhingra, Dinesh; Bansal, Sudha

2015-10-01

Plumbagin has been reported to be neuroprotective, so it might possess antidepressant activity. Therefore, the present study was designed to explore the antidepressant potential of plumbagin in unstressed and stressed mice. Depression-like behavior was induced in Swiss male albino mice by subjecting them to unpredictable mild stress daily for 21 successive days. Plumbagin (4, 8 and 16mg/kg, po) and imipramine (15mg/kg, po) were administered for 3 successive weeks to separate groups of unstressed and stressed mice. Tail suspension test and sucrose preference test were used to evaluate antidepressant effect of the drugs. Highest dose (16mg/kg) of plumbagin and imipramine significantly decreased immobility period of unstressed and stressed mice in tail suspension test as compared to their respective controls. These drugs significantly restored the reduced sucrose preference (%) in stressed mice. The drugs did not significantly affect locomotor activity of mice. Antidepressant-like activity of plumbagin was found to be comparable to imipramine. Plumbagin and imipramine significantly inhibited brain MAO-A activity, decreased plasma nitrite, brain malondialdehyde and catalase levels; and increased reduced glutathione levels of unstressed and stressed mice. The drugs significantly reversed stress-induced increase in plasma corticosterone levels. Antidepressant-like activity of plumbagin in unstressed and stressed mice might be through inhibition of brain MAO-A activity and improvement of antioxidant status. Reversal of stress-induced increase in plasma corticosterone levels might also be responsible for antidepressant-like activity of plumbagin in stressed mice. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

THE EFFICACY OF THREE MEDICINAL PLANTS; GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM: II-HISTOLOGICAL CHANGES.

PubMed

Abouel-Nour, Mohamed F; El-Shewehy, Dina Magdy M; Hamada, Shadia F; Morsy, Tosson A

2016-04-01

Cryptosporidiosis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells of man and animals causing a major health problem. This study was oriented to evaluate the protective and curative capacity of garlic, ginger and mirazid in comparison with metronidazole drug (commercially known) against Cryptosporidium in experimental mice. Male Swiss Albino mice experimentally infected with C. parvum were treated with medicinal plants extracts (Ginger, Mirazid, and Garlic) as compared to chemical drug Metronidazole. Importantly, C. parvum-infected mice treated with ginger, Mirazid, garlic and metronidazole showed a complete elimination in shedding oocysts by 9th day PI. The reduction and elimination of shedding oocysts in response to the treatments might be attributable to a direct effect on parasite growth in intestines, sexual phases production and/or the formation of oocysts. The results were evaluated histopathological examination of ideum section of control mice (uninfected, untreated) displayed normal architecture of the villi. Examiination of infected mice ileum section (infected, untreated) displayed histopathological alterations from uninfected groups. Examination of ileum section prepared from mice treated with garlic, ginger, mirazid, and metronidazole displayed histopathological alterations from that of the control groups, and showed marked histologic correction in the pattern with the four regimes used in comparison to control mice. Garlic successfully eradicated oocysts of infected mice from stool and intestine. Supplementation of ginger to infected mice markedly corrected elevation in the inflammatory risk factors and implied its potential antioxidant, anti-inflammatory and immunomodulatory capabilities. Infected mice treated with ginger, mirazid, garlic and metronidazole showed significant symptomatic improvements during treatment.

A quantitative study of the effects of vasectomy on spermatogenesis in rats.

PubMed Central

McDonald, S W; Scothorne, R J

1988-01-01

A large sample of cross sectional profiles of seminiferous tubules from the left testes of five Albino Swiss rats 6 months after left unilateral vasectomy was compared with those of sham-operated controls. Using the classification of Leblond & Clermont (1952), based primarily on the morphology of the spermatids, the frequency of each stage of the seminiferous cycle was recorded. Profiles were also analysed for distension, reduction in epithelial area and changes in spermatocyte numbers. The lack of significant alterations in either the seminiferous cycle, the numbers of pachytene spermatocyte nuclei or epithelial area in the tubular profiles indicated that there was no alteration in spermatogenic rate after vasectomy. The lack of tubular distension, reduction in spermatocytes per unit length of perimeter or of the presence of mature spermatozoa at inappropriate stages of the cycle indicated the absence of sperm retention. The study makes clear that, at least in Albino Swiss rats 6 months after vasectomy, the apparently healthy tubules were indeed normal. PMID:3248969

Serological changes induced by blend of sunset yellow, metanil yellow and tartrazine in swiss albino rat, rattus norvegicus.

PubMed

Saxena, Beenam; Sharma, Shiv

2014-01-01

The present study was carried out to evaluate the toxic effect of blend of some food colors on Swiss albino rats. A blend (1:1:1) of sunset yellow, metanil yellow and tartrazine showed additive effects on serological parameters which indicate that addition of these dye together in food stuff may give rise to more toxic effects than are produced by each dye individually. Animals were divided into four groups (I, II, III, and IV). First group was treated as control and respective group of animals received 25, 50 and 75 mg/kg body weight blend of food colors by gavaging up to 30 days. The serological study showed a decrease in total protein and albumin and an increase in alkaline phosphatase, SGPT and total bilirubin. The results revealed that oral administration of these blend did not affect the body weight gain. The prolonged consumption of the blend may cause adverse effect on human health.

The effects of Urtica dioica L. leaf extract on aniline 4-hydroxylase in mice.

PubMed

Ozen, Tevfik; Korkmaz, Halil

2009-01-01

The effects of hydroalcoholic (80% ethanol-20% water) extract of Urtica dioica L. on microsomal aniline 4-hydroxylase (A4H) were investigated in the liver of Swiss albino mice (8- 10-weeks-old) treated with two doses (50 and 100 mg/kg body weight, given orally for 14 days ). The activities of A4H showed a significant increase in the liver at both dose levels of extract treatment. The hydroalcoholic extract of Urtica dioica induced the activities of A4H that had been increased by treatment of metal ions (Mg2+ and Ca2+) and the mixture of cofactors (NADH and NADPH). At saturated concentration of cofactor, microsomal A4H exhibited significantly even higher activities in the presence of the mixture of cofactors than NADPH and NADH. Mg2+ and Ca2+ ions acted as stimulants in vitro. The present results suggest that the hydroalcoholic extract of Urtica dioica may have modalatory effect on aniline hydroxylase at least in part and enhance the activity of A4H adding metals ions and cofactors.

Environmental impoverishment and aging alter object recognition, spatial learning, and dentate gyrus astrocytes.

PubMed

Diniz, Daniel G; Foro, César A R; Rego, Carla M D; Gloria, David A; de Oliveira, Fabio R R; Paes, Juliana M P; de Sousa, Aline A; Tokuhashi, Tatyana P; Trindade, Lucas S; Turiel, Maíra C P; Vasconcelos, Erick G R; Torres, João B; Cunnigham, Colm; Perry, Victor H; Vasconcelos, Pedro F da Costa; Diniz, Cristovam W P

2010-08-01

Environmental and age-related effects on learning and memory were analysed and compared with changes observed in astrocyte laminar distribution in the dentate gyrus. Aged (20 months) and young (6 months) adult female albino Swiss mice were housed from weaning either in impoverished conditions or in enriched conditions, and tested for episodic-like and water maze spatial memories. After these behavioral tests, brain hippocampal sections were immunolabeled for glial fibrillary acid protein to identify astrocytes. The effects of environmental enrichment on episodic-like memory were not dependent on age, and may protect water maze spatial learning and memory from declines induced by aging or impoverished environment. In the dentate gyrus, the number of astrocytes increased with both aging and enriched environment in the molecular layer, increased only with aging in the polymorphic layer, and was unchanged in the granular layer. We suggest that long-term experience-induced glial plasticity by enriched environment may represent at least part of the circuitry groundwork for improvements in behavioral performance in the aged mice brain.

Pharmacological preconditioning by milrinone: memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice.

PubMed

Saklani, Reetu; Jaggi, Amteshwar; Singh, Nirmal

2010-07-01

We tested the neuroprotective effect of milrinone, a phosphodiesterase III inhibitor, in pharmacological preconditioning. Bilateral carotid artery occlusion for 12 min followed by reperfusion for 24 h produced ischemia-reperfusion (I/R) cerebral injury in male Swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using the Morris water maze test, and motor coordination was evaluated using the inclined beam walking test, rota-rod test, and lateral push test. Milrinone (50 microg/kg & 100 microg/kg i.v.) was administered 24 h before surgery in a separate group of animals to induce pharmacological preconditioning. I/R increased cerebral infarct size and impaired memory and motor coordination. Milrinone treatment significantly decreased cerebral infarct size and reversed I/R-induced impairments in memory and motor coordination. This neuroprotective effect was blocked by ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker. These findings indicate that milrinone preconditioning exerts a marked neuroprotective effect on the ischemic brain, putatively due to increased intracellular calcium levels activating calcium-sensitive signal transduction cascades.

Riboflavin as adjuvant with cisplatin: study in mouse skin cancer model.

PubMed

Salman, Maria; Naseem, Imrana

2015-01-01

Cisplatin used in treatment of solid tumor induces oxidative stress which leads to hepatotoxicity and nephrotoxicity. New strategies are therefore needed to combat toxicity and optimize its therapeutic potential. Riboflavin (VitaminB2) under photoillumination works as an anti proliferative agent and induces apoptosis. These properties of riboflavin have been exploited to mitigate cisplatin induced toxicities. 9,10-dimethylbenz(a)anthracene /12-O-tetradecanoylphorbol-13-acetate  were used to induce skin tumor in Swiss albino mice. The tumor induced mice were treated with cisplatin, riboflavin as well as their combination under photo illumination. In comparison to tumor control group the cisplatin and riboflavin treated groups showed a compromised level of antioxidant enzymes, functional markers and a higher degree of lipid peroxidation. However these parameters tended towards normal in the combination treated group. The results from histopathology indicate that apoptosis was favored mode of cell death and that necrosis was reduced in combination treated groups. Our findings indicate that combination of cisplatin with riboflavin under photo illumination synergizes its anti cancer activity towards cancer cells and attenuates the cisplatin induced toxicities.

Hepatoprotective and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice.

PubMed

Karuppanan, Muthupillai; Krishnan, Manigandan; Padarthi, Pavankumar; Namasivayam, Elangovan

2014-01-01

To explore the antioxidant and hepatoprotective effect of ethanolic Mangifera indica (EMI) and methanolic Mangifera indica (MMI) leaf extracts in mercuric chloride (HgCl 2 ) induced toxicity in Swiss albino mice. Toxicity in mice was induced with HgCl 2 (5.0 mg/kg, i.p.), followed by oral intervention with EMI and MMI extracts (25 mg and 50 mg/kg. body wt.) for 30 days. The extent of liver damage was assessed from the extents of histopathological, morphological, antioxidant and liver enzymes. Mercuric chloride-induced mice showed an increased cellular damage whereas leaf extracts of EMI and MMI-treated mice showed recovery of damaged hepatocytes. Mercuric chloride intoxicated mice exhibited a significant (p < 0.05) elevation in the liver enzymes (Aspartate amino transferase and Alanine amino transferase) and gradual decline in the cellular radical scavenging enzyme levels (Catalase, Glutathione-s-transferase and Glutathione peroxidase. The combined treatment with EMI and MMI leaf extracts significantly (p < 0.05) reversed these parameters. However, the effects of MMI leaf extract (50 mg/kg) were superior to those of EMI- treated mice possibly due to its potent radical scavenging property. These results suggest that oral supplementation of Mangifera indica extract remarkably reduces hepatotoxicity in mice possibly through its antioxidant potentials. How to cite this article: Karuppanan M, Krishnan M, Padarthi P, Namasivayam E. Hepatoprotec-tive and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice. Euroasian J Hepato-Gastroenterol 2014;4(1):18-24.

Hepatoprotective and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice

PubMed Central

Karuppanan, Muthupillai; Krishnan, Manigandan; Padarthi, Pavankumar

2014-01-01

ABSTRACT Background To explore the antioxidant and hepatoprotective effect of ethanolic Mangifera indica (EMI) and methanolic Mangifera indica (MMI) leaf extracts in mercuric chloride (HgCl2) induced toxicity in Swiss albino mice. Materials and methods Toxicity in mice was induced with HgCl2 (5.0 mg/kg, i.p.), followed by oral intervention with EMI and MMI extracts (25 mg and 50 mg/kg. body wt.) for 30 days. Results and discussion The extent of liver damage was assessed from the extents of histopathological, morphological, antioxidant and liver enzymes. Mercuric chloride-induced mice showed an increased cellular damage whereas leaf extracts of EMI and MMI-treated mice showed recovery of damaged hepatocytes. Mercuric chloride intoxicated mice exhibited a significant (p < 0.05) elevation in the liver enzymes (Aspartate amino transferase and Alanine amino transferase) and gradual decline in the cellular radical scavenging enzyme levels (Catalase, Glutathione-s-transferase and Glutathione peroxidase. The combined treatment with EMI and MMI leaf extracts significantly (p < 0.05) reversed these parameters. However, the effects of MMI leaf extract (50 mg/kg) were superior to those of EMI- treated mice possibly due to its potent radical scavenging property. These results suggest that oral supplementation of Mangifera indica extract remarkably reduces hepatotoxicity in mice possibly through its antioxidant potentials. How to cite this article: Karuppanan M, Krishnan M, Padarthi P, Namasivayam E. Hepatoprotec-tive and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice. Euroasian J Hepato-Gastroenterol 2014;4(1):18-24. PMID:29264314

Intranasal delivery of cyclobenzaprine hydrochloride-loaded thiolated chitosan nanoparticles for pain relief.

PubMed

Patel, Deepa; Naik, Sachin; Chuttani, Krishna; Mathur, Rashi; Mishra, Anil K; Misra, Ambikanandan

2013-09-01

The purpose of present investigation was to formulate and characterize the cyclobenzaprine HCl (CBZ)-loaded thiolated chitosan nanoparticles and assessment of in-vitro cell viability, trans-mucosal permeability on RPMI2650 cell monolayer, in-vivo pharmacokinetic and pharmacodynamic study of thiolated chitosan nanoparticles on Swiss albino mice after intranasal administration. A significant high permeation of drug was observed from thiolated chitosan nanoparticles with less toxicity on nasal epithelial cells. Brain uptake of the drug after (99m)Tc labeling was significantly enhanced after thiolation of chitosan. CBZ-loaded thiolated chitosan NPs significantly reverse the N-Methyl-.-Aspartate (NMDA)-induced hyperalgesia by intranasal administration than the CBZ solution. The studies of present investigation revealed that thiolation of chitosan significantly reduce trans-mucosal toxicity with enhanced trans-mucosal permeability via paracellular pathway and brain uptake of a hydrophilic drug (normally impermeable across blood brain barrier) and pain alleviation activity via intranasal route.

Seabuckthron (Hippophae rhamnoides L.) leaf extract ameliorates the gamma radiation mediated DNA damage and hepatic alterations.

PubMed

Khan, Amitava; Manna, Krishnendu; Chinchubose; Das, Dipesh Kr; Sinha, Mahuya; Kesh, Swaraj Bandhu; Das, Ujjal; Dey, Rakhi Sharma; Banerji, Asoke; Dey, Sanjit

2014-10-01

In vitro assessment showed that H. rhamnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (gamma) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of beta radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkappaB (p65) and IkappaBalpha increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures.

Antiestrogenic and Anti-Inflammatory Potential of n-Hexane Fraction of Vitex negundo Linn Leaf Extract: A Probable Mechanism for Blastocyst Implantation Failure in Mus musculus.

PubMed

Jivrajani, Mehul; Ravat, Nirav; Anandjiwala, Sheetal; Nivsarkar, Manish

2014-01-01

The anti-implantation potential of different fractions of Vitex negundo Linn leaf extract was evaluated in female Swiss Albino mice. Animals from different groups were dosed orally either with 0.2% agar (vehicle) or with fractions of V. negundo leaf extract (n-hexane, chloroform, n-butanol, and remnant fractions) at 10:00 a.m., from day 1 to day 6 of pregnancy. The pregnant females from each group were sacrificed on different days of pregnancy (n = 6), and uterus was excised and used for estimation of lipid peroxidation and assay of superoxide dismutase activity as a marker for blastocyst implantation. Animals treated with n-hexane fraction showed altered level of superoxide anion radical and superoxide dismutase activity as compared to control animals. The probable mechanism by which this extract exhibits inhibition of blastocyst implantation is through the anti-inflammatory and antiestrogenic potential.

Anti-cancer, pharmacokinetics and tumor localization studies of pH-, RF- and thermo-responsive nanoparticles.

PubMed

Sanoj Rejinold, N; Thomas, Reju George; Muthiah, Muthunarayanan; Chennazhi, K P; Manzoor, K; Park, In-Kyu; Jeong, Yong Yeon; Jayakumar, R

2015-03-01

The curcumin-encapsulated chitosan-graft-poly(N-vinyl caprolactam) nanoparticles containing gold nanoparticles (Au-CRC-TRC-NPs) were developed by ionic cross-linking method. After "optimum RF exposure" at 40 W for 5 min, Au-CRC-TRC-NPs dissipated heat energy in the range of ∼42°C, the lower critical solution temperature (LCST) of chitosan-graft-poly(N-vinyl caprolactam), causing controlled curcumin release and apoptosis to cancer cells. Further, in vivo PK/PD studies on swiss albino mice revealed that Au-CRC-TRC-NPs could be sustained in circulation for a week with no harm to internal organs. The colon tumor localization studies revealed that Au-CRC-TRC-NPs were retained in tumor for a week. These results throw light on their feasibility as multi-responsive nanomedicine for RF-assisted cancer treatment modalities. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxicity studies of a polyurethane rigid foam

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Schneider, J. E.

1977-01-01

Relative toxicity tests were performed on a polyurethane foam containing a trimethylopropane-based polyol and an organophosphate flame retardant. The routine screening procedure involved the exposure of four Swiss albino male mice in a 4.2 liter hemispherical chamber to the products generated by pyrolyzing a 1.00 g sample at a heating rate of 40 deg C/min from 200 to 800 C in the absence of air flow. In addition to the routine screening, experiments were performed with a very rapid rise to 800 C, with nominal 16 and 48 ml/sec air flow and with varying sample rates. No unusual toxicity was observed with either gradual or rapid pyrolysis to 800 C. Convulsions and seizures similar to those previously reported were observed when the materials were essentially flash pyrolyzed at 800 C in the presence of air flow, and the toxicity appeared unusual because of low sample weights required to produce death.

Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential

PubMed Central

ALAM, BADRUL; MAJUMDER, RAJIB; AKTER, SHAHINA; LEE, SANG-HAN

2015-01-01

The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (P<0.05). Hematological and serum biochemical profiles were restored to normal levels in the extract-treated mice compared with the EAC control mice. MPBL and EPBL treatment significantly decreased lipid peroxidation (P<0.05) and restored GSH, SOD and CAT levels towards normal compared with the EAC control. Taken together, the results of the present study demonstrated that Piper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential. PMID:25624910

Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

PubMed

Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

2015-02-01

The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (P<0.05). Hematological and serum biochemical profiles were restored to normal levels in the extract-treated mice compared with the EAC control mice. MPBL and EPBL treatment significantly decreased lipid peroxidation (P<0.05) and restored GSH, SOD and CAT levels towards normal compared with the EAC control. Taken together, the results of the present study demonstrated that Piper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

Potential effects of Cramoll 1,4 lectin on murine Schistosomiasis mansoni.

PubMed

Melo, Cristiane Moutinho Lagos de; de Lima, Amanda Lucena Rosendo; Beltrão, Eduardo Isidoro Carneiro; Cavalcanti, Carmelita C Bezerra; de Melo-Júnior, Mário Ribeiro; Montenegro, Silvia Maria L; Coelho, Luana Cassandra B Barroso; Correia, Maria Tereza dos Santos; Carneiro-Leão, Ana Maria dos Anjos

2011-05-01

Cratylia mollis is a natural forage plant from the Northeast of Brazil. C. mollis seed lectin (Cramoll) containing molecular forms 1 and 4 (Cramoll 1,4) has shown anti-inflammatory and wound-healing activities. This work analyzed the effect of Cramoll 1,4 on experimental schistosomiasis in mice. Experimental groups (n=15/group) were composed of female albino Swiss mice, which were subcutaneously and caudally infected with Schistosoma mansoni (BH strain, 100 cercariae/mouse) and were treated with an intraperitoneal dose after infection as follows: (1) Cramoll 1,4 (50 mg kg(-1) single dose - after 40 days of infection), (2) Cramoll 1,4 (7 mg kg(-1) daily dose - for 7 days after infection) and control (untreated mice). Mice were sacrificed 8 weeks after infection and adult worms were recovered from the portal-hepatic system. Livers were fixed in 10% (v/v) formaldehyde/0.15M NaCl and tissue sections were processed for haematoxilin and Masson's trichrome stainings. Mice infected subcutaneously harboured no or very few worms and hence the effect of Cramoll 1,4 could not be assessed. Results (P≤0.05) were obtained with Cramoll 1,4 using the two treatments, with reduction of: egg excretion (79 and 80%), adult worm recovery (71 and 79%) and liver granulomas (40 and 73.5%) in relation to control. This study showed the potential anti-helminthic activity of Cramoll 1,4 when tested against Schistosomiasis mansoni infection in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Reduction of Sodium Arsenite-Mediated Adverse Effects in Mice using Dietary Supplementation of Water Hyacinth (Eichornia crassipes) Root Powder.

PubMed

Sarker, Rim Sabrina Jahan; Ahsan, Nazmul; Hossain, Khaled; Ghosh, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Akhand, Anwarul Azim

2012-07-01

In this study, we evaluated the protective effects of water Hyacinth Root Powder (HRP) on arsenic-mediated toxic effects in mice. Swiss albino mice, used in this study, were divided into four different groups (for each group n=5). The control group was supplied with normal feed and water, Arsenic group (As-group) was supplied with normal feed plus arsenic (sodium arsenite)-containing water, and arsenic+hyacinth group (As+Hy group) was supplied with feed supplemented with HRP plus arsenic water. The remaining Hy-group was supplied with feed supplemented with HRP plus normal water. Oral administration of arsenic reduced the normal growth of the mice as evidenced by weight loss. Interestingly, tip of the tails of these mice developed wound that caused gradual reduction of the tail length. Supplementation of HRP in feed significantly prevented mice growth retardation and tail wounding in As+Hy group mice. However, the growth pattern in Hy-group mice was observed to be almost similar to that of the control group indicating that HRP itself has no toxic or negative effect in mice. Ingested arsenic also distorted the shape of the blood cells and elevated the serum enzymes such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and serum glutamic pyruvic transaminase (SGPT). Importantly, elevation of these enzymes and distortion of blood cell shape were partially reduced in mice belong to As+Hy group, indicating HRP-mediated reduction of arsenic toxicity. Therefore, the preventive effect of hyacinth root on arsenic-poisoned mice suggested the future application of hyacinth to reduce arsenic toxicity in animal and human.

Reduction of Sodium Arsenite-Mediated Adverse Effects in Mice using Dietary Supplementation of Water Hyacinth (Eichornia crassipes) Root Powder

PubMed Central

Sarker, Rim Sabrina Jahan; Ahsan, Nazmul; Hossain, Khaled; Ghosh, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Akhand, Anwarul Azim

2012-01-01

Background In this study, we evaluated the protective effects of water Hyacinth Root Powder (HRP) on arsenic-mediated toxic effects in mice. Methods Swiss albino mice, used in this study, were divided into four different groups (for each group n=5). The control group was supplied with normal feed and water, Arsenic group (As-group) was supplied with normal feed plus arsenic (sodium arsenite)-containing water, and arsenic+hyacinth group (As+Hy group) was supplied with feed supplemented with HRP plus arsenic water. The remaining Hy-group was supplied with feed supplemented with HRP plus normal water. Results Oral administration of arsenic reduced the normal growth of the mice as evidenced by weight loss. Interestingly, tip of the tails of these mice developed wound that caused gradual reduction of the tail length. Supplementation of HRP in feed significantly prevented mice growth retardation and tail wounding in As+Hy group mice. However, the growth pattern in Hy-group mice was observed to be almost similar to that of the control group indicating that HRP itself has no toxic or negative effect in mice. Ingested arsenic also distorted the shape of the blood cells and elevated the serum enzymes such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and serum glutamic pyruvic transaminase (SGPT). Importantly, elevation of these enzymes and distortion of blood cell shape were partially reduced in mice belong to As+Hy group, indicating HRP-mediated reduction of arsenic toxicity. Conclusion Therefore, the preventive effect of hyacinth root on arsenic-poisoned mice suggested the future application of hyacinth to reduce arsenic toxicity in animal and human. PMID:23407303

Bacopa monniera Stabilized Silver Nanoparticles Attenuates Oxidative Stress Induced by Aluminum in Albino Mice.

PubMed

Mahitha, B; Deva Prasad Raju, B; Mallikarjuna, K; Durga Mahalakshmi, Ch N; Sushmal, N John

2015-02-01

In the recent years usage of nanomedicine plays a promising strategy in the improvement of medical treatment. The ecofriendly synthesized silver nanoparticles has introduced a new opportunity to increase the efficacy of drug by reducing its side effects. In the present study, we investigated the antioxidant property of Bacopa monniera stabilized silver nanoparticles against aluminum induced toxicity in albino mice. Forty male albino mice were randomly divided into five groups. First group was treated as control, second group received aluminum acetate (5 mg/kg b . w), third group received Bacopa monniera extract (5 mg/kg b . w), fourth group received BmSNPs (5 mg/kg b . w), fifth group received aluminum acetate plus BmSNPs. Exposure to aluminum acetate significantly increased lipid peroxidation levels with a significant decrease in the antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase activities in the brain, liver and kidney of mice. Degenerative changes were also observed in brain, liver and kidney of aluminum treated mice. No significant changes in the oxidative stress were observed in the Bacopa monniera and BmSNPs alone treated mice. Whereas, co-administration of BmSNPs to Al treated mice showed a significant decrease in lipid peroxidation levels with a significant increase of SOD, CAT and GPx indicating the antioxidant potential of nanoparticles and in counteracting Al induced oxidative stress and histological response in male albino mice. These findings clearly implicate that BmSNPs are able to eradicate the oxidative stress and prevent the tissue damage in aluminum exposed mice.

Evaluation of morning glory (Jacquemontia tamnifolia (L.) Griseb) leaves for antioxidant, antinociceptive, anticoagulant and cytotoxic activities.

PubMed

Hossain, Mohammad Shahadat; Reza, A S M Ali; Rahaman, Md Masudur; Nasrin, Mst Samima; Rahat, Mohammed Rasib Uddin; Islam, Md Rabiul; Uddin, Md Josim; Rahman, Md Atiar

2018-06-27

The present study was planned to investigate the phytochemical, antioxidant, antinociceptive, anticoagulant and cytotoxic activities of the Jacquemontia tamnifolia (L.) Griseb leaf methanol extract (MExJT) in the laboratory using both in vitro and in vivo methods. Phytochemical values, namely, total phenolic and flavonoid contents, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging effect and FeCl3 reducing power effects, were studied by established methods. In vivo antinociceptive activity was performed by acidic acid-induced writhing test and formalin-induced pain test on Swiss albino mice at doses of 125, 250 and 500 mg/kg body weight. The clot lysis and brine shrimp lethality bioassay in vitro were used to evaluate the thrombolytic and cytotoxic activities of the plant extract, respectively. Phytochemical screening illustrates the presence of tannins, saponins, flavonoids, gums and carbohydrates, steroids, alkaloids and reducing sugars in the extract. The results showed the total phenolic content (146.33 g gallic acid equivalents/100 g extract) and total flavonoid content (133.33 g quercetin/100 g). Significant (p<0.05) IC50 values compared to respective standards were recorded in DPPH radical scavenging (289.5 μg/mL) and FeCl3 reduction (245.2 μg/mL). The antinociceptive effect was evaluated in the acetic acid-induced writhing test and formalin-induced pain models in Swiss albino mice with doses of 125, 250 and 500 mg/kg body weight. Significant (p<0.05) inhibition (72.87±2.73%) of writhing response compared to diclofenac sodium was achieved by 500 mg/kg body weight. The extract also significantly inhibited the licking response in both the early phase (51.59±1.57%, p<0.05) and the late phase (64.82±1.87%, p<0.05) in the formalin-induced writhing test. MExJT also showed (38.10±1.79%) clot lytic activity in the thrombolytic test and cytotoxicity with an LC50 value of 31.70 μg/mL in the brine shrimp lethality bioassay. The plant is a potential source of antioxidants and might have one or more secondary metabolite(s) with central and peripheral analgesic activity. The results also demonstrate that MExJT has moderate thrombolytic and lower cytotoxic properties that may warrant further exploration.

L-threo 3,4-dihydroxyphenylserine treatment during mouse perinatal and rat postnatal development does not alter the impact of dietary copper deficiency

PubMed Central

Pyatskowit, Joshua W.; Prohaska, Joseph R.

2009-01-01

Dietary copper (Cu) deficiency was induced perinatally in Swiss Albino mice and postnatally in male Holtzman rats to investigate the effect of L-threo 3,4-dihydroxyphenylserine (DOPS) on pup survival and catecholamine levels in a 2 × 2 factorial design. Mouse dams were placed on one of four treatments 14 days after mating and rats at postnatal day 19 (P19). Treatments were Cu-adequate (Cu +) and Cu-deficient (Cu −) diets with or without DOPS (1 mg/ml) in the drinking water. Mouse pups were killed at P14 and rats at P49. Mortality in Cu − pups was 46% and not significantly improved by DOPS, 39%. A repeat study with mice adding ascorbic acid in the water with DOPS showed no improvement. Compared to Cu + animals, Cu − animals were smaller, anemic and had a 92% reduction in liver Cu. DOPS treatment made no improvement to and in some cases exacerbated the Cu deficiency. Catecholamine levels measured in heart and brain by LCEC showed decreased NE levels and increased DA levels in Cu − animals compared to controls. DOPS treatment did not alter this pattern. Although DOPS was present in treated animal’s tissues, survival in mice and catecholamine levels in mice and rats were not altered by the 1 mg/ml dose of DOPS. PMID:16117185

Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

PubMed

Ayuob, Nasra Naeim; El Wahab, Manal Galal Abd; Ali, Soad Shaker; Abdel-Tawab, Hanem Saad

2018-06-01

Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

Effect of Methanolic Leaf Extract of Ocimum basilicum L. on Benzene-Induced Hematotoxicity in Mice

PubMed Central

Saha, S.; Mukhopadhyay, M. K.; Ghosh, P. D.; Nath, D.

2012-01-01

The aim of the present study was to investigate the protective role of methanolic leaf extract of Ocimum basilicum L. against benzene-induced hematotoxicity in Swiss albino mice. GC analysis and subacute toxicity level of the extract were tested. Mice were randomly divided into three groups among which II and III were exposed to benzene vapour at a dose 300 ppm × 6 hr/day × 5 days/week for 2 weeks and group I was control. Group III of this experiment was treated with the leaf methanolic extract at a dose of 100 mg/kg body weight, a dose in nontoxic range. Hematological parameters (Hb%, RBC and WBC counts), cell cycle regulatory proteins expression and DNA fragmentation analysis of bone marrow cells was performed. There was an upregulation of p53 and p21 and downregulation of levels of CDK2, CDK4, CDK6, and cyclins D1 and E in leaf extract-treated group. DNA was less fragmented in group III compared to group II (P < 0.05). The present study indicates that the secondary metabolites of O. basilicum L. methanolic leaf extract, comprising essential oil monoterpene geraniol and its oxidized form citral as major constituents, have modulatory effect in cell cycle deregulation and hematological abnormalities induced by benzene in mice. PMID:22988471

Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice

PubMed Central

Khalifa, Hesham A.; Al-Quraishy, Saleh A.

2017-01-01

The current study was designed to investigate the beneficial role of diosmin, a biologically active flavonoid, against methotrexate- (MTX-) induced hepatic, renal, and cardiac injuries in mice. Male Swiss albino mice received a single intraperitoneal injection of MTX (at 20 mg/kg, body weight) either alone or in combination with oral diosmin (at 50 or 100 mg/kg body weight, for 10 days). Serum was used to evaluate tissue injury markers, while hepatic, renal, and cardiac tissue samples were obtained for determination of antioxidant activity as well as histopathological examination. Diosmin treatment ameliorated the MTX-induced elevation of serum alkaline phosphatase, aminotransferases, urea, creatinine, lactate dehydrogenase, and creatine kinases as well as plasma proinflammatory cytokines (interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha). Additionally, both diosmin doses significantly reduced tissue levels of malondialdehyde and nitric oxide and increased those of glutathione, glutathione peroxidase, glutathione reductase, glutathione S-transferase, superoxide dismutase, and catalase, compared to the MTX-intoxicated group. Histopathological examination showed that diosmin significantly minimized the MTX-induced histological alterations and nearly restored the normal architecture of hepatic, renal, and cardiac tissues. Based on these findings, diosmin may be a promising agent for protection against MTX-induced cytotoxicity in patients with cancer and autoimmune diseases. PMID:28819543

In vivo toxicity of the culturable marine cyanobacterium Geitlerinema pseudacutissimum CNP 1019 extract on male Swiss albino mice (Mus musculus).

PubMed

Maruthanayagam, Veerabadhran; Nagarajan, Manivel; Sundararaman, Muthuraman

2014-01-01

In this study, we investigated the in vivo toxicity of Geitlerinema pseudacutissimum CNP 1019 organic extract in a murine host. A single intraperitoneal injection of 1 g extract kg⁻¹ body weight (BW) did not exhibit mortality, whereas 3 g extract kg⁻¹ BW (approximate lethal dose) resulted in mortality within 5 days. To perform subchronic exposure toxicity analyses (i.e., daily exposure for a total of 14 days), a maximum concentration of ≤1 g extract kg⁻¹ BW was used. Subchronic toxicity studies in the treated mice, showed fluctuations of feed intake, loss of body weight, increase in specific activity of serum lactate dehydrogenase, alanine aminotransferase and decrease in whole serum protein concentration. LDH isoenzyme expression was found, and levels of the various isoforms were decreased as a result of the treatment. Histopathology studies in liver, kidney, and spleen isolated from the treated mice showed the presence of necrotic debris, hemorrhage, and micronuclei revealing the toxicity of the extract. The dose-dependent alterations in biochemical parameters in conjunction with the histological lesions noted in the animals treated with the prepared extract illustrate the likely potential toxicity to mammals from any encounters with the studied cyanobacterium.

Ruanjian Sanjie decoction exhibits antitumor activity by inducing cell apoptosis in breast cancer.

PubMed

Zhao, Xiumei; Zhao, Jing; Hu, Renjie; Yao, Qiang; Zhang, Guixian; Shen, Hongsheng; Yagüe, Ernesto; Hu, Yunhui

2017-05-01

Traditional Chinese medicine, based on theories developed and practiced for >2,000 years, is one of the most common complementary and alternative types of medicine currently used in the treatment of patients with breast cancer. Ruanjian Sanjie (RJSJ) decoction, is composed of four herbs, including Ban xia (Pinellia ternata), Xia ku cao (Prunella vulgaris), Shan ci gu (Cremastra appendiculata) and Hai zao (Sargassum pallidum), and has traditionally been used for softening hard lumps and resolving hard tissue masses. However, the active compounds and mechanisms of action of RJSJ remain unknown. The present study demonstrated the antitumor activity of RJSJ against Ehrlich ascites carcinoma in Swiss albino mice and breast cancer xenografts in nude mice. Notably, RJSJ does not induce body weight loss, immune function toxicity or myelosuppression in mice, indicating that it is safe and well tolerated. In addition, RJSJ shows potent cytotoxicity against breast cancer cells in vitro by the suppression of the anti-apoptotic proteins B-cell lymphoma 2 and survivin, leading to the activation of caspase-3/7 and caspase-9, and the apoptotic cascade. These findings provide a clear rationale to explore the therapeutic strategy of using RJSJ alone or in combination with chemotherapeutic agents for breast cancer patients and the characterization of its active principles.

The effect of GABA transporter 1 (GAT1) inhibitor, tiagabine, on scopolamine-induced memory impairments in mice.

PubMed

Sałat, Kinga; Podkowa, Adrian; Mogilski, Szczepan; Zaręba, Paula; Kulig, Katarzyna; Sałat, Robert; Malikowska, Natalia; Filipek, Barbara

2015-12-01

GABAergic neurotransmission is involved in long-term potentiation, a neurophysiological basis for learning and memory. On the other hand, GABA-enhancing drugs may impair memory and learning in humans and animals. The present study aims at investigating the effect of GAT1 inhibitor tiagabine on memory and learning. Albino Swiss (CD-1) and C57BL/6J mice were used in the passive avoidance (PA), Morris water maze (MWM) and radial arm water maze (RAWM) tasks. Scopolamine (1mg/kg ip) was applied to induce cognitive deficits. In the retention trial of PA scopolamine reduced step-through latency as compared to vehicle-treated mice, and pretreatment with tiagabine did not have any influence on this effect. In MWM the results obtained for vehicle-treated mice, scopolamine-treated group and combined scopolamine+tiagabine-treated mice revealed variable learning abilities in these groups. Tiagabine did not impair learning in the acquisition trial. In RAWM on day 1 scopolamine-treated group made nearly two-fold more errors than vehicle-treated mice and mice that received combined scopolamine and tiagabine. Learning abilities in the latter group were similar to those of vehicle-treated mice in the corresponding trial block on day 1, except for the last trial block, during which tiagabine+scopolamine-injected mice made more errors than control mice and the scopolamine-treated group. In all groups a complete reversal of memory deficits was observed in the last trial block of day 2. The lack of negative influence of tiagabine on cognitive functions in animals with scopolamine-induced memory impairments may be relevant for patients treated with this drug. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Antioxidative effects of the spice cardamom against non-melanoma skin cancer by modulating nuclear factor erythroid-2-related factor 2 and NF-κB signalling pathways.

PubMed

Das, Ila; Acharya, Asha; Berry, Deborah L; Sen, Supti; Williams, Elizabeth; Permaul, Eva; Sengupta, Archana; Bhattacharya, Sudin; Saha, Tapas

2012-09-28

The role of dietary factors in inhibiting or delaying the development of non-melanoma skin cancer (NMSC) has been investigated for many years. Cardamom, which is a dietary phytoproduct, has been commonly used in cuisines for flavour and has numerous health benefits, such as improving digestion and stimulating metabolism and having antitumorigenic effects. We have investigated the efficacy of dietary cardamom against 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin papillomatogenesis in Swiss albino mice that closely resembles human NMSC. Mice were grouped into normal wild type (untreated), vehicle-treated (acetone), carcinogen-treated (DMBA), and DMBA and cardamom-treated (DMBA+CARD) to delineate the role of cardamom against DMBA-induced papillomatogenesis. Oral administration of cardamom to DMBA-treated mice up-regulated the phase II detoxification enzymes, such as glutathione-S-transferase and glutathione peroxidase, probably via activation of nuclear factor erythroid-2-related factor 2 transcription factor in 'DMBA+CARD' mice. Furthermore, reduced glutathione, glutathione reductase, superoxide dismutase and catalase were also up-regulated by cardamom in the same 'DMBA+CARD' group of mice compared with DMBA-treated mice. Cardamom ingestion in DMBA-treated mice blocked NF-κB activation and down-regulated cyclo-oxygenase-2 expression. As a consequence, both the size and the number of skin papillomas generated on the skin due to the DMBA treatment were reduced in the 'DMBA+CARD' group. Thus, the results from the present study suggest that cardamom has a potential to become a pivotal chemopreventive agent to prevent papillomagenesis on the skin.

Protective effect of esculin against prooxidant aflatoxin B1-induced nephrotoxicity in mice.

PubMed

Naaz, Farah; Abdin, M Z; Javed, Saleem

2014-02-01

The study was designed to investigate the protective effect of esculin against pro-oxidant aflatoxin B1 (AFB1)-induced nephrotoxicity in mice. In this study toxicity was developed by oral administration of AFB1 at a dose of 66.60 μg/kg bw/day for 90 days in male Swiss albino mice. Esculin (150 mg/kg bw/0.2 ml/day) and standard compound ascorbic acid (300 mg/kg bw/0.2 ml/day) was given after 30 min of AFB1 administration for 90 days. Protective efficacy was assessed by measuring the levels of lipid peroxidation (LPO) and non-enzymatic antioxidants such as reduced glutathione (GSH) and also by measuring activities of enzymatic antioxidants such as glutathione peroxidase (GPX), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) in kidney. Results were analysed at the 30(th), 60(th) and 90(th) day of the daily treatments, which showed a decrease in the level of LPO and an increase in the levels of enzymatic and non-enzymatic antioxidants. The protective effect of esculin was further proved by histopathological findings as it exhibited regenerative activities in mice renal tubules against AFB1-induced nephrotoxicity. The results obtained clearly demonstrate that the protective efficacy of esculin against pro-oxidant AFB1-induced nephrotoxicity in mice might be due to its antioxidants and free radical scavenging properties.

Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation.

PubMed

Vedi, Mahima; Sabina, Evan Prince

2016-10-01

Bromobenzene is a well-known environmental toxin which causes liver and kidney damage through CYP450-mediated bio-activation to generate reactive metabolites and, consequently, oxidative stress. The present study aimed to evaluate the possible protective role of withaferin A against bromobenzene-induced liver and kidney damage in mice. Withaferin A (10 mg/kg) was administered orally to the mice for 8 days before intragastric intubation of bromobenzene (10 mmol/kg). As results of this experiment, the levels of liver and kidney functional markers, lipid peroxidation, and cytokines (TNF-α and IL-1β) presented an increase and there was a decrease in anti-oxidant activity in the bromobenzene-treated group of mice. Pre-treatment with withaferin A not only significantly decreased the levels of liver and kidney functional markers and cytokines but also reduced oxidative stress, as evidenced by improved anti-oxidant status. In addition, the mitochondrial dysfunction shown through the decrease in the activities of mitochondrial enzymes and imbalance in the Bax/Bcl-2 expression in the livers and kidneys of bromobenzene-treated mice was effectively prevented by pre-administration of withaferin A. These results validated our conviction that bromobenzene caused liver and kidney damage via mitochondrial pathway and withaferin A provided significant protection against it. Thus, withaferin A may have possible usage in clinical liver and kidney diseases in which oxidative stress and mitochondrial dysfunction may be existent.

Impact of oral cadmium intoxication on levels of different essential trace elements and oxidative stress measures in mice: a response to dose.

PubMed

Kumar, Narendra; Kumari, Vandna; Ram, Chand; Bharath Kumar, Bagepalli Sathyanarayana; Verma, Sunita

2018-02-01

The study evaluated the effect of oral intoxication of cadmium and the possible causes of oxidative stress and its preferential accumulation in different organs as well as sub-sequential effects in mice. Twenty-four Swiss albino male mice were divided into three groups viz., normal control group without cadmium chloride (CdCl 2 ), whereas a daily dose of 0.5 and 1.2 mg of CdCl 2 was orally administered for a period of a week to dose group 1 (DG-1) and dose group 2 (DG-2), respectively. A significant increase in the severity of cadmium toxicity was observed in animals as evidenced by aggravation in liver enzymes viz., serum alanine aminotransferase and aspartate transaminase, whereas lower levels of antioxidative stress markers in liver and kidney tissues of treated mice were observed as compared to normal control group. A significant depletion of calcium levels in liver tissues of DG-1 (217.36 ± 1.73 μg/g of wet tissues) and DG-2 (186.41 ± 1.56 μg/g of wet tissues) groups, along with Cd accumulation, was observed. To summarize, the current study would increase our understanding with respect to dose-dependent absorption of Cd and its toxicity led to mortality as well as adverse health effects in the body of mice. Graphical abstract ᅟ.

Statins enhance cognitive performance in object location test in albino Swiss mice: involvement of beta-adrenoceptors.

PubMed

Vandresen-Filho, Samuel; França, Lucas Moreira; Alcantara-Junior, José; Nogueira, Lucas Caixeta; de Brito, Thiago Marques; Lopes, Lousã; Junior, Fernando Mesquita; Vanzeler, Maria Luzinete; Bertoldo, Daniela Bohn; Dias, Paula Gomes; Colla, André R S; Hoeller, Alexandre; Duzzioni, Marcelo; Rodrigues, Ana Lúcia S; de Lima, Thereza C M; Tasca, Carla Inês; Viola, Giordano Gubert

2015-05-01

Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby inhibiting cell synthesis of cholesterol and isoprenoids. Moreover, several studies have been evaluating pleiotropic effects of statins, mainly because they present neuroprotective effects in various pathological conditions. However, knowledge about behavioral effects of statins per se is relatively scarce. Considering these facts, we aimed to analyze behavioral responses of atorvastatin or simvastatin-treated mice in the open field test, elevated plus maze and object location test. Atorvastatin treatment for 7 consecutive days at 1 mg/kg or 10 mg/kg (v.o.) or simvastatin 10 mg/kg or 20 mg/kg enhanced cognitive performance in object location test when compared to control group (saline-treated mice). Simvastatin effects on mice performance in the object location test was abolished by post-training infusion of the beta-adrenoceptor antagonist propranolol. Atorvastatin and simvastatin did not change the behavioral response in open field and elevated plus-maze (EPM) tests in any of the used doses. These data demonstrate the positive effects of both statins in cognitive processes in mice, without any alteration in locomotor parameters in the open field test or anxiolytic-like behavior in EPM. In conclusion, we demonstrate that atorvastatin and simvastatin per se improve the cognitive performance in a rodent model of spatial memory and this effect is related to beta-adrenergic receptors modulation. Copyright © 2015 Elsevier Inc. All rights reserved.

Baclofen prevents the elevated plus maze behavior and BDNF expression during naloxone precipitated morphine withdrawal in male and female mice.

PubMed

Pedrón, Valeria T; Varani, André P; Balerio, Graciela N

2016-05-01

In previous studies we have shown that baclofen, a selective GABAB receptor agonist, prevents the somatic expression and reestablishes the dopamine and μ-opioid receptors levels, modified during naloxone-precipitated morphine withdrawal syndrome in male and female mice. There are no previous reports regarding sex differences in the elevated plus maze (EPM) and the expression of BDNF in morphine-withdrawn mice. The present study analyses the behavioral and biochemical variations during morphine withdrawal in mice of both sexes, and whether these variations are prevented with baclofen. Swiss-Webster albino prepubertal mice received morphine (2 mg/kg, i.p.) twice daily, for 9 consecutive days. On the 10th day, one group of morphine-treated mice received naloxone (opioid receptor antagonist; 6 mg/kg, i.p.) 1 h after the last dose of morphine to precipitate withdrawal. A second group received baclofen (2 mg/kg, i.p.) before naloxone administration. The EPM behavior was measured during 15 min after naloxone injection. The expression of BDNF-positive cells was determined by immunohistochemistry. Withdrawn male mice showed a higher percentage of time spent and number of entries to the open arms compared to withdrawn female mice. Baclofen prevented this behavior in both sexes. BDNF expression decreased in the AcbC, BNST, CeC, and CA3 of the hippocampus while increased in the BLA of morphine withdrawn male. Baclofen pretreatment prevented the BDNF expression observed in morphine withdrawn male mice in all the brain areas studied except in the CeC. Baclofen prevention of the EPM behavior associated to morphine withdrawal could be partially related to changes in BDNF expression. © 2016 Wiley Periodicals, Inc.

Three-dimensional morphometric analysis of microglial changes in a mouse model of virus encephalitis: age and environmental influences.

PubMed

de Sousa, Aline A; Dos Reis, Renata R; de Lima, Camila M; de Oliveira, Marcus A; Fernandes, Taiany N; Gomes, Giovanni F; Diniz, Daniel G; Magalhães, Nara M; Diniz, Cristovam G; Sosthenes, Marcia C K; Bento-Torres, João; Diniz, José Antonio P; Vasconcelos, Pedro F da C; Diniz, Cristovam Wanderley P

2015-08-01

Many RNA virus CNS infections cause neurological disease. Because Piry virus has a limited human pathogenicity and exercise reduces activation of microglia in aged mice, possible influences of environment and aging on microglial morphology and behavior in mice sublethal encephalitis were investigated. Female albino Swiss mice were raised either in standard (S) or in enriched (EE) cages from age 2 to 6 months (young - Y), or from 2 to 16 months (aged - A). After behavioral tests, mice nostrils were instilled with Piry-virus-infected or with normal brain homogenates. Brain sections were immunolabeled for virus antigens or microglia at 8 days post-infection (dpi), when behavioral changes became apparent, and at 20 and 40 dpi, after additional behavioral testing. Young infected mice from standard (SYPy) and enriched (EYPy) groups showed similar transient impairment in burrowing activity and olfactory discrimination, whereas aged infected mice from both environments (EAPy, SAPy) showed permanent reduction in both tasks. The beneficial effects of an enriched environment were smaller in aged than in young mice. Six-hundred and forty microglial cells, 80 from each group were reconstructed. An unbiased, stereological sampling approach and multivariate statistical analysis were used to search for microglial morphological families. This procedure allowed distinguishing between microglial morphology of infected and control subjects. More severe virus-associated microglial changes were observed in young than in aged mice, and EYPy seem to recover microglial homeostatic morphology earlier than SYPy . Because Piry-virus encephalitis outcomes were more severe in aged mice, it is suggested that the reduced inflammatory response in those individuals may aggravate encephalitis outcomes. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Impact of a novel synbiotic supplementation during gestation and lactation on immune responses in the Swiss albino mice offspring.

PubMed

Nallagatla, Himaja; Hemalatha, Rajkumar; Kondapalli, Narendra Babu; Mohammed, Shujauddin

2017-06-01

Prebiotics from various regularly consumed cereals and novel substrates are currently being utilised as functional foods. The aim of this study was to determine the effect of synbiotic, formulated with prebiotic extracted from natural resources like green gram (Vigna radiata) along with probiotic Lactobacillus rhamnosus GG (LGG) in modulating immune responses in the offspring when supplemented during gestation and lactation. Synbiotic supplementation was effective in improving cell mediated immunity and humoral immunity among F0 dams. Among F1 pups (F1 Syn + and F1 Syn-), synbiotic supplementation showed significantly heightened (P < 0.05) splenocyte proliferation, increased interleukin-10, interferon gamma and interleukin-17 responses, leucocyte phagocytic ability and increased secretory-immunoglobulin A. However, four-fold increase in IgG titres to Hepatitis-B vaccine was observed only in those mice that were supplemented with synbiotic postweaning (F1 Syn+). Synbiotic supplementation to pregnant dams affected the offspring's cellular and mucosal immunity favorably. However, IgG response to Hepatitis-B vaccine was influenced positively only when the supplementation was extended to the offsprings in the post weaning period. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

[Cadmium citotoxicity in mice hepatocytes and implications on tropical environments].

PubMed

Marcano, Letty; Faría, Clarisa de R; Carruyo, Ingrid; Montiel, Xiomara

2006-06-01

We analyzed phenotypic, structural and ultrastructural alterations induced by Cd+2 in hepatocytes extracted from Swiss Albino mice. Cadmium was given orally in watery solution of CdCl2 during 100 days at concentrations of 50 ppm, 100 ppm and 150 ppm. In controls, distilled water alone was used. The samples were processed with the paraffin inclusion and hematoxilin-eosin coloration techniques for light microscopy. For transmission electron microscopy we used the conventional technique. We found phenotypic (size and weight differences) and physiologic changes (muscular weakness, unrest); at the structural level we noticed loss of trabecular disposition and of lobulillar architecture, lymphocyte agglomeration, vacuolization, dilatation of sinusoid and central vein, among others. The ultrastructural study evidenced alterations coincident with those seen with light microscopy, which were accentuated with the increase of metal concentration: nucleolus with a high number of fibrillar centers (50 ppm); voluminous lipidic drops in the cytoplasm, loose endoplasmic rough reticulum, citoplasmatic vacuolization, altered lisosomes and peroxisomes (100 ppm); contracted nuclei with condensed cromatine, dilatation of intracellular space and mitochondria, and loss of fibrillar areas (150 ppm). Cadmium produces a toxic effect in the hepatic cells; the effect is more severe at higher concentration, leading to cellular necrosis.

Extraction Optimization of Tinospora cordifolia and Assessment of the Anticancer Activity of Its Alkaloid Palmatine

PubMed Central

Ali, Huma; Dixit, Savita

2013-01-01

Objective. To optimize the conditions for the extraction of alkaloid palmatine from Tinospora cordifolia by using response surface methodology (RSM) and study its anticancerous property against 7,12-dimethylbenz(a)anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice. Methods. The effect of three independent variables, namely, extraction temperature, time, and cycles was investigated by using central composite design. A single topical application of DMBA (100 μg/100 μL of acetone), followed 2 weeks later by repeated application of croton oil (1% in acetone three times a week) for 16 weeks, exhibited 100 percent tumor incidence (Group 2). Results. The highest yield of alkaloid from Tinospora cordifolia could be achieved at 16 hours of extraction time under 40°C with 4 extraction cycles. Alkaloid administration significantly decreases tumor size, number, and the activity of serum enzyme when compared with the control (Group 2). In addition, depleted levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase and increased DNA damage were restored in palmatine treated groups. Conclusion. The data of the present study clearly indicate the anticancer potential of palmatine alkaloid in DMBA induced skin cancer model in mice. PMID:24379740

Zoonotic sporotrichosis of lymphocutaneous type in a man acquired from a domesticated feline source: report of a first case in southern Karnataka, India.

PubMed

Yegneswaran, Prakash Peralam; Sripathi, Handattu; Bairy, Indira; Lonikar, Vrushali; Rao, Rhagavendra; Prabhu, Smitha

2009-11-01

Sporotrichosis is commonly encountered due to traumatic implantation of thorns or decayed vegetation with the dimorphic fungi, Sporothrix schenckii. Zoonotic spread of Sporotrichosis is rare and we describe here the first case of feline transmission of lymphocutaneous sporotrichiosis encountered in India. An excision biopsy of nodulo-ulcerative lesion from the patients right elbow and forearm were collected for histopathology and portion of the specimen processed for mycological work up. Animal pathogenicity test performed in Swiss albino mice with intraperitoneal & foot pad inoculation. In addition an investigation of the ulcerative skin lesion from the domesticated cat was carried out. Histopathology examination of tissue sample from the patient and feline lesion revealed granulomatous reaction and a few slender elongated yeast cells consistent with Sporotrichosis. The diagnosis was confirmed by culturing Sporothrix schenkii and demonstration of thermal dimorphism. Pathogenicity testing in mice lead to orchitis in 12-15 days and the organism was re-isolated in pure culture. The patient was treated with oral saturated potassium iodide solution with complete resolution of the lesions. Close contact with infected domesticated feline can be a potential source of transmission for Sporotrichosis as evidenced in this report.

In vivo antimutagenic and antiatherogenic effects of the (1 → 3)(1 → 6)-β-d- glucan botryosphaeran.

PubMed

Silva-Sena, Geralda Gillian; Malini, Maressa; Delarmelina, Juliana Macedo; Dutra, Jean Carlos Vencioneck; Gervásio, Suiany Vitorino; Leal, Marcos André Soares; Costa Pereira, Thiago de Melo; Barbosa-Dekker, Aneli M; Dekker, Robert F H; de Paula, Flavia; Batitucci, Maria do Carmo Pimentel

2018-02-01

The antimutagenic effect of botryosphaeran, an exocellular (1 → 3)(1 → 6)-β-d-glucan, from the ascomyceteous and plant-borne endophytic fungus, Botryosphaeria rhodina MAMB-05, was evaluated in young (6-8 weeks) and elderly (18 months) Swiss albino mice of both genders. The hypolipidemic, hypoglycemic and antiatherogenic potential was also evaluated in 18-month old male LDL receptor knockout (LDLr -/- ) mice. Administration of botryosphaeran by gavage (doses: 7.5, 15, 30 mg/kg b.w./day) in a 30-day pretreatment protocol (young mice), or 15-day protocol (older mice), did not cause genotoxicity as assessed by the micronucleus test in peripheral blood (PB) and bone marrow cells (BMCs). Furthermore, there was no cytotoxic effect of this β-d-glucan in the treatments. A lower frequency of micronuclei was observed in BMCs from young and old mice that received botryosphaeran, indicating its antimutagenic effect. Botryosphaeran (30 mg/kg b.w./day) promoted 102.22% (young) and 103.45% (elderly) reductions in cyclophosphamide-induced damage in male mice. Botryosphaeran also exerted chemoprotective effects in LDLr -/- and wild-type (C57BL/6) mice. Botryosphaeran treatment for 15 days at a dose of 30 mg/kg b.w./day improved the lipidic profile (reductions of 53.8-84.3%), and decreased aortic lipid deposition (32.8%) in the LDLr -/- atherosclerotic mice. The results indicate botryosphaeran has relevant biologic effects, making it a promising candidate for the development of new therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of L-cysteine on lead acetate induced neurotoxicity in albino mice.

PubMed

Mahmoud, Y I; Sayed, S S

2016-07-01

Lead is a toxic heavy metal that adversely affects nervous tissues; it often occurs as an environmental pollutant. We investigated histological changes in the cerebral cortex, hippocampus and cerebellum of adult albino mice following exposure to lead acetate. We also studied the possible ameliorative effect of the chelating agent, L-cysteine, on lead-induced neurotoxicity. We divided albino mice into six groups: 1) vehicle-only control, 2) L-cysteine control, 3 and 4) treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, and 5 and 6) treated for 7 days with 20 and 40 mg/kg lead acetate, respectively, followed by 50 mg/kg L-cysteine for 7 days. Lead acetate administration caused disorganization of cell layers, neuronal loss and degeneration, and neuropil vacuolization. Brain sections from lead-intoxicated mice treated with L-cysteine showed fewer pathological changes; the neuropil showed less vacuolization and the neurons appeared less damaged. L-cysteine at the dose we used only marginally alleviated lead-induced toxicity.

PGE from Octopus aegina Induces Apoptosis in Ehrlich's Ascites Carcinoma of Mice.

PubMed

Karthigayan, S; Balasubashini, M Sri; Balasubramanian, T; Somasundaram, S T

2007-01-01

ABSTRACT The present study was carried out to assess the antitumor effect of venomous peptide from the cephalopod Octopus aegina on Ehrlich's ascites carcinoma (EAC). Male albino Swiss mice were used in the present study. Four groups of animals were treated with three doses of the sublethal dose of venom, 15, 75, and 150 mug/kg body weight (intraperitoneal injection), along with the standard drug 5-fluorouracil (20 mg/kg b.w.). After 10 days of treatment, six animals from each group were sacrificed for the biochemical analysis and the rest were left to calculate the mean survival time. In EAC-bearing mice, mean lifespan, tumor volume, hemoglobin, red blood cells, and lymphocytes were significantly decreased when compared to the normal animals. While body weight, neutrophils, and viable tumor cell count were increased in the EAC-bearing mice, these changes were brought back to near normal levels in different treatment groups. The macromolecule concentration of peritoneal cells, such as DNA, RNA, and protein, were altered in the EAC-bearing mice and observed to be near normal in the treatment groups. The caspase-3 activity was significantly increased in the peritoneal cells of the treatment groups when compared to the EAC-bearing mice. The role of apoptotic cascade in EAC cell death was confirmed by the DNA fragmentation on agarose gel. Apart from the antitumor effect, octopus venom reduced the tumor burden on the liver and altered the changes in the activities of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Therefore, the venom from O. aegina has a potential antitumor effect on the EAC-bearing mice.

Modulatory influence of sandalwood oil on mouse hepatic glutathione S-transferase activity and acid soluble sulphydryl level.

PubMed

Banerjee, S; Ecavade, A; Rao, A R

1993-02-01

The effect of the oil from the wood of Santalum album on glutathione S-transferase (GST) activity and acid soluble sulphydryl (SH) levels in the liver of adult male Swiss albino mice was investigated. Oral feeding by gavage to mice each day with 5 and 15 microliters sandalwood oil for 10 and 20 days exhibited an increase in GST activity in time- and dose-responsive manners. Feeding a dose of 5 microliters sandalwood oil for 10 and 20 days caused, respectively, a 1.80-fold (P < 0.001) and 1.93-fold (P < 0.001) increase in GST enzyme activity, while feeding a dose of 15 microliters of the oil per day for 10 and 20 days induced, respectively, 4.73-fold (P < 0.001) and 6.10-fold (P < 0.001) increases in the enzyme's activity. In addition, there were 1.59-fold (P < 0.001) and 1.57 (P < 0.001) increases in acid-soluble SH levels in the hepatic tissue of the mice following feeding of the oil at the dose levels of 5 and 15 microliters for 10 days. Furthermore, mice fed on a diet containing 1% 2(3)-butyl-4-hydroxyanisole (positive control) also showed an increase in hepatic GST activity and SH levels. Enhancement of GST activity and acid-soluble SH levels are suggestive of a possible chemopreventive action of sandalwood oil on carcinogenesis through a blocking mechanism.

Evaluation of analgesic activity of various extracts of Sida tiagii Bhandari.

PubMed

Kumawat, Ram Kumar; Kumar, Suresh; Sharma, Sunil

2012-01-01

Sida tiagii Bhandari mostly found in India and Pakistan which belongs to family Malvaceae, is traditionally used as analgesic, anti-inflammatory, sedative, anxiolytic, anti-seizure and anti-platelet. The present study was done to explore the analgesic activity of various extracts of fruits of the plant Sida tiagii Bhandari. The grinded fruits were extracted with 90% ethanol and partitioned with n-hexane (n-hexane extract; HS) and ethyl acetate (ethyl acetate extract; EAS), successively. The residual ethanol fraction (residual ethanol extract; RES) was also prepared by drying on water bath separately. All three extracts were administered orally at a dose of 200 mg/kg and 500 mg/kg of body weight. The analgesic activity of above extracts was evaluated by using acetic acid induced writhing, tail immersion and tail flick tests in Swiss albino mice. The EAS extract was found to reduce pain and RES extract of Sida tiagii B. was found to have good analgesic activity in comparison to other extracts.

Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals

PubMed Central

Farazuddin, Mohammad; Dua, Bhavyata; Zia, Qamar; Khan, Aijaz Ahmad; Joshi, Beenu; Owais, Mohammad

2014-01-01

Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham) microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice. PMID:24627632

Synergistic Interaction of Retigabine with Levetiracetam in the Mouse Maximal Electroshock-Induced Seizure Model: A Type II Isobolographic Analysis.

PubMed

Luszczki, Jarogniew J; Zagaja, Mirosław; Miziak, Barbara; Florek-Luszczki, Magdalena; Czuczwar, Stanislaw J

2015-01-01

To assess interactions between retigabine and levetiracetam in suppressing maximal electroshock-induced tonic seizures in Albino Swiss mice, type II isobolographic analysis was used. Total brain antiepileptic drug concentrations were measured with high pressure liquid chromatography. The combinations of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 were supra-additive (synergistic; p < 0.05) in terms of seizure suppression, while the combinations at the fixed-ratios of 1:1 and 1:2 were additive. No pharmacokinetic changes in total brain concentrations of levetiracetam and retigabine were documented, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse maximal electroshock-induced tonic seizure model. The combination of retigabine with levetiracetam at the fixed-ratios of 1:5 and 1:10 appears to be particularly beneficial combination exerting supra-additive interaction in suppressing maximal electroshock-induced tonic seizures. © 2015 S. Karger AG, Basel.

Virulence of geographically different Cryptosporidium parvum isolates in experimental animal model

PubMed

Sayed, Fatma G.; Hamza, Amany I.; Galal, Lamia A.; Sayed, Douaa M.; Gaber, Mona

2016-10-01

Cryptosporidium parvum is a coccidian parasite which causes gastrointestinal disease in humans and a variety of other mammalian species. Several studies have reported different degrees of pathogenicity and virulence among Cryptosporidium species and isolates of the same species as well as evidence of variation in host susceptibility to infection. The study aimed to investigate infectivity and virulence of two Cryptosporidium parvum “Iowa isolate” (CpI) and a “local water isolate” (CpW). Thirty-three Swiss albino mice have been divided into three groups: Negative control Group (C), the CpI group infected with “Iowa isolate “and the CpW group infected with C. parvum oocysts isolated from a local water supply. Infectivity and virulence have been measured by evaluating clinical, parasitological and histological aspects of infection. Significant differences were detected regarding oocysts shedding rate, clinical outcomes, and the histopathological picture of the intestine, lung, and brain. It was concluded that the local water isolate is significantly more virulent than the exported one.

Oral supplementation of Lanthanum Zirconate nanoparticles moderately affected behavior but drastically disturbed leukocyte count, serum cholesterol levels and antioxidant parameters from vital organs of albino mice in a gender specific manner.

PubMed

Aftab, Muhammad Nazar; Akram, Irum Naz; Khosa, Tafheem; Zahra, Syeda Qandeel; Bashir, Irum; Ashiq, Muhammad Naeem; Iqbal, Furhan

2018-05-21

Lanthanum Zirconate nanoparticles (NPs) are used in blades of gas turbine engines to thermally insulate them and to protect them against hot and corrosive gas streams. However, the information regarding their biocompatibility is limited. The present study was aimed to report the effect of Lanthanum Zirconate NPs on selected aspects of behavior, serum biochemistry, complete blood count and antioxidant parameters from vital organs of albino mice in a gender specific manner. Albino mice, seven weeks old, were orally treated with 75 mg/ml solvent/Kg body weight of Lanthanum Zirconate nanoparticles for consecutive 22 days. Saline treated control groups were maintained in parallel. It was observed that rearing frequency was significantly decreased (P = 0.01) in NPs treated male mice. Complete blood count analysis indicated that NPs treated female mice had significantly reduced white blood cells (P = 0.05) and lymphocytes count (P = 0.03). NPs treated male had significantly reduced serum cholesterol levels (P = 0.05) than control group. It was observed that Superoxide dismutase concentrations in liver (P = 0.025) and kidney (P = 0.008), Malondialdehyde concentrations in liver (P = 0.044) of female and Malondialdehyde concentrations in kidney (P < 0.001) and brain (P < 0.001) and catalase concentrations in liver (P = 0.05) of NPs treated male mice were significantly higher than their respective control groups.. In conclusion, we are reporting that oral supplementation with 75 mg/ml solvent/Kg body weight of Lanthanum Zirconate nanoparticles can affect the behavior, leukocyte count, serum cholesterol and antioxidant metabolites from vital organs of albino mice in a gender specific manner.

In-vivo wound healing modulation after irradiation with a blue LED photocoagulator

NASA Astrophysics Data System (ADS)

Rossi, Francesca; Cicchi, Riccardo; Magni, Giada; Tatini, Francesca; Bacci, Stefano; Paroli, Gaia; Alfieri, Domenico; Tripodi, Cristina; De Siena, Gaetano; Pavone, Francesco S.; Pini, Roberto

2017-07-01

A faster healing process was observed in superficial skin wounds after irradiation with a blue LED (EmoLED) photocoagulator. EmoLED is a compact handheld device, used to induce a thermal effect and thus coagulation in superficial abrasions. We present the results of an in vivo study, conducted in different mouse model, to analyze the induced wound healing. Two superficial abrasions were produced on the back of the mice: one area was treated with EmoLED (1.4 W/cm2, 30 s treatment time), while the other one was left naturally recovering. During the treatment, a temperature around 40-45°C was induced on the abrasion surface. Mice back healthy skin was used as a control. We compared the treatment in black mice, healthy albino mice, diabetic albino mice and albino mice with coagulation problem. The animals underwent a follow up study and were sacrificed at 0, 3, 6, 9, 18, 24 hours p.o.. Samples from the two abraded areas were harvested and examined by histopathological and immunofluorescence analysis, SHG imaging and confocal microscopy. The aim of the study was to compare the effects in the different target groups and to investigate the early phase of the wound healing process. Our results show that the effects are comparable in all the treated groups and that the healing process appears to be faster in respect to the naturally recovered wounds. This study confirms the previous results obtained in a study on a rat model an in a study on healthy albino mice: the selective photothermal effect we used for inducing immediate coagulation in superficial wounds seems to be associated to a faster and improved healing process.

Investigating the role of nisoldipine in foot-shock-induced post-traumatic stress disorder in mice.

PubMed

Verma, Meenu; Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar S

2016-04-01

This study was designed to investigate the effectiveness of nisoldipine, an L-type voltage-sensitive calcium channel blocker, to ameliorate anxiety and fear response in a mouse model of post-traumatic stress disorder (PTSD). Acute trauma was induced in Swiss albino mice in a 2-day electric foot-shock paradigm consisting of 15 intermittent foot-shocks of 0.8 mA intensity, 10-s duration and 10-s intershock interval, during 5 min, followed by 3 weekly situational reminders, that is, once per week in the same context on three successive weeks. PTSD-induced behavioral changes were assessed using actophotometer, open-field, social interaction test, and freezing behavior. Biochemically, the serum corticosterone levels were estimated. Electric foot-shock and situational reminders produced behavioral alterations and decreased corticosterone levels, assessed on the 21st day following the traumatic event. Administration of sertraline (Ser 15 mg/kg), a selective serotonin reuptake inhibitor (SSRI) and nisoldipine (20 and 40 mg/kg), significantly attenuated the foot-shock-trauma-induced behavioral changes along with normalization of the corticosterone levels. It may be concluded that nisoldipine produces beneficial effects in re-establishing behavioral alterations, which may be due to normalization of reduced corticosterone levels in PTSD in mice. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Amelioration of lead-induced hepatotoxicity by Allium sativum extracts in Swiss albino mice

PubMed Central

Sharma, Arti; Sharma, Veena; Kansal, Leena

2010-01-01

Lead is a blue–gray and highly toxic divalent metal that occurs naturally in the earth's crust and is spread throughout the environment by various human activities. The efficacy of garlic (Allium sativum) to reduce hepatotoxicity induced by lead nitrate was evaluated experimentally in male mice. Oral treatment with lead nitrate at a dose of 50 mg/kg body weight daily for 40 days (1/45 of LD50) induced a significant increase in the levels of hepatic aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, cholesterol, lipid peroxidation, and lead nitrate. In parallel, hepatic protein levels in lead-exposed mice were significantly depleted. Lead nitrate exposure also produced detrimental effects on the redox status of the liver indicated by a significant decline in the levels of liver antioxidants such as superoxide dismutase, catalase, and glutathione. After exposure to lead nitrate (50 mg/kg body weight for 10 days), the animals received aqueous garlic extract (250 mg/kg body weight and 500 mg/kg body weight) and ethanolic garlic extract (100 mg/kg body weight and 250 mg/kg body weight), and partially restored the deranged parameters significantly. Histological examination of the liver also revealed pathophysiological changes in lead nitrate-exposed group and treatment with garlic improved liver histology. Our data suggest that garlic is a phytoantioxidant that can counteract the deleterious effects of lead nitrate. PMID:21483544

In vivo enzyme inhibition improves the targeting of [177Lu]DOTA-GRP(13-27) in GRPR-positive tumors in mice.

PubMed

Marsouvanidis, Panteleimon J; Melis, Marleen; de Blois, Erik; Breeman, Wout A P; Krenning, Eric P; Maina, Theodosia; Nock, Berthold A; de Jong, Marion

2014-11-01

Gastrin-releasing peptide receptors (GRPR) and GRP-derived analogs have attracted attention due to high receptor expression in frequently occurring human neoplasia. The authors recently synthesized a series of GRPR-affine peptide analogs based on the 27-mer GRP and derivatized with the DOTA chelator at the N-terminus for (111)In-labeling. In this study, the authors evaluated the most promising from these series, DOTA-GRP(13-27), after radiolabeling with (177)Lu for future therapeutic applications. In addition, to improve in vivo stability of the peptide against in vivo degradation by the protease neutral endopeptidase (NEP), the authors coinjected [(177)Lu]DOTA-GRP(13-27) with the potent NEP inhibitor phosphoramidon (PA). The authors also aimed at reducing renal uptake by coadministration of lysine. In vivo stability studies were performed in Swiss albino mice. Biodistribution studies were conducted in NMRI nu/nu mice bearing prostate cancer (PC)-3 xenografts. Ex vivo autoradiography was performed using frozen sections from PC-3 xenografts and kidneys. Coadministration of PA significantly increased the percentage of intact radiopeptide in the mouse circulation. From biodistribution and ex vivo autoradiography studies, coadministration of both lysine and PA with [(177)Lu]DOTA-GRP(13-27) appeared to induce a clear improvement of tumor uptake as well as lower levels of renal radioactivity, causing a promising ninefold increase in tumor/kidney ratios.

Mangiferin prevents corticosterone-induced behavioural deficits via alleviation of oxido-nitrosative stress and down-regulation of indoleamine 2,3-dioxygenase (IDO) activity.

PubMed

Luo, Gao-Quan; Liu, Ling; Gao, Qu-Wen; Wu, Xiao-Na; Xiang, Wei; Deng, Wen-Ting

2017-08-01

In recent years, a substantial amount of experimental studies have demonstrated that exogenous administration of corticosterone causes anxiety and depressive-like behaviour in rodents which involves hypothalamic-pituitary-adrenal axis dysregulation. Our present study aimed to explore the neuroprotective potential of mangiferin against corticosterone-induced anxiety and depressive-like behaviour. Corticosterone (40 mg/kg; subcutaneously) was administered once daily in swiss albino mice for 21 days. Mice were treated simultaneously with mangiferin (40 mg/kg; p.o.), 30 min prior to the corticosterone injection. Chronic administration of corticosterone caused anxiety and depressive-like behaviour in mice which was significantly alleviated by mangiferin treatment. Biochemical analysis revealed that mangiferin treatment significantly attenuated corticosterone-induced oxido-nitrosative stress and neuroinflammation in the hippocampus region. Furthermore, concomitant treatment with mangiferin significantly enhanced the hippocampal brain-derived neurotrophic factor (BDNF) level and decreased the serum corticosterone level in the corticosterone-treated animals. Western blotting analysis revealed that corticosterone administration significantly up-regulated the indoleamine 2,3-dioxygenase (IDO) protein expression level in the hippocampus which was significantly reduced by mangiferin treatment. Taken together, our results suggest that mangiferin exerts anti-anxiety and antidepressant effect in corticosterone-treated rats, which is probably mediated through up-regulation of BDNF level along with inhibition of oxido-nitrosative stress, neuroinflammation and IDO up-regulation in the hippocampus region.

Radioprotective Effects of Gallic Acid in Mice

PubMed Central

Nair, Gopakumar Gopinathan

2013-01-01

Radioprotecting ability of the natural polyphenol, gallic acid (3,4,5-trihydroxybenzoic acid, GA), was investigated in Swiss albino mice. Oral administration of GA (100 mg/kg body weight), one hour prior to whole body gamma radiation exposure (2–8 Gy; 6 animals/group), reduced the radiation-induced cellular DNA damage in mouse peripheral blood leukocytes, bone marrow cells, and spleenocytes as revealed by comet assay. The GA administration also prevented the radiation-induced decrease in the levels of the antioxidant enzyme, glutathione peroxidise (GPx), and nonprotein thiol glutathione (GSH) and inhibited the peroxidation of membrane lipids in these animals. Exposure of mice to whole body gamma radiation also caused the formation of micronuclei in blood reticulocytes and chromosomal aberrations in bone marrow cells, and the administration of GA resulted in the inhibition of micronucleus formation and chromosomal aberrations. In irradiated animals, administration of GA elicited an enhancement in the rate of DNA repair process and a significant increase in endogenous spleen colony formation. The administration of GA also prevented the radiation-induced weight loss and mortality in animals (10 animals/group) exposed to lethal dose (10 Gy) of gamma radiation. (For every experiment unirradiated animals without GA administration were taken as normal control; specific dose (Gy) irradiated animals without GA administration serve as radiation control; and unirradiated GA treated animals were taken as drug alone control). PMID:24069607

Effect of anhydrosophoradiol-3-acetate of Calotropis gigantea (Linn.) flower as antitumoric agent against Ehrlich's ascites carcinoma in mice.

PubMed

Habib, Muhammad R; Karim, Muhammad R

2013-01-01

Over 60% of currently used anti-cancer agents are derived in one-way or another from natural sources, including plants, marine organisms and microorganisms. Calotropis gigantea (Linn.) (Family: Asclepiadaceae) is a perennial shrub and it is used as a traditional folk medicine for the treatment of various health complications. But there is no report on isolation of anticancerous chemicals from the flower of Calotropis gigantea. The objective of the present study is to explore the antitumor effect of anhydrosophoradiol-3-acetate (A3A), isolated from the flower of Calotropis gigantea (Linn.) against Ehrlich's ascites carcinoma (EAC) in Swiss albino mice. Antitumoric effect of A3A was assessed by evaluating viable tumor cell count, survival time, body weight gain due to tumor burden, hematological and biochemical (glucose, cholesterol, triglyceride, blood urea, SALP, SGPT and SGOT) parameters of EAC bearing host at doses of 10 and 20 mg/kg body weight. Treatment with A3A decreased the viable tumor cells and body weight gain thereby increasing the life span of EAC bearing mice. A3A also brought back the altered hematological (Hb, total RBC and total WBC) and biochemical parameters more or less to normal level. Results of this study conclude that in vivo the A3A was effective in inhibiting the growth of EAC with improving in cancer induced complications.

Virulence variation among epidemic and non-epidemic strains of Saint Louis encephalitis virus circulating in Argentina

PubMed Central

Rivarola, María Elisa; Tauro, Laura Beatriz; Llinás, Guillermo Albrieu; Contigiani, Marta Silvia

2014-01-01

Saint Louis encephalitis virus caused an outbreak of febrile illness and encephalitis cases in Córdoba, Argentina, in 2005. During this outbreak, the strain CbaAr-4005 was isolated from Culex quinquefasciatus mosquitoes. We hypothesised that this epidemic variant would be more virulent in a mouse model than two other non-epidemic strains (78V-6507 and CorAn-9275) isolated under different epidemiological conditions. To test this hypothesis, we performed a biological characterisation in a murine model, including mortality, morbidity and infection percentages and lethal infection indices using the three strains. Mice were separated into age groups (7, 10 and 21-day-old mice) and analysed after infection. The strain CbaAr-4005 was the most infective and lethal of the three variants, whereas the other two strains exhibited a decreasing mortality percentage with increasing animal age. The strain CbaAr-4005 produced the highest morbidity percentages and no significant differences among age groups were observed. The epidemic strain caused signs of illness in all inoculated animals and showed narrower ranges from the onset of symptoms than the other strains. CbaAr-4005 was the most virulent for Swiss albino mice. Our results highlight the importance of performing biological characterisations of arbovirus strains likely to be responsible for emerging or reemerging human diseases. PMID:24810175

Antidepressant Activity of Brahmi in Albino Mice

PubMed Central

Kadali, SLDV Ramana Murty; M.C., Das; Rao A.S.R., Srinivasa; Sri G, Karuna

2014-01-01

Context: In traditional system of medicine brahmi has been used to enhance memory. Recently it has been reported to have action in psychiatric disorders. With these backgrounds the work has been undertaken to study antidepressant activity of brahmi in albino mice. Aim: To evaluate antidepressant activity of brahmi in experimental models. Materials and Methods: The antidepressant activity was studied in albino mice using forced swimming test (FST), tail suspension test (TST) and shock induced depression (SID). Imipramine (10mg/kg), fluoxetine (30mg/kg) were used as standard drugs and brahmi (10, 20, 30mg/kg) was used as test drug. Results: Brahmi exhibited significant decrease in duration of immobility in FST and reduced the shock induced decrease in activity in SID models. It didn’t show any activity in the TST model. Conclusion: Brahmi has shown antidepressant activity in FST and SID. PMID:24783074

Effect of Variable Doses of Zinc Oxide Nanoparticles on Male Albino Mice Behavior.

PubMed

Zahra, Javeria; Iqbal, Shahid; Zahra, Kiran; Javed, Zulha; Shad, Muhammad Aslam; Akbar, Atif; Ashiq, Muhammad Naeem; Iqbal, Furhan

2017-02-01

Zinc oxide nanoparticles (ZnO NPs) have diverse utility these days ranging from being part of nanosensors to be ingredient of cosmetics. Present study was designed to report the effect of variable doses of ZnO NPs on selected aspects of male albino mice behavior. Nano particles were synthesized by sol-gel auto-combustion method (Data not shown here). 10 week old male albino mice were divided into four experimental groups; group A, B and C were orally supplemented with 50 (low dose), 300 (medium dose) and 600 mg/ml solvent/kg body weight (high dose) of ZnO NPs for 4 days. Group D (control) orally received 0.2 M sodium phosphate buffer (solvent for ZnO NPs) for the same duration. A series of neurological tests (Rota rod, open field, novel object and light-dark box test) were conducted in all groups and performance was compared between ZnO NPs treated and control group. Muscular functioning during rota rod test was significantly improved in all ZnO NPs treated mice as compared to control group. While no significant differences in open field, novel object and light-dark box test performance were observed when data from studied parameters of specific ZnO NPs treatment were compared with the control group indicating that applied doses of ZnO NPs did not affect the exploratory, anxiolytic behavior and object recognition capability of adult male albino mice.

Effect of alprazolam on anxiety and cardiomyopathy induced by doxorubicin in mice.

PubMed

Anwar, Md Jamir; Pillai, Krishna K; Khanam, Razia; Akhtar, Mohammad; Vohora, Divya

2012-06-01

Anxiety following heart failure (HF) and/or myocardial infarction (MI) can impede recovery and constitute a major risk factor for further cardiac events. The present study was aimed to evaluate anxiety following doxorubicin (DOX)-induced cardiomyopathy, a rodent model for HF, in mice. Furthermore, the study investigated the effect of alprazolam on anxiety and cardiomyopathy in this model. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg i.v. Alprazolam was administered at doses of 0.5, 1 and 2 mg/kg po for 7 days' pre- and 7 days' post-DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogel's conflict test. On 14th day, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and hearts were dissected out for estimation of thiobarbituric acid reactive substance and Transmission Electron Microscopy (TEM) studies. Our results showed that DOX administration induced cardiomyopathy in mice. This was evidenced by an increased serum LDH and tissue malondialdehyde (MDA) and was confirmed by TEM studies. Alprazolam treatment for 14 days dose dependently reversed DOX-induced increase in LDH and MDA as well as the morphological alterations induced by DOX in TEM studies. Furthermore, alprazolam also reversed the anxiety-like effects induced by DOX in both the tests for anxiety. Thus, alprazolam appears to be a good candidate for alleviating anxiety in patients following MI or HF. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

The in vivo trypanocidal effect of the diterpene 5-epi-icetexone obtained from Salvia gilliesii.

PubMed

Lozano, E; Strauss, M; Spina, R; Cifuente, D; Tonn, C; Rivarola, H W; Sosa, M A

2016-02-01

The search for new compounds with trypanocidal activity is crucial for the treatment of Chagas' disease. Previous in vitro studies have shown that the diterpene 5-epi-icetexone (ICTX) is active against Trypanosoma cruzi. The aim of this work was to evaluate the effect of ICTX on the parasites in infected mice, in an experimental model that mimics the acute phase of the disease. Swiss albino mice were infected with T. cruzi and treated daily with 10mg/kg/day ICTX (i.p.). Infected mice and mice injected with either saline or the vehicle DMSO were used as controls. Animals' survival and parasitemia were monitored once a week and histological studies were made at necropsy by the 5th week after infection. It was observed that the administration of ICTX increased the survival of mice infected, and induced a significant decrease in the parasitemia, as compared to controls. A similar protective effect was observed when animals were treated orally with benznidazole (BZN, used as a control of antiparasitic effect). By the 5th week post-infection, the presence of amastigote nests was observed within the fibers of the cardiac and skeletal muscle in controls, but not in animals treated with either ICTX or BZN. In addition, inflammatory infiltrates were observed in the tissues of controls, but not in animals treated with the drugs. We conclude that ICTX has an antiparasitic effect against T. cruzi, thus constituting an interesting option for the treatment of Chagas' disease, alone or combined with other drugs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Estradiol enhances object recognition memory in Swiss female mice by activating hippocampal estrogen receptor α.

PubMed

Pereira, Luciana M; Bastos, Cristiane P; de Souza, Jéssica M; Ribeiro, Fabíola M; Pereira, Grace S

2014-10-01

In rodents, 17β-estradiol (E2) enhances hippocampal function and improves performance in several memory tasks. Regarding the object recognition paradigm, E2 commonly act as a cognitive enhancer. However, the types of estrogen receptor (ER) involved, as well as the underlying molecular mechanisms are still under investigation. In the present study, we asked whether E2 enhances object recognition memory by activating ERα and/or ERβ in the hippocampus of Swiss female mice. First, we showed that immediately post-training intraperitoneal (i.p.) injection of E2 (0.2 mg/kg) allowed object recognition memory to persist 48 h in ovariectomized (OVX) Swiss female mice. This result indicates that Swiss female mice are sensitive to the promnesic effects of E2 and is in accordance with other studies, which used C57/BL6 female mice. To verify if the activation of hippocampal ERα or ERβ would be sufficient to improve object memory, we used PPT and DPN, which are selective ERα and ERβ agonists, respectively. We found that PPT, but not DPN, improved object memory in Swiss female mice. However, DPN was able to improve memory in C57/BL6 female mice, which is in accordance with other studies. Next, we tested if the E2 effect on improving object memory depends on ER activation in the hippocampus. Thus, we tested if the infusion of intra-hippocampal TPBM and PHTPP, selective antagonists of ERα and ERβ, respectively, would block the memory enhancement effect of E2. Our results showed that TPBM, but not PHTPP, blunted the promnesic effect of E2, strongly suggesting that in Swiss female mice, the ERα and not the ERβ is the receptor involved in the promnesic effect of E2. It was already demonstrated that E2, as well as PPT and DPN, increase the phospho-ERK2 level in the dorsal hippocampus of C57/BL6 mice. Here we observed that PPT increased phospho-ERK1, while DPN decreased phospho-ERK2 in the dorsal hippocampus of Swiss female mice subjected to the object recognition sample phase. Taken together, our results suggest that the type of receptor as well as the molecular mechanism used by E2 to improve object memory may differ in Swiss female mice. Copyright © 2014 Elsevier Inc. All rights reserved.

Chemopreventive efficacy of betel leaf extract and its constituents on 7,12-dimethylbenz(a)anthracene induced carcinogenesis and their effect on drug detoxification system in mouse skin.

PubMed

Azuine, M A; Amonkar, A J; Bhide, S V

1991-04-01

Effects of topically applied betel leaf extract (BLE) and its constituents. beta-carotene, alpha-tocopherol, eugenol and hydroxychavicol on 7,12-dimethylbenz(a)anthracene (DMBA) induced skin tumors were evaluated in two strains of mice. BLE, beta-carotene and alpha-tocopherol, significantly inhibited the tumor formation by 83, 86, 86% in Swiss mice and 92, 94 and 89% in male Swiss bare mice respectively. Hydroxychavicol showed 90% inhibition in Swiss bare mice at 24 weeks of treatment. Eugenol showed minimal protection in both strains of mice. The mean latency period and survivors in BLE, beta-carotene, alpha-tocopherol and hydroxychavicol treated groups were remarkably high as compared to DMBA alone treated group. Intraperitoneal injection of betal leaf constituents showed a significant effect on both glutathione and glutathione S-transferase levels in the Swiss mouse skin.

Inhibitory effect of a mixture containing vitamin C, lysine, proline, epigallocatechin gallate, zinc and alpha-1-antitrypsin on lung carcinogenesis induced by benzo(a) pyrene in mice.

PubMed

Ibrahim, Ahmed Mohamed; Borai, Ibrahim Hassan; Ali, Mamdouh Moawad; Ghanem, Hala Mostafa; Hegazi, Azza El-Sayed Ahmed; Mousa, Amria Mamdouh

2013-05-01

This study was aimed to evaluate protective and therapeutic effects of a specific mixture, containing vitamin C, lysine, proline, epigallocatechin gallate and zinc, as well as alpha-1-antitrypsin protein on lung tumorigenesis induced by benzo(a) pyrene [B(a)P] in mice. Swiss albino mice were divided into two main experiments, experiment (1) the mice were injected with 100 mg/kg B(a)P and lasted for 28 weeks, while experiment (2) the mice were injected with 8 doses each of 50 mg/kg B(a)P and lasted for 16 weeks. Each experiment (1 and 2) divided into five groups, group (I) received vehicle, group (II) received the protector mixture, group (III) received the carcinogen B(a)P, group (IV) received the protector together with the carcinogen (simultaneously) and group (V) received the carcinogen then the protector (consecutively). Total sialic acid, thiobarbituric acid reactive substances, vascular epithelial growth factor, hydroxyproline levels, as well as elastase and gelatinase activities showed significant elevation in group (III) in the two experiments comparing to control group (P < 0.001). These biochemical alterations were associated with histopathological changes. Administration of the protector in group IV and group V causes significant decrease in such parameters with improvement in histopathological alterations with improvement in histopathological alterations when compared with group III in the two experiments (P < 0.001). The present protector mixture has the ability to suppress neoplastic alteration and restore the biochemical and histopathological parameters towards normal on lung carcinogenesis induced by benzo(a) pyrene in mice. Furthermore, the present mixture have more protective rather than therapeutic action.

Zanthoxylum alatum abrogates lipopolysaccharide-induced depression-like behaviours in mice by modulating neuroinflammation and monoamine neurotransmitters in the hippocampus.

PubMed

Barua, Chandana Choudhury; Haloi, Prakash; Saikia, Beenita; Sulakhiya, Kunjbihari; Pathak, Debesh Chandra; Tamuli, Shantanu; Rizavi, Hooriah; Ren, Xinguo

2018-12-01

Depression is an inflammatory, commonly occurring and lethal psychiatric disorder having high lifetime prevalence. Zanthoxylum alatum Roxb. (Rutaceae), commonly called Timur, has high medicinal value and is used ethnomedicinally for the treatment of various diseases. To evaluate the effect of hexane extract of Z. alatum seeds (ZAHE) on lipopolysaccharide (LPS)-induced depression-like behaviour in Swiss albino mice. Mice were treated with ZAHE (100 and 200 mg/kg, p.o.) and imipramine (10 mg/kg injected i.p.) for 14 days. On 14th day of the treatment, depression-like behaviour was induced by LPS (0.83 mg/kg injected i.p.) and after 24 h of LPS administration, it was assessed by measuring behavioural parameters and biochemical estimations. Behavioural tests, including the open field test, forced swimming test, tail suspension test and sucrose preference test revealed that ZAHE (100 and 200 mg/kg, p.o.) and imipramine (10 mg/kg injected i.p.) alleviated the depression symptoms of LPS-induced mice. Moreover, ZAHE treatments reversed the LPS-induced alterations in the concentrations of norepinephrine and serotonin (5-HT) and inhibited the expression of brain-derived neurotrophic factor, pro-inflammatory cytokines and oxido-nitrosative stress in the mice. Acute toxicity was calculated to be LD 50 > 2500 mg/kg. This study showed that LPS-induced depression in mice was significantly prevented by ZAHE at both the dosages. In conclusion, ZAHE exhibited an antidepressant activity by altering monoaminergic neurotransmitters in the brain combined with its anti-inflammatory potential. Thus, it could be an effective therapeutic against inflammation-induced depression and other brain disorders.

Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma

PubMed Central

Nath, Lekshmi R.; Gorantla, Jaggaiah N.; Thulasidasan, Arun Kumar T.; Vijayakurup, Vinod; Shah, Shabna; Anwer, Shabna; Joseph, Sophia M.; Antony, Jayesh; Veena, Kollery Suresh; Sundaram, Sankar; Marelli, Udaya K.; Lankalapalli, Ravi S.; Anto, Ruby John

2016-01-01

We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0.5 μM) than sorafenib (IC50: 5.8 μM), the only FDA-approved drug for liver cancer. Moreover, it induces cytotoxicity in all liver cancer cell lines, irrespective of their HBV status, while being non-toxic to normal immortalized hepatocytes. It induces apoptosis in HepG2 cells by down-regulating mainly the activation of MAPK and mTOR pathways. The drastic reduction in HepG2-xenograft tumor size achieved by uttroside B in NOD-SCID mice and substantiation of its biological safety through both acute and chronic toxicity studies in Swiss albino mice warrants clinical validation of the molecule against hepatic cancer, for which, the chemotherapeutic armamentarium currently has limited weapons. PMID:27808117

Tannic acid mitigates the DMBA/croton oil-induced skin cancer progression in mice.

PubMed

Majed, Ferial; Rashid, Summya; Khan, Abdul Quaiyoom; Nafees, Sana; Ali, Nemat; Ali, Rashid; Khan, Rehan; Hasan, Syed Kazim; Mehdi, Syed Jafar; Sultana, Sarwat

2015-01-01

Skin cancer is the most common malignancy in the world and also one of the major causes of death worldwide. The toxic environmental pollutant 7,12-dimethylbenz[a]anthracene (DMBA) is a skin-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemical-induced toxicities and carcinogenesis as well. In the present study, we have evaluated the therapeutic potential of tannic acid in DMBA + croton oil-induced skin cancer in Swiss albino mice. Protective effect of TA against skin cancer was evaluated in terms of antioxidant enzymes activities, lipid peroxidation, histopathological changes and expression of inflammation and early tumour markers. DMBA + croton oil causes depletion of antioxidant enzymes (p < 0.001) and elevation of early inflammatory and tumour promotional events. TA prevents the DMBA + croton oil-induced toxicity through a protective mechanism that involves the reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression and level of proinflammatory cytokine such as IL-6 release at a very significant level (p < 0.001). It could be concluded from our results that TA attenuates DMBA + croton oil-induced tumour promotional potential possibly by inhibiting oxidative and inflammatory responses and acts as antioxidant, anti-inflammatory and antiproliferative agent.

Anticancer activity of Cynodon dactylon L. root extract against diethyl nitrosamine induced hepatic carcinoma

PubMed Central

Kowsalya, R.; Kaliaperumal, Jagatheesh; Vaishnavi, M.; Namasivayam, Elangovan

2015-01-01

Background: Hepatocellular carcinoma is one of the most common cancers and a lethal disease. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. Materials and Methods: The methanolic extract of roots of Cynodon dactylon was screened for its hepato-protective activity in diethyl nitrosamine (DEN) induced liver cancer in Swiss albino mice. The plant extract at a dose of 50 mg/kg was administered orally once a week, up to 30 days after DEN administration. The animals were sacrificed; blood sample and liver tissue were collected and used for enzyme assay such as, asparatate amino transferase (AST), alanine aminotransferase (ALT), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The liver marker enzymes AST and ALT produced significant results in the protective action. Results: The antioxidant enzyme assay results concerning the improved activity of GPx, GST and CAT. These results concluded that enhanced levels of antioxidant enzyme and reduced amount of serum amino transaminase, which are suggested to be the major mechanisms of C. dactylon root extract in protecting the mice from hepatocarcinoma induced by DEN. These biochemical observations were supplemented by histopathological examination of liver sections. Conclusion: The methanolic extract of C. dactylon possesses significant anticancer properties PMID:25992348

Anticancer activity of Cynodon dactylon L. root extract against diethyl nitrosamine induced hepatic carcinoma.

PubMed

Kowsalya, R; Kaliaperumal, Jagatheesh; Vaishnavi, M; Namasivayam, Elangovan

2015-01-01

Hepatocellular carcinoma is one of the most common cancers and a lethal disease. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. The methanolic extract of roots of Cynodon dactylon was screened for its hepato-protective activity in diethyl nitrosamine (DEN) induced liver cancer in Swiss albino mice. The plant extract at a dose of 50 mg/kg was administered orally once a week, up to 30 days after DEN administration. The animals were sacrificed; blood sample and liver tissue were collected and used for enzyme assay such as, asparatate amino transferase (AST), alanine aminotransferase (ALT), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The liver marker enzymes AST and ALT produced significant results in the protective action. The antioxidant enzyme assay results concerning the improved activity of GPx, GST and CAT. These results concluded that enhanced levels of antioxidant enzyme and reduced amount of serum amino transaminase, which are suggested to be the major mechanisms of C. dactylon root extract in protecting the mice from hepatocarcinoma induced by DEN. These biochemical observations were supplemented by histopathological examination of liver sections. The methanolic extract of C. dactylon possesses significant anticancer properties.

Strychnine inhibits inflammatory angiogenesis in mice via down regulation of VEGF, TNF-α and TGF-β.

PubMed

Saraswati, Sarita; Agarwal, S S

2013-05-01

Strychnine is known to possess anti-inflammatory and antitumour activity, but its roles in tumour angiogenesis, the key step involved in tumour growth and metastasis, and the involved molecular mechanism are still unknown. We aimed to investigate the effects of strychnine on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and strychnine (0.25, and 0.5 mg/kg/day) was given through installed cannulas for 9 days. The implants collected at day 9 postimplantation were processed for the assessment of haemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) and collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Strychnine treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α and transforming growth factor (TGF-β). A regulatory function of strychnine on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of strychnine. Copyright © 2013 Elsevier Inc. All rights reserved.

Amelioration of oxidative stress in bio-membranes and macromolecules by non-toxic dye from Morinda tinctoria (Roxb.) roots.

PubMed

Bhakta, Dipita; Siva, Ramamoorthy

2012-06-01

Plant dyes have been in use for coloring and varied purposes since prehistoric times. A red dye found in the roots of plants belonging to genus Morinda is a well recognized coloring ingredient. The dye fraction obtained from the methanolic extract of the roots of Morinda tinctoria was explored for its role in attenuating damages caused by H(2)O(2)-induced oxidative stress. The antioxidant potential of the dye fraction was assessed through DPPH radical scavenging, deoxyribose degradation and inhibition of lipid peroxidation in mice liver. It was subsequently screened for its efficiency in extenuating damage incurred to biomembrane (using erythrocytes and their ghost membranes) and macromolecules (pBR322 DNA, lipids and proteins) from exposure to hydrogen peroxide. In addition, the non-toxic nature of the dye was supported by the histological evaluation conducted on the tissue sections from the major organs of Swiss Albino mice as well as effect on Hep3B cell line (human hepatic carcinoma). The LC-MS confirms the dye fraction to be morindone. Our study strongly suggests that morindone present in the root extracts of M. tinctoria, in addition to being a colorant, definitely holds promise in the pharmaceutical industry. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of Excess Iodide Intake on Salivary Glands in a Swiss Albino Mice Model

PubMed Central

Ross, Gloria Romina; Fabersani, Emanuel; Russo, Matías; Gómez, Alba; Japaze, Hugo; González, Silvia Nelina

2017-01-01

Iodine is an important micronutrient required for nutrition. Excess iodine has adverse effects on thyroid, but there is not enough information regarding its effect on salivary glands. In addition to food and iodized salt, skin disinfectants and maternal nutritional supplements contain iodide, so its intake could be excessive during pregnancy, lactation, and infancy. The aim of this work was to evaluate the effect of excess iodide ingestion on salivary glands during mating, gestation, lactation, and postweaning period in mouse. During assay, mice were allocated into groups: control and treatment groups (received distilled water with NaI 1 mg/mL). Water intake, glandular weight, and histology were analyzed. Treatment groups showed an increase in glandular weight and a significantly (p < 0.05) higher water intake than control groups. Lymphocyte infiltration was observed in animals of treatment groups, while there was no infiltration in glandular sections of control groups. Results demonstrated that a negative relationship could exist between iodide excess and salivary glands. This work is novel evidence that high levels of iodide intake could induce mononuclear infiltration in salivary glands. These results should be considered, especially in pregnant/lactating women, to whom a higher iodine intake is usually recommended. PMID:29250546

The Combination of Antidepressant Duloxetine with Piracetam in Mice does not Produce Enhancement of Nootropic Activity.

PubMed

Kale, Pravin Popatrao; Addepalli, Veeranjaneyulu; Sarkar, Amrita; Patel, Sonam; Savai, Jay

2014-09-01

There is a strong association between depression and memory impairment. The present study aims to assess the nootropic activity of duloxetine and piracetam combination. Male Swiss Albino mice were divided randomly into 4 groups. Treatment of normal saline (10 ml/kg), duloxetine (10 mg/kg), piracetam (100 mg/kg), and duloxetine (5 mg/kg) plus piracetam (50 mg/kg) were given through intra-peritoneal route to group I-IV, respectively. Transfer latency in elevated plus maze (EPM) and time spent in target quadrant in Morris water maze (MWM) were recorded. Estimation of brain monoamines in hippocampus, cerebral cortex, and whole brain were done using HPLC with fluorescence detector. Piracetam treated group showed significant decrease in transfer latency in EPM and increase in time spent in target quadrant recorded in MWM. Combination treated group failed to produce statistically significant nootropic effect in both EPM and MWM. Combination treated group failed to increase brain monoamine levels when compared against duloxetine and piracetam treated groups, separately. But there was exception of significant increase in norepinephrine levels in hippocampi when compared against duloxetine treated group. Results indicate no cognitive benefits with piracetam plus duloxetine combination. These findings can be further probed with the aim of understanding the interaction between duloxetine and piracetam as a future endeavor.

Tumor control by hypoxia-specific chemotargeting of iron-oxide nanoparticle - Berberine complexes in a mouse model.

PubMed

Sreeja, S; Krishnan Nair, C K

2018-02-15

To evaluate the therapeutic efficacy of hypoxic cell-sensitizer Sanazole (SAN) -directed targeting of cytotoxic drug Berberine (BBN) and Iron-oxide nanoparticle (NP) complexes, to solid tumor in Swiss albino mice. NP-BBN-SAN complexes were characterized by FTIR, XRD, TEM and Nano-size analyzer. This complex was orally administered to mice-bearing solid tumor in hind limb. Tumor regression was analysed by measuring tumor volume. Cellular DNA damages were assessed by comet assay. Transcriptional expression of genes related to tumor hypoxia and apoptosis was evaluated by quantitative real-time PCR and morphological changes in tissues were analysed by histopathology. Also levels of antioxidants and tumor markers in tissues and serum biochemical parameters were analysed. Administration of NP-BBN-SAN complexes reduced tumor volume and studies were focussed on the underlying mechanisms. Extensive damage to cellular-DNA; down-regulated transcription of hif-1α, vegf, akt and bcl2; and up-regulated expression of bax and caspases, were observed in tumor. Results on tumor markers, antioxidant-status and serum parameters corroborated the molecular findings. Histopathology of tumor, liver and kidney revealed the therapeutic specificity of NP-BBN-SAN. Thus SAN and NP can be used for specific targeting of drugs, to hypoxic solid tumor, to improve therapeutic efficacy. Copyright © 2017. Published by Elsevier Inc.

Role of phenolics from Spondias pinnata bark in amelioration of iron overload induced hepatic damage in Swiss albino mice.

PubMed

Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Mandal, Nripendranath

2016-07-26

Crude Spondias pinnata bark extract was previously assessed for its antioxidant, anticancer and iron chelating potentials. The isolated compounds gallic acid (GA) and methyl gallate (MG) were evaluated for their curative potential against iron overload-induced liver fibrosis and hepatocellular damage. In vitro iron chelation property and in vivo ameliorating potential from iron overload induced liver toxicity of GA and MG was assessed by different biochemical assays and histopathological studies. MG and GA demonstrated excellent reducing power activities but iron chelation potential of MG is better than GA. Oral MG treatment in mice displayed excellent efficacy (better than GA) to significantly restore the levels of liver antioxidants, serum markers and cellular reactive oxygen species in a dose-dependent fashion. Apart from these, MG exceptionally prevented lipid peroxidation and protein oxidation whereas GA demonstrated better activity to reduce collagen content, thereby strengthening its position as an efficient drug against hepatic damage/fibrosis, which was further supported by histopathological studies. Alongside, MG efficiently eliminated the cause of liver damage, i.e., excess iron, by chelating free iron and reducing the ferritin-bound iron. The present study confirmed the curative effect of GA and MG against iron overload hepatic damage via their potent antioxidant and iron-chelating potential.

Effect of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of classical antiepileptic drugs against maximal electroshock-induced seizures in mice.

PubMed

Zagaja, Miroslaw; Pyrka, Daniel; Skalicka-Wozniak, Krystyna; Glowniak, Kazimierz; Florek-Luszczki, Magdalena; Glensk, Michał; Luszczki, Jarogniew J

2015-09-01

The effects of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) were studied in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (25 mA, 500 V, 50 Hz, 0.2 s stimulus duration) delivered via auricular electrodes. Total brain concentrations of antiepileptic drugs were measured by fluorescence polarization immunoassay to ascertain any pharmacokinetic contribution to the observed anticonvulsant effects. Results indicate that xanthotoxin (50 and 100 mg/kg, i.p.) significantly potentiated the anticonvulsant activity of carbamazepine against maximal electroshock-induced seizures (P<0.05 and P<0.001, respectively). Similarly, xanthotoxin (100 mg/kg, i.p.) markedly enhanced the anticonvulsant action of valproate in the maximal electroshock seizure test (P<0.001). In contrast, xanthotoxin (100 mg/kg, i.p.) did not affect the protective action of phenobarbital and phenytoin against maximal electroshock-induced seizures in mice. Moreover, xanthotoxin (100 mg/kg, i.p.) significantly increased total brain concentrations of carbamazepine (P<0.001) and valproate (P<0.05), but not those of phenytoin and phenobarbital, indicating pharmacokinetic nature of interactions between drugs. In conclusion, the combinations of xanthotoxin with carbamazepine and valproate, despite their beneficial effects in terms of seizure suppression in mice, were probably due to a pharmacokinetic increase in total brain concentrations of these antiepileptic drugs in experimental animals. Copyright © 2015. Published by Elsevier B.V.

Reduced estradiol synthesis by letrozole, an aromatase inhibitor, is protective against development of pentylenetetrazole-induced kindling in mice.

PubMed

Rashid, Davood; Panda, B P; Vohora, Divya

2015-11-01

Neurosteroids, such as testosterone and their metabolites, are known to modulate neuronal excitability. The enzymes regulating the metabolism of these neurosteroids, thus, may be targeted as a noval strategy for the development of new antiepileptic drugs. The present work targeted two such enzymes i,e aromatase and 5α-reductase in order to explore the potential of letrozole (an aromatase inhibitor) on pentylenetetrazole (PTZ)-induced kindling in mice and the ability of finasteride (a 5α-reductase inhibitor) to modulate any such effects. PTZ (30 mg/kg, i.p.), when administered once every two days (for a total of 24 doses) induced kindling in Swiss albino mice. Letrozole (1 mg/kg, p.o.), administered prior to PTZ, significantly reduced the % incidence of kindling, delayed mean onset time of seizures and reduced seizure severity score. Letrozole reduced the levels of plasma 17β-estradiol after induction of kindling. The concurrent administration of finasteride and letrozole produced effects similar to letrozole on PTZ-kindling and on estradiol levels. This implies that the ability of letrozole to redirect the synthesis of dihydrotestosterone (DHT) and 5α-androstanediol from testosterone doesn't appear to play a significant role in the protective effects of letrozole against PTZ kindling. Letrozole, however, increased the levels of 5α-DHT in mice plasma. The aromatase inhibitors, thus, may be exploited for inhibiting the synthesis of proconvulsant (17β-estradiol) and/or redirecting the synthesis of anticonvulsant (DHT and 5α-androstanediol) neurosteroids. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice.

PubMed

Rajasekar, N; Dwivedi, Subhash; Tota, Santosh Kumar; Kamat, Pradeep Kumar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

2013-09-05

Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment. © 2013 Elsevier B.V. All rights reserved.

Evaluation of wound-healing formulation against sulphur mustard-induced skin injury in mice.

PubMed

Lomash, V; Jadhav, S E; Ahmed, F; Vijayaraghavan, R; Pant, S C

2012-06-01

Sulphur mustard (SM) is a bifunctional alkylating agent that causes cutaneous blisters in human and animals. Remedies to SM-induced dermatotoxicity are still in experimental stage. Due to inevitable requirement of a wound-healing formulation against SM-induced skin lesions, efficacy of formulations including povidone iodine, Aloe vera gel, betaine or framycetin sulphate was evaluated in present study. SM was applied percutaneously (5 mg/kg) once on back region of Swiss albino mice; and after 24 hours, DRDE/WH-02 (Defence Research and Development Establishment/ Wound Healant- 02, containing polyvinylpyrrolidone [PVP], A. vera gel and betaine), Ovadine, Soframycin or A. vera gel were applied topically, daily for 3 or 7 days in different groups. Skin sections were subjected to histopathology, histomorphologic grading, tissue leukocytosis, terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and immunohistochemistry of inflammatory-reparative biomarkers. DRDE/WH-02 treated mice received highest score on the basis of histomorphologic scale and lowest number of TUNEL-positive cells compared to other groups. DRDE/WH-02 showed better wound healing as evidenced by widespread re-epithelialization, homogenous fibroplasias well supported by the expression of transforming growth factor-α, endothelial nitric oxide synthase (eNOS) and fibroblast growth factor. Upregulation of interleukin 6 in DRDE/WH-02-treated mice skin resulted in increased tissue leukocytosis and an early removal of tissue debris that initiated reparative process at faster rate compared to other groups. In conclusion, DRDE/WH-02 provided better healing effect and can be recommended as an effective wound healant against SM-induced skin injury.

Lycopene Attenuates Tulathromycin and Diclofenac Sodium-Induced Cardiotoxicity in Mice.

PubMed

Abdel-Daim, Mohamed M; Eltaysh, Rasha; Hassan, Azza; Mousa, Shaker A

2018-01-24

Recent experiments showed a potential cardiotoxic effect of the macrolide antibiotic (tulathromycin). This study was performed to investigate whether diclofenac sodium (DFS) potentiates the cardiotoxicity of tulathromycin and increases the cardioprotective effects of lycopene against DFS and tulathromycin. Seven groups (eight per group) of adult Swiss albino mice received saline (control), tulathromycin (a single subcutaneous dose of 28 mg/kg/bw on day 14), DFS (a single oral dose of 100 mg/kg/bw on day 14), tulathromycin plus DFS, or lycopene (oral, 10 mg/kg/bw daily for 15 d) combined with tulathromycin, DFS, or both. Compared to the control group, the administration of tulathromycin or DFS (individually or in combination) caused significantly elevated ( p < 0.05) serum levels of Creatine kinase-myocardial B fraction (CK-MB), lactate dehydrogenase, and cardiac-specific troponin-T and tissue levels of nitric oxide and malondialdehyde that were accompanied by significantly decreased tissue reduced glutathione content and glutathione peroxidase, superoxide dismutase, and catalase antioxidant enzyme activity. Upon histopathological and immunohistochemical examination, the mean pathology scores and the percentages of caspase-3-, Bax-, and CK-positive regions were significantly higher in the tulathromycin- and/or DFS-treated groups than in control mice. For all these parameters, the pathological changes were more significant in the tulathromycin-DFS combination group than in mice treated with either drug individually. Interestingly, co-administration of lycopene with tulathromycin and/or DFS significantly ameliorated the changes described above. In conclusion, DFS could potentiate the cardiotoxic effects of tulathromycin, whereas lycopene can serve as a cardioprotective agent against DFS and tulathromycin.

Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor-9 in mice.

PubMed

Kaur, Sandeep; Mukhopadhyay, C S; Sethi, R S

2016-11-01

Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor 9 (TLR-9) in mice. In this study, healthy male Swiss albino mice (n=30) aging 8-10 weeks were used to evaluate TLR-9 expression in lungs of mice following indoxacarb exposure with and without lipopolysaccharide (LPS). Indoxacarb was administered orally dissolved in groundnut oil at 4 and 2 mg/kg/day for 90 days. On day 91, five animals from each group were challenged with LPS/normal saline solution at 80 µg/animal. The lung tissues were processed for real time and immunohistochemical studies. LPS resulted increase in fold change m-RNA expression level of TLR-9 as compare to control, while indoxacarb (4 mg/kg) alone and in combination with LPS resulted 16.21-fold change and 29.4-fold change increase in expression of TLR-9 m-RNA, respectively, as compared to control. Similarly, indoxacarb (2 mg/kg) alone or in combination with LPS also altered TLR-9 expression. Further at protein level control group showed minimal expression of TLR-9 in lungs as compare to other groups, however, LPS group showed intense positive staining in bronchial epithelium as well as in alveolar septal cells. Indoxacarb at both doses individually showed strong immuno-positive reaction as compare to control, however when combined with LPS resulted intense staining in airway epithelium as compare to control. Chronic oral administration of indoxacarb for 90 days (4 and 2 mg/kg) alters expression of TLR-9 at m-RNA and protein level and co-exposure with LPS exhibited synergistic effect.

Influence of xanthotoxin (8-methoxypsoralen) on the anticonvulsant activity of various novel antiepileptic drugs against maximal electroshock-induced seizures in mice.

PubMed

Zagaja, Mirosław; Andres-Mach, Marta; Patrzylas, Paweł; Pyrka, Daniel; Szpringer, Monika; Florek-Łuszczki, Magdalena; Żółkowska, Dorota; Skalicka-Woźniak, Krystyna; Łuszczki, Jarogniew J

2016-12-01

The aim of this study was to determine the effects of xanthotoxin (8-methoxypsoralen) on the protective action of 5 various second- and third-generation antiepileptic drugs (i.e., lacosamide, lamotrigine, oxcarbazepine, pregabalin and topiramate) in the mouse maximal electroshock-induced seizure model. Seizure activity was evoked in adult male albino Swiss mice by a current (25mA, 500V, 0.2s stimulus duration) delivered via auricular electrodes. Drug-related adverse effects were determined in the chimney, grip-strength and passive avoidance tests. Total brain antiepileptic drug concentrations were measured to confirm pharmacodynamic nature of observed interactions with xanthotoxin. Results indicate that xanthotoxin (100mg/kg, i.p.) significantly enhanced the anticonvulsant action of lacosamide (P<0.01), oxcarbazepine (P<0.05), pregabalin (P<0.01), and topiramate (P<0.001), but not that of lamotrigine in the maximal electroshock-induced seizure test. Moreover, xanthotoxin (50mg/kg) still significantly potentiated the anticonvulsant action of lacosamide (P<0.05), pregabalin (P<0.05), and topiramate (P<0.001) in this seizure test. Xanthotoxin had no significant impact on total brain concentrations of the studied antiepileptic drugs in mice. Furthermore, combinations of xanthotoxin with oxcarbazepine or topiramate produced no adverse effects. However, xanthotoxin in combination with lacosamide, lamotrigine or pregabalin significantly reduced muscular strength in mice in the grip-strength test. In the chimney test, only the combinations of xanthotoxin with pregabalin significantly impaired motor coordination in mice. In conclusion, the combinations of xanthotoxin with oxcarbazepine and topiramate produce beneficial anticonvulsant pharmacodynamic interactions in the maximal electroshock-induced seizure test. A special caution is advised when combining xanthotoxin with pregabalin due to appearance of acute adverse effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Mucuna pruriens reduces inducible nitric oxide synthase expression in Parkinsonian mice model.

PubMed

Yadav, Satyndra Kumar; Rai, Sachchida Nand; Singh, Surya Pratap

2017-03-01

Parkinson's disease is one of the most common neurodegenerative disease found in aged peoples. Plentiful studies are being conducted to find a suitable and effective cure for this disease giving special impetus on use of herbal plants. The study aimed at investigating the effect of ethanolic extract of Mucuna pruriens (Mp) on level of nitric oxide (NO) in paraquat (PQ) induced Parkinson's disease (PD) mouse model and its subsequent contribution to lipid peroxidation. Twenty four Swiss albino mice were divided into three groups; Control, PQ and PQ+Mp. PQ doses were given intraperitoneally, twice in a week and oral dose of ethanolic extract of Mp seed was given for 9 weeks. Nitrite content and lipid peroxidation was measured in all treated groups along with respective controls. RNA was isolated from the nigrostriatal tissue of control and the treated mice and was reverse transcribed into cDNA. PCR was performed to amplify iNOS mRNA and western blot analysis was performed to check its protein level. We had also perfused the mice in all treated group and performed Tyrosine hydroxylase (TH) and iNOS immunoreactivity in substantia nigra region of mice brain. PQ-treatment increased nitrite content, expression of iNOS and lipid peroxidation compared to respective controls. Mp treatment resulted in a significant attenuation of iNOS expression, nitrite content and lipid peroxidation demonstrating that it reduces nitric oxide in PQ-induced Parkinson's disease. Interestingly; we also observed that mRNA, protein expression and immunoreactivity of iNOS was significantly decreased after Mp treatment and TH immunoreactivity was significantly improved after the treatment of Mp. Our results demonstrated that Mp protects the dopaminergic neurons from the NO injury in substantia nigra. Copyright © 2016 Elsevier B.V. All rights reserved.

Partial Reversal of Obesity-Induced Insulin Resistance Owing to Anti-Inflammatory Immunomodulatory Potential of Flaxseed Oil.

PubMed

Bashir, Samina; Ali, Shakir; Khan, Farah

2015-01-01

The present study was designed to assess the potential of supplementation of diet with Flaxseed (Linum usitatissimum, L.) oil (FXO), on obesity-related inflammation and reversal of obesity-induced insulin resistance. Swiss Albino mice, C57bl/6 mice and co-culture of 3T3-L1 adipocytes - RAW 264.7 macrophages to mimick obese adipose tissue environment were used for the study. Oral gavage of FXO at concentrations of 4, 8 or 16 mg/kg body weight (bwt) for 4 weeks or high-fat diet (HFD, 60% energy as fat) supplemented with dietary FXO (4, 8 or 16 mg/kg bwt) was given to the mice. FXO was characterised using gas chromatography - mass spectrometry. FXO supplemented HFD-fed mice (4 mg/kg bwt exhibited reduced adiposity index, serum glucose levels and triglycerides (8 and 16 mg/kg bwt) and improvement in insulin sensitisation (4, 8 and 16 mg/kg bwt) when compared with HFD mice. The co-culture showed a dose-dependent shift in cytokines towards anti-inflammatory (IL-4) state, with a decrease in pro-inflammatory TNF-α (p < 0.05). For immunomodulatory studies a dose-dependent increase (p < 0.05) was observed in antigen-specific levels of Th2 (IL-4) cytokine, serum anti-ova IgG1 and IgE levels. Suppression in anti-ova IgG2a, IgG2b, and IgG3 and antigen-specific Th1 cytokines like TNF-α and IFN-γ significantly (p < 0.05) was observed at 16 mg/kg bwt dosage. The results indicate that FXO exhibits an anti-inflammatory immunomodulatory potential and may partially relieve symptoms of obesity-associated insulin resistance.

Effect of extract of Hibiscus on the ultrastructure of the testis in adult mice.

PubMed

Mahmoud, Yomna Ibrahim

2012-07-01

Hibiscus sabdariffa extract is a popular beverage in many tropical and sub-tropical countries. Although, Hibiscus tea is known for its medicinal effects for thousands of years, scientific evidence of its systemic safety is very limited. The current study aimed to assess the potential adverse effects of H. sabdariffa extract on sperm morphology and testicular ultrastructure of albino mice. Thirty adult male albino mice were divided into three equal groups and were given: (a) distilled water, (b) cold Hibiscus aqueous extract, and (c) boiled Hibiscus aqueous extract. Hibiscus extract was administered orally daily for 4 weeks in a dose of 200 mg/kg body weight/mouse. Twenty-four hours after the last treatment, mice were decapitated and the testes and epididymides were excised and processed for transmission electron microscopy to assess ultrastructural and sperm abnormalities. The results clearly demonstrate that aqueous extracts from dried calyx of H. sabdariffa, either cold or boiled, alter normal sperm morphology and testicular ultrastructure and adversely influence the male reproductive fertility in albino mice. The current data suggest that Hibiscus extract should be consumed with caution, and reasonable estimates of the human risk associated with its consumption should be provided. Copyright © 2011 Elsevier GmbH. All rights reserved.

The tobacco cembranoid (1S,2E,4S,7E,11E)-2,7,11-cembratriene-4,6-diol as a novel angiogenesis inhibitory lead for the control of breast malignancies.

PubMed

Hailat, Mohammad M; Ebrahim, Hassan Y; Mohyeldin, Mohamed M; Goda, Amira A; Siddique, Abu Bakar; El Sayed, Khalid A

2017-08-01

(1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) and its 4-epi-analog (2) are diterpene precursors of the key flavor components in most Nicotiana (tobacco) species that purposely degraded during commercial tobacco fermentation. Angiogenesis, recruitment of new blood vessels, is important for tumor growth, survival and metastasis that can be targeted to control cancer. This study shows evidences and potential of the cembranoid 1 as a potent angiogenesis modulator through targeting VEGFR 2 . In silico study suggested favorable docking scores and binding affinity of 1 at the ATP binding pocket of VEGFR 2 . The binding mode of 1 was parallel to the standard FDA-approved antiangiogenic drug sunitinib (4). In vitro, cembranoid 1 significantly reduced the activated VEGFR 2 levels in multiple breast cancer cell lines. Intraperitoneal 40mg/kg, 3X/week treatment of 1 significantly reduced the MDA-MB-231 cells breast tumor size in mice. Immunohistochemistry and Western blotting analysis of the treated mice tumors showed significant downregulation of the vasculogenesis marker CD31 and suppressed activated VEGFR 2 -paxillin-FAK pathway. Matrigel study in Swiss albino mice showed similar trend. The tobacco cembranoid 1 is a potential antiangiogenic lead useful for future use to control breast malignancies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of WIN 55,212-2 (a synthetic cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various novel antiepileptic drugs against 6 Hz-induced psychomotor seizures in mice.

PubMed

Florek-Luszczki, Magdalena; Wlaz, Aleksandra; Zagaja, Mirosław; Andres-Mach, Marta; Kondrat-Wrobel, Maria W; Luszczki, Jarogniew J

2015-03-01

The purpose of this study was to determine the influence of WIN 55,212-2 mesylate (WIN-a non-selective cannabinoid CB1 and CB2 receptor agonist) on the anticonvulsant activity of various second- and third-generation antiepileptic drugs (i.e., gabapentin, lacosamide, levetiracetam, oxcarbazepine, pregabalin and tiagabine) in the mouse 6 Hz-induced psychomotor seizure model. Psychomotor seizures were evoked in albino Swiss mice by a current (32 mA, 6 Hz, 3s stimulus duration) delivered via ocular electrodes. Additionally, total brain antiepileptic drug concentrations were measured. Results indicate that WIN (5 mg/kg, administered i.p.) significantly potentiated the anticonvulsant action of gabapentin (P < 0.05) and levetiracetam (P < 0.01), but not that of lacosamide, oxcarbazepine, pregabalin or tiagabine in the mouse psychomotor seizure model. Moreover, WIN (2.5 mg/kg) had no significant effect on the anticonvulsant activity of all tested antiepileptic drugs in the 6 Hz test in mice. Measurement of total brain antiepileptic drug concentrations revealed that WIN (5 mg/kg) had no impact on gabapentin or levetiracetam total brain concentrations, indicating the pharmacodynamic nature of interaction between these antiepileptic drugs in the mouse 6Hz model. In conclusion, WIN in combination with gabapentin and levetiracetam exerts beneficial anticonvulsant pharmacodynamic interactions in the mouse psychomotor seizure model. Copyright © 2015 Elsevier Inc. All rights reserved.

Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of (60)Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration.

PubMed

Bala, Madhu; Gupta, Manish; Saini, Manu; Abdin, M Z; Prasad, Jagdish

2015-01-01

A single dose (30 mg/kg body weight) of standardized sea buckthorn leaf extract (SBL-1), administered 30 min before whole body (60)Co-gamma-irradiation (lethal dose, 10 Gy), protected >90% of mice population. The purpose of this study was to investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9-week-old inbred male Swiss albino Strain 'A' mice demonstrated that SBL-1 treatment before (60)Co-gamma-irradiation (10 Gy) significantly (p < 0.05) countered radiation induced decreases in jejunum crypts (1.27-fold), villi number (1.41-fold), villus height (1.25-fold), villus cellularity (2.27-fold), cryptal Paneth cells (1.89-fold), and Bcl2 level (1.54-fold). It countered radiation induced increases in cryptal apoptotic cells (1.64-fold) and Bax levels (1.88-fold). It also countered radiation (2 Gy and 3 Gy) induced bone marrow apoptosis (1.59-fold and 1.85-fold) and micronuclei frequency (1.72-fold and 2.6-fold). SBL-1 rendered radiation protection by promoting cryptal stem cells proliferation, by regulating apoptosis, and by countering radiation induced chromosomal damage. Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and thiols detected in SBL-1 may have contributed to radiation protection by neutralization of radiation induced oxidative species, supporting stem cell proliferation and tissue regeneration.

Sperm abnormalities induced by pre-pubertal exposure to cyclophosphamide are effectively mitigated by Moringa oleifera leaf extract.

PubMed

Nayak, G; Vadinkar, A; Nair, S; Kalthur, S G; D'Souza, A S; Shetty, P K; Mutalik, S; Shetty, M M; Kalthur, G; Adiga, S K

2016-03-01

Moringa oleifera L. is a medicinal plant with potential antioxidant property. This study was aimed at investigating the chemoprotective effect of Moringa oleifera leaf extract (MOE) on cyclophosphamide (CP)-induced testicular toxicity. Two-week-old male Swiss albino mice were intraperitoneally injected with phosphate-buffered saline, 50 mg kg(-1) of CP and 25 mg kg(-1) of MOE. In combination treatment, mice were injected with 25 mg kg(-1) of MOE 24 h prior to CP injection, 24 h prior and post-CP injection and 24 h post-CP injection for 5 consecutive days (10 mg kg(-1) ). Six weeks later, mice were sacrificed to assess epididymal sperm parameters. MOE alone did not have any significant effect on sperm parameters. However, acute injection of CP resulted in significant decline in motility (P < 0.001), increase in head abnormality (P < 0.01) and DNA damage (P < 0.05). Combining MOE with CP increased the sperm density, motility and reduced head defect and DNA damage, irrespective of the schedule and dosage of MOE. Administration of MOE prior to CP significantly elevated the level of superoxide dismutase and catalase with concomitant decrease in lipid peroxidation in the testicular tissue. In conclusion, MOE may have potential benefit in reducing the loss of male gonadal function following chemotherapy. © 2015 Blackwell Verlag GmbH.

Evaluation of antibacterial, antioxidant and nootropic activities of Tiliacora racemosa Colebr. leaves: In vitro and in vivo approach.

PubMed

T, Vivek Kumar; M, Vishalakshi; M, Gangaraju; Das, Parijat; Roy, Pratiti; Banerjee, Anindita; Dutta Gupta, Sayan

2017-02-01

The antibacterial and antioxidant potential of Tiliacora racemosa leaf extracts in various solvents (methanolic, hexane, chloroform and ethyl acetate) was determined. Additionally, the presence of bisbenzylisoquinoline alkaloids in the plant prompted us to evaluate the nootropic activity of the methanolic extract in mice. Further, we seek to verify the nootropic effect by examining the anticholinesterase inhibition potential of the methanolic extract. The leaf extracts in various solvents were evaluated for their antibacterial and antioxidant activity by agar diffusion technique and α, α-diphenyl-β-picrylhydrazyl (DPPH) free radical scavenging method, respectively. The ex vivo acetylcholine esterase inhibitory activity of the methanolic extract was carried out by Ellman's method in male Wistar rats. The nootropic capacity of the methanolic extract was examined in Swiss albino mice by utilizing the diazepam induced acute amnesic model. The chloroform/n-hexane and ethyl acetate fraction showed promising antioxidant and antibacterial (Gram positive and Gram negative bacteria) property, respectively. The methanolic extract was able to diminish the amnesic effect induced by diazepam (1mg/kg i.p.) in mice. The extract also showed significant acetyl cholinesterase inhibition in rats. The findings prove that the memory enhancing capability is due to increased acetyl choline level at the nerve endings. The strong antioxidant nature and potential nootropic activity shown by the extract suggests its future usage in the treatment of neurodegenerative disorders such as dementia and Alzheimer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Retinal compensatory changes after light damage in albino mice

PubMed Central

Montalbán-Soler, Luis; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Salinas-Navarro, Manuel; Galindo-Romero, Caridad; Bezerra de Sá, Fabrízio; García-Ayuso, Diego; Avilés-Trigueros, Marcelino; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

2012-01-01

Purpose To investigate the anatomic and functional changes triggered by light exposure in the albino mouse retina and compare them with those observed in the albino rat. Methods BALB/c albino mice were exposed to 3,000 lx of white light during 24 h and their retinas analyzed from 1 to 180 days after light exposure (ALE). Left pupil mydriasis was induced with topical atropine. Retinal function was analyzed by electroretinographic (ERG) recording. To assess retinal degeneration, hematoxylin and eosin staining, the TdT-mediated dUTP nick-end labeling (TUNEL) technique, and quantitative immunohistofluorescence for synaptophysin and protein kinase Cα (PKCα) were used in cross sections. Intravenous injection of horseradish peroxidase and Fluoro-Gold™ tracing were used in whole-mounted retinas to study the retinal vasculature and the retinal ganglion cell (RGC) population, respectively. Results Light exposure caused apoptotic photoreceptor death in the central retina. This death was more severe in the dorsal than in the ventral retina, sparing the periphery. Neither retinal vascular leakage nor retinal ganglion cell death was observed ALE. The electroretinographic a-wave was permanently impaired, while the b-wave decreased but recovered gradually by 180 days ALE. The scotopic threshold responses, associated with the inner retinal function, diminished at first but recovered completely by 14 days ALE. This functional recovery was concomitant with the upregulation of protein kinase Cα and synaptophysin. Similar results were obtained in both eyes, irrespective of mydriasis. Conclusions In albino mice, light exposure induces substantial retinal damage, but the surviving photoreceptors, together with compensatory morphological/molecular changes, allow an important restoration of the retinal function. PMID:22509098

Sesame indicum, a nutritional supplement, elicits antiamnesic effect via cholinergic pathway in scopolamine intoxicated mice.

PubMed

Chidambaram, Saravana Babu; Pandian, Anbarasi; Sekar, Sathiya; Haridass, Sumathy; Vijayan, Ranju; Thiyagarajan, Lakshmi Kantham; Ravindran, Jayasree; Balaji Raghavendran, Hanumantha Rao; Kamarul, Tunku

2016-12-01

Present study was undertaken to evaluate the antiamnesic effect of Sesamum indicum (S. indicum) seeds (standardized for sesamin, a lignan, content) in scopolamine, a muscarinic antagonist intoxicated mice. Male Swiss albino mice (18-22 g bw) were pretreated with methanolic extract of sesame seeds (MSSE) (100 and 200 mg/kg/day, p.o) for a period of 14 days. Scopolamine (0.3 mg/kg, i.p.) was injected on day 14, 45 ± 10 min after MSSE administration. Antiamnesic effect of MSSE was evaluated using step-down latency (SDL) on passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. To unravel the mechanism of action, we examined the effects of MSSE on the genes such as acetyl cholinesterase (AChE), muscarinic receptor M1 subtype (mAChRM 1 ), and brain derived neurotrophic factor (BDNF) expression within hippocampus of experimental mice. Further, its effects on bax and bcl-2 were also evaluated. Histopathological examination of hippocampal CA 1 region was performed using cresyl violet staining. MSSE treatment produced a significant and dose dependent increase in step down latency in passive avoidance test and decrease in transfer latency in elevated plus maze in scopolamine intoxicated injected mice. MSSE down-regulated AChE and mAChRM 1 and up-regulated BDNF mRNA expression. Further, it significantly down-regulated the bax and caspase 3 and up-regulated bcl-2 expression in scopolamine intoxicated mice brains. Mice treated with MSSE showed increased neuronal counts in hippocampal CA 1 region when compared with scopolamine-vehicle treated mice. Sesame seeds have the ability to interact with cholinergic components involved in memory function/restoration and also an interesting candidate to be considered for future cognitive research. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1955-1963, 2016. © 2015 Wiley Periodicals, Inc.

Antimalarial activity of 80 % methanolic extract of Brassica nigra (L.) Koch. (Brassicaceae) seeds against Plasmodium berghei infection in mice.

PubMed

Muluye, Abrham Belachew; Melese, Eshetie; Adinew, Getnet Mequanint

2015-10-15

Resistances to currently available drugs and insecticides, significant drug toxicities and costs and lack of vaccines currently complicated the treatment of malaria. A continued search for safe, effective and affordable plant-based antimalarial agents thus becomes crucial and vital in the face of these difficulties. The aim of the study was to evaluate the antimalarial activity of 80 % methanolic extract of the seeds of Brassica nigra against Plasmodium berghei infection in mice. Chloroquine sensitive Plasmodium berghei (ANKA strain) was used to test the antimalarial activity of the extract. In suppressive and prophylactic models, Swiss albino male mice were randomly grouped into five groups of five mice each. Group I mice were treated with the vehicle, group II, III and IV were treated with 100, 200, and 400 mg/kg of the extract, respectively and the last group (V) mice were treated with chloroquine (10 mg/kg). The level of parasitemia, survival time and variation in weight of mice were used to determine the antimalarial activity of the extract. Chemosuppressive activities produced by the extract of the seeds of Brassica nigra were 21.88, 50.00 (P < 0.01) and 53.13 % (P < 0.01), while the chemoprophylactic activities were 17.42, 21.21 and 53.79 % (P < 0.05) at 100, 200 and 400 mg/kg of the extract, respectively as compared to the negative control. Mice treated with 200 and 400 mg/kg extract were significantly (P < 0.05) lived longer and gained weight as compared to negative control in 4-day suppressive test. From this study, it can be concluded that the seed extract of Brassica nigra showed good chemosuppressive and moderate chemoprophylactic activities and the plant may contain biologically active principles which are relevant in the treatment and prophylaxis of malaria, thus supporting further studies of the plant for its active components.

Podophyllum hexandrum (Himalayan mayapple) extract provides radioprotection by modulating the expression of proteins associated with apoptosis.

PubMed

Kumar, Raj; Singh, Pankaj Kumar; Sharma, Ashok; Prasad, Jagdish; Sagar, Ravinder; Singh, Surender; Arora, Rajesh; Sharma, Rakesh Kumar

2005-08-01

Podophyllum hexandrum Royale (Himalayan mayapple), a high-altitude Himalayan plant, has been shown to provide over 80% whole-body radioprotection in mice. To investigate the radioprotective potential of P. hexandrum at the molecular level, expression patterns of various proteins associated with apoptosis were studied in the spleen of male Swiss albino strain A mice by immunoblotting. Treatment with P. hexandrum [200 mg/kg of body weight; an ethanolic 50% (w/v) extract delivered intraperitoneally] 2 h before irradiation resulted in MAPKAP (mitogen-activated protein kinase-activated protein) kinase-2 activation along with HSF-1 (heat-shock transcription factor-1), leading to up-regulation of HSP-70 (heat-shock protein-70) as compared with sham-irradiated (10 Gy) mice. Strong inhibition of AIF (apoptosis-inducing factor) expression was observed in the mice treated with P. hexandrum 2 h before irradiation as compared with the sham-irradiated group. Inhibition in the translocation of free NF-kappaB (nuclear factor kappaB) from cytoplasm to nucleus was observed upon P. hexandrum pretreatment 2 h before irradiation when compared with radiation-treated mice. P. hexandrum pre-treatment (2 h before irradiation) resulted in inhibition of NF-kappaB translocation, and the expression of tumour suppressor protein p53 was observed to be down-regulated as compared with sham-irradiated control. An increase in the expression of proteins responsible for cell proliferation [Bcl-2 (B-cell chronic lymphocytic lymphoma 2), Ras-GAP (Ras-GTPase-activating protein) and PCNA (proliferating cell nuclear antigen)] was observed in the P. hexandrum-pretreated irradiated mice as compared with sham-irradiated controls. Caspase 3 activation resulted PARP [poly(ADP-ribose) DNA polymerase] cleavage, and DNA degradation was strongly inhibited in the mice treated with P. hexandrm (+/-irradiation) as compared with the mice treated with radiation (+/-heat shock). The present study thus clearly demonstrated that P. hexandrum extract provides protection from gamma-radiation by the modulation of expression of proteins associated with cell death.

Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents

PubMed Central

Husain, Asif; Ahmad, Aftab; Khan, Shah Alam; Asif, Mohd; Bhutani, Rubina; Al-Abbasi, Fahad A.

2015-01-01

The aim of this study was to design and synthesize pharmaceutical agents containing imidazolidine heterocyclic ring in the hope of developing potent, safe and orally active anti-inflammatory agents. A number of substituted-imidazolidine derivatives (3a–k) were synthesized starting from ethylene diamine and aromatic aldehydes. The imidazolidine derivatives (3a–k) were investigated for their anticipated anti-inflammatory, and analgesic activity in Wistar albino rats and Swiss albino mice, respectively. Bioactivity score, molecular and pharmacokinetic properties of the imidazolidine derivatives were calculated by online computer software programs viz. Molinspiration and Osiris property explorer. The results of biological testing indicated that among the synthesized compounds only three imidazolidine derivatives namely 4-[1,3-Bis(2,6-dichlorobenzyl)-2-imidazolidinyl]phenyl-diethylamine (3g), 4-[1,3-Bis(3-hydroxy-4-methoxybenzyl)-2-imidazolidinyl]phenyl-diethylamine (3i) and 4-(1,3-Bis(4-methoxybenzyl)-4-methylimidazolidin-2-yl)-phenyl-diethylamine (3j) possess promising anti-inflammatory and analgesic actions. Additionally these derivatives displayed superior GI safety profile (low severity index) with respect to the positive control, Indomethacin. All synthesized compounds showed promising bioactivity score for drug targets by Molinspiration software. Almost all the compounds were predicted to have very low toxicity risk by Osiris online software. Compound number (3i) emerged as a potential candidate for further research as it obeyed Lipinski’s rule of five for drug likeness, exhibited promising biological activity in-vivo and showed no risk of toxicity in computer aided screening. PMID:26903774

Codominant expression of genes coding for different sets of inducible salivary polypeptides associated with parotid hypertrophy in two inbred mouse strains.

PubMed

López-Solís, Remigio O; Kemmerling, Ulrike

2005-05-01

Experimental mouse parotid hypertrophy has been associated with the expression of a number of isoproterenol-induced salivary proline-rich polypeptides (IISPs). Mouse salivary proline-rich proteins (PRPs) have been mapped both to chromosomes 6 and 8. Recently, mice of two inbred strains (A/Snell and A. Swiss) have been found to differ drastically in the IISPs. In this study, mice of both strains were used for cross-breeding experiments addressed to define the pattern of inheritance of the IISP phenotype and to establish whether the IISPs are coded on a single or on several chromosomes. The IISP phenotype of individual mice was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole saliva collected after three daily stimulations by isoproterenol. Parental A/Snell and A. Swiss mice were homogeneous for distinctive strain-associated IISP-patterns. First filial generation (F1) mice obtained from the cross of A/Snell with A. Swiss mice expressed with no exception both the A/Snell and A. Swiss IISPs (coexpression). In the second filial generation (F2) both parental IISP phenotypes reappeared together with a majority of mice expressing the F1-hybrid phenotype (1:2:1 ratio). Backcrosses of F1 x A/Snell and F1 x A. Swiss produced offsprings displaying the F1 and the corresponding parental phenotypes with a 1:1 ratio. No recombinants were observed among F2 mice or among mice resulting from backcrosses. Thus, genes coding for the IISPs that are expressed differentially in both mouse strains are located on the same chromosome, probably at the same locus (alleles) or at quite closely linked loci (nonalleles). 2005 Wiley-Liss, Inc

Microarray Analysis of Iris Gene Expression in Mice with Mutations Influencing Pigmentation

PubMed Central

Trantow, Colleen M.; Cuffy, Tryphena L.; Fingert, John H.; Kuehn, Markus H.

2011-01-01

Purpose. Several ocular diseases involve the iris, notably including oculocutaneous albinism, pigment dispersion syndrome, and exfoliation syndrome. To screen for candidate genes that may contribute to the pathogenesis of these diseases, genome-wide iris gene expression patterns were comparatively analyzed from mouse models of these conditions. Methods. Iris samples from albino mice with a Tyr mutation, pigment dispersion–prone mice with Tyrp1 and Gpnmb mutations, and mice resembling exfoliation syndrome with a Lyst mutation were compared with samples from wild-type mice. All mice were strain (C57BL/6J), age (60 days old), and sex (female) matched. Microarrays were used to compare transcriptional profiles, and differentially expressed transcripts were described by functional annotation clustering using DAVID Bioinformatics Resources. Quantitative real-time PCR was performed to validate a subset of identified changes. Results. Compared with wild-type C57BL/6J mice, each disease context exhibited a large number of statistically significant changes in gene expression, including 685 transcripts differentially expressed in albino irides, 403 in pigment dispersion–prone irides, and 460 in exfoliative-like irides. Conclusions. Functional annotation clusterings were particularly striking among the overrepresented genes, with albino and pigment dispersion–prone irides both exhibiting overall evidence of crystallin-mediated stress responses. Exfoliative-like irides from mice with a Lyst mutation showed overall evidence of involvement of genes that influence immune system processes, lytic vacuoles, and lysosomes. These findings have several biologically relevant implications, particularly with respect to secondary forms of glaucoma, and represent a useful resource as a hypothesis-generating dataset. PMID:20739468

Comparison of the acute ultraviolet photoresponse in congenic albino hairless C57BL/6J mice relative to outbred SKH1 hairless mice

PubMed Central

Konger, Raymond L.; Derr-Yellin, Ethel; Hojati, Delaram; Lutz, Cathleen; Sundberg, John P.

2016-01-01

Hairless albino Crl:SKH1-Hrhr mice are commonly utilized for studies in which hair or pigmentation would introduce an impediment to observational studies. Being an outbred strain, the SKH1 model suffers from key limitations that are not seen with congenic mouse strains. Inbred and congenic C57BL/6J mice are commonly utilized for modified genetic mouse models. We compare the acute UV-induced photoresponse between outbred SKH1 mice and an immune competent, hairless, albino C57BL/6J congenic mouse line [B6.Cg-Tyrc-2J Hrhr/J]. Histologically, B6.Cg-Tyrc-2J Hrhr/J skin is indistinguishable from that of SKH1 mice. The skin of both SKH1 and B6.Cg-Tyrc-2J Hrhr/J mice exhibited a reduction in hypodermal adipose tissue, the presence of utricles and dermal cystic structures, the presence of dermal granulomas, and epidermal thickening. In response to a single 1500 J/m2 UVB dose, the edema and apoptotic response was equivalent in both mouse strains. However, B6.Cg-Tyrc-2J Hrhr/J mice exhibited a more robust delayed sunburn reaction, with an increase in epidermal erosion, scab formation, and myeloperoxidase activity relative to SKH1 mice. Compared with SKH1 mice, B6.Cg-Tyrc-2J Hrhr/J also exhibited an aberrant proliferative response to this single UV exposure. Epidermal Ki67 immunopositivity was significantly suppressed in B6.Cg-Tyrc-2J Hrhr/J mice at 24 hours post-UV. A smaller non-significant reduction in Ki67 labeling was observed in SKH1 mice. Finally, at 72 hours post-UV, SKH1 mice, but not B6.Cg-Tyrc-2J Hrhr/J mice, exhibited a significant increase in Ki67 immunolabeling relative to non-irradiated controls. Thus, B6.Cg-Tyrc-2J Hrhr/J mice are suitable for photobiology experiments. PMID:27095432

Anti-spermatogenic activity of ethanol extract of Dalbergia sissoo Roxb. stem bark.

PubMed

Vasudeva, Neeru; Vats, Manisha

2011-06-01

The study was undertaken to evaluate the anti-spermatogenic efficacy of ethanol extract of stem bark of Dalbergia sissoo Roxb. For the in vitro study, semen samples were obtained from 15 healthy fertile men aged 25-35 years. Sperm motility was examined by the Sander-Cramer method. A dose-dependent and time-dependent effect of ethanol extract on sperm motility and sperm viability were observed. Various concentrations affected the motility of sperm. Ethanol extract at a concentration of 20 mg/mL caused complete immobilization within 3 minutes. Sperm viability and hypo-osmotic swelling was significantly reduced at this concentration. The in vivo studies were carried out on Swiss male albino mice. Ethanol extract at a dose of 200 mg/kg body weight resulted in a significant decrease (p<0.001) in weight of the testis and epididymis. A significant decrease (p<0.01) in sperm motility and sperm count in the epididymis were observed. Histological changes in the epididymis and testis were also investigated. Copyright © 2011 Korean Pharmacopuncture Institute. Published by .. All rights reserved.

Immunomodulatory effect of ethanolic extract of Shirishadi compound

PubMed Central

Kajaria, Divya; Tripathi, Jyoti Shankar; Tiwari, Shri Kant; Pandey, Bajrangi Lal

2013-01-01

Immunomodulators are substances that helps to regulate the immune system. The basic mechanisms by which the herbs defend the body against infection have two probable ways- one by destroying pathogens and other by enhancing the body immunity. Shirishadi compound is a polyherbal drug used in Ayurvedic system of medicine for the management of allergic disorders such as allergic rhinitis, allergic asthma etc., The present study was carried out to evaluate the immunomodulatory activity of ethanolic extract of polyherbal compound “Shirishadi” on Swiss albino mice. Cyclophosphamide (CP) induced immunosuppression model was used to assess the activity of drug. CP was given in the dose of 30 mg/kg body weight through i.p route. 500 mg/kg body weight of Shirishadi polyherbal drug was given through oral route. The extent of protection against immunosuppression caused by CP was evaluated after 14 days of drug administration, by estimating hematological parameters and neutrophil adhesion test. Ethanolic extracts of Shirishadi compound showed pronounced immunoprotective activity by increasing the depleted levels of total WBC count and RBC, % Hb, and % neutrophils adhesion. The extract was found to be an effective immunomodulatory agent. PMID:24501532

Antitubercular activity of ZnO nanoparticles prepared by solution combustion synthesis using lemon juice as bio-fuel.

PubMed

Gopala Krishna, Prashanth; Paduvarahalli Ananthaswamy, Prashanth; Trivedi, Priyanka; Chaturvedi, Vinita; Bhangi Mutta, Nagabhushana; Sannaiah, Ananda; Erra, Amani; Yadavalli, Tejabhiram

2017-06-01

In this study, we report the synthesis, structural and morphological characteristics of zinc oxide (ZnO) nanoparticles using solution combustion synthesis method where lemon juice was used as the fuel. In vitro anti-tubercular activity of the synthesized ZnO nanoparticles and their biocompatibility studies, both in vitro and in vivo were carried out. The synthesized nanoparticles showed inhibition of Mycobacterium tuberculosis H37Ra strain at concentrations as low as 12.5μg/mL. In vitro cytotoxicity study performed with normal mammalian cells (L929, 3T3-L1) showed that ZnO nanoparticles are non-toxic with a Selectivity Index (SI) >10. Cytotoxicity performed on two human cancer cell lines DU-145 and Calu-6 indicated the anti-cancer activity of ZnO nanoparticles at varied concentrations. Results of blood hemolysis indicated the biocompatibility of ZnO nanoparticles. Furthermore, in vivo toxicity studies of ZnO nanoparticles conducted on Swiss albino mice (for 14days as per the OECD 423 guidelines) showed no evident toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Sperm-derived factors enhance the in vitro developmental potential of haploid parthenotes.

PubMed

Nair, Ramya; Aboobacker, Shahin; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

2017-12-01

Parthenotes are characterized by poor in vitro developmental potential either due to the ploidy status or the absence of paternal factors. In the present study, we demonstrate the beneficial role of sperm-derived factors (SDF) on the in vitro development of mouse parthenotes. Mature (MII) oocytes collected from superovulated Swiss albino mice were activated using strontium chloride (SrCl2) in the presence or absence of various concentrations of SDF in M16 medium. The presence of SDF in activation medium did not have any significant influence on the activation rate. However, a significant increase in the developmental potential of the embryos and increased blastocyst rate (P < 0.01) was observed at 50 µg/ml concentration. Furthermore, the activated oocytes from this group exhibited early cleavage and cortical distribution of cortical granules that was similar to that of normally fertilized zygotes. Culturing 2-cell stage parthenotes in the presence of SDF significantly improved the developmental potential (P < 0.05) indicating that they also play a significant role in embryo development. In conclusion, artificial activation of oocytes with SDF can improve the developmental potential of parthenotes in vitro.

Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays

PubMed Central

Oyeyemi, Ifeoluwa Temitayo; Yekeen, Olaide Maruf; Odusina, Paul Olayinka; Ologun, Taiwo Mary; Ogbaide, Orezimena Michelle; Olaleye, Olayinka Israel

2015-01-01

Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group) treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS. PMID:27486380

Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays.

PubMed

Oyeyemi, Ifeoluwa Temitayo; Yekeen, Olaide Maruf; Odusina, Paul Olayinka; Ologun, Taiwo Mary; Ogbaide, Orezimena Michelle; Olaleye, Olayinka Israel; Bakare, Adekunle A

2015-12-01

Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group) treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS.

THE EFFECT OF FICUS CARICA L. (ANJIR) LEAF EXTRACT ON GENTAMICIN INDUCED NEPHROTOXICITY IN ADULT MALE ALBINO MICE.

PubMed

Ghaffar, Ammara; Tahir, Mohammad; Lone, Khalid Pervez; Faisal, Bushra; Latif, Waqas

2015-01-01

Gentamicin is an aminoglycoside isolated from Micromonospora purpurea known for its nephrotoxicity. Ficus carica L is known to treat many ailments. This study was designed to investigate the effects of Ficus carica L. (Anjir) leaf extract on renal oxidative stress induced by gentamicin in albino mice. In this laboratory based experimental study 30 mice were divided into three groups, containing 10 mice each. Group A being the control; groups B and C were experimental and treated with gentamicin 200 mg/kg/day intraperitoneally and, Ficus carica L. leaf extract 400 mg/kg/day orally with gentamicin 200 mg/kg/day intraperitoneally respectively for a period of 8 days. Blood samples were taken 24 hours after completion of the experimental period by cardiac puncture under anesthesia and kidneys of each mouse were taken out for microscopic examination. Gentamicin treatment increased serum urea and creatinine levels (group B). Ficus carica L. leaf extract treated animals showed significant reduction in biochemical markers of kidney functions in group C. The histopathological examination of group A showed normal renal structure which was deranged in group B treated with only gentamicin, whereas, group C exhibited marked improvement in histological structure. Ficus carica L. leaf extract is effective in preventing gentamicin induced functional and structural changes in kidney of albino mice.

Studies on cerebral protection of digoxin against ischemia/reperfusion injury in mice.

PubMed

Kaur, Shaminder; Rehni, Ashish K; Singh, Nirmal; Jaggi, Amteshwar S

2009-04-01

The present study was designed to investigate the possible neuroprotective effect of digoxin induced pharmacological preconditioning (PP) and its probable mechanism. Bilateral carotid artery occlusion (BCAO) of 17 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion (I/R) induced cerebral injury in male swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using elevated plus maze test. Degree of motor incoordination was evaluated using inclined beam walking test, rota rod test and lateral push test. Digoxin (0.08 mg/kg, i.p.) was administered 24 h before surgery in a separate group of animals to induce PP. BCAO followed by reperfusion, produced significant rise in cerebral infarct size along with impairment of memory and motor coordination. Digoxin treatment produced a significant decrease in cerebral infarct size and reversal of I/R induced impairment of memory and motor incoordination. Digoxin induced neuroprotective effect was abolished significantly by verapamil (15 mg/kg, i.p.), a L-type calcium channel blocker, ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker and 3,4-dichlorobenzamil (Na(+)/Ca(2+) exchanger inhibitor). These findings indicate that digoxin preconditioning exerts a marked neuroprotective effect on the ischemic brain, which is possibly linked to digitalis induced increase in intracellular calcium levels eventually leading to the activation of calcium sensitive signal transduction cascades.

Evidence of significant synergism between antibiotics and the antipsychotic, antimicrobial drug flupenthixol.

PubMed

Jeyaseeli, L; Dasgupta, A; Dastidar, S G; Molnar, J; Amaral, L

2012-06-01

Previously, the antipsychotic, non-antibiotic compound flupenthixol dihydrochloride (Fp) was shown to exhibit distinct in vitro antibacterial activity against Gram-positive and Gram-negative bacteria and to significantly protect Swiss albino mice challenged with a known mouse virulent salmonella. The present study was designed to ascertain whether this drug could efficiently augment the action of an antibiotic or a non-antibiotic when tested in combination. A total of 12 bacterial strains belonging to various genera were selected for this study and were sensitive to the antibiotics penicillin (Pc), ampicillin, chloramphenicol, tetracycline, streptomycin, gentamicin, erythromycin, ciprofloxacin, and to the non-antibiotics methdilazine, triflupromazine, promethazine, and Fp. Pronounced and statistically significant synergism (p < 0.01) was observed when Fp was combined with Pc following the disc diffusion assay system. With the help of the checkerboard method, the fractional inhibitory concentration (FIC) index of this pair was found to be 0.375, confirming synergism. This pair of Fp+ Pc was then subjected to in vivo experiments in mice challenged with Salmonella enterica serovar Typhimurium NCTC 74. Statistical analysis of the mouse protection test suggested that this combination was highly synergistic (p < 0.001, Chi-squared analysis). Fp also revealed augmentation of its antimicrobial property when combined with streptomycin, gentamicin, ciprofloxacin, and the non-antibiotic methdilazine. The results of this study may provide alternatives for the therapy of problematic infections such as those associated with Salmonella spp.

Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

PubMed

Sameer, Shaikh M; Chakraborty, Suwarna S; Ugale, Rajesh R

2013-04-01

The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents. Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1.25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively. Agmatine inhibited the acquisition but not the expression of ethanol CPP. Furthermore, both the I₁ receptor antagonist, efaroxan (9 mg/kg) and the I₂ receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition. In contrast, the I₂ receptor agonist, 2-BFI (5 mg/kg) and I₁ receptor agonist, moxonidine (0.4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP. Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity. Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I₁ or I₂) receptors. In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

Astaxanthin ameliorates aluminum chloride-induced spatial memory impairment and neuronal oxidative stress in mice.

PubMed

Al-Amin, Md Mamun; Reza, Hasan Mahmud; Saadi, Hasan Mahmud; Mahmud, Waich; Ibrahim, Abdirahman Adam; Alam, Musrura Mefta; Kabir, Nadia; Saifullah, A R M; Tropa, Sarjana Tarannum; Quddus, A H M Ruhul

2016-04-15

Aluminum chloride induces neurodegenerative disease in animal model. Evidence suggests that aluminum intake results in the activation of glial cells and generation of reactive oxygen species. By contrast, astaxanthin is an antioxidant having potential neuroprotective activity. In this study, we investigate the effect of astaxanthin on aluminum chloride-exposed behavioral brain function and neuronal oxidative stress (OS). Male Swiss albino mice (4 months old) were divided into 4 groups: (i) control (distilled water), (ii) aluminum chloride, (iii) astaxanthin+aluminum chloride, and (iv) astaxanthin. Two behavioral tests; radial arm maze and open field test were conducted, and OS markers were assayed from the brain and liver tissues following 42 days of treatment. Aluminum exposed group showed a significant reduction in spatial memory performance and anxiety-like behavior. Moreover, aluminum group exhibited a marked deterioration of oxidative markers; lipid peroxidation (MDA), nitric oxide (NO), glutathione (GSH) and advanced oxidation of protein products (AOPP) in the brain. To the contrary, co-administration of astaxanthin and aluminum has shown improved spatial memory, locomotor activity, and OS. These results indicate that astaxanthin improves aluminum-induced impaired memory performances presumably by the reduction of OS in the distinct brain regions. We suggest a future study to determine the underlying mechanism of astaxanthin in improving aluminum-exposed behavioral deficits. Copyright © 2016 Elsevier B.V. All rights reserved.

Finger millet arabinoxylan protects mice from high-fat diet induced lipid derangements, inflammation, endotoxemia and gut bacterial dysbiosis.

PubMed

Sarma, Siddhartha Mahadeva; Singh, Dhirendra Pratap; Singh, Paramdeep; Khare, Pragyanshu; Mangal, Priyanka; Singh, Shashank; Bijalwan, Vandana; Kaur, Jaspreet; Mantri, Shrikant; Boparai, Ravneet Kaur; Mazumder, Koushik; Bishnoi, Mahendra; Bhutani, Kamlesh Kumar; Kondepudi, Kanthi Kiran

2018-01-01

Arabinoxylan (AX), a non-starch polysaccharide extracted from cereals such as wheat, rice and millets, is known to impart various health promoting effects. Our earlier study suggested that finger millet (FM) could ameliorate high fat diet (HFD)-induced metabolic derangements. The present study is aimed to evaluate the effect of FM-AX supplementation, a key bioactive from finger millet, on HFD-induced metabolic and gut bacterial derangements. Male Swiss albino mice were fed with normal chow diet (NPD) or HFD (60%kcal from fat) for 10 weeks. FM-AX was orally supplemented at doses of 0.5 and 1.0g/kg bodyweight on every alternate day for 10 weeks. Glucose tolerance, serum hormones, hepatic lipid accumulation and inflammation, white adipose tissue marker gene expression, adipocyte size and inflammation; metagenomic alterations in cecal bacteria; cecal short chain fatty acids and colonic tight junction gene expressions were studied. FM-AX supplementation prevented HFD-induced weight gain, alerted glucose tolerance and serum lipid profile, hepatic lipid accumulation and inflammation. Hepatic and white adipose tissue gene expressions were beneficially modulated. Further, AX supplementation prevented metagenomic alterations in cecum; improved ileal and colonic health and overall prevented metabolic endotoxemia. Present work suggests that AX from finger millet can be developed as a nutraceutical for the management of HFD- induced obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Mangiferin ameliorates aluminium chloride-induced cognitive dysfunction via alleviation of hippocampal oxido-nitrosative stress, proinflammatory cytokines and acetylcholinesterase level.

PubMed

Kasbe, Prajapati; Jangra, Ashok; Lahkar, Mangala

2015-01-01

Mangiferin is a phytochemical primarily present in the stem, leaves and bark of Mangifera indica. It offers neuroprotection mainly through inhibition of oxidative stress, and decreasing proinflammatory cytokines level in the brain. Aluminium has been reported to cause oxidative stress-associated damage in the brain. In the present investigation, protective effect of mangiferin against aluminium chloride (AlCl3)-induced neurotoxicity and cognitive impairment was studied in male Swiss albino mice. AlCl3 (100 mg/kg) was administered once daily through oral gavage for 42 days. Mangiferin (20 and 40 mg/kg, p.o.) was given to mice for last 21 days of the study. We found cognitive dysfunction in AlCl3-treated group, which was assessed by Morris water maze test, and novel object recognition test. AlCl3-treated group showed elevated level of oxidative stress markers, proinflammatory cytokines level and lowered hippocampal brain-derived neurotrophic factor (BDNF) content. Mangiferin (40 mg/kg) prevented the cognitive deficits, hippocampal BDNF depletion, and biochemical anomalies induced by AlCl3-treatment. In conclusion, our data demonstrated that mangiferin offers neuroprotection in AlCl3-induced neurotoxicity and it may be a potential therapeutic approach in the treatment of oxido-nitrosative stress and inflammation-associated neurotoxicity. Copyright © 2015 Elsevier GmbH. All rights reserved.

Scaling of metabolic rate on body mass in small laboratory mammals

NASA Technical Reports Server (NTRS)

Pace, N.; Rahlmann, D. F.; Smith, A. H.

1980-01-01

The scaling of metabolic heat production rate on body mass is investigated for five species of small laboratory mammal in order to define selection of animals of metabolic rates and size range appropriate for the measurement of changes in the scaling relationship upon exposure to weightlessness in Shuttle/Spacelab experiment. Metabolic rates were measured according to oxygen consumption and carbon dioxide production for individual male and female Swiss-Webster mice, Syrian hamsters, Simonsen albino rats, Hartley guinea pigs and New Zealand white rabbits, which range in mass from 0.05 to 5 kg mature body size, at ages of 1, 2, 3, 5, 8, 12, 18 and 24 months. The metabolic intensity, defined as the heat produced per hour per kg body mass, is found to decrease dramatically with age until the animals are 6 to 8 months old, with little or no sex difference. When plotted on a logarithmic graph, the relation of metabolic rate to total body mass is found to obey a power law of index 0.676, which differs significantly from the classical value of 0.75. When the values for the mice are removed, however, an index of 0.749 is obtained. It is thus proposed that six male animals, 8 months of age, of each of the four remaining species be used to study the effects of gravitational loading on the metabolic energy requirements of terrestrial animals.

Radioprotective Efficacy of Lutein in Ameliorating Electron Beam Radiation-induced Oxidative Injury in Swiss Albino Mice

PubMed Central

Vasudeva, Vidya; Tenkanidiyoor, Yogish Somayaji; Peter, Alex John; Shetty, Jayaram; Lakshman, Srikant Patil; Fernandes, Ronald; Patali, Krishna Ananthapura

2018-01-01

Background: Lutein, a carotenoid compound, has previously been studied for its antioxidant and medicinal properties as well as the moderate protection it confers against gamma radiation. This study aimed at evaluating the effects of lutein against radiation-induced hematological and biochemical changes in mice. Methods: The optimized dose of the compound was orally administered for 15 days, and the mice were irradiated (6 Gy) on day 15 after the administration of the compound. The groups were divided (6 mice in each group) into normal control, radiation control, gallic acid control, 10% DMSO control, lutein control, and irradiated groups pretreated with gallic acid, 10% DMSO, and lutein. Gallic acid was used to maintain a standard since it is a proven radioprotector. Within 24 hours post irradiation, the animals were anesthetized and sacrificed. The hematological, biochemical, and antioxidant changes were determined using suitable methods. Data were analyzed by the Kaplan–Meier curve (log-rank test) and ANOVA (the Tukey test). The independent t test was used to compare the independent groups. SPSS (ver. 16) was employed. Results: Maximum survival was observed with a dose of 250 mg/kg b.wt lutein. The total leukocyte count and the percentage lymphocyte count exhibited a significant decline in the irradiated groups pretreated with gallic acid and lutein in comparison to their controls, whereas the percentage granulocyte count showed a significant rise. Antioxidant activity had markedly declined in the irradiated groups, indicating oxidative stress. Lutein pretreatment reduced the damage and maintained the antioxidant system. Conclusion: The present study suggests a protective role for lutein in palliating radiation-induced oxidative changes and maintaining the antioxidant system in vivo. PMID:29398751

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation.

PubMed

Jangra, Ashok; Sriram, Chandra Shaker; Dwivedi, Shubham; Gurjar, Satendra Singh; Hussain, Md Iftikar; Borah, Probodh; Lahkar, Mangala

2017-01-01

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

Edaravone abrogates LPS-induced behavioral anomalies, neuroinflammation and PARP-1.

PubMed

Sriram, Chandra Shaker; Jangra, Ashok; Gurjar, Satendra Singh; Mohan, Pritam; Bezbaruah, Babul Kumar

2016-02-01

Poly(ADP-ribose) polymerase-1 (PARP-1) is a DNA nick-sensor enzyme that functions at the center of cellular stress response and affects the immune system at several key points, and thus modulates inflammatory diseases. Our previous study demonstrated that lipopolysaccharide (LPS)-induced depressive-like behavior in mice can be ameliorated by 3-aminobenzamide, which is a PARP-1 inhibitor. In the present study we've examined the effect of a free radical scavenger, edaravone pretreatment against LPS-induced anxiety and depressive-like behavior as well as various hippocampal biochemical parameters including PARP-1. Male Swiss albino mice were treated with edaravone (3 & 10mg/kgi.p.) once daily for 14days. On the 14th day 30min after edaravone treatment mice were challenged with LPS (1mg/kgi.p.). After 3h and 24h of LPS administration we've tested mice for anxiety and depressive-like behaviors respectively. Western blotting analysis of PARP-1 in hippocampus was carried out after 12h of LPS administration. Moreover, after 24h of LPS administration serum corticosterone, hippocampal BDNF, oxido-nitrosative stress and pro-inflammatory cytokines were estimated by ELISA. Results showed that pretreatment of edaravone (10mg/kg) ameliorates LPS-induced anxiety and depressive-like behavior. Western blotting analysis showed that LPS-induced anomalous expression of PARP-1 significantly reverses by the pretreatment of edaravone (10mg/kg). Biochemical analyses revealed that LPS significantly diminishes BDNF, increases pro-inflammatory cytokines and oxido-nitrosative stress in the hippocampus. However, pretreatment with edaravone (10mg/kg) prominently reversed all these biochemical alterations. Our study emphasized that edaravone pretreatment prevents LPS-induced anxiety and depressive-like behavior, mainly by impeding the inflammation, oxido-nitrosative stress and PARP-1 overexpression. Copyright © 2015. Published by Elsevier Inc.

Adaptogenic Activity of Lyophilized Hydroethanol Extract of Pandanus odoratissimus in Swiss Albino Mice

PubMed Central

Jadhav, Pranita P.; Ambavade, Shirishkumar D.; Shelke, Tushar

2014-01-01

Background. The leaves of Pandanus odoratissimus Linn have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, hydroethanol extract of leaves of Pandanus odoratissimus Linn (LEPO) were evaluated for antistress activity in normal and stress induced mice. Furthermore, the extract was studied for nootropic (adaptogenic) activity in mice and in vitro antioxidant potential to correlate with its adaptogenic and antistress activity. LEPO (100 and 200 mg/kg p.o) was evaluated against forced swimming endurance stress test, anoxia stress tolerance and immobilization stress and chronic cold resistant stress tests, and biomarkers (serum glucose, Corticosterone, WBC, RBC, and DLC count) to assess the antistress activity in mice. Withania somnifera (WS) (100 mg/kg p.o) was selected as reference standard. The parameters like anoxia stress tolerance time were recorded in anoxia stress and estimation of biochemical marker levels and determination of organs weight were carried out in immobilization stress models. Results. Concomitant treatment with LEPO 200 mg/kg significantly increased in anoxia stress tolerance time. Dose dependent significant reduction in serum glucose, corticosterone, and WBC, RBC, and DLC was observed in immobilisation stress model as compared to stressed group. LEOP 200 mg/kg and WS 100 mg/kg significantly reversed/inhibited the stress induced changes in these parameters. The results from the present study indicate that these values also express that dose dependent significant adaptogenic activity in stressed animals. Conclusion. The present study provides scientific support for the antistress (adaptogenic) and nootropic activities of lyophilized hydroethanol extract of Pandanus odoratissimus Linn and substantiate the traditional claims for the usage of Pandanus in stress induced disorders. PMID:27379263

Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice

PubMed Central

Dhingra, Dinesh; Kumar, Vaibhav

2008-01-01

Objectives: The present study was undertaken to investigate the effect of the ethanolic extract of Allium sativum L. (Family: Lilliaceae), commonly known as garlic, on depression in mice. Materials and Methods: Ethanolic extract of garlic (25, 50 and 100 mg/kg) was administered orally for 14 successive days to young Swiss albino mice of either sex and antidepressant-like activity was evaluated employing tail suspension test (TST) and forced swim test (FST). The efficacy of the extract was compared with standard antidepressant drugs like fluoxetine and imipramine. The mechanism of action of the extract was investigated by co-administration of prazosin (α1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), baclofen (GABAB agonist) and p-CPA (serotonin antagonist) separately with the extract and by studying the effect of the extract on brain MAO-A and MAO-B levels. Results: Garlic extract (25, 50 and 100 mg/kg) significantly decreased immobility time in a dose-dependent manner in both TST and FST, indicating significant antidepressant-like activity. The efficacy of the extract was found to be comparable to fluoxetine (20 mg/kg p.o.) and imipramine (15 mg/kg p.o.) in both TST and FST. The extract did not show any significant effect on the locomotor activity of the mice. Prazosin, sulpiride, baclofen and p-CPA significantly attenuated the extract-induced antidepressant-like effect in TST. Garlic extract (100 mg/kg) administered orally for 14 successive days significantly decreased brain MAO-A and MAO-B levels, as compared to the control group. Conclusion: Garlic extract showed significant antidepressant-like activity probably by inhibiting MAO-A and MAO-B levels and through interaction with adrenergic, dopaminergic, serotonergic and GABAergic systems. PMID:20040952

Chemopreventive effect and HPTLC fingerprinting analysis of Jasminum sambac (L.) Ait. Extract against DLA-induced lymphoma in experimental animals.

PubMed

Kalaiselvi, M; Narmadha, R; Ragavendran, P; Vidya, B; Gomathi, D; Raj, C Arul; Starlinraj, T; Gopalakrishnan, V K; Uma, C; Kalaivani, K

2013-02-01

The anticancer activity of the ethanolic extract of Jasminum sambac against Dalton's lymphoma ascites-induced lymphatic cancer in Swiss albino mice was investigated. The anticancer activity of J. sambac was studied against lymphoma using lipid profiles, biochemical parameters, and membrane-bound marker enzymes by standard procedures. A high-performance thin-layer chromatography fingerprinting analysis showed the presence of terpenoids and flavonoids. The levels of cholesterol, triglyceride, VLDL cholesterol, and LDL cholesterol were significantly decreased in tumor-induced mice, while HDL cholesterol showed increased levels compared with those profiles. On treatment with J. sambac, the levels were brought back to near normal. The albumin, creatinine, total protein, urea, and uric acid contents were also approaching normal values. There was s significant increase in the levels of ATPase in group II. These levels were brought back to normal upon plant extract treatment of mice. DNA fragmentation occurred in the tumor-induced group of tissue, and treatment with ethanolic extract reduced the DNA damage caused by lymphoma. Expression of lactate dehydrogenase (LDH) isoenzymes shows an increase in the levels of LDH-4 and LDH-5 in cancer-bearing animals which is brought back to near normal. Histopathological investigation showed normal sections of liver tissues in the treatment group. The results found in mice treated with ethanolic extract 100 mg kg(-1) body weight quite promising and were comparable with the standard drug 5-fluorouracil. The statistically processed results support the conclusion that the ethanolic extract of J. sambac flower (100 mg kg(-1)) possesses a dose-dependent significant anticancer activity against lymphoma.

Effects of Cyclooxygenase on the Urothelium of the Urinary Bladder of Mice Exposed to Pelvic Radiation.

PubMed

Ozbilgin, M Kemal; Onal, Tuna; Ozcan, Cemil; Temel, Merve; Aktas, Caner; Gareveran, Manuchehr Salehi; Uluer, Elgin Turkoz; Inan, Sevinc; Kurtman, Cengiz

2016-04-01

To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. In the immunohistochemical examination the COX-1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation exposed groups than in the normal control group (group 1) (p < 0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p < 0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p < 0.005). COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radiation, supplying differentiation and restoration of the urothelium.

Effects of WIN 55,212-2 mesylate on the anticonvulsant action of lamotrigine, oxcarbazepine, pregabalin and topiramate against maximal electroshock-induced seizures in mice.

PubMed

Luszczki, Jarogniew J; Wlaz, Aleksandra; Karwan, Slawomir; Florek-Luszczki, Magdalena; Czuczwar, Stanislaw J

2013-11-15

The aim of this study was to determine the effect of WIN 55,212-2 mesylate (WIN - a non-selective cannabinoid CB1 and CB2 receptor agonist) on the protective action of four second-generation antiepileptic drugs (lamotrigine, oxcarbazepine, pregabalin and topiramate) in the mouse maximal electroshock seizure model. Tonic hind limb extension (seizure activity) was evoked in adult male albino Swiss mice by a current (sine-wave, 25 mA, 500 V, 50 Hz, 0.2s stimulus duration) delivered via auricular electrodes. Drug-related adverse effects were ascertained by use of the chimney test (evaluating motor performance), the step-through passive avoidance task (assessing long-term memory) and the grip-strength test (evaluating skeletal muscular strength). Total brain concentrations of antiepileptic drugs were measured by high-pressure liquid chromatography to ascertain any pharmacokinetic contribution to the observed antiseizure effect. Results indicate that WIN (5mg/kg, i.p.) significantly enhanced the anticonvulsant action of lamotrigine (P<0.05), pregabalin (P<0.001) and topiramate (P<0.05), but not that of oxcarbazepine in the maximal electroshock-induced tonic seizure test in mice. Furthermore, none of the investigated combinations of WIN with antiepileptic drugs were associated with any concurrent adverse effects with regards to motor performance, long-term memory or muscular strength. Pharmacokinetic characterization revealed that WIN had no impact on total brain concentrations of lamotrigine, oxcarbazepine, pregabalin and topiramate in mice. These preclinical data would suggest that WIN in combination with lamotrigine, pregabalin and topiramate is associated with beneficial anticonvulsant pharmacodynamic interactions in the maximal electroshock-induced tonic seizure test. © 2013 Published by Elsevier B.V.

Reno-protective effects of propolis on gentamicin-induced acute renal toxicity in swiss albino mice.

PubMed

Aldahmash, Badr Abdullah; El-Nagar, Doaa Mohamed; Ibrahim, Khalid Elfakki

Kidney is a vital organ which plays an important and irreplaceable role in detoxification and removal of xenobiotics. And therefore is vulnerable to develop various forms of injuries. Hence, making it immensely important to search for natural reno-protective compounds. This study therefore, aims to evaluate the reno-protective properties of propolis against gentamicin induced renal toxicity in mice. Three groups of 10 male mice each were used for this study. First group served as control, the second group (Gm group) was administered orally 80mg/kg body weight gentamicin for 7 days, and the third group (GmP group) was administered same dose of gentamicin with propolis (500mg/kg body weight) for 7 days. Various parameters were used to study the renal toxicity. Gentamicin caused significant renal damage as evident by the rise in BUN levels, diminished glomeruli hypocellularity, moderately dilated tubules, and mild loss of brush border, severe infiltration, extensive tubular degeneration and presence of tubular cast. Histochemistry results show presence of collagen and reticular fibres. Immunohistochemical reactions show kidney injury (Kim-1 gene-expression), oxidative stress (MDA gene-expression), and an increase in apoptosis (caspase-3 gene-expression). Co-administration of propolis with gentamicin showed significant decrease in BUN levels, appearance of healthy glomeruli with normal cellularity, reduction of tubular injury, decrease of collagen and reticular fibres deposition, reduction of apoptosis, kidney injury and oxidative stress. Results presented in this study clearly show the reno-protective role of propolis against gentamicin-induced toxicity on mice kidney. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Adverse health effects due to arsenic exposure: modification by dietary supplementation of jaggery in mice.

PubMed

Singh, Nrashant; Kumar, D; Lal, Kewal; Raisuddin, S; Sahu, Anand P

2010-02-01

Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene and other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic. Copyright 2009 Elsevier Inc. All rights reserved.

Isomalto-oligosaccharides, a prebiotic, functionally augment green tea effects against high fat diet-induced metabolic alterations via preventing gut dysbacteriosis in mice.

PubMed

Singh, Dhirendra Pratap; Singh, Jagdeep; Boparai, Ravneet Kaur; Zhu, JianHua; Mantri, Shrikant; Khare, Pragyanshu; Khardori, Romesh; Kondepudi, Kanthi Kiran; Chopra, Kanwaljit; Bishnoi, Mahendra

2017-09-01

High fat diet (HFD)-induced alterations in gut microbiota and resultant 'leaky gut' phenomenon promotes metabolic endotoxemia, ectopic fat deposition, and low-grade systemic inflammation. Here we evaluated the effects of a combination of green tea extract (GTE) with isomalto-oligosaccharide (IMOs) on HFD-induced alterations in mice. Male Swiss albino mice were fed with HFD (58% fat kcal) for 12 weeks. Systemic adiposity, gut derangement parameters and V3-V4 region based 16S rRNA metagenomic sequencing, ectopic fat deposition, liver metabolome analysis, systemic and tissue inflammation, and energy homeostasis markers along with gene expression analysis in multiple tissues were done in mice supplemented with GTE, IMOs or their combination. The combination of GTE and IMOs effectively prevented HFD-induced adiposity and lipid accumulation in liver and muscle while normalizing fasting blood glucose, insulin, glucagon, and leptin levels. Co-administration of GTE with IMOs effectively modulated liver metabolome associated with lipid metabolism. It also prevented leaky gut phenotype and HFD-induced increase in circulating lipopolysaccharides and pro-inflammatory cytokines (e.g. resistin, TNF-α, and IL-1β) and reduction in anti-inflammatory cytokines (e.g. adiponectin and IL-6). Gene expression analysis across multiple tissues further supported these functional outcomes. Most importantly, this combination improved beneficial gut microbiota (Lactobacillus sp., Bifidobacteria, Akkermansia muciniphila, Roseburia spp.) abundances, restored Firmicutes/Bacteriodetes and improved Prevotella/Bacteroides proportions. In particular, a combination of these two agents has shown improved beneficial effects on multiple parameters studied. Data presented herein suggests that strategically chosen food components might be highly effective in the prevention of HFD-induced alterations and may further be developed as functional foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

A murine model of type 2 diabetes mellitus developed using a combination of high fat diet and multiple low doses of streptozotocin treatment mimics the metabolic characteristics of type 2 diabetes mellitus in humans.

PubMed

Nath, Sayantan; Ghosh, Sankar Kumar; Choudhury, Yashmin

A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg -1 body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg -1 bw daily) and metformin (50mgkg -1 bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology and oxidative stress using tissues including liver, kidney and heart. Diabetic mice showed significant alterations in lipid profile, tissue histopathology, impaired glucose tolerance, lower insulin sensitivity and elevated lipid peroxidation and protein carbonylation, with depressed catalase activity, when compared to age and gender-matched controls. Metformin and vildagliptin ameliorated the abovementioned diabetic conditions, with vildagliptin found to be more effective. A murine model developed by the combination of HFD and multiple low dose of STZ mimics the metabolic characteristics of type 2 diabetes mellitus in humans, and may be useful for antidiabetic drug screening. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor-9 in mice

PubMed Central

Kaur, Sandeep; Mukhopadhyay, C. S.; Sethi, R. S.

2016-01-01

Aim: Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor 9 (TLR-9) in mice. Materials and Methods: In this study, healthy male Swiss albino mice (n=30) aging 8-10 weeks were used to evaluate TLR-9 expression in lungs of mice following indoxacarb exposure with and without lipopolysaccharide (LPS). Indoxacarb was administered orally dissolved in groundnut oil at 4 and 2 mg/kg/day for 90 days. On day 91, five animals from each group were challenged with LPS/normal saline solution at 80 µg/animal. The lung tissues were processed for real time and immunohistochemical studies. Results: LPS resulted increase in fold change m-RNA expression level of TLR-9 as compare to control, while indoxacarb (4 mg/kg) alone and in combination with LPS resulted 16.21-fold change and 29.4-fold change increase in expression of TLR-9 m-RNA, respectively, as compared to control. Similarly, indoxacarb (2 mg/kg) alone or in combination with LPS also altered TLR-9 expression. Further at protein level control group showed minimal expression of TLR-9 in lungs as compare to other groups, however, LPS group showed intense positive staining in bronchial epithelium as well as in alveolar septal cells. Indoxacarb at both doses individually showed strong immuno-positive reaction as compare to control, however when combined with LPS resulted intense staining in airway epithelium as compare to control. Conclusion: Chronic oral administration of indoxacarb for 90 days (4 and 2 mg/kg) alters expression of TLR-9 at m-RNA and protein level and co-exposure with LPS exhibited synergistic effect. PMID:27956782

Antipsychotic-like activity of Noni (Morinda citrifolia Linn.) in mice

PubMed Central

2012-01-01

Background Noni fruit is widely consumed in tropical regions of Indonesia to the Hawaiian Islands. The noni plant has a long history of use as a medicinal plant to treat a wide variety of ailments including CNS disorders. The present investigation was designed to evaluate the antipsychotic effect of noni fruits (Morinda citrifolia Linn.) using mouse models of apomorphine-induced climbing behaviour and methamphetamine-induced stereotypy (licking, biting, gnawing and sniffing). Methods In acute study, the methanolic extract of Morinda citrifolia (MMC) at different doses 1, 3, 5, 10 g/kg was administered orally one hour prior to apomorphine (5 mg/kg, i.p) and methamphetamine ( 5 mg/kg, i.p) injection respectively in Swiss albino mice. In chronic studies, (TAHITIAN NONI® Juice, TNJ) was made available freely in daily drinking water at 30, 50 and 100% v/v for 7 days; 30 and 50% v/v for 21 days respectively. On the test day, an equivalent average daily divided dose of TNJ was administered by oral gavage one hour prior to apomorphine treatment. Immediately after apomorphine/ methamphetamine administration, the animals were placed in the cylindrical metal cages and observed for climbing behaviour/ stereotypy and climbing time. Results The acute treatment of MMC (1, 3, 5, 10 g/kg, p.o) significantly decreased the apomorphine-induced cage climbing behaviour and climbing time in mice in a dose dependent manner. The MMC also significantly inhibited methamphetamine-induced stereotypy behaviour and climbing time in mice dose-dependently. The 7 and 21 days treatment of TNJ in drinking water at 50 and 100%v/v significantly alleviated the apomorphine-induced climbing behaviour and climbing time in mice. Conclusions The present study results demonstrated the antidopaminergic effect of Morinda citrifolia Linn. in mice, suggesting that noni has antipsychotic-like activity which can be utilized in the treatment of psychiatric disorders. However further studies are warranted to identify the active principles responsible for the antipsychotic activity of noni. PMID:23082808

Antipsychotic-like activity of noni (Morinda citrifolia Linn.) in mice.

PubMed

Pandy, Vijayapandi; Narasingam, Megala; Mohamed, Zahurin

2012-10-19

Noni fruit is widely consumed in tropical regions of Indonesia to the Hawaiian Islands. The noni plant has a long history of use as a medicinal plant to treat a wide variety of ailments including CNS disorders. The present investigation was designed to evaluate the antipsychotic effect of noni fruits (Morinda citrifolia Linn.) using mouse models of apomorphine-induced climbing behaviour and methamphetamine-induced stereotypy (licking, biting, gnawing and sniffing). In acute study, the methanolic extract of Morinda citrifolia (MMC) at different doses 1, 3, 5, 10 g/kg was administered orally one hour prior to apomorphine (5 mg/kg, i.p) and methamphetamine (5 mg/kg, i.p) injection respectively in Swiss albino mice. In chronic studies, (TAHITIAN NONI® Juice, TNJ) was made available freely in daily drinking water at 30, 50 and 100% v/v for 7 days; 30 and 50% v/v for 21 days respectively. On the test day, an equivalent average daily divided dose of TNJ was administered by oral gavage one hour prior to apomorphine treatment. Immediately after apomorphine/ methamphetamine administration, the animals were placed in the cylindrical metal cages and observed for climbing behaviour/ stereotypy and climbing time. The acute treatment of MMC (1, 3, 5, 10 g/kg, p.o) significantly decreased the apomorphine-induced cage climbing behaviour and climbing time in mice in a dose dependent manner. The MMC also significantly inhibited methamphetamine-induced stereotypy behaviour and climbing time in mice dose-dependently. The 7 and 21 days treatment of TNJ in drinking water at 50 and 100%v/v significantly alleviated the apomorphine-induced climbing behaviour and climbing time in mice. The present study results demonstrated the antidopaminergic effect of Morinda citrifolia Linn. in mice, suggesting that noni has antipsychotic-like activity which can be utilized in the treatment of psychiatric disorders. However further studies are warranted to identify the active principles responsible for the antipsychotic activity of noni.

A comparative study on the anti-schistosomal and hepatoprotective effects of vinpocetine and isosorbide-5-mononitrate on Schistosoma mansoni-infected mice.

PubMed

Alhusseiny, Samar M; El-Beshbishi, Samar N; Hashim, Maha M Abu; El-Nemr, Hosam El-Dein E; Handoussa, Aya E

2017-12-01

Schistosomiasis is a remarkable public health problem in developing countries. Presently, praziquantel is the optional drug for all human schistosomiasis. Owing to the increased praziquantel resistance, there is an urgent need to develop new alternatives. This study aims at determining the anti-schistosomal and/or the hepatoprotective effects of the anti-inflammatory drug; vinpocetine, and the vasodilator and the nitric oxide donor; isosorbide-5-mononitrate, in comparison to praziquantel. In the present research, the therapeutic efficacies of these drugs were assessed in Swiss albino female mice (CD-I strain) experimentally infected with an Egyptian strain of Schistosoma mansoni, using some general, parasitological, and histopathological parameters. In this work, praziquantel significantly reduced worm burden and hepatic egg load, increased the percentage of dead eggs in the small intestine and decreased granuloma count, but did not reduce granuloma diameter. While, either vinpocetine or isosorbide-5-mononitrate monotherapy did not induce significant reduction in the worm count, hepatic egg load or shift in the oogram pattern, but significantly reduced granuloma count and diameter. Moreover, isosorbide-5-mononitrate significantly reduced hepatic inflammation and necrosis. The best results were obtained in the mice groups treated with isosorbide-5-mononitrate combined with praziquantel or vinpocetine. Our results point to vinpocetine and isosorbide-5-mononitrate as a convenient and promising adjuvant to praziquantel for ameliorating schistosomal liver pathology. Further studies are recommended to reveal the actual pathways responsible for the different activities of vinpocetine and isosorbide-5-mononitrate. Copyright © 2017 Elsevier B.V. All rights reserved.

Sea Buckthorn Leaf Extract Protects Jejunum and Bone Marrow of 60Cobalt-Gamma-Irradiated Mice by Regulating Apoptosis and Tissue Regeneration

PubMed Central

Gupta, Manish; Saini, Manu; Abdin, M. Z.; Prasad, Jagdish

2015-01-01

A single dose (30 mg/kg body weight) of standardized sea buckthorn leaf extract (SBL-1), administered 30 min before whole body 60Co-gamma-irradiation (lethal dose, 10 Gy), protected >90% of mice population. The purpose of this study was to investigate the mechanism of action of SBL-1 on jejunum and bone marrow, quantify key bioactive compounds, and analyze chemical composition of SBL-1. Study with 9-week-old inbred male Swiss albino Strain ‘A' mice demonstrated that SBL-1 treatment before 60Co-gamma-irradiation (10 Gy) significantly (p < 0.05) countered radiation induced decreases in jejunum crypts (1.27-fold), villi number (1.41-fold), villus height (1.25-fold), villus cellularity (2.27-fold), cryptal Paneth cells (1.89-fold), and Bcl2 level (1.54-fold). It countered radiation induced increases in cryptal apoptotic cells (1.64-fold) and Bax levels (1.88-fold). It also countered radiation (2 Gy and 3 Gy) induced bone marrow apoptosis (1.59-fold and 1.85-fold) and micronuclei frequency (1.72-fold and 2.6-fold). SBL-1 rendered radiation protection by promoting cryptal stem cells proliferation, by regulating apoptosis, and by countering radiation induced chromosomal damage. Quercetin, Ellagic acid, Gallic acid, high contents polyphenols, tannins, and thiols detected in SBL-1 may have contributed to radiation protection by neutralization of radiation induced oxidative species, supporting stem cell proliferation and tissue regeneration. PMID:26421051

Bacopa monnieri: An evaluation of antihyperglycemic and antinociceptive potential of methanolic extract of whole plants.

PubMed

Taznin, Inin; Mukti, Mohsina; Rahmatullah, Mohammed

2015-11-01

Antihyperglycemic and antinociceptive activity studies were carried out with methanolic extract of whole plants of Bacopa monnieri, respectively, through oral glucose tolerance test and gastric pain model induced by acetic acid in Swiss albino mice. In OGTT (oral glucose tolerance tests) conducted with glucose-challenged mice, the extract, administered at four doses of 50, 100, 200 and 400mg per kg body weight, dose-dependently and significantly inhibited the increase in serum glucose concentrations, respectively, by 33.3, 34.2, 42.1 and 44.2%. A standard antihyperglycemic drug, glibenclamide, when administered at a dose of 10mg per kg body weight, inhibited increase in serum glucose concentration by 50.7%. From the results, it can be concluded that the methanolic extract of the plant possess significant antihyperglycemic potential. In antinociceptive activity tests, administration of the extract at the aforementioned four doses also significantly and dose-dependently reduced the number of acetic acid-induced gastric constrictions in mice. The percent inhibitions in gastric constrictions were, respectively, 43.4, 46.6, 50.0, and 53.4 at the above four doses. A reference antinociceptive drug, aspirin, when administered at a dose of 200 mg per kg body weight, reduced the number of gastric constrictions by 40.0%. Thus the extract at even the lowest dose of 50 mg, demonstrated antinociceptive activity better than that of aspirin, and which activity was much more than aspirin at the other three higher doses tested. The results demonstrate that the plant can be an excellent candidate for further studies towards isolation of antihyperglycemic and pain-killing compounds.

Influence of picolinic acid on seizure susceptibility in mice.

PubMed

Cioczek-Czuczwar, Anna; Czuczwar, Piotr; Turski, Waldemar Andrzej; Parada-Turska, Jolanta

2017-02-01

The mechanism of drug resistance in epilepsy remains unknown. Picolinic acid (PIC) is an endogenous metabolite of the kynurenine pathway and a chelating agent added to dietary supplements. Both inhibitory and excitatory properties of PIC were reported. The aim of this study was to determine the influence of exogenously applied PIC upon the electroconvulsive threshold and the activity of chemical convulsants in eight models of epilepsy in mice. All experiments were performed on adult male Swiss albino mice. Electroconvulsions were induced through ear clip electrodes. The electroconvulsive threshold (current strength necessary to induce tonic seizures in 50% of the tested group - CS 50 ) was estimated for control animals and animals pretreated with PIC. To determine the possible convulsant activity of PIC, it was administered subcutaneously or intracerebroventricularly in increasing doses to calculate the CD 50 values (doses of convulsants necessary to produce seizures in 50% of the animals). Chemical convulsions were induced by challenging the animals with increasing doses of convulsant to calculate the CD 50 values. The following convulsants were used: 4-aminopyridine, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, bicuculline, N-methyl-d-aspartate, nicotine, pentylenetrazole, pilocarpine hydrochloride and strychnine nitrate. PIC significantly decreased the electroconvulsive threshold and, after intracerebroventricular injection, but not subcutaneous, produced convulsions. Of the studied convulsants, only the activity of pilocarpine hydrochloride was significantly enhanced by PIC. PIC enhances seizure activity and potentially may play a role in the pathogenesis of drug resistant epilepsy. Future studies should focus on the interactions between PIC and antiepileptic drugs. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

In vivo and in vitro evaluation of an Acetobacter xylinum synthesized microbial cellulose membrane intended for guided tissue repair

PubMed Central

Mendes, Péricles Nóbrega; Rahal, Sheila Canevese; Pereira-Junior, Oduvaldo Câmara Marques; Fabris, Viciany Erique; Lenharo, Sara Lais Rahal; de Lima-Neto, João Ferreira; da Cruz Landim-Alvarenga, Fernanda

2009-01-01

Background Barrier materials as cellulose membranes are used for guided tissue repair. However, it is essential that the surrounding tissues accept the device. The present study histologically evaluated tissue reaction to a microbial cellulose membrane after subcutaneous implantation in mice. Furthermore, the interaction between mesenchymal stem cells and the biomaterial was studied in vitro to evaluate its ability to act as cellular scaffold for tissue engineering. Methods Twenty-five Swiss Albino mice were used. A 10 × 10 mm cellulose membrane obtained through biosynthesis using Acetobacter xylinum bacteria was implanted into the lumbar subcutaneous tissue of each mouse. The mice were euthanatized at seven, 15, 30, 60, and 90 days, and the membrane and surrounding tissues were collected and examined by histology. Results A mild inflammatory response without foreign body reaction was observed until 30 days post-surgery around the implanted membrane. Polarized microscopy revealed that the membrane remained intact at all evaluation points. Scanning electron microscopy of the cellulose membrane surface showed absence of pores. The in vitro evaluation of the interaction between cells and biomaterial was performed through viability staining analysis of the cells over the biomaterial, which showed that 95% of the mesenchymal stem cells aggregating to the cellulose membrane were alive and that 5% were necrotic. Scanning electron microscopy showed mesenchymal stem cells with normal morphology and attached to the cellulose membrane surface. Conclusion The microbial cellulose membrane evaluated was found to be nonresorbable, induced a mild inflammatory response and may prove useful as a scaffold for mesenchymal stem cells. PMID:19317903

Effect of Nigella sativa (black seeds) against methotrexate-induced nephrotoxicity in mice.

PubMed

Ahmed, Jawad Hassan; Abdulmajeed, Isra Mohammed

2017-01-01

To evaluate the protective effect of Nigella sativa (NS) against nephrotoxicity of methotrexate (MTX) in mice. Four groups of Swiss albino male mice, eight in each group were used. The study was carried on between October 2014 and April 2015. Group 1 (control) were administered 0.3 ml distilled water orally daily for 21 days and injected with normal saline (0.25 ml) IP weekly. Group 2 (MTX group) were treated with MTX, 10 mg/kg IP weekly, while Group 3 were treated with 0.125 ml of NS oil by mouth daily and injected with normal saline (0.25 ml) IP weekly. Group 4 received 0.125 ml of NS oil by mouth daily and injected with 10 mg/kg MTX IP weekly. Oral treatments were administered using a special curved smooth tip nontraumatic metal needle and IP injections were given for 3 weeks at days 7, 14 and 21. Animals were sacrificed at day 23. Malondialdehyde (MDA) and glutathione (GSH) measurements were performed on kidney homogenate. Histopathology of the kidneys were prepared and examined. MTX has resulted in a small elevation in MDA and reduction in GSH levels in kidney homogenate which was returned back to control values when NS and MTX were administered in combination. Statistical significance was achieved with elevation of GSH by MTX and NS compared to MTX alone. MTX caused histopathological changes suggesting nephrotoxicity in 6 animals out of 8, while no changes were found in all animals treated with MTX and NS. NS is protective against MTX-induced nephrotoxicity.

Lipopolysaccharide-Induced Behavioral Alterations Are Alleviated by Sodium Phenylbutyrate via Attenuation of Oxidative Stress and Neuroinflammatory Cascade.

PubMed

Jangra, Ashok; Sriram, Chandra Shaker; Lahkar, Mangala

2016-08-01

Oxido-nitrosative stress, neuroinflammation, and reduced level of neurotrophins are implicated in the pathophysiology of anxiety and depressive illness. A few recent studies have revealed the role of endoplasmic reticulum (ER) stress in the pathophysiology of stress and depression. The aim of the present study is to investigate the neuroprotective potential of sodium phenylbutyrate (SPB), an ER stress inhibitor against lipopolysaccharide (LPS)-induced anxiety and depressive-like behavior in Swiss albino mice. Anxiety and depressive-like behavior was induced by LPS (0.83 mg/kg; i.p.) administration. Various behavioral tests were conducted to evaluate the anxiety and depressive-like behavior in mice. Real-time PCR was employed for the detection and expression of ER stress markers (78-kDa glucose-regulated protein (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Pretreatment with SPB significantly ameliorated the LPS-induced anxiety and depressive-like behavior as revealed by behavioral paradigm results. LPS-induced oxidative stress was ameliorated by SPB pretreatment in hippocampus (HC) and prefrontal cortex (PFC) region. Neuroinflammation was significantly reduced by SPB pretreatment in LPS-treated mice as evident from reduction in proinflammatory cytokines (IL-1β and TNF-α). Importantly, LPS administration significantly up-regulated the GRP78 mRNA expression level in the HC which suggests the involvement of unfolded protein response (UPR) in LPS-evoked behavioral anomalies. These results highlight the neuroprotective potential of SPB in LPS-induced anxiety and depressive illness model which may be partially due to inhibition of oxidative stress-neuroinflammatory cascade.

Phytochemical, chromatographic and spectroscopic investigation of Carum copticum seeds and their potential as immunomodulatory agents.

PubMed

Sonar, Pankaj K; Singh, Ranjit; Saraf, Shailendra K

2016-01-01

Carum copticum seeds have been prescribed in the traditional system of medicine for the treatment of immune disorders, such as asthma and rheumatism. The objective of this study was to determine immunomodulatory effects of the alcoholic extract and isolated compounds in Swiss albino mice. Seeds of C. copticum were extracted with 95% v/v alcohol. The immunomodulatory activity of the crude extract was evaluated at the doses of 100, 300, and 500 mg/kg body weight of mice, administered in mice once daily (orally) for 25 days. Volatile oil of C. copticum was isolated by steam distillation and was characterized by GLC and HPLC. Bio-assay-guided fractionation and isolation were carried out and the isolated compounds were characterized and subjected to immunomodulatory activity studies. The n-hexane fraction yielded p-cymene, carvacrol, and α-pinene. The LD50 value of the crude extract was found to be 4500 mg/kg and the values reported for p-cymene, carvacrol, and α-pinene in the literature were 4750, 810, and 3700 mg/kg, respectively. The oral administration of crude extract, n-hexane fraction (HEF), and isolated oils at the dose of 500, 150, and 50 mg/kg body weight, respectively, showed a significant increase in the HA titers, DTH-response, and phagocytosis. The stimulatory effect observed, on humoral and cellular immunity, was compared with the standard (levamisole treated) and control groups. The results obtained in the study endorse the traditional use of the seeds of C. copticum and the isolated constituents act as immunostimulants.

Can Ocimum basilicum relieve chronic unpredictable mild stress-induced depression in mice?

PubMed

Ayuob, Nasra Naeim; Firgany, Alaa El-Din L; El-Mansy, Ahmed A; Ali, Soad

2017-10-01

Depression is one of the important world-wide health problems. This study aimed to assess the ameliorative effect of Ocimum basilicum (OB) essential oil on the behavioral, biochemical and histopathological changes resulted from exposure to chronic unpredictable mild stress (CUMS). It also aimed to investigate the underlying mechanism in an animal model of depression. Forty male Swiss albino mice were divided into four groups (n=10): control, CUMS (exposed to CUMS for 4weeks), CUMS plus fluoxetine, and CUMS plus OB. At the end of the experiment, behavioral changes, serum corticosterone level, protein and gene expressions of brain derived neurotropic factor (BDNF) and glucocorticoid receptors (GR) in the hippocampus was all assessed. Immunoexpression of surface makers of glial fibrillary acidic protein (GFAP), Ki67, Caspase-3, BDNF and GR in the hippocampus were estimated. Data were analyzed by using the statistical package for the social sciences (SPSS). OB alleviated both behavioral and biochemical changes recorded in mice after exposure to CUMS. It also reduced neuronal atrophy observed in the hippocampal region III cornu ammonis (CA3) and dentate gyrus and restored back astrocyte number. OB decreased apoptosis in both neurons and glial cells and increased neurogenesis in the dentate gyrus in a pattern comparable to that of fluoxetine. Increased BDNF and GR gene and protein expressions seems to be behind the antidepressant-like effect of OB. Ocimum basilicum ameliorates the changes induced after exposure to the chronic stress. Assessing Ocimum basilicum efficacy on human as antidepressant is recommended in further studies. Copyright © 2017. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Nrashant; Department of Medical Elementology and Toxicology, Jamia Hamdard; Kumar, D.

Populations of villages of eastern India and Bangladesh and many other parts of the world are exposed to arsenic mainly through drinking water. Due to non-availability of safe drinking water they are compelled to depend on arsenic-contaminated water. Generally, poverty level is high in those areas and situation is compounded by the lack of proper nutrition. The hypothesis that the deleterious health effects of arsenic can be prevented by modification of dietary factors with the availability of an affordable and indigenous functional food jaggery (sugarcane juice) has been tested in the present study. Jaggery contains polyphenols, vitamin C, carotene andmore » other biologically active components. Arsenic as sodium-m-arsenite at low (0.05 ppm) and high (5 ppm) doses was orally administered to Swiss male albino mice, alone and in combination with jaggery feeding (250 mg/mice), consecutively for 180 days. The serum levels of total antioxidant, glutathione peroxidase and glutathione reductase were substantially reduced in arsenic-exposed groups, while supplementation of jaggery enhanced their levels in combined treatment groups. The serum levels of interleukin-1beta, interleukin-6 and TNF-alpha were significantly increased in arsenic-exposed groups, while in the arsenic-exposed and jaggery supplemented groups their levels were normal. The comet assay in bone marrow cells showed the genotoxic effects of arsenic, whereas combination with jaggery feeding lessened the DNA damage. Histopathologically, the lung of arsenic-exposed mice showed the necrosis and degenerative changes in bronchiolar epithelium with emphysema and thickening of alveolar septa which was effectively antagonized by jaggery feeding. These results demonstrate that jaggery, a natural functional food, effectively antagonizes many of the adverse effects of arsenic.« less

[Neural pathway of Powassan virus spread in the central nervous system of white mice].

PubMed

Sobolev, S G; Shestopalova, N M

1978-01-01

Electron microscopic investigation of the brains and lumbar spinal cords of adult albino mice infected with Powassan virus was carried out. Virus particles were found within all parts of neurons (perikarya, dendrites, axon), as well as within synaptic apparatus and intercellular gaps of the central nervous tissue. The possibility of the virus spread both throughout the cytoplasm of nerve cells and their processes and the extracellular spaces of the brain was confirmed. Localization of virions within neurons, synapses and myelinated fibers of the spinal cord after intracerebral inoculation suggests that virus spread in the CNS can occur through the CNS parenchyma and also through the nervous conduction pathways. The possible mechanisms of virus dissemination in the CNS of albino mice with experimental Powassan virus encephalomyelitis are discussed.

Infrared photobiomodulation (PBM) therapy improves glucose metabolism and intracellular insulin pathway in adipose tissue of high-fat fed mice.

PubMed

Silva, Gabriela; Ferraresi, Cleber; de Almeida, Rodrigo Teixeira; Motta, Mariana Lopes; Paixão, Thiago; Ottone, Vinicius Oliveira; Fonseca, Ivana Alice; Oliveira, Murilo Xavier; Rocha-Vieira, Etel; Dias-Peixoto, Marco Fabrício; Esteves, Elizabethe Adriana; Coimbra, Cândido Celso; Amorim, Fabiano Trigueiro; de Castro Magalhães, Flávio

2018-04-01

Obesity represents a continuously growing global epidemic and is associated with the development of type 2 diabetes mellitus. The etiology of type 2 diabetes is related to the resistance of insulin-sensitive tissues to its action leading to impaired blood glucose regulation. Photobiomodulation (PBM) therapy might be a non-pharmacological, non-invasive strategy to improve insulin resistance. It has been reported that PBM therapy in combination with physical exercise reduces insulin resistance. Therefore, the aim of this study was to investigate the effects of PBM therapy on insulin resistance in obese mice. Male Swiss albino mice received low-fat control diet (n = 16, LFC) or high-fat diet (n = 18, HFD) for 12 weeks. From 9th to 12th week, the mice received PBM therapy (LASER) or Sham (light off) treatment and were allocated into four groups: LFC Sham (n = 8), LFC PBM (n = 8), HFD Sham (n = 9), and HFD PBM (n = 9). The PBM therapy was applied in five locations: to the left and right quadriceps muscle, upper limbs and center of the abdomen, during 40 s at each point, once a day, 5 days a week, for 4 weeks (780 nm, 250 mW/cm 2 , 10 J/cm 2 , 0.4 J per site; 2 J total dose per day). Insulin signaling pathway was evaluated in the epididymal adipose tissue. PBM therapy improved glucose tolerance and phosphorylation of Akt (Ser473) and reversed the HFD-induced reduction of GLUT4 content and phosphorylation of AS160 (Ser588). Also, PBM therapy reversed the increased area of epididymal and mesenteric adipocytes. The results showed that chronic PBM therapy improved parameters related to obesity and insulin resistance in HFD-induced obesity in mice.

Studies on promoting action in skin carcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saffiotti, U.; Shubik, P.

1963-01-01

A number of substances were tested for carcinogenic promoting activity in Swiss mice by applying them twice weekly to the clipped dorsal skin, beginning 1 wk after a single application of 9,10-dimethyl-1, 2-benzanthracene (DMBA; 1 to 1.5% in mineral oil). Tests with silver nitrate (10% aqueous), iodoacetic acid (0.9% in acetone, fumaric acid (1% in acetone), ethylphenylpropiolate (5% in acetone), trihydroxymethylanthraquinone. (Emodin; 0.5% in acetone), oleic alcohol, monostearin (5% in acetone) and sorbitan monolaurate were essentially negative; when a single application of croton oil (5% in mineral oil) was interspersed between the carcinogen and silver nitrate, 6/20 mice developed 14more » benign tumors and 1 carcinoma. N-Dodecane showed moderate promoting activity (26 tumors, with 2 carcinomas, in 12/30 mice). Tests of several petroleum fractions showed high initial promoting activity (404 tumors, with 31 carcinomas, in 36/50 mice), but the activity disappeared on storage; while there was no carcinogenic activity in mice, in New Zealand albino rabbits the petroleum fractions alone produced considerable numbers of tumors. One application of DMBA, however, did increase tumor incidence and shorten the latent period. The hexane-eluted fraction of a methanolic extract of croton seeds (which had little vesicant activity), had all the promoting activity of the original croton oil; this could be demonstrated with uethan (20 mg/day ip for 5 days) as the initiator as well as with DMBA. In conclusion, the authors distinguish sharply between the promoting activity of compounds such as croton oil, which lead mostly to benign tumors (many of which regress spontaneously), and the additive effects of carcinogenic substances which may have a stimulatory effect on the second stage of carcinogenesis; for this additive carcinogenic effect, they suggest the term developing action. Other studies on croton oil are also reviewed.« less

Pharmacological evaluation of Musa seminifera Lour. fruit.

PubMed

Saha, Sanjib; Hossain, Faroque; Anisuzzman, Md; Islam, Md Khirul

2013-07-01

To study potential antioxidant, analgesic, antidiarrheal, and antibacterial activities of the ethanol extract of Musa seminifera Lour. fruit in different established in vivo and in vitro experimental models. In vitro antioxidant activity was studied in 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay. Phenolic content was determined using Folin-Ciocalteu's reagent. Reducing ability was evaluated by ferric reducing power assay. Peripherally and centrally acting analgesic activity was studied in three different in vivo models, namely, acetic acid-induced writhing, hot-plate test, and tail-flick test in Swiss albino mice. In vivo antidiarrheal activity was evaluated in castor oil- and magnesium sulfate-induced diarrhea in mice. Gastrointestinal motility test was also carried out in mice. All studies in mice were undertaken at the doses of 250 and 500 mg/kg body weight. Antibacterial activity was assessed by disk diffusion assay against some Gram-positive and Gram-negative bacterial strains. Acute toxicity test was conducted to assess the safe doses of the extract. The extract showed 50% inhibitory concentration value of 12.65 μg/mL in DPPH radical-scavenging assay. Phenolic content was found to be 589.83 mg gallic acid equivalent per 100 g of dried fruits extract. Reducing power was in a concentration-dependent manner, and strongly comparable with the standard ascorbic acid. The extract demonstrated significant inhibition of writhing in acetic acid-induced writhing test at both dose levels (P<0.01). The extract also raised pain threshold in both hot-plate and tail-flick test in a dose-dependent manner, and the results were statistically significant (P<0.01). The extract significantly (P<0.01) increased latent period, and decreased defecation in both castor oil- and magnesium sulfate-induced diarrhea. The extract also decreased gastrointestinal motility in mice. In disk diffusion assay, the extract showed potential antibacterial activity against all the tested bacterial strains. The results suggest that the ethanol extract of M. seminifera fruit has potential antioxidant, analgesic, antidiarrheal, and antibacterial activities.

Evaluation of the co-agglutination test in diagnosis of experimental microsporidiosis.

PubMed

Gaafar, Maha R

2011-05-01

Microsporidiosis is an emerging and opportunistic infection associated with wide range of clinical syndromes in humans. Confirmation of the presence of microsporidia in different samples is laborious, costly and often difficult. The present study was designed to evaluate the utility of the Co-agglutination test (Co-A test) for detection of urinary, fecal and circulating microsporidial antigens in experimentally infected mice. One hundred and twenty male Swiss albino mice were divided into non infected control and infected experimental groups which were further subdivided into two equal subgroups; immunosuppressed and immunocompetent. Microsporidial spores were isolated from human stools and identified to be Encephalitozoon intestinalis by the molecular methods. They were used to infect each subgroup of mice, then their urine, stools and sera were collected at the 1st, 3rd, 5th, 7th and 9th days post-infection (PI). Co-A test, using prepared hyperimmune serum, was used to detect antigens in all samples collected. The cross reactivity of microsporidial hyperimmune sera with antigens of Cyclospora cyatenensis and Cryptosporidium parvum was investigated by Co-A test. The results showed that Co-A test was effective in detecting microsporidial antigen in stool of immunosuppressed infected mice from the 1st day PI, and in urine and serum from the 3rd day PI till the end of the study. In the immunocompetent subgroup, Co-A test detected microsporidial antigens in stool, serum and urine of mice from the 1st day, 3rd day and the 5th day PI, respectively till the end of the study, without cross reactivity with C. cyatenensis or C. parvum in both subgroups. Co-A test proved to be simple and suitable tool for detecting microsporidial antigen in different specimens and did not need sophisticated equipment. It is very practical under field or rural conditions and in poorly equipped clinical laboratories. Copyright © 2011 Elsevier Inc. All rights reserved.

Age, environment, object recognition and morphological diversity of GFAP-immunolabeled astrocytes.

PubMed

Diniz, Daniel Guerreiro; de Oliveira, Marcus Augusto; de Lima, Camila Mendes; Fôro, César Augusto Raiol; Sosthenes, Marcia Consentino Kronka; Bento-Torres, João; da Costa Vasconcelos, Pedro Fernando; Anthony, Daniel Clive; Diniz, Cristovam Wanderley Picanço

2016-10-10

Few studies have explored the glial response to a standard environment and how the response may be associated with age-related cognitive decline in learning and memory. Here we investigated aging and environmental influences on hippocampal-dependent tasks and on the morphology of an unbiased selected population of astrocytes from the molecular layer of dentate gyrus, which is the main target of perforant pathway. Six and twenty-month-old female, albino Swiss mice were housed, from weaning, in a standard or enriched environment, including running wheels for exercise and tested for object recognition and contextual memories. Young adult and aged subjects, independent of environment, were able to distinguish familiar from novel objects. All experimental groups, except aged mice from standard environment, distinguish stationary from displaced objects. Young adult but not aged mice, independent of environment, were able to distinguish older from recent objects. Only young mice from an enriched environment were able to distinguish novel from familiar contexts. Unbiased selected astrocytes from the molecular layer of the dentate gyrus were reconstructed in three-dimensions and classified using hierarchical cluster analysis of bimodal or multimodal morphological features. We found two morphological phenotypes of astrocytes and we designated type I the astrocytes that exhibited significantly higher values of morphological complexity as compared with type II. Complexity = [Sum of the terminal orders + Number of terminals] × [Total branch length/Number of primary branches]. On average, type I morphological complexity seems to be much more sensitive to age and environmental influences than that of type II. Indeed, aging and environmental impoverishment interact and reduce the morphological complexity of type I astrocytes at a point that they could not be distinguished anymore from type II. We suggest these two types of astrocytes may have different physiological roles and that the detrimental effects of aging on memory in mice from a standard environment may be associated with a reduction of astrocytes morphological diversity.

Lupeol induces p53 and cyclin-B-mediated G2/M arrest and targets apoptosis through activation of caspase in mouse skin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nigam, Nidhi; Prasad, Sahdeo; George, Jasmine

2009-04-03

Lupeol, present in fruits and medicinal plants, is a biologically active compound that has been shown to have various pharmacological properties in experimental studies. In the present study, we demonstrated the modulatory effect of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced alterations on cell proliferation in the skin of Swiss albino mice. Lupeol treatment showed significant (p < 0.05) preventive effects with marked inhibition at 48, 72, and 96 h against DMBA-mediated neoplastic events. Cell-cycle analysis showed that lupeol-induced G2/M-phase arrest (16-37%) until 72 h, and these inhibitory effects were mediated through inhibition of the cyclin-B-regulated signaling pathway involving p53, p21/WAF1, cdc25C, cdc2,more » and cyclin-B gene expression. Further lupeol-induced apoptosis was observed, as shown by an increased sub-G1 peak (28%) at 96 h, with upregulation of bax and caspase-3 genes and downregulation of anti-apoptotic bcl-2 and survivin genes. Thus, our results indicate that lupeol has novel anti-proliferative and apoptotic potential that may be helpful in designing strategies to fight skin cancer.« less

Design and Optimization of Domperidone Fast Dissolving Tablet Using Central Composite Design.

PubMed

Shailendra, Bhatt; Shailendra, Mandge; Manish, Jaimini; Singh, Tanwar Yuveraj; Priti, Trivedi

2015-01-01

The main aim present work was to optimize fast dissolving tablet (FDT) formulation using response surface approach. The variables studied were sodium bicarbonate (X1), citric acid (X2), and superdisintegrant, Ac-Di-Sol (X3). The main aspect of present work was to develop FDT of Domperidone which possesses fast disintegration and high mechanical strength. It was found that the response was affected by all the three factors studied. The statistical models were successfully used to prepare FDT of Domperidone with fast disintegration (31.08 seconds) and adequate hardness (4.1 kg/cm(2)). Pharmacokinetic studies in rats showed statistically insignificant difference (p>0.05) between Domperidone fast dissolving tablet (DFDT) and market product. This concluded that optimized FDT is bioequivalent with the marketed formulation. The values of Tmax were found to be 0.5 h and 0.75 h for DFDT and reference product, respectively. Conditioned place aversion study was performed on Swiss Albino mice and the study showed the better anti emetic potency of optimized FDT in nauseated condition over market product (p<0.05). Thus, the present investigation conclusively demonstrates the potential role in terms of rapid disintegration and high mechanical strength.

Additive interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and clobazam in the mouse maximal electroshock-induced tonic seizure model--an isobolographic analysis for parallel dose-response relationship curves.

PubMed

Andres-Mach, Marta; Haratym-Maj, Agnieszka; Zagaja, Mirosław; Luszczki, Jarogniew J

2014-01-01

The aim of this study was to characterize the anticonvulsant effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ) in combination with clobazam (CLB) in the mouse maximal electroshock-induced seizure (MES) model. The anticonvulsant interaction profile between 1-MeTHIQ and CLB in the mouse MES model was determined using an isobolographic analysis for parallel dose-response relationship curves. Electroconvulsions were produced in albino Swiss mice by a current (sine wave, 25 mA, 500 V, 50 Hz, 0.2-second stimulus duration) delivered via auricular electrodes by a Hugo Sachs generator. There was an additive effect of the combination of 1-MeTHIQ with CLB (at the fixed ratios of 1:3, 1:1 and 3:1) in the mouse MES-induced tonic seizure model. The additive interaction of the combination of 1-MeTHIQ with CLB (at fixed-ratios of 1:3, 1:1 and 3:1) in the mouse MES model seems to be pharmacodynamic in nature and worth of considering in further clinical practice. © 2014 S. Karger AG, Basel.

Protective Effect of Zingiber officinale Against Dalton's Lymphoma Ascites Tumour by Regulating Inflammatory Mediator and Cytokines.

PubMed

Rubila, Sundararaj; Ranganathan, Thottiam Vasudevan; Sakthivel, Kunnathur Murugesan

2016-12-01

The aim of the present investigation was to evaluate Zingiber officinale paste against Dalton's lymphoma ascites (DLA)-induced tumours in Swiss albino mice. Experimental animals received Z. officinale paste (low dose 100 mg/kg bw and high dose 500 mg/kg bw) orally for eight alternative days. Treatment with Z. officinale paste showed significant increase in haemoglobin level and decrease in aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (γ-GT) level. Z. officinale paste reduced the inflammatory mediators and cytokine levels, such as inducible nitric oxide (iNOS), tumour necrosis factor level (TNF-α) and interleukin-1β (IL-1β). Treatment with Z. officinale paste also significantly increased the antioxidant enzyme level, such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione transferase (GST), and decreased the lipid peroxidation. Treatment also increased the vitamin C and E levels in treated animals compared with the DLA-bearing host. Histopathological studies also confirmed the protective influence of Z. officinale paste against DLA. The present study suggested that Z. officinale paste could be used as natural spice and a potent antitumour agent.

The effects of pre- and postnatal exposure to the nonsteroidal antiandrogen flutamide on testis descent and morphology in the Albino Swiss rat

PubMed Central

KASSIM, NORMADIAH M.; McDONALD, S. W.; REID, O.; BENNETT, N. K.; GILMORE, D. P.; PAYNE, A. P.

1997-01-01

Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen flutamide during the period from gestational day (d) 10 to birth resulted in feminisation of the external genitalia and the suppression of growth of the male reproductive tract. In adulthood, testes were found to be located in diverse positions. True cryptorchidism occurred in 10% of cases, whereas 50% of testes descended to the scrotum and 40% were located in a suprainguinal ectopic region. Varying degrees of tubule abnormality were seen in the testes of flutamide-treated animals, ranging from completely normal tubules with full spermatogenesis (and the expected frequency of the stages of spermatogenesis) to severely abnormal tubules lined with Sertoli cells only. For each individual testis, the overall severity of tubule damage was strongly correlated with its adult location, with intra-abdominal testes worst affected and scrotally-located testes least; only the latter contained normal tubules. Similarly, intra-abdominal testes were the smallest in weight and contained the least testosterone. By contrast, postnatal treatment of male rats with flutamide from birth to postnatal d 14 did not impair development of the external genitalia, the process of testicular descent or adult spermatogenesis. These findings confirm that androgen blockade during embryonic development interferes with testicular descent but also demonstrate that (1) prenatal flutamide treatment per se has a detrimental effect on adult testis morphology but (2) the degree of abnormality of the testes is strongly influenced by location. PMID:9183680

A proposal for refining the forced swim test in Swiss mice.

PubMed

Costa, Ana Paula Ramos; Vieira, Cintia; Bohner, Lauren O L; Silva, Cristiane Felisbino; Santos, Evelyn Cristina da Silva; De Lima, Thereza Christina Monteiro; Lino-de-Oliveira, Cilene

2013-08-01

The forced swim test (FST) is a preclinical test to the screening of antidepressants based on rats or mice behaviours, which is also sensitive to stimulants of motor activity. This work standardised and validated a method to register the active and passive behaviours of Swiss mice during the FST in order to strength the specificity of the test. Adult male Swiss mice were subjected to the FST for 6 min without any treatment or after intraperitoneal injection of saline (0.1 ml/10 g), antidepressants (imipramine, desipramine, or fluoxetine, 30 mg/kg) or stimulants (caffeine, 30 mg/kg or apomorphine, 10mg/kg). The latency, frequency and duration of behaviours (immobility, swimming, and climbing) were scored and summarised in bins of 6, 4, 2 or 1 min. Parameters were first analysed using Principal Components Analysis generating components putatively related to antidepressant (first and second) or to stimulant effects (third). Antidepressants and stimulants affected similarly the parameters grouped into all components. Effects of stimulants on climbing were better distinguished of antidepressants when analysed during the last 4 min of the FST. Surprisingly, the effects of antidepressants on immobility were better distinguished from saline when parameters were scored in the first 2 min. The method proposed here is able to distinguish antidepressants from stimulants of motor activity using Swiss mice in the FST. This refinement should reduce the number of mice used in preclinical evaluation of antidepressants. Copyright © 2013 Elsevier Inc. All rights reserved.

Preparation of five 3-MCPD fatty acid esters and the effects of their chemical structures on acute oral toxicity in Swiss mice

USDA-ARS?s Scientific Manuscript database

Fatty acid esters of 3-monochloro-1, 2-propanediol (3-MCPDEs), including 1-stearic, 1-oleic, 1-linoleic, 1-linoleic-2-palmitic and 1-palmitic-2-linoleic acid esters, were synthetized and examined for their acute oral toxicities in Swiss mice. 3-MCPDEs were obtained through the reaction of 3-MCPD and...

Structural characterization of a novel derivative of myricetin from Mimosa pudica as an anti-proliferative agent for the treatment of cancer.

PubMed

Jose, Joby; Dhanya, A T; Haridas, Karickal R; Sumesh Kumar, T M; Jayaraman, Sony; Variyar, E Jayadevi; Sudhakaran, Sudheesh

2016-12-01

The study was initiated to determine the anticancer activity of a novel compound isolated from the plant Mimosa pudica. The structure of the compound was identified as a derivative of myricetin having alkyl, hydroxy alkyl and methyl substitutions on the basis of spectral evidences (UV-vis, FT-IR, 1 H NMR and Mass spectra). The isolated compound was interpreted as 2-(2',6'-dimethyl-3',4',5'-alkyl or hydroxy alkyl substituted phenyl)-3-oxy-(alkyl or hydoxy alkyl)- 5,7-dihydroxy-chromen-4-one. In vitro evaluation of anticancer activity against human lung adenocarcinoma cell line (A549) and human erythroleukemic cell line (K562) were conducted using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. In vivo anticancer activity was determined against Dalton's Ascites Lymphoma (DAL) in Swiss albino mice. The mice were treated with intraperitoneal administration of the compound at 25mg/kg and 100mg/kg body weight and were compared with the normal, DAL control and standard drug cyclophosphamide treated groups. The histology revealed that the compound could protect the cellular architecture of liver and kidney. The results from the in vitro, in vivo and histological examinations confirmed the ethnopharmacological significance of the isolated compound and could be considered further for the development of an effective drug against cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Rapid and direct detection of Invivo kinetics of pathogenic bacterial infection from mouse blood and urine.

PubMed

Gopal, Judy; Lee, Chia-Hsun; Wu, Hui-Fen

2012-06-06

This study demonstrates the first use of matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) to trace the Invivo infection kinetics of the well known deadly pathogen Staphylococcus aureus in Swiss albino mice. The growth curve of the bacteria from the point of injection (200μL of bacterial suspension (10(8)cfu/mL)) into the mouse blood till mortality (death) was periodically analyzed using the plate counting method and MALDI-MS. Bacterial counts of 10(3)cfu/mL were observed in the log phase of the growth curve in the blood and 10(2)cfu/mL were observed in the urine samples. Death occurred in the log phase of the growth curve, where the bacterial counts showed steady increase. In other cases, the bacteria counts started decreasing after 48h and by 96h the bacteria got totally eliminated from the mouse and these mice survived. Direct MALDI-MS was not feasible for tracking the bacteria in the infected blood. However, ionic liquid 1-Butyl-3-methylimidazolium tetrafluoroborate was successful in enabling bacterial detection amidst the strong blood peaks. But, in the case of the urine analysis, it was observed that direct MALDI-MS was adequate to enable detection. The results obtained prove the efficacy of MALDI-MS for analyzing pathogenic bacteria in clinical samples. This article is part of a Special Issue entitled: Proteomics: The clinical link. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesis and biological evaluation of some novel 1-substituted fentanyl analogs in Swiss albino mice

PubMed Central

Yadav, Shiv Kumar; Maurya, Chandra Kant; Gupta, Pradeep Kumar; Jain, Ajai Kumar; Ganesan, Kumaran

2014-01-01

Fentanyl [N-(1-phenethyl-4-piperidinyl)propionanilide] is a potent opioid analgesic agent, but a has narrow therapeutic index. We reported earlier on the synthesis and bioefficacy of fentanyl and its 1-substituted analogs (1–4) in mice. Here we report the synthesis and biological evaluation of four additional analogs, viz. N-isopropyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (5), N-t-butyl-3-(4-(N-phenylpropionamido)piperidin-1-yl)propanamide (6), isopropyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (7) and t-butyl 2-[4-(N-phenylpropionamido)piperidin-1-yl]propionate (8). The median lethal dose (LD50) determined by intravenous, intraperitoneal and oral routes suggests these analogs to be comparatively less toxic than fentanyl. On the basis of observational assessment on spontaneous activities of the central, peripheral, and autonomic nervous systems, all the analogs were found to be similar to fentanyl. Naloxone hydrochloride abolished the neurotoxic effects of these analogs, thereby ascertaining their opioid receptor-mediated effects. All the analogs displayed significant analgesic effects, measured by formalin-induced hind paw licking and tail immersion tests at their respective median effective dose (ED50). They also exhibited 8–12 fold increase in therapeutic index over fentanyl. However, 5 and 6 alone produced lower ED50 (20.5 and 21.0 µg/kg, respectively) and higher potency ratio (1.37 and 1.33, respectively) compared to fentanyl. They could thus be considered for further studies on pain management. PMID:26109885

Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms.

PubMed

Gaballah, Hanaa H; Gaber, Rasha A; Mohamed, Darin A

2017-02-01

Although 5- Fluorouracil (5-FU) has exhibited effectiveness against cancer, novel therapeutic strategies are needed to enhance its antitumor efficiency and modulate its cytotoxity. Apigenin, a flavonoid present in fruits and vegetables, is a potent dietary phytochemical effective in cancer chemoprevention. This study was undertaken to investigate the potential synergistic antitumor activity of apigenin and 5-FU on Solid Ehrlich carcinoma (SEC). Eighty Swiss albino male mice were divided into four equal groups: vehicle treated control SEC, SEC+5-FU, SEC+apigenin, SEC+ 5-FU+apigenin. Beclin-1 and caspases 3, 9 and JNK activities were estimated by ELISA; mRNA expression levels of the antiapoptotic gene Mcl-1 were estimated using quantitative real-time RT-PCR, while tissue malondialdehyde (MDA), glutathione peroxidase and total antioxidant capacity were evaluated spectrophotometrically. A part of the tumor was examined for histopathological and Ki-67 immunohistochemistry analysis. 5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities, MDA with significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity and alleviated the histopathological changes with significant decrease of Ki-67 proliferation index compared to vehicle treated SEC control group. The combination of 5-FU and apigenin had a greater effect than each of 5-FU or apigenin alone against solid Ehrlich carcinoma in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

The N-terminal-truncated recombinant fibrin(ogen)olytic serine protease improves its functional property, demonstrates in vivo anticoagulant and plasma defibrinogenation activity as well as pre-clinical safety in rodent model.

PubMed

Bora, Bandana; Gogoi, Debananda; Tripathy, Debabrata; Kurkalang, Sillarine; Ramani, Sheetal; Chatterjee, Anupam; Mukherjee, Ashis K

2018-05-01

An N-terminal truncated fibrino(geno)lytic serine protease gene encoding a ~42kDa protein from Bacillus cereus strain AB01 was produced by error prone PCR, cloned into pET19b vector, and expressed in E5 coli BL21 DE3 cells. The deletion of 24 amino acid residues from N-terminal of wild-type Bacifrinase improves the catalytic activity of [Bacifrinase (ΔN24)]. The anticoagulant potency of [Bacifrinase (ΔN24)] was comparable to Nattokinase and Warfarin and results showed that its anticoagulant action is contributed by progressive defibrinogenation and antiplatelet activities. Nonetheless, at the tested concentration of 2.0μM [Bacifrinase (ΔN24)] did not show in vitro cytotoxicity or chromosomal aberrations on human embryonic kidney cells-293 (HEK-293) and human peripheral blood lymphocytes (HPBL) cells. [Bacifrinase (ΔN24)], at a dose of 2mg/kg, did not show toxicity, adverse pharmacological effects, tissue necrosis or hemorrhagic effect after 72h of its administration in Swiss albino mice. However, at the tested doses of 0.125 to 0.5mg/kg, it demonstrated significant in anticoagulant effect as well as defibrinogenation after 6h of administration in mice. We propose that [Bacifrinase (ΔN24)] may serve as prototype for the development of potent drug to prevent hyperfibrinogenemia related disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of parsley (Petroselinum crispum, Apiaceae) juice against cadmium neurotoxicity in albino mice (Mus musculus).

PubMed

Maodaa, Saleh N; Allam, Ahmed A; Ajarem, Jamaan; Abdel-Maksoud, Mostafa A; Al-Basher, Gadah I; Wang, Zun Yao

2016-02-04

Parsley was employed as an experimental probe to prevent the behavioral, biochemical and morphological changes in the brain tissue of the albino mice following chronic cadmium (Cd) administration. Non-anesthetized adult male mice were given parsley juice (Petroselinum crispum, Apiaceae) daily by gastric intubation at doses of 10 and 20 g/kg/day. The animals were divided into six groups: Group A, mice were exposed to saline; Groups B and C, were given low and high doses of parsley juice, respectively; Group D, mice were exposed to Cd; Groups E and F, were exposed to Cd and concomitantly given low and high doses of parsley, respectively. Cd intoxication can cause behavioral abnormalities, biochemical and histopathological disturbances in treated mice. Parsley juice has significantly improved the Cd-associated behavioral changes, reduced the elevation of lipid peroxidation and normalized the Cd effect on reduced glutathione and peroxidase activities in the brain of treated mice. Histological data have supported these foundations whereas Cd treatment has induced neuronal degeneration, chromatolysis and pyknosis in the cerebrum, cerebellum and medulla oblongata. The low dose (5 g/kg/day) of parsley exhibited beneficial effects in reducing the deleterious changes associated with Cd treatment on the behavior, neurotransmitters level, oxidative stress and brain neurons of the Cd-treated mice.

Light-induced migration of retinal microglia into the subretinal space.

PubMed

Ng, T F; Streilein, J W

2001-12-01

To explore the effects of light exposure and deprivation on the distribution and function of microglia in the subretinal space of mice. Using a monoclonal antibody, 5D4, that identifies resting, ramified microglia, the distribution and density of microglia in the retina, and the subretinal space were determined by confocal microscopy and by immunohistochemistry of cryopreserved sections of eyes of albino and pigmented mice exposed to diverse levels of light, ranging from complete darkness to intense brightness. Axotomized retinal ganglion cells were retrograde labeled by fluorescent tracer to determine whether the marker colocalizes to 5D4+ cells. Electron microscopy was used to evaluate microglia for evidence of phagocytosis. 5D4+ microglia in pigmented eyes were limited to the inner retinal layers, but in albino eyes 5D4+ cells were found in the outer retinal layers and subretinal space as well. The subretinal space of eyes of albino mice raised from birth in complete darkness contained few 5D4+ cells, but exposure to light caused the rapid accumulation of 5D4+ cells at this site. 5D4+ cell density in the subretinal space correlated directly with intensity of ambient light. Retrograde labeling of axotomized ganglion cells resulted in 5D4+ cells in the subretinal space that contained the retrograde label. Subretinal microglia contained phagocytized rod outer segment discs. On intense light exposure, 5D4+ cells adopted an active morphology, but failed to express class II major histocompatibility complex (MHC) molecules. Light exposure induced retinal microglia migration into the subretinal space in albino mice. Subretinal microglia appeared to augment through phagocytosis the capacity of pigment epithelium to take up the photoreceptor debris of light toxicity. The unexpected presence of these cells in the subretinal space raises questions concerning their potential contribution to immune privilege in this space and to the fate of retinal transplants.

Comparison of pro-amnesic efficacy of scopolamine, biperiden, and phencyclidine by using passive avoidance task in CD-1 mice.

PubMed

Malikowska, Natalia; Sałat, Kinga; Podkowa, Adrian

2017-07-01

Memory disorders accompany numerous diseases and therapies, and this is becoming a growing medical issue worldwide. Currently, various animal models of memory impairments are available; however, many of them require high financial outlay and/or are time-consuming. A simple way to achieve an efficient behavioral model of cognitive disorders is to inject defined drug that has pro-amnesic properties. Since the involvement of cholinergic and glutamatergic neurotransmission in cognition is well established, the utilization of a nonselective muscarinic receptor antagonist, scopolamine (SCOP), a selective M1 muscarinic receptor antagonist, biperiden (BIP), and a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine (PCP) seems to be reliable tools to induce amnesia. As the determination of their effective doses remains vague and the active doses vary significantly in laboratory settings and in mouse species being tested, the aim of this study was to compare these three models of amnesia in CD-1 mice. Male Swiss Albino mice were used in passive avoidance (PA) test. All the compounds were administered intraperitoneally (ip) at doses 1mg/kg, 5mg/kg, and 10mg/kg (SCOP and BIP), and 1mg/kg, 3mg/kg, and 6mg/kg (PCP). In the retention trial of the PA task, SCOP and PCP led to the reduction of step-through latency at all the tested doses as compared to control, but BIP was effective only at the dose of 10mg/kg. This study revealed the effectiveness of SCOP, PCP, and BIP as tools to induce amnesia, with the PCP model being the most efficacious and SCOP being the only model that demonstrates a clear dose-response relationship. Copyright © 2017. Published by Elsevier Inc.

Dietary flavonoid fisetin regulates aluminium chloride-induced neuronal apoptosis in cortex and hippocampus of mice brain.

PubMed

Prakash, Dharmalingam; Sudhandiran, Ganapasam

2015-12-01

Dietary flavonoids have been suggested to promote brain health by protecting brain parenchymal cells. Recently, understanding the possible mechanism underlying neuroprotective efficacy of flavonoids is of great interest. Given that fisetin exerts neuroprotection, we have examined the mechanisms underlying fisetin in regulating Aβ aggregation and neuronal apoptosis induced by aluminium chloride (AlCl3) administration in vivo. Male Swiss albino mice were induced orally with AlCl3 (200 mg/kg. b.wt./day/8 weeks). Fisetin (15 mg/Kg. b.wt. orally) was administered for 4 weeks before AlCl3-induction and administered simultaneously for 8 weeks during AlCl3-induction. We found aggregation of Amyloid beta (Aβ 40-42), elevated expressions of Apoptosis stimulating kinase (ASK-1), p-JNK (c-Jun N-terminal Kinase), p53, cytochrome c, caspases-9 and 3, with altered Bax/Bcl-2 ratio in favour of apoptosis in cortex and hippocampus of AlCl3-administered mice. Furthermore, TUNEL and fluoro-jade C staining demonstrate neurodegeneration in cortex and hippocampus. Notably, treatment with fisetin significantly (P<0.05) reduced Aβ aggregation, ASK-1, p-JNK, p53, cytochrome c, caspase-9 and 3 protein expressions and modulated Bax/Bcl-2 ratio. TUNEL-positive and fluoro-jade C stained cells were also significantly reduced upon fisetin treatment. We have identified the involvement of fisetin in regulating ASK-1 and p-JNK as possible mediator of Aβ aggregation and subsequent neuronal apoptosis during AlCl3-induced neurodegeneration. These findings define the possibility that fisetin may slow or prevent neurodegneration and can be utilised as neuroprotective agent against Alzheimer's and Parkinson's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of arachidonyl-2'-chloroethylamide (ACEA) on the protective action of various antiepileptic drugs in the 6-Hz corneal stimulation model in mice.

PubMed

Luszczki, Jarogniew J; Patrzylas, Pawel; Zagaja, Miroslaw; Andres-Mach, Marta; Zaluska, Katarzyna; Kondrat-Wrobel, Maria W; Szpringer, Monika; Chmielewski, Jaroslaw; Florek-Luszczki, Magdalena

2017-01-01

Accumulating evidence indicates that cannabinoid CB1 receptor ligands play a pivotal role in seizures, not only in preclinical studies on animals, but also in clinical settings. This study was aimed at characterizing the influence of arachidonyl-2'-chloroethylamide (ACEA-a selective cannabinoid CB1 receptor agonist) co-administered with phenylmethylsulfonyl fluoride (PMSF) on the anticonvulsant potency of various antiepileptic drugs (clobazam, lacosamide, levetiracetam, phenobarbital, tiagabine and valproate) in the 6-Hz corneal stimulation model. Psychomotor seizures in male albino Swiss mice were evoked by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via corneal electrodes. Potential adverse effects produced by the antiepileptic drugs in combination with ACEA+PMSF were assessed using the chimney test (motor performance), passive avoidance task (remembering and acquisition of learning), and grip-strength test (muscular strength). Brain concentrations of antiepileptic drugs were measured by HPLC to exclude any pharmacokinetic contribution to the observed effect. ACEA (5 mg/kg, i.p.) + PMSF (30 mg/kg, i.p.) significantly potentiated the anticonvulsant potency of levetiracetam (P<0.05), but not that of clobazam, lacosamide, phenobarbital, tiagabine or valproate in the 6-Hz corneal stimulation model. Moreover, ACEA+PMSF did not significantly affect total brain concentrations of levetiracetam in mice. No behavioral side effects were observed in animals receiving combinations of the studied antiepileptic drugs with ACEA+PMSF. In conclusion, the combined administration of ACEA+PMSF with levetiracetam is associated with beneficial anticonvulsant pharmacodynamic interaction in the 6-Hz corneal stimulation model. The selective activation of cannabinoid CB1 receptor-mediated neurotransmission in the brain may enhance levetiracetam-related suppression of seizures in epilepsy patients, contributing to the efficacious treatment of epilepsy in future.

Possible role of pannexin 1/P2x7 purinoceptor in neuroprotective mechanism of ischemic postconditioning in mice.

PubMed

Mahi, Namarta; Kumar, Amit; Jaggi, Amteshwar S; Singh, Nirmal; Dhawan, Ravi

2015-06-01

Previous studies have suggested a significant role of pannexin 1 (Panx1)/P2X7 receptor complex in cardioprotective mechanism of ischemic preconditioning and postconditioning (IPC). The present study has been undertaken to investigate whether Panx1/P2X7 purinoceptors are also involved in the neuroprotective mechanism of IPC in mice. Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was used to produce ischemia-reperfusion-induced cerebral injury in Swiss albino mice. For IPC immediately after BCAO of 12 min, three cycles of 10-s ischemia and reperfusion each were given and then prolonged reperfusion of 24 h was used. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using a Morris water maze test. Rotarod test, inclined beam walking test, and neurologic severity score (NSS) were used to assess motor dysfunction. Acetylcholine esterase levels, brain thiobarbituric acid reactive species, and glutathione level were also estimated. BCAO followed by reperfusion produced a significant increase in cerebral infarct size, NSS along with impairment of memory and motor dysfunction. It also increased brain acetylcholine esterase, thiobarbituric acid reactive species levels, and decreased the glutathione level. IPC produced a significant decrease in the cerebral infarct size and NSS along with reversal of ischemia-reperfusion-induced impairment of memory, motor dysfunction, and altered biochemical levels in the brain. IPC-induced neuroprotective effects were significantly abolished by pretreatment of mefloquine (15.0 mg/kg orally; 30.0 mg/kg orally), blocker of Panx1/P2X7 purinoceptor. Therefore, activation of Panx1/P2X7 purinoceptors appears to play a significant role in the neuroprotective mechanism of IPC. Copyright © 2015 Elsevier Inc. All rights reserved.

Diphenylmethyl selenocyanate attenuates malachite green induced oxidative injury through antioxidation & inhibition of DNA damage in mice

PubMed Central

Das, Jayanta Kumar; Sarkar, Sibani; Hossain, Sk Ugir; Chakraborty, Pramita; Das, Rajat Kumar; Bhattacharya, Sudin

2013-01-01

Background & objectives: Malachite green (MG), an environmentally hazardous material, is used as a non permitted food colouring agent, especially in India. Selenium (Se) is an essential nutritional trace element required for animals and humans to guard against oxidative stress induced by xenobiotic compounds of diverse nature. In the present study, the role of the selenium compound diphenylmethyl selenocyanate (DMSE) was assessed on the oxidative stress (OS) induced by a food colouring agent, malachite green (MG) in vivo in mice. Methods: Swiss albino mice (Mus musculus) were intraperitoneally injected with MG at a standardized dose of 100 μg/ mouse for 30 days. DMSE was given orally at an optimum dose of 3 mg/kg b.w. in pre (15 days) and concomitant treatment schedule throughout the experimental period. The parameters viz. ALT, AST, LPO, GSH, GST, SOD, CAT, GPx, TrxR, CA, MN, MI and DNA damage have been evaluated. Results: The DMSE showed its potential to protect against MG induced hepatotoxicity by controlling the serum alanine aminotransferase and aspartate amino transferase (ALT and AST) levels and also ameliorated oxidative stress by modulating hepatic lipid peroxidation and different detoxifying and antioxidative enzymes such as glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and also the selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) and reduced glutathione level which in turn reduced DNA damage. Interpretation & conclusions: The organo-selenium compound DMSE showed significant protection against MG induced heptotoxicity and DNA damage in murine model. Better protection was observed in pretreatment group than in the concomitant group. Further studies need to be done to understand the mechanism of action. PMID:23852297

Effects of arachidonyl-2’-chloroethylamide (ACEA) on the protective action of various antiepileptic drugs in the 6-Hz corneal stimulation model in mice

PubMed Central

Patrzylas, Pawel; Zagaja, Miroslaw; Andres-Mach, Marta; Zaluska, Katarzyna; Kondrat-Wrobel, Maria W.; Szpringer, Monika; Chmielewski, Jaroslaw; Florek-Luszczki, Magdalena

2017-01-01

Accumulating evidence indicates that cannabinoid CB1 receptor ligands play a pivotal role in seizures, not only in preclinical studies on animals, but also in clinical settings. This study was aimed at characterizing the influence of arachidonyl-2′-chloroethylamide (ACEA–a selective cannabinoid CB1 receptor agonist) co-administered with phenylmethylsulfonyl fluoride (PMSF) on the anticonvulsant potency of various antiepileptic drugs (clobazam, lacosamide, levetiracetam, phenobarbital, tiagabine and valproate) in the 6-Hz corneal stimulation model. Psychomotor seizures in male albino Swiss mice were evoked by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via corneal electrodes. Potential adverse effects produced by the antiepileptic drugs in combination with ACEA+PMSF were assessed using the chimney test (motor performance), passive avoidance task (remembering and acquisition of learning), and grip-strength test (muscular strength). Brain concentrations of antiepileptic drugs were measured by HPLC to exclude any pharmacokinetic contribution to the observed effect. ACEA (5 mg/kg, i.p.) + PMSF (30 mg/kg, i.p.) significantly potentiated the anticonvulsant potency of levetiracetam (P<0.05), but not that of clobazam, lacosamide, phenobarbital, tiagabine or valproate in the 6-Hz corneal stimulation model. Moreover, ACEA+PMSF did not significantly affect total brain concentrations of levetiracetam in mice. No behavioral side effects were observed in animals receiving combinations of the studied antiepileptic drugs with ACEA+PMSF. In conclusion, the combined administration of ACEA+PMSF with levetiracetam is associated with beneficial anticonvulsant pharmacodynamic interaction in the 6-Hz corneal stimulation model. The selective activation of cannabinoid CB1 receptor-mediated neurotransmission in the brain may enhance levetiracetam-related suppression of seizures in epilepsy patients, contributing to the efficacious treatment of epilepsy in future. PMID:28859122

Protective and Anti-Pathology Effects of Sm Fructose-1,6-Bisphosphate Aldolase-Based DNA Vaccine against Schistosoma mansoni by Changing Route of Injection

PubMed Central

Saber, Mohamed; Hammam, Olft; Karim, Amr; Medhat, Amina; Khela, Mamdouh; El-Dabaa, Ehab

2013-01-01

This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously (SC), or intraperitoneally (IP) (50 µg/mouse). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and anti-pathology vaccine candidate against S. mansoni infection. PMID:23710082

Involvement of NMDA receptor in low-frequency magnetic field-induced anxiety in mice.

PubMed

Salunke, Balwant P; Umathe, Sudhir N; Chavan, Jagatpalsingh G

2014-12-01

It had been reported that exposure to extremely low-frequency magnetic field (ELFMF) induces anxiety in human and rodents. Anxiety mediates via the activation of N-methyl-d-aspartate (NMDA) receptor, whereas activation of γ-aminobutyric acid (GABA) receptor attenuates the same. Hence, the present study was carried out to understand the contribution of NMDA and/or GABA receptors modulation in ELFMF-induced anxiety for which Swiss albino mice were exposed to ELFMF (50 Hz, 10 G) by subjecting them to Helmholtz coils. The exposure was for 8 h/day for 7, 30, 60, 90 and 120 days. Anxiety level was assessed in elevated plus maze, open field test and social interaction test, on 7th, 30th, 60th, 90th and 120th exposure day, respectively. Moreover, the role of GABA and glutamate in ELFMF-induced anxiety was assessed by treating mice with muscimol [0.25 mg/kg intraperitoneally (i.p.)], bicuculline (1.0 mg/kg i.p.), NMDA (15 mg/kg i.p.) and MK-801 (0.03 mg/kg i.p.), as a GABAA and NMDA receptor agonist and antagonist, respectively. Glutamate receptor agonist exacerbated while inhibitor attenuated the ELFMF-induced anxiety. In addition, levels of GABA and glutamate were determined in regions of the brain viz, cortex, striatum, hippocampus and hypothalamus. Experiments demonstrated significant elevation of GABA and glutamate levels in the hippocampus and hypothalamus. However, GABA receptor modulators did not produce significant effect on ELFMF-induced anxiety and elevated levels of GABA at tested dose. Together, these findings suggest that ELFMF significantly induced anxiety behavior, and indicated the involvement of NMDA receptor in its effect.

Protective and anti-pathology effects of Sm fructose-1,6-bisphosphate aldolase-based DNA vaccine against schistosoma mansoni by changing route of injection.

PubMed

Saber, Mohamed; Diab, Tarek; Hammam, Olft; Karim, Amr; Medhat, Amina; Khela, Mamdouh; El-Dabaa, Ehab

2013-04-01

This study aimed to evaluate the efficacy of fructose-1,6-bis phosphate aldolase (SMALDO) DNA vaccination against Schistosoma mansoni infection using different routes of injection. The SMALDO has been cloned into the eukaryotic expression vector pcDNA3.1/V5-His TOPO-TA and was used in injecting Swiss albino mice intramuscularly (IM), subcutaneously (SC), or intraperitoneally (IP) (50 µg/mouse). Mice vaccinated with non-recombinant pcDNA3.1 served as controls. Each group was immunized 4 times at weeks 0, 2, 4, and 6. Two weeks after the last booster dose, all mice groups were infected with 80 S. mansoni cercariae via tail immersion. At week 8 post-infection, animals were sacrificed for assessment of parasitological and histopathological parameters. High anti-SMALDO IgG antibody titers were detected in sera of all vaccinated groups (P<0.01) compared to the control group. Both the IP and SC vaccination routes resulted in a significant reduction in worm burden (46.2% and 28.9%, respectively, P<0.01). This was accompanied by a significant reduction in hepatic and intestinal egg counts (41.7% and 40.2%, respectively, P<0.01) in the IP group only. The number of dead eggs was significantly increased in both IP and IM groups (P<0.01). IP vaccination recorded the highest significant reduction in granuloma number and diameter (54.7% and 29.2%, respectively, P<0.01) and significant increase in dead miracidia (P<0.01). In conclusion, changing the injection route of SMALDO DNA vaccination significantly influenced the efficacy of vaccination. SMALDO DNA vaccination via IP route could be a promising protective and anti-pathology vaccine candidate against S. mansoni infection.

Disruption of thyroid hormone functions by low dose exposure of tributyltin: an in vitro and in vivo approach.

PubMed

Sharan, Shruti; Nikhil, Kumar; Roy, Partha

2014-09-15

Triorganotins, such as tributyltin chloride (TBTCl), are environmental contaminants that are commonly found in the antifouling paints used in ships and other vessels. The importance of TBTCl as an endocrine-disrupting chemical (EDC) in different animal models is well known; however, its adverse effects on the thyroid gland are less understood. Hence, in the present study, we aimed to evaluate the thyroid-disrupting effects of this chemical using both in vitro and in vivo approaches. We used HepG2 hepatocarcinoma cells for the in vitro studies, as they are a thyroid hormone receptor (TR)-positive and thyroid responsive cell line. For the in vivo studies, Swiss albino male mice were exposed to three doses of TBTCl (0.5, 5 and 50μg/kg/day) for 45days. TBTCl showed a hypo-thyroidal effect in vivo. Low-dose treatment of TBTCl exposure markedly decreased the serum thyroid hormone levels via the down-regulation of the thyroid peroxidase (TPO) and thyroglobulin (Tg) genes by 40% and 25%, respectively, while augmenting the thyroid stimulating hormone (TSH) levels. Thyroid-stimulating hormone receptor (TSHR) expression was up-regulated in the thyroid glands of treated mice by 6.6-fold relative to vehicle-treated mice (p<0.05). In the transient transactivation assays, TBTCl suppressed T3 mediated transcriptional activity in a dose-dependent manner. In addition, TBTCl was found to decrease the expression of TR. The present study thus indicates that low concentrations of TBTCl suppress TR transcription by disrupting the physiological concentrations of T3/T4, followed by the recruitment of NCoR to TR, providing a novel insight into the thyroid hormone-disrupting effects of this chemical. Copyright © 2014 Elsevier Inc. All rights reserved.

Mouse strain-dependent differences in estrogen sensitivity during vaginal candidiasis.

PubMed

Mosci, Paolo; Pietrella, Donatella; Ricci, Giovanni; Pandey, Neelam; Monari, Claudia; Pericolini, Eva; Gabrielli, Elena; Perito, Stefano; Bistoni, Francesco; Vecchiarelli, Anna

2013-02-01

The animal models available for studying the immune response to genital tract infection require induction of a pseudo estrous state, usually achieved by administration of 17-β-estradiol. In our experimental model of vaginal candidiasis, under pseudo estrus, different strains of mice were used. We observed major differences in the clearance of Candida albicans infection among the different strains, ascribable to differing susceptibility to estradiol treatment. In the early phase of infection CD1, BALB/c, C57BL/6 albino and C57BL/6 mice were colonized to similar levels, while in the late phase of infection, BALB/c mice, which are considered genetically resistant to C. albicans infection, exhibited greater susceptibility to vaginal candidiasis than CD1 and C57BL/6 albino strains of mice. This was because estradiol induced "per se" enlarged and fluid-filled uteri, more pronounced in infected mice and consistently more evident in BALB/c and C57BL/6 mice than in CD1 mice. Unlike CD1, BALB/c and C57BL/6 mice showed a heavy fungal colonization of the uterus, even though C57BL/6 mice apparently cleared C. albicans from the vagina. The presence of C. albicans in the vagina and uterus was accompanied by a heavy bacterial load. Collectively these observations prompted us to carry out a careful analysis of estradiol effects in a mouse model of vaginal infection.

Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice.

PubMed

Anderson, Nicholas J; King, Matthew R; Delbruck, Lina; Jolivalt, Corinne G

2014-06-01

One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype. © 2014. Published by The Company of Biologists Ltd.

Comparative distribution of misonidazole and its amine metabolite in female Swiss Webster mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Born, J.L.; Hadley, W.M.

1985-06-01

The distribution of misonidazole and its terminal reduction product 1-(2-amino-1-imidazolyl)-3-methoxy-2-propanol (misoamine) were compared in female Swiss Webster mice to determine if either misonidazole or misoamine is distributed to peripheral nerves. Female Swiss Webster mice received a 100 mg/kg (5 ..mu..Ci/..mu..mole) i.p. dose of either /sup 3/H-misonidazole or /sup 3/H-miso-amine and the distribution of radioactivity was determined in various tissues including sciatic nerves and other myelinated nerves. Misonidazole produced higher initial tissue concentrations of radioactivity than did miso-amine. The relative tissue concentrations of radioactivity produced by misonidazole or miso-amine were similar, although not identical, 48 hours after administration of the drugs.more » Both sciatic and other myelinated nerves were found to retain radioactivity following the administration of either misonidazole or miso-amine.« less

Antidiabetic activity and phytochemical screening of extracts of the leaves of Ajuga remota Benth on alloxan-induced diabetic mice.

PubMed

Tafesse, Tadesse Bekele; Hymete, Ariaya; Mekonnen, Yalemtsehay; Tadesse, Mekuria

2017-05-02

Ajuga remota Benth is traditionally used in Ethiopia for the management of diabetes mellitus. Since this claim has not been investigated scientifically, the aim of this study was to evaluate the antidiabetic effect and phytochemical screening of the aqueous and 70% ethanol extracts on alloxan-induced diabetic mice. After acute toxicity test, the Swiss albino mice were induced with alloxan to get experimental diabetes animals. The fasting mean blood glucose level before and after treatment for two weeks in normal, diabetic untreated and diabetic mice treated with aqueous and 70% ethanol extracts were performed. Data were statistically evaluated by using Statistical Package for the Social Sciences software version 20. P-value <0.05 was considered statistically significant. The medium lethal doses (LD 50 ) of both extracts were higher than 5000 mg/kg, indicating the extracts are not toxic under the observable condition. Aqueous extracts of A.remota (300 mg/kg and 500 mg/kg body weight) reduced elevated blood glucose levels by 27.83 ± 2.96% and 38.98 ± 0.67% (P < 0.0001), respectively while the 70% ethanol extract caused a reduction of 27.94 ± 1.92% (300 mg/kg) & 28.26 ± 1.82% (500 mg/kg). Treatment with the antidiabetic drug, Glibenclamide (10 mg/kg body weight) lowered blood glucose level by 51.06% (p < 0.05). Phytochemical screening of both extracts indicated the presence of phenolic compounds, flavonoids, saponins, tannins, and steroids, which might contribute to the antidiabetic activity. The extracts, however, did not contain alkaloids and anthraquinones. The aqueous extract (500 mg/kg) showed the highest percentage reduction in blood glucose levels and the ability of A. remota extracts in reducing blood glucose levels presumably due to the presence of antioxidant constituents such as flavonoids. The effect of the extract supported the traditional claim of the plant.

Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice.

PubMed

Iqbal, Ramsha; Jain, Gaurav K; Siraj, Fouzia; Vohora, Divya

2018-07-01

Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABA A receptor modulating neurosteroid. The present study evaluated whether inhibition of aromatase inhibitor letrozole protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Letrozole (1 mg/kg, i.p.) administered one hour prior to KA significantly increased the onset time of seizures and reduced the% incidence of seizures. Pretreatment with finasteride, a selective inhibitor of 5α-reductase and indomethacin, a selective inhibitor of 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR), reversed the protective effects of letrozole in KA-induced seizures in mice. Microscopic examination using cresyl violet staining revealed that letrozole did not modify KA-induced neurotoxicity in the CA1, CA3 and DG region of the hippocampus. Letrozole treatment resulted in the reduced levels of 17-β estradiol and elevated the levels of 5α-dihydrotestosterone (DHT) and 3α-Diol in the hippocampus. Finasteride and indomethacin attenuated letrozole-induced elevations of 5α-DHT and 3α-Diol. Our results indicate the potential anticonvulsant effects of letrozole against KA-induced seizures in mice that might be mediated by inhibiting aromatization of testosterone to 17β-estradiol, a proconvulsant hormone and by redirecting the synthesis to anticonvulsant metabolites, 5α-DHT and 3α-Diol. Acute aromatase inhibition, thus, might be used as an adjuvant in the treatment of status epilepticus and can be pursued further. Copyright © 2018 Elsevier B.V. All rights reserved.

Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p{sup 53} and p{sup 21/WAF1} proteins in skin of mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saxena, Neha; Ansari, Kausar M.; Kumar, Rahul

2009-01-15

Patulin (PAT), a mycotoxin found in apples, grapes, oranges, pear and peaches, is a potent genotoxic compound. WHO has highlighted the need for the study of cutaneous toxicity of PAT as manual labour is employed during pre and post harvest stages, thereby causing direct exposure to skin. In the present study cutaneous toxicity of PAT was evaluated following topical application to Swiss Albino mice. Dermal exposure of PAT, to mice for 4 h resulted in a dose (40-160 {mu}g/animal) and time (up to 6 h) dependent enhancement of ornithine decarboxylase (ODC), a marker enzyme of cell proliferation. The ODC activitymore » was found to be normal after 12 and 24 h treatment of patulin. Topical application of PAT (160 {mu}g/100 {mu}l acetone) for 24-72 h caused (a) DNA damage in skin cells showing significant increase (34-63%) in olive tail moment, a parameter of Comet assay (b) significant G 1 and S-phase arrest along with induction of apoptosis (2.8-10 folds) as shown by annexin V and PI staining assay through flow cytometer. Moreover PAT leads to over expression of p{sup 21/WAF1} (3.6-3.9 fold), pro apoptotic protein Bax (1.3-2.6) and tumor suppressor wild type p{sup 53} (2.8-3.9 fold) protein. It was also shown that PAT induced apoptosis was mediated through mitochondrial intrinsic pathway as revealed through the release of cytochrome C protein in cytosol leading to enhancement of caspase-3 activity in skin cells of mice. These results suggest that PAT has a potential to induce DNA damage leading to p{sup 53} mediated cell cycle arrest along with intrinsic pathway mediated apoptosis that may also be correlated with enhanced polyamine production as evident by induction of ODC activity, which may have dermal toxicological implications.« less

Strain differences in the susceptibility to the gut-brain axis and neurobehavioural alterations induced by maternal immune activation in mice.

PubMed

Morais, Livia H; Felice, Daniela; Golubeva, Anna V; Moloney, Gerard; Dinan, Timothy G; Cryan, John F

2018-04-01

There is a growing realization that the severity of the core symptoms of autism spectrum disorders and schizophrenia is associated with gastrointestinal dysfunction. Nonetheless, the mechanisms underlying such comorbidities remain unknown. Several genetic and environmental factors have been linked to a higher susceptibility to neurodevelopmental abnormalities. The maternal immune activation (MIA) rodent model is a valuable tool for elucidating the basis of this interaction. We induced MIA with polyinosinic-polycytidylic acid (poly I:C) at gestational day 12.5 and assessed behavioural, physiological and molecular aspects relevant to the gut-brain axis in the offspring of an outbred (NIH Swiss) and an inbred (C57BL6/J) mouse strain. Our results showed that the specific MIA protocol employed induces social deficits in both strains. However, alterations in anxiety and depression-like behaviours were more pronounced in NIH Swiss mice. These strain-specific behavioural effects in the NIH Swiss mice were associated with marked changes in important components of gut-brain axis communication: the endocrine response to stress and gut permeability. In addition, MIA-induced changes in vasopressin receptor 1a mRNA expression in the hypothalamus were observed in NIH Swiss mice only. Taken together, these data suggest that genetic background is a critical factor in susceptibility to the gut-brain axis effects induced by MIA.

Evaluation of Traditional and Contemporary Methods for Detecting Syphacia obvelata and Aspiculuris tetraptera in Laboratory Mice

PubMed Central

Gerwin, Philip M; Arbona, Rodolfo J Ricart; Riedel, Elyn R; Lepherd, Michelle L; Henderson, Ken S; Lipman, Neil S

2017-01-01

There is no consensus regarding the best practice for detecting murine pinworm infections. Initially, we evaluated 7 fecal concentration methods by using feces containing Aspiculuris tetraptera (AT) eggs (n = 20 samples per method). Sodium nitrate flotation, sodium nitrate centrifugation, Sheather sugar centrifugation, and zinc sulfate centrifugation detected eggs in 100% of samples; zinc sulfate flotation and water sedimentation detected eggs in 90%. All had better detection rates than Sheather sugar flotation (50%). To determine optimal detection methods, Swiss Webster mice were exposed to Syphacia obvelata (SO; n = 60) or AT (n = 60). We compared the following methods at days 0, 30, and 90, beginning 21 or 28 d after SO and AT exposure, respectively: fecal concentration (AT only), anal tape test (SO only), direct examination of intestinal contents (cecum and colon), Swiss roll histology (cecum and colon), and PCR analysis (pooled fur swab and feces). Detection rates for SO-exposed mice were: PCR analysis, 45%; Swiss roll histology, 30%; intestinal content exam, 27%; and tape test, 27%. The SO detection rate for PCR analysis was significantly greater than that for the tape test. Detection rates for AT-exposed mice were: intestinal content exam, 53%; PCR analysis, 33%; fecal flotation, 22%; and Swiss roll histology, 17%. The AT detection rate of PCR analysis combined with intestinal content examination was greater than for PCR analysis only and the AT detection rate of intestinal content examination was greater than for Swiss roll histology. Combining PCR analysis with intestinal content examination detected 100% of infected animals. No single test detected all positive animals. We recommend combining PCR analysis with intestinal content examination for optimal pinworm detection. PMID:28905712

The course of experimental staphylococcus infection in albino mice during action of certain factors of space flight

NASA Technical Reports Server (NTRS)

Prokhorov, V. Y.; Shilov, V. M.; Borman, E. A.

1980-01-01

A study was made of the effect of certain factors of space flight, acceleration and hypokinesia, on the course of experimental staphylococcus infection in mice. Combined action of hypokinesia and acceleration caused a marked depression of the phagocytic activity of leukocytes and formation of a considerable amount of alpha toxin.

The effect of intrauterine position on the survival, reproduction and home range size of female house mice (Mus musculus)

Treesearch

W. J. Zielinski; F. S. vom Saal; J. G. Vandenbergh

1992-01-01

In laboratory studies using albino house mice, a female's prior intrauterine position can affect many postnatal physiological, morphological and behavioral characteristics. Females flanked by males in utero (2M females) exhibit more aggressive dominance than females flanked by females (OM females). Thus, wild 2M...

In vivo and in vitro characterization of the biochemical and pathological changes induced by lionfish (pterios volitans) venom in mice.

PubMed

Balasubashini, M Sri; Karthigayan, S; Somasundaram, S T; Balasubramanian, T; Viswanathan, P; Menon, Venugopal P

2006-01-01

Accidents caused by lionfish (Pterios volitans) envenomation are characterized by edema, intense pain, and necrosis at the site of sting. The mode of action and biochemistry of venoms are obviously complex and require a better knowledge and investigation to explore the toxic action and resulting biochemical changes. In the present study the LD(50) value of lionfish venom was found to be 42.5 mug/kg body weight (intraperitoneal injection) in Albino Swiss mice and was associated with reduced motor activity and asphyxiation followed by respiratory failure. The effect on vital organs revealed spongiosis in brain, vascular congestion in liver, cloudy swelling of renal tubules, congested blood vessels in renal tubules, and degeneration of myofibrils in heart. Whereas, the 10% of LD(50) (was 4.25 mug/kg b.w.), the sublethal dose showed reversible changes in the hematological (blood cell count, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and platelet count) parameters, serum enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and creatinine phosphokinase), blood sugar, urea, creatinine, triglycerides, cholesterol, and total protein in mouse in vivo. The in vitro analysis of lionfish venom on mouse brain acetyl cholinesterase and Na(+), K(+), ATPase showed significant increased activity in a dose-dependent manner (10 to 40 mug). Moreover, the lionfish venom was observed to have a protease with a molecular weight of 45 kDa. Hence, the present study suggests the presence of bioactive proteins and peptides with excellent target specificity, which could be trapped for drug development in near future.

Boric acid enhances in vivo Ehrlich ascites carcinoma cell proliferation in Swiss albino mice.

PubMed

Qureshi, S; Al-Shabanah, O A; Al-Harbi, M M; Al-Bekairi, A M; Raza, M

2001-08-13

The influence of boric acid, a boron carrier, on Ehrlich ascites carcinoma (EAC) cell-bearing mice was investigated in view of its importance in the boron neutron capture therapy and the influence of boron on proliferation and progression of cancer cells mediated by proteoglycans and collagen. The present study included the evaluation of boric acid for the effects on total count and viability of EAC cells in addition to their non-protein sulfhydryls (NP-SH) and malondialdehyde (MDA) contents as parameters for conjugative detoxication potency and possible oxidative damage. The EAC cell-bearing animals were also observed for the effect on survival, body weight changes, and histopathological evaluation of the tumors grown at the site of inoculation. The treatment with boric acid significantly increased the total number of peritoneal EAC cells and their viability. A significant increase in the body weight was observed that dose-dependently reached plateau levels by 20 days of treatment. Conversely, a reduction in the duration of survival of these animals was evident with the same protocol. Boric acid treatment resulted in a decrease in NP-SH contents with a concomitant increase in MDA levels in EAC cells as revealed by the results of the biochemical analysis. These data are supported by our results on histopathological investigations, which apparently showed fast growth, in addition to several mitotic figures and mixed inflammatory reaction, after treatment with boric acid. It seems likely that a particular combination of properties of boric acid, rather than a single characteristic alone, will provide useful information on the use of this boron carrier in neutron capture therapy.

The influence of caffeine on the activity of moclobemide, venlafaxine, bupropion and milnacipran in the forced swim test in mice.

PubMed

Poleszak, Ewa; Szopa, Aleksandra; Wyska, Elżbieta; Wośko, Sylwia; Serefko, Anna; Wlaź, Aleksandra; Pieróg, Mateusz; Wróbel, Andrzej; Wlaź, Piotr

2015-09-01

Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. It is thus possible to demonstrate the usefulness of caffeine and its derivatives in the treatment of depression. The main goal of the present studywas to evaluate the influence of caffeine (5mg/kg) on the activity of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg), bupropion (10 mg/kg), and milnacipran (1.25 mg/kg). Moreover, we assessed the influence of caffeine on their serum and brain levels using highperformance liquid chromatography. The experiment was carried out on naïve adult male Albino Swiss mice. Caffeine and tested drugs were administered intraperitoneally. The influence of caffeine on the activity of selected antidepressant drugs was evaluated in forced swim test (FST). Locomotor activity was estimated to verify and exclude false positive/negative results. To assess the influence of caffeine on the levels of studied antidepressant drugs, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. Caffeine potentiated activity of all antidepressants examined in FST and the observed effects were not due to the increase in locomotor activity in the animals. Only in the case of co-administration of caffeine and milnacipran an increased milnacipran concentration in serum was observed without affecting its concentration in the brain. Caffeine potentiates the activity of antidepressant drugs from different chemical groups. The interactions of caffeine with venlafaxine, bupropion and moclobemide occur in pharmacodynamic phase, whereas the interaction of caffeine–milnacipran occurs, at least partially, in pharmacokinetic phase.

Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

PubMed

Das, Ujjal; Manna, Krishnendu; Khan, Amitava; Sinha, Mahuya; Biswas, Sushobhan; Sengupta, Aaveri; Chakraborty, Anindita; Dey, Sanjit

2017-01-01

The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy.

PubMed

Thulasidasan, Arun Kumar T; Retnakumari, Archana P; Shankar, Mohan; Vijayakurup, Vinod; Anwar, Shabna; Thankachan, Sanu; Pillai, Kavya S; Pillai, Jisha J; Nandan, C Devika; Alex, Vijai V; Chirayil, Teena Jacob; Sundaram, Sankar; Kumar, Gopalakrishnapillai Sankaramangalam Vinod; Anto, Ruby John

2017-12-08

Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time. Earlier reports of improvement in bioavailability and retention of drugs upon nanoencapsulation have motivated us in developing various nanoformulations of curcumin, which were found to exhibit significant enhancement in bioavailability and retention time as assessed by our previous in vitro studies. Among the various formulations tested, curcumin-entrapped in PLGA-PEG nanoparticles conjugated to folic acid (PPF-curcumin) displayed maximum cell death. In the present study, we have demonstrated the efficacy of this formulation in augmenting the bioavailability and retention time of curcumin, in vivo , in Swiss albino mice. Further, the acute and chronic toxicity studies proved that the formulation is pharmacologically safe. We have also evaluated its potential in chemosensitizing cervical cancer cells to paclitaxel and have verified the results using cervical cancer xenograft model in NOD-SCID mice. Folic acid conjugation significantly enhanced the efficacy of curcumin in down-regulating various survival signals induced by paclitaxel in cervical cancer cells and have considerably improved its potential in inhibiting the tumor growth of cervical cancer xenografts. The non-toxic nature coupled with improved chemosensitization potential makes PPF-curcumin a promising candidate formulation for clinical trials.

Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy

PubMed Central

Shankar, Mohan; Vijayakurup, Vinod; Anwar, Shabna; Thankachan, Sanu; Pillai, Kavya S.; Pillai, Jisha J.; Nandan, C. Devika; Alex, Vijai V.; Chirayil, Teena Jacob; Sundaram, Sankar; Kumar, Gopalakrishnapillai Sankaramangalam Vinod; Anto, Ruby John

2017-01-01

Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time. Earlier reports of improvement in bioavailability and retention of drugs upon nanoencapsulation have motivated us in developing various nanoformulations of curcumin, which were found to exhibit significant enhancement in bioavailability and retention time as assessed by our previous in vitro studies. Among the various formulations tested, curcumin-entrapped in PLGA-PEG nanoparticles conjugated to folic acid (PPF-curcumin) displayed maximum cell death. In the present study, we have demonstrated the efficacy of this formulation in augmenting the bioavailability and retention time of curcumin, in vivo, in Swiss albino mice. Further, the acute and chronic toxicity studies proved that the formulation is pharmacologically safe. We have also evaluated its potential in chemosensitizing cervical cancer cells to paclitaxel and have verified the results using cervical cancer xenograft model in NOD-SCID mice. Folic acid conjugation significantly enhanced the efficacy of curcumin in down-regulating various survival signals induced by paclitaxel in cervical cancer cells and have considerably improved its potential in inhibiting the tumor growth of cervical cancer xenografts. The non-toxic nature coupled with improved chemosensitization potential makes PPF-curcumin a promising candidate formulation for clinical trials. PMID:29296172

Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones

PubMed Central

Sarkar, Souvik; Siddiqui, Asim A.; Saha, Shubhra J.; De, Rudranil; Mazumder, Somnath; Banerjee, Chinmoy; Iqbal, Mohd S.; Nag, Shiladitya; Adhikari, Susanta

2016-01-01

We synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. These hydrazones concentration-dependently chelated free iron and offered antimalarial activity. Upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. Compound 5f also interacted with free heme (KD [equilibrium dissociation constant] = 1.17 ± 0.8 μM), an iron-containing tetrapyrrole released after hemoglobin digestion by the parasite, and inhibited heme polymerization by parasite lysate. Structure-activity relationship studies indicated that a nitrogen- and sulfur-substituted five-membered aromatic ring present within the benzothiazole hydrazones might be responsible for their antimalarial activity. The dose-dependent antimalarial and heme polymerization inhibitory activities of the lead compound 5f were further validated by following [3H]hypoxanthine incorporation and hemozoin formation in parasite, respectively. It is worth mentioning that compound 5f exhibited antiplasmodial activity in vitro against a chloroquine/pyrimethamine-resistant strain of Plasmodium falciparum (K1). We also evaluated in vivo antimalarial activity of compound 5f in a murine model where a lethal multiple-drug-resistant strain of Plasmodium yoelii was used to infect Swiss albino mice. Compound 5f significantly suppressed the growth of parasite, and the infected mice experienced longer life spans upon treatment with this compound. During in vitro and in vivo toxicity assays, compound 5f showed minimal alteration in biochemical and hematological parameters compared to control. In conclusion, we identified a new class of hydrazone with therapeutic potential against malaria. PMID:27139466

Comparative effects of pyrolytic products of fiber reinforced plastic and wood shavings on the respiratory variables in mice.

PubMed

Kumar, Pravin; Deb, Utsab; Gautam, Anshoo; Vijayaraghavan, R; Ratna, Debdatta; Chakraborty, B C

2010-08-01

Comparative inhalation toxicity studies of pyrolytic products (smoke) from synthetic polymer, fiberglass reinforced plastic (FRP) and teak wood shavings were carried out in male Swiss albino mice. The breathing pattern and the respiratory variables were monitored using a computer program that recognizes the modifications of the respiratory pattern. Exposure to the smoke from both the polymers caused a concentration dependent decrease in normal breathing and an increase in sensory irritation measure. The acute lethal concentration 50 values for a 15 min static inhalation exposure to the smoke from FRP and teak wood shavings were found to be > 200.00 and 62.99 g/m(3), respectively. Hence the inhalation toxicity of smoke from FRP sample on a mass basis is approximately one-third that of the smoke from teak wood. The concentration of smoke causing 50% respiratory depression of the exposed animals were found to be 6.877 and 0.106 g/m(3) for FRP and teak wood samples, respectively. Thus the sensory irritancy of the smoke from FRP sample is approximately 65 times lesser than the smoke from teak wood. The higher sensory irritancy potential of wood smoke as compared to FRP smoke may be caused by a greater number of submicron particles (size range of 2 micron and less) and greater percentage of gases present in wood smoke as compared to FRP smoke. Thus in case of accidental fires, synthetic polymers like FRP may be a safer choice for structural parts and interiors than the natural wood.

Histaminergic regulation of natural killer cell-mediated clearance of tumour cells in mice.

PubMed

Asea, A; Hermodsson, S; Hellstrand, K

1996-01-01

Treatment of Swiss albino mice with histamine enhanced the clearance of natural killer (NK)-cell sensitive YAC-1 lymphoma and B16/F10 melanoma cells from lung tissue in vivo, but did not affect the elimination of NK-cell-insensitive P815 mastocytoma cells. The effect of histamine was apparently mediated by H2-type histamine receptors (H2R) since it was blocked by ranitidine, and H2R antagonist. Histamine did not affect clearance of tumour cells in animals depleted of NK cells in vivo by treatment with antibodies to asialo-GM1 or NK1.1. The effect of histamine was time-dependent: pretreatment with histamine for 3 h significantly augmented the clearance of YAC-1 cells, whereas, pretreatment with histamine for 5 min was ineffective. Histamine potentiated the anti-tumour properties of NK-cell activators such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha) in vivo. None of these lymphokines significantly affected the clearance of YAC-1 cells unless animals were concomitantly treated with histamine. Treatment with ranitidine alone reduced the in vivo clearance of YAC-1 cells from lungs but did not affect the clearance of NK-cell-insensitive P815 cells. Effects of ranitidine on NK-cell function in vivo were not shared by a chemical control to ranitidine, AH20239AA, thus indicating that the inhibition of NK-cells results from H2R antagonism rather than non-specific toxicity. It is concluded that histaminergic mechanisms may be involved in the regulation of NK cell function in vivo.

In vivo postirradiation protection by a vitamin E analog, alpha-TMG.

PubMed

Satyamitra, Merriline; Uma Devi, P; Murase, Hironobu; Kagiya, V T

2003-12-01

The water-soluble vitamin E derivative alpha-TMG is an excellent radical scavenger. A dose of 600 mg/kg TMG significantly reduced radiation clastogenicity in mouse bone marrow when administered after irradiation. The present study was aimed at investigating the radioprotective effect of postirradiation treatment with alpha-TMG against a range of whole-body lethal (8.5-12 Gy) and sublethal (1-5 Gy) doses of radiation in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from micronuclei and chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 600 mg/kg TMG within 10 min of lethal irradiation increased survival, giving a dose modification factor (DMF) of 1.09. TMG at doses of 400 mg/kg and 600 mg/kg significantly reduced the percentage of aberrant metaphases, the different types of aberrations, and the number of micronucleated erythrocytes. DMFs of 1.22 and 1.48 for percentage aberrant metaphases and 1.6 and 1.98 for micronuclei were obtained for 400 mg/kg and 600 mg/kg TMG, respectively. No drug toxicity was observed at these doses. The effectiveness of TMG when administered postirradiation suggests its possible utility for protection against unplanned radiation exposures.

Assessment of Genotoxic Potential of Hridayarnava Rasa (A Herbo-Mineralo-Metallic Ayurvedic Formulation) Using Chromosomal Aberration and Sperm Abnormality Assays

PubMed Central

Jagtap, Chandrashekhar Y.; Chaudhari, Swapnil Y.; Thakkar, Jalaram H.; Galib, R.; Prajapati, P. K.

2014-01-01

Objectives: Herbo-mineral formulations are being successfully used in therapeutics since centuries. But recently, they came under the scanner for their metallic contents especially the presence of heavy metals. Hence it is the need of the hour to assess and establish the safety of these formulations through toxicity studies. In line with the various toxicity studies that are being carried out, Government of India expressed the need for conducting genotoxicity studies of different metal- or mineral-based drugs. Till date very few Ayurvedic herbo-mineral formulations have been studied for their genotoxic potential. The present study is aimed to evaluate the genotoxic potential of Hridayarnava Rasa. Materials and Methods: It was prepared as per classical guidelines and administered to Swiss albino mice for 14 consecutive days. Chromosomal aberration and sperm abnormality assay were done to evaluate the genotoxic potential of the test drugs. Cyclophosphamide (CP) was taken as positive group and results were compared. Results: All treated groups exhibited significant body weight gain in comparison to CP group. Results revealed no structural deformity in the above parameters in comparison to the CP-treated group. Conclusion: Reported data showed that both tested samples of Hridayarnava Rasa does not possess genotoxic potential under the experimental conditions and can be safely used. PMID:25948961

Liposome-encapsulated diacyl glycerol and inositol triphosphate-induced delayed oocyte activation and poor development of parthenotes.

PubMed

Nair, Ramya; Manikkath, Jyothsna; Hegde, Aswathi R; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

2017-09-01

To explore the ability of diacyl glycerol (DAG) and inositol triphosphate (IP3), two major secondary messengers in the calcium signaling pathway, in activating oocytes. Oocyte cumulus complex obtained from superovulated Swiss albino mice were incubated in M16 medium with liposome-encapsulated 1,2-Dipalmitoyl-sn-glycerol (LEDAG) and/or IP3 for 3 h. Strontium chloride was used as positive control. The activation potential, ploidy status, and blastocyst rate was calculated. Both DAG and IP3, individually, induced activation in ~98% of oocytes, which was significantly higher (p<0.01) than activation induced by strontium chloride (60%). Delayed pronucleus formation and a higher percentage of diploid parthenotes was observed in oocytes activated with LEDAG and/or IP3. However, these embryos failed to progress beyond the 6-8-cell stage. Only when the medium was supplemented with LEDAG (5 μg/mL) and IP3 (10 μg/mL) could activated oocytes progress till the blastocyst stage (5.26%), which was lower than the blastocyst rate in the positive controls (13.91%). The results of the present study indicate that DAG and IP3 can induce delayed oocyte activation and poor development of parthenotes in vitro.

Antioxidant, antimicrobial, toxicity and analgesic properties of ethanol extract of Solena amplexicaulis root.

PubMed

Kabir, Md Golam; Rahman, Md Monsor; Ahmed, Nazim Uddin; Fakruddin, Md; Islam, Saiful; Mazumdar, Reaz Mohammad

2014-08-19

This study was subjected to investigate different pharmacological properties of ethanol extract of Solena amplexicaulis root. The extract contains flavonoid, alkaloid, saponin and steroid compounds. The extract exhibited excellent antioxidant activity in DPPH radical scavenging activity. The extract also showed potent activity in brine shrimp lethality bioassay. The LC50 value was found to 44.677 μg/ml. The extract showed better anti-bacterial activity against gram-negative bacteria. In antifungal assay, the maximum 79.31% of anti-mycotic activity was observed against Aspergillus ochraceus while minimum 44.2% against Rhizopus oryzae. MIC value ranged between 1500-3000 μg/ml. The extract was found moderately toxic with a 24-hr LD50 value of 81.47 mg/kg in Swiss albino mice. The degree of inhibition by the ethanolic extract of the root was found less than that of standard analgesic drug diclofenac sodium. The extract also showed moderate anti-inflammatory and antinociceptive activity and anti-diabetic property. Reducing power of the extract was comparable with standard ascorbic acid. Moderate in vitro thrombolytic activity, lipid peroxidation inhibition property, metal chelating ability and stress-protective activity was also observed. Ethanol extract of Solena amplexicaulis root can be valuable for treatment of different diseases.

Nullification of aspirin induced gastrotoxicity and hepatotoxicity by prior administration of wheat germ oil in Mus musculus: histopathological, ultrastructural and molecular studies.

PubMed

Mohamed, H R H; Hamad, S R

2017-08-30

Aspirin (acetyl salicylic acid) is used worldwide to treat various inflammatory conditions and prevent cardiovascular disease, along with reducing the risk of cancer. However, administration of aspirin causes toxic effects, especially in the stomach and liver. Thus, our study examined the protective effect of wheat germ oil on aspirin-induced toxicity in the stomach and liver tissues of Swiss albino mice. Administration of wheat germ oil before aspirin has restored normal hepatic and gastric tissue architecture and DNA integrity has become better than that of a negative health control group compared with the aspirin only treated group. The elevated gastric nitric oxide content in the aspirin only treated group was significantly decreased by wheat germ oil prior administration as a result of reduced the expression of inducible nitric synthase and increased the expression of endothelial nitric oxide synthase compared to their expression in the aspirin administered group. Wheat germ oil pre-administration significantly reduced the level of malondialdehyde, increased the level of glutathione and catalase and superoxide dismutase activities compared with those in aspirin only treated group. We conclude that wheat germ oil has a potential protective effect against aspirin induced gastro- and hepato-toxicity because of its free radical scavenging ability.

Efficacy and safety evaluation of a novel trioxaquine in the management of cerebral malaria in a mouse model.

PubMed

Odhiambo, Onyango C; Wamakima, Hannah N; Magoma, Gabriel N; Kirira, Peter G; Malala, Bonface J; Kimani, Francis T; Muregi, Francis W

2017-07-03

The emergence of multidrug-resistant strains of Plasmodium falciparum poses a great threat of increased fatalities in cases of cerebral and other forms of severe malaria infections in which parenteral artesunate monotherapy is the current drug of choice. The study aimed to investigate in a mouse model of human cerebral malaria whether a trioxaquine chemically synthesized by covalent linking of a 4,7-dichloroquinoline pharmacophore to artesunate through a recent drug development approach termed 'covalent bitherapy' could improve the curative outcomes in cerebral malaria infections. Human cerebral malaria rodent model, the C57BL/6 male mice were infected intraperitoneally (ip) with Plasmodium berghei ANKA and intravenously (iv) treated with the trioxaquine from day 8 post-infection (pi) at 12.5 and 25 mg/kg, respectively, twice a day for 3 days. Treatments with the trioxaquine precursors (artesunate and 4,7-dichloroquine), and quinine were also included as controls. In vivo safety evaluation for the trioxaquine was done according to Organization for Economic Co-operation and Development (OECD) guidelines 423, where female Swiss albino mice were orally administered with either 300 or 2000 mg/kg of the trioxaquine and monitored for signs of severity, and or mortality for 14 days post-treatment. The trioxaquine showed a potent and a rapid antiplasmodial activity with 80% parasite clearance in the first 24 h for the two dosages used. Long-term parasitaemia monitoring showed a total parasite clearance as the treated mice survived beyond 60 days post-treatment, with no recrudescence observed. Artesunate treated mice showed recrudescence 8 days post-treatment, with all mice in this group succumbing to the infection. Also, 4,7-dichloroquinoline and quinine did not show any significant parasitaemia suppression in the first 24 h post-treatment, with the animals succumbing to the infection. Covalent bitherapy proves to be a viable source of urgently needed new anti-malarials for management of cerebral malaria, and this polypharmacology approach could be a potential strategy to protect artesunate from parasite resistance and in potentially improving clinical outcomes in severe forms of malaria infections.

Evaluation of Sub-acute Oral Toxicity of Lithium Carbonate Microemulsion (Nano Size) on Liver and Kidney of Mice

PubMed Central

Kalantari, Heibatullah; Salimi, Anayatollah; Rezaie, Anahita; Jazayeri Shushtari, Fereshteh; Goudarzi, Mehdi

2015-01-01

Background: The development of drug delivery systems has improved the therapeutic and toxic properties of existing drugs in therapy. Microemulsion systems are novel vehicles for drug delivery, which have been developed in recent years. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating into a wide range of drug molecules. Although these systems improved solubility and bioavailability of drugs, they may have potential toxic effects on the body organs. Objectives: The purpose of this study was to examine a possible hepatotoxic and nephrotoxic effect of lithium carbonate microemulsion (LCME) in a mice model. Materials and Methods: Eighty male Swiss albino mice were randomly allocated to eight experimental groups, as follows: Group 1, as negative control group were treated orally with normal saline (0.9% NaCl); Group 2, received microemulsion base without drug as control group; Groups 3 to 5, received lithium carbonate (LC) solution in doses of 50, 100, and 200 mg/kg, respectively; Groups 6 to 8, received LCME orally in doses of 50, 100, and 200 mg/kg, respectively. All drugs were administered orally for ten consecutive days. Serum glutamate pyruvate aminotransferase (SGPT), serum glutamate oxaloacetate aminotransferase (SGOT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and plasma creatinine (Cr), as markers of liver and kidney toxicity in treated mice, were measured. Furthermore, the changes of tissue were assessed by histopathologic examination. Results: The findings showed that serum activity of ALP, SGOT, and SGPT and the levels of BUN and Cr in microemulsion base group was greater than normal saline group. However, this difference was not significant. Administration of LC and LCME in all doses resulted in a significant increase in the levels of BUN and serum activity of SGOT and SGPT in comparison to normal saline group (P < 0.05). Histopathological changes were observed in mice treated with LC or LCME. Conclusions: This study showed that subacute oral administration of different doses of LCME with severe toxicity in comparison to the same dose of LC. PMID:25866723

9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the first stage, each of 40 Swiss mice, each weighing 16 to 20 grams, shall be injected subcutaneously... hours postinjection, the injected mice and 10 additional mice designated controls shall be challenged... die from erysipelas within 7 days post-challenge, the test is invalid. All dead mice shall be examined...

9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the first stage, each of 40 Swiss mice, each weighing 16 to 20 grams, shall be injected subcutaneously... hours postinjection, the injected mice and 10 additional mice designated controls shall be challenged... die from erysipelas within 7 days post-challenge, the test is invalid. All dead mice shall be examined...

9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the first stage, each of 40 Swiss mice, each weighing 16 to 20 grams, shall be injected subcutaneously... hours postinjection, the injected mice and 10 additional mice designated controls shall be challenged... die from erysipelas within 7 days post-challenge, the test is invalid. All dead mice shall be examined...

9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the first stage, each of 40 Swiss mice, each weighing 16 to 20 grams, shall be injected subcutaneously... hours postinjection, the injected mice and 10 additional mice designated controls shall be challenged... die from erysipelas within 7 days post-challenge, the test is invalid. All dead mice shall be examined...

Influence of chewing behaviour on memory and spatial learning in albino BALB/c mice.

PubMed

Aguirre Siancas, E E

2017-05-01

Since the relationship between chewing and cognitive functions has not been fully elucidated, this study aimed to determine the impact of chewing behaviour on spatial learning and memory in albino male BALB/c mice. Twenty mice aged 8 weeks were divided into 2 equal groups. The regular chewing group was fed with uncrushed grains (the same diet given to all 20 mice since they were weaned) and the limited chewing group was fed with crushed grains. At 16 weeks of age, the mice were evaluated over 5 days, including a 4-day acquisition phase prior to a probe test of spatial learning and memory in the Morris water maze on the fifth day. A comparison of the regular chewing group and the limited chewing group found no significant differences in either the acquisition phase or the probe test. However, there were significant differences in the acquisition phase for just the regular chewing group when comparing results from the first day to those from the other 3 days. The results suggest that regular chewing affects spatial learning and memory since mice in the regular chewing group decreased their times to find the hidden platform during the acquisition phase. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

29 CFR 780.120 - Raising of “livestock.”

Code of Federal Regulations, 2010 CFR

2010-07-01

..., mules, donkeys, and goats. It does not include such animals as albino and other rats, mice, guinea pigs... F. 2d 1), but employees employed in propagating or farming of fish may qualify for exemption under...

[Effects of a new derivative of 5-alkyl-3N-furanones on the colonization resistance of the intestine in albino mice].

PubMed

Tomnikov, A Iu; Shub, G M

1990-05-01

By its antagonistic function normal microflora provides the intestine with resistance to colonization with exogenic opportunistic and pathogenic microorganisms. The drug was effective in inducing a decrease in the intestine colonization resistance which in its turn leads to filling of free ecological niches with exogenic microflora. In this connection the suggestion that specification of a new chemical agent should include along with other criteria its effect on colonization resistance is valid. It was shown with the use of indicator microorganisms that when administered per os in doses of 40 and 80 mg/kg daily for 3 and 6 days, respectively, a new original compound 1929, a derivative of 5-alkyl-3H-furanones, with high antimicrobial activity induced no significant or more pronounced changes in the colonization resistance of the gastrointestinal tract of noninbred albino mice than furagin used as the reference drug.

[Experimental model of activated Lamblia (Giardia) muris infection in albino mice].

PubMed

Irikov, O A; Kovalenko, F P

2007-01-01

Experimental L. muris infection was reproduced in 100% of the intact albino mice intragastrically given levomycin in an average total dose of 15.88-34.84 or 0.88-1.02 g/kg for 18-34 days. With levomycin administration, the intensity of giardiasis was 1121.6-8540.1 (mean 4830.9) thousand L. muris trophozoites per animal. The total number of trophozoites per animal decreased to 302.2-3481.4 (mean 1546.4) thousand and 28.1-324.0 (mean 109.4) thousand specimens 5-8 and 11-13 days after discontinuation of the antibiotic, respectively. The maximum number of L. muris trophozoites was observed in the proximal and middle portions of the murine small intestine during and after the administration oflevomycin. The highest isolation of cysts was seen 12-14 days after the initiation of administration of the antibiotic. Following 8-10 days of terminations of a course of levomycin therapy the native smear of animal feces showed no Lamblia cysts. In mice with activated infection, the isolation rate of Lamblia cysts was directly related to the intensity of intestinal infection with trophozoites of the parasite.

Antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom in experimental animal models.

PubMed

Ghosh, Susmita; Saha, Partha Pratim; Dasgupta, Subir C; Gomes, Antony

2016-09-01

Pain and inflammation are intimately associated with rheumatoid arthritis, a growing bone-joint related problem of the modern society. Though several therapeutic managements are available for arthritis, their side effects not only limit their use, but also advocate the quest for natural therapies. In this study, we explored the antinociceptive, anti-inflammatory and antiarthritic activities of Bungarus fasciatus venom (BFV) in experimental animal models. Rheumatoid arthritis was induced by Freund’s complete adjuvant (FCA) in male Wistar albino rats. Lyophilized BFV was diluted in 0.9% NaCl. Antiarthritic activity showed that BFV significantly reduced the paw and ankle diameters; urinary hydroxyproline, glucosamine levels and serum ACP/ALP/TNF-α/IL-1β/IL-17/Cathepsin-K/MMP-1 levels. These parameters were significantly increased in FCA induced arthritic animals. Joint histopathology study indicated the partial restoration of joint structure. Treatment with BFV significantly reduced the mean latency time of tail flick response, acetic acid induced writhing response and formalin induced licking response in male albino mice. BFV treatment also significantly reduced carrageenan induced paw edema and xylene induced ear edema in male albino mice. The results indicated that BFV possess antinociceptive, anti-inflammatory and antiarthritic properties and further studies are warranted to find the active constituents present in BFV.

Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice

PubMed Central

Ezz El-Arab, Aly M; Girgis, Shenouda M; Hegazy, Eman M; Abd El-Khalek, Azzat B

2006-01-01

Background Bee honey is a functional food which has a unique composition, antimicrobial properties and bifidogenic effect. In order to assess whether honey can inhibit the toxic effect of mycotoxins, the present study was undertaken. Methods Production of biomass and toxins by Aspergillus parasiticus and Aspergillus ochraceus were followed in media without and with honey. Although aflatoxins and ochratoxin A. were administrated to male Swiss albino mice up to 1 μg and 10 ng/kg body weight/day respectively. The experimental animals were fed diets without our with 10% honey for two months. The changes in colonic probiotic bacteria, determintal colon enzyme glucuronidases, and genotoxicity were followed. Results Addition of 32% in its media increased the biomass of A parasiticus, while the biomass of A. ochraceus decreased and Ochratoxin A. was not produced. When the honey was added at the ratio of 32 and 48% in the medium. No relationship was found between mycelium weight and production of mycotoxins. Oral administration of aflatoxins (mixture of B1, B2, G1 and G2) and Ochratoxin A. induced structural and numerical chromosomal aberrations in bone marrow and germ cells of male mice, whereas, honey treatment reduced the genotoxicity of mycotoxins. Also both toxins induced histopathological changes in liver and kidney. Feeding on diet supplemented with honey improved the histopathological changes in case of aflatoxin group, but not in the case of ochratoxin A. group (except of kidney in two cases). No significant differences were found in the activity of colon β-glucuronidase between group fed diet with or without honey. On the other hand, the colon bifido bacteria and lactobacilli counts were increased markedly in group receiving diet supplemented with honey. Conclusion Substituting sugars with honey in processed food can inhibit the harmful and genotoxic effects of mycotoxins, and improve the gut microflora. PMID:16533410

Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria

PubMed Central

Hiben, Mebrahtom Gebrelibanos; Sibhat, Gereziher Gebremedhin; Fanta, Biruk Sintayehu; Gebrezgi, Haile Desta; Tesema, Shewaye Belay

2015-01-01

The emergence of malarial resistance to most antimalarial drugs is the main factor driving the continued effort to identify/discover new agents for combating the disease. Moreover, the unacceptably high mortality rate in severe malaria has led to the consideration of adjuvant therapies. Senna singueana leaves are traditionally used against malaria and fever. Extracts from the leaves of this plant demonstrated in vitro and in vivo antioxidant activities, which in turn could reduce the severity of malaria. Extracts from the root bark of this plant exhibited antiplasmodial activity; however, the leaves are the more sustainable resource. Thus, S. singueana leaf was selected for in vivo evaluation as a potential alternative or adjuvant therapy for malaria. Using malaria [Plasmodium berghei ANKA, chloroquine (CQ) sensitive]-infected Swiss albino mice of both sexes, 70% ethanol extract of S. singueana leaves (alone and in combination with CQ) was tested for antimalarial activity and adjuvancy potential. The 4-day suppressive test was used to evaluate antimalarial activity. The dose of S. singueana extract administered was safe to mice and exhibited some parasite suppression effect: extract doses of 200 mg/kg/d, 400 mg/kg/d, and 800 mg/kg/d caused 34.54%, 44.52%, and 47.32% parasite suppression, respectively. Concurrent administration of the extract with CQ phosphate at varied dose levels indicated that the percentage of parasite suppression of this combination was higher than administering CQ alone, but less than the sum of the effects of the extract and CQ acting separately. In conclusion, the study indicated that 70% ethanol extract of S. singueana leaf was safe to mice and possessed some parasite suppression effect. Coadministration of the extract with CQ appeared to boost the overall antimalarial effect, indicating that the combination may have a net health benefit if used as an adjuvant therapy. PMID:26870688

Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria.

PubMed

Hiben, Mebrahtom Gebrelibanos; Sibhat, Gereziher Gebremedhin; Fanta, Biruk Sintayehu; Gebrezgi, Haile Desta; Tesema, Shewaye Belay

2016-01-01

The emergence of malarial resistance to most antimalarial drugs is the main factor driving the continued effort to identify/discover new agents for combating the disease. Moreover, the unacceptably high mortality rate in severe malaria has led to the consideration of adjuvant therapies. Senna singueana leaves are traditionally used against malaria and fever. Extracts from the leaves of this plant demonstrated in vitro and in vivo antioxidant activities, which in turn could reduce the severity of malaria. Extracts from the root bark of this plant exhibited antiplasmodial activity; however, the leaves are the more sustainable resource. Thus, S. singueana leaf was selected for in vivo evaluation as a potential alternative or adjuvant therapy for malaria. Using malaria [Plasmodium berghei ANKA, chloroquine (CQ) sensitive]-infected Swiss albino mice of both sexes, 70% ethanol extract of S. singueana leaves (alone and in combination with CQ) was tested for antimalarial activity and adjuvancy potential. The 4-day suppressive test was used to evaluate antimalarial activity. The dose of S. singueana extract administered was safe to mice and exhibited some parasite suppression effect: extract doses of 200 mg/kg/d, 400 mg/kg/d, and 800 mg/kg/d caused 34.54%, 44.52%, and 47.32% parasite suppression, respectively. Concurrent administration of the extract with CQ phosphate at varied dose levels indicated that the percentage of parasite suppression of this combination was higher than administering CQ alone, but less than the sum of the effects of the extract and CQ acting separately. In conclusion, the study indicated that 70% ethanol extract of S. singueana leaf was safe to mice and possessed some parasite suppression effect. Coadministration of the extract with CQ appeared to boost the overall antimalarial effect, indicating that the combination may have a net health benefit if used as an adjuvant therapy.

Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice.

PubMed

Ezz El-Arab, Aly M; Girgis, Shenouda M; Hegazy, Eman M; Abd El-Khalek, Azzat B

2006-03-14

Bee honey is a functional food which has a unique composition, antimicrobial properties and bifidogenic effect. In order to assess whether honey can inhibit the toxic effect of mycotoxins, the present study was undertaken. Production of biomass and toxins by Aspergillus parasiticus and Aspergillus ochraceus were followed in media without and with honey. Although aflatoxins and ochratoxin A. were administrated to male Swiss albino mice up to 1 mug and 10 ng/kg body weight/day respectively. The experimental animals were fed diets without our with 10% honey for two months. The changes in colonic probiotic bacteria, determintal colon enzyme glucuronidases, and genotoxicity were followed. Addition of 32% in its media increased the biomass of A parasiticus, while the biomass of A. ochraceus decreased and Ochratoxin A. was not produced. When the honey was added at the ratio of 32 and 48% in the medium. No relationship was found between mycelium weight and production of mycotoxins. Oral administration of aflatoxins (mixture of B1, B2, G1 and G2) and Ochratoxin A. induced structural and numerical chromosomal aberrations in bone marrow and germ cells of male mice, whereas, honey treatment reduced the genotoxicity of mycotoxins. Also both toxins induced histopathological changes in liver and kidney. Feeding on diet supplemented with honey improved the histopathological changes in case of aflatoxin group, but not in the case of ochratoxin A. group (except of kidney in two cases). No significant differences were found in the activity of colon beta-glucuronidase between group fed diet with or without honey. On the other hand, the colon bifido bacteria and lactobacilli counts were increased markedly in group receiving diet supplemented with honey. Substituting sugars with honey in processed food can inhibit the harmful and genotoxic effects of mycotoxins, and improve the gut microflora.

Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity

PubMed Central

Nahar, Laizuman; Nasrin, Fatema; Zahan, Ronok; Haque, Anamul; Haque, Ekramul; Mosaddik, Ashik

2014-01-01

Background: Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. Objective: The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI). Materials and Methods: Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed. Results: There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity. Conclusion: These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress. PMID:24761124

Differential expression of isoproterenol-induced salivary polypeptides in two mouse strains that are congenic for the H-2 histocompatibility gene complex.

PubMed

López Solís, Remigio O; Weis, Ulrike Kemmerling; Ceballos, Alicia Ramos; Salas, Gustavo Hoecker

2003-12-01

Two inbred mouse strains, A/Snell and A.Swiss, which were produced as congenic with regard to the H-2 histocompatibility gene complex, are homozygous for two different groups of isoproterenol-induced salivary polypeptides (IISP). These polypeptides, which have been considered as markers of the hypertrophic growth of the parotid acinar cells, are members of the complex family of salivary proline-rich proteins (PRP) on the basis of both their massive accumulation in the parotid acinar cells in response to chronic isoproterenol, secretory character, high solubility in trichloroacetic acid and metachromatic staining by Coomassie blue. IISP expressed in both mouse strains were identified by unidimensional SDS-polyacrylamide electrophoresis and Coomassie blue staining both in parotid gland homogenates and in whole salivas obtained from mice repeatedly stimulated at 24-h intervals with isoproterenol. Parotid glands from 40 mice (20 A/Snell and 20 A.Swiss) and salivas from 270 mice (200 A/Snell and 70 A.Swiss) were analyzed. One of the congenic strains (A/Snell) expressed five IISP (Mr 65, 61, 51.5, 38, and 37 kDa) and the other strain (A.Swiss) expressed six IISP (Mr 59, 57, 54.5, 46, 36, and 34 kDa). No inter-individual intra-strain variations were observed, thus defining strain-associated patterns of IISP (PRP). Copyright 2003 Wiley-Liss, Inc.

9 CFR 113.454 - Clostridium Perfringens Type C Antitoxin.

Code of Federal Regulations, 2011 CFR

2011-01-01

... sickness or death in injected mice. (iii) L + dose. The smallest quantity of toxin which can be mixed with one unit of Standard Antitoxin and cause death in at least 80 percent of injected mice. (iv) Standard... of mice can be made. (vi) Five Swiss white mice, each weighing 16-20 grams, shall be used for each...

9 CFR 113.455 - Clostridium Perfringens Type D Antitoxin.

Code of Federal Regulations, 2011 CFR

2011-01-01

... cause sickness or death in injected mice. (iii) L + dose. The smallest quantity of toxin which can be mixed with one-tenth unit of Standard Antitoxin and cause death in at least 80 percent of injected mice... until injections of mice can be made. (vi) Five Swiss white mice, each weighing 16-20 grams, shall be...

Evaluation of antihyperlipidemic and antitumor activities of isolated coumarins from Salvadora indica.

PubMed

Iyer, Deepa; Patil, U K

2014-01-01

Salvadora indica Wight (Salvadoraceae) contains a number of medically beneficial properties including abrasives, astringents and antiseptics. Traditionally, it was used by ancient Arabs to whiten and polish teeth. This study explores the antihyperlipidemic and antitumor effects of an ethanol extract of S. indica and its isolated phytoconstituents in rodents. Flash chromatography was used for the isolation of phytoconstituents from the stems of S. indica. An antihyperlipidemic study was carried out in Triton loaded rats. Animal groups were given intraperitoneal (i.p.) injection of Triton WR 1339 at dose of 400 mg/kg body weight (b.w.). Furthermore, antitumor activity was investigated in hybrid mice (of C57BL strain + Swiss albino strain). The animals were observed for tumor growth after injection of B16F10 melanoma cells into the dorsal skin of mice. The stems of S. indica yielded xanthotoxin and umbelliferone through chromatographic separation techniques. The structures of the compounds were elucidated by spectroscopic data interpretation and showed antihyperlipidemic activity. The study showed significant reduction in total cholesterol (TC) (p < 0.01), triglycerides (TGs) (p < 0.001), low-density lipoproteins (p < 0.01) level whereas increased in high-density lipoprotein (p < 0.01) at a significant level, after the treatment. Pretreatment with the extract and phytoconstituents also showed delayed tumor growth by increasing the volume doubling time (VDT) (p < 0.01), growth delay (GD) (p < 0.01) and mean survival time (p < 0.001). Acute treatment caused a stimulatory effect on high density lipoprotein level and inhibition in TC and TG elevation induced by Triton. Tumor regression studies showed a regression response for tumor growth in vivo of murine mouse melanoma as demonstrated by increasing the VDT and GD.

Activation of AKT/GSK3β pathway by TDZD-8 attenuates kainic acid induced neurodegeneration but not seizures in mice.

PubMed

Bhowmik, Malay; Khanam, Razia; Saini, Neeru; Vohora, Divya

2015-01-01

Activation of glycogen synthase kinase3β (GSK3β), an enzyme that regulates a multitude of cellular signaling pathways, is implicated in neurodegenerative processes observed in an array of CNS diseases. We examined the hypothesis that the pathological changes in an acute kainic acid (KA) induced excitotoxicity model, relevant to human temporal lobe epilepsy (TLE), could be sensitive to inhibition of GSK3β by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) treatment in Swiss albino mice. Immediate seizure responses due to KA were recorded. Neurodegenerative and morphogenic changes were examined by western blot analysis and light microscopy, respectively, 48 h after KA administration. Although tonic-clonic seizure episodes evoked by KA were unaffected, TDZD-8 pretreatment decreased KA mediated elevation in caspase-3 cleavage as well as increased Bcl2 and phospho-GSK3β (Ser9; pGSK3β(Ser9)) expression. Likewise, microscopic examination also revealed that pretreatment with TDZD-8 attenuated cell damage elicited by KA in the CA1, CA3 and DG regions. In all the above parameters, the combined effect of a sub-effective dose of sodium valproate (SVP) with TDZD-8 was higher than that of solitary TDZD-8 treatment. The findings suggest that activated GSK3β orchestrated neurodegenerative alterations following KA treatment and its inhibition by TDZD-8 affords a distinct neuroprotective profile by activating Akt/GSK3β pathway which might act upstream of Bax/Bcl2 and caspase-3 pathways. Compounds targeting GSK3β activity might represent a novel therapeutic option for exploration as an adjunct to conventional anti-epileptic drugs in preventing neurodegenerative processes in TLE. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of storage temperature on the quantity and integrity of genomic DNA extracted from mice tissues: A comparison of recovery methods

PubMed Central

Al-Griw, Huda H.; Zraba, Zena A.; Al-Muntaser, Salsabiel K.; Draid, Marwan M.; Zaidi, Aisha M.; Tabagh, Refaat M.; Al-Griw, Mohamed A.

2017-01-01

Efficient extraction of genomic DNA (gDNA) from biological materials found in harsh environments is the first step for successful forensic DNA profiling. This study aimed to evaluate two methods for DNA recovery from animal tissues (livers, muscles), focusing on the best storage temperature for DNA yield in term of quality, quantity, and integrity for use in several downstream molecular techniques. Six male Swiss albino mice were sacrificed, liver and muscle tissues (n=32) were then harvested and stored for one week in different temperatures, -20°C, 4°C, 25°C and 40°C. The conditioned animal tissues were used for DNA extraction by Chelex-100 method or NucleoSpinC Blood and Tissue kit. The extracted gDNA was visualized on 1.5% agarose gel electrophoresis to determine the quality of gDNA and analysed spectrophotometrically to determine the DNA concentration and the purity. Both methods, Chelex-100 and NucleoSpin Blood and Tissue kit found to be appropriate for yielding high quantity of gDNA, with the Chelex 100 method yielding a greater quantity (P < 0.045) than the kit. At -20°C, 4°C, and 25°C temperatures, the concentration of DNA yield was numerically lower than at 40°C. The NucleoSpinC Blood and Tissue kit produced a higher (P=0.031) purity product than the Chelex-100 method, particularly for muscle tissues. The Chelex-100 method is cheap, fast, effective, and is a crucial tool for yielding DNA from animal tissues (livers, muscles) exposed to harsh environment with little limitations. PMID:28884076

In vivo radioprotection by alpha-TMG: preliminary studies.

PubMed

Satyamitra, M; Devi, P U; Murase, H; Kagiya, V T

2001-08-08

alpha-TMG is a novel water-soluble derivative of Vitamin E that has shown excellent antioxidant activity. The parent compound has demonstrated protection against radiation induced chromosomal damage in vivo. Hence, the preliminary experiments to determine the radioprotective activity of alpha-TMG were carried out in adult Swiss albino mice. Acute toxicity of the drug was studied taking 24h, 72 h and 30 day mortality after a single intraperitoneal injection of 500-2000 mg/kg body weight of the drug. The drug LD(50) for 24h and 72 h/30 day survival were found to be 1120 and 1000 mg/kg body weight, respectively. The optimum time of drug administration and drug dose-dependent effect on in vivo radiation protection of bone marrow chromosomes was studied in mice. Injection of 600 mg/kg of the drug 15 min before or within 5, 15 or 30min after 3Gy whole body gamma radiation resulted in a significant decrease in the aberrant metaphases percent at 24h post-irradiation; the maximum effect was seen when the drug was given immediately after irradiation. Injection of 200-800 mg/kg TMG within 5 min of irradiation with 3 Gy produced a significant dose-dependent reduction in the radiation induced percent aberrant metaphases and in the frequency of micronucleated erythrocytes at 24h after exposure, with a corresponding decrease in the different types of aberrations. The optimum dose for protection without drug toxicity was 600 mg/kg body weight. At this dose, TMG produced 70 and >60% reduction in the radiation induced percent aberrant metaphases and micronucleated erythrocytes, respectively. The high water solubility and effectiveness when administered post-irradiation favor TMG as a likely candidate for protection in case of accidental exposures.

Anti-inflammatory and analgesic activities of solvent fractions of the leaves of Moringa stenopetala Bak. (Moringaceae) in mice models.

PubMed

Tamrat, Yohannes; Nedi, Teshome; Assefa, Solomon; Teklehaymanot, Tilahun; Shibeshi, Workineh

2017-09-29

Many people still experience pain and inflammation regardless of the available drugs for treatments. In addition, the available drugs have many side effects, which necessitated a quest for new drugs from several sources in which medicinal plants are the major one. This study evaluated the analgesic and anti- inflammatory activity of the solvent fractions of Moringa stenopetala in rodent models of pain and inflammation. Successive soxhlet and maceration were used as methods of extractions using solvents of increasing polarity; chloroform, methanol and water. Swiss albino mice models were used in radiant tail flick latency, acetic acid induced writhing and carrageenan induced paw edema to assess the analgesic and anti-inflammatory activities. The test groups received different doses (100 mg/kg, 200 mg/kg and 400 mg/kg) of the three fractions (chloroform, methanol and aqueous). The positive control groups received morphine (20 mg/kg) or aspirin (100 mg/kg or 150 mg/kg) based on the respective models. The negative control groups received the 10 ml/kg of vehicles (distilled water or 2% Tween 80). In all models, the chloroform fraction had protections only at a dose of 400 mg/kg. However, the methanol and aqueous fraction at all doses have shown significant central and peripheral analgesic activities with a comparable result to the standards. The aqueous and methanol fractions significantly reduced carrageenan induced inflammation in a dose dependent manner, in which the highest reduction of inflammation was observed in aqueous fraction at 400 mg/kg. This study provided evidence on the traditionally claimed uses of the plant in pain and inflammatory diseases, and Moringa stenopetala could be potential source for development of new analgesic and anti-inflammatory drugs.

Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones.

PubMed

Sarkar, Souvik; Siddiqui, Asim A; Saha, Shubhra J; De, Rudranil; Mazumder, Somnath; Banerjee, Chinmoy; Iqbal, Mohd S; Nag, Shiladitya; Adhikari, Susanta; Bandyopadhyay, Uday

2016-07-01

We synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. These hydrazones concentration-dependently chelated free iron and offered antimalarial activity. Upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. Compound 5f also interacted with free heme (KD [equilibrium dissociation constant] = 1.17 ± 0.8 μM), an iron-containing tetrapyrrole released after hemoglobin digestion by the parasite, and inhibited heme polymerization by parasite lysate. Structure-activity relationship studies indicated that a nitrogen- and sulfur-substituted five-membered aromatic ring present within the benzothiazole hydrazones might be responsible for their antimalarial activity. The dose-dependent antimalarial and heme polymerization inhibitory activities of the lead compound 5f were further validated by following [(3)H]hypoxanthine incorporation and hemozoin formation in parasite, respectively. It is worth mentioning that compound 5f exhibited antiplasmodial activity in vitro against a chloroquine/pyrimethamine-resistant strain of Plasmodium falciparum (K1). We also evaluated in vivo antimalarial activity of compound 5f in a murine model where a lethal multiple-drug-resistant strain of Plasmodium yoelii was used to infect Swiss albino mice. Compound 5f significantly suppressed the growth of parasite, and the infected mice experienced longer life spans upon treatment with this compound. During in vitro and in vivo toxicity assays, compound 5f showed minimal alteration in biochemical and hematological parameters compared to control. In conclusion, we identified a new class of hydrazone with therapeutic potential against malaria. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Low power laser irradiation stimulates cell proliferation via proliferating cell nuclear antigen and Ki-67 expression during tissue repair

NASA Astrophysics Data System (ADS)

Prabhu, Vijendra; Rao, Bola Sadashiva Satish; Mahato, Krishna Kishore

2015-03-01

Low power laser irradiation (LPLI) is becoming an increasingly popular and fast growing therapeutic modality in dermatology to treat various ailments without any reported side effects. In the present study an attempt was made to investigate the proliferative potential of red laser light during tissue repair in Swiss albino mice. To this end, full thickness excisional wounds of diameter 15 mm created on mice were exposed to single dose of Helium-Neon laser (632.8 nm; 7 mW; 4.02 mWcm-2; Linear polarization) at 2 Jcm-2 and 10 Jcm-2 along with un-illuminated controls. The granulation tissues from all the respective experimental groups were harvested on day 10 post-wounding following euthanization. Subsequently, tissue regeneration potential of these laser doses under study were evaluated by monitoring proliferating cell nuclear antigen and Ki-67 following the laser treatment and comparing it with the un-illuminated controls. The percentages of Ki-67 or PCNA positive cells were determined by counting positive nuclei (Ki-67/PCNA) and total nuclei in five random fields per tissue sections. Animal wounds treated with single exposure of the 2 Jcm-2 indicated significant elevation in PCNA (P<0.01) and Ki-67 (P<0.05 compared to un-illuminated control and P<0.01 compared to 10 Jcm-2) expression as compared to other tested experimental groups as evidenced by the microscopy results in the study. In summary, the findings of the present study have clearly demonstrated the regulation of cell proliferation by LPLI via PCNA and Ki-67 expression during tissue regeneration.

Anti-Eimeria activity of berberine and identification of associated gene expression changes in the mouse jejunum infected with Eimeria papillata.

PubMed

Dkhil, Mohamed A; Metwaly, Mahmoud S; Al-Quraishy, Saleh; Sherif, Nour E; Delic, Denis; Al Omar, Suliman Y; Wunderlich, Frank

2015-04-01

Plant-based natural products are promising sources for identifying novel agents with potential anti-Eimeria activity. This study explores possible effects of berberine on Eimeria papillata infections in the jejunum of male Swiss albino mice. Berberine chloride, when daily administered to mice during infection, impairs intracellular development and multiplication of E. papillata, evidenced as 60% reduction of maximal fecal output of oocysts on day 5 p.i. Concomitantly, berberine attenuates the inflammatory response, evidenced as decreased messenger RNA (mRNA) expression of IL-1β, IL-6, TNFα, IFNγ, and iNOS, as well as the oxidative stress response, evidenced as impaired increase in malondialdehyde, nitrate, and H2O2 and as prevented decrease in glutathione and catalase activity. Berberine also alters gene expression in the infected jejunum. On day 5 p.i., mRNA expression of 29 genes with annotated functions is more than 10-fold upregulated and that of 14 genes downregulated. Berberine downregulates the genes Xaf1, Itgb3bp, and Faim3 involved in apoptotic processes and upregulates genes involved in innate immune responses, as e.g., Colec11, Saa2, Klra8, Clec1b, and Crtam, especially the genes Cpa3, Fcer1a, and Mcpt1, Mcpt2, and Mcpt4 involved in mast cell activity. Additionally, 18 noncoding lincRNA species are differentially expressed more than 10-fold under berberine. Our data suggest that berberine induces hosts to exert anti-Eimeria activity by attenuating the inflammatory and oxidative stress response, by impairing apoptotic processes, and by activating local innate immune responses and epigenetic mechanisms in the host jejunum. Berberine has the potential as an anti-Eimeria food additive in animal farming.

Antimicrobial, antiplasmodial, haemolytic and antioxidant activities of crude extracts from three selected Togolese medicinal plants.

PubMed

Karou, Simplice D; Tchacondo, Tchadjobo; Ouattara, Lassina; Anani, Kokou; Savadogo, Aly; Agbonon, Amegnona; Attaia, Mossaclok Ben; de Souza, Comlan; Sakly, Mohsen; Simpore, Jacques

2011-10-01

To investigate the antioxidant, antimicrobial, antiplasmodial, acute toxicity and haemolytic activities of methanolic extracts of three plants. Phytochemical analysis to determine the phenolic contents was also carried out. The 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical scavenging, NCCLS broth microdilution and Plasmodium Lactate Dehydrogenase (pLDH) assays were used to determine antioxidant, antimicrobial and antiplasmodial activities, respectively. Haemolysis assay was conducted on A(+) human red blood cells and acute toxicity on male Swiss albino mice. Phenolics were quantitatively determined using spectrophotometric methods. The DPPH assay yielded interesting antioxidant activities of methanolic extract of Parinari curatellifolia (P. curatellifolia) and Entada africana (E. africana) (IC(50) were 0.20±0.01 μg/mL and 0.47±0.01 μg/mL, respectively). This activity was highly correlated with phenolic contents of extracts. The antimicrobial tests displayed minimal inhibitory concentrations (MICs) values ranging from 0.90 to 1.80 mg/mL for Serratia marcescens (S. marcescens) the most susceptible bacterial strain. MIC value was 1.20 mg/mL for susceptible fungal strains including Mucor rouxi (M. rouxi), Fusarium oxyporum (F. oxyporum) and Rhizopus nigricans (R. nigricans). pLDH assay showed moderate antiplasmodial activity of Balanites aegyptiaca (B. aegyptiaca) (IC(50) = 24.56±3.45 μg/mL), however this extract was highly haemolytic and toxic in mice (LD(50) = 625±128 mg/kg). Our results support in part the use of the selected plants in the treatment of microbial infections. In addition the plant showed interesting antioxidant activity that could be useful in the management of oxidative stress. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Lethality In Mice Following Localized Photodynamic Therapy

NASA Astrophysics Data System (ADS)

Ferrario, Angela; Gomer, Charles J.; Murphree, A. L.

1989-06-01

Porphyrin photodynamic therapy directed specifically to the hind leg of various strains of mice was found to induce a high percentage of lethality at dosages which would be required to achieve cures in tumor bearing mice. Toxicity was observed in both pigmented and albino mouse strains. An inverse relationship between light dose rate and lethality was documented. Anti-coagulant drugs and anti-inflammatory agents which inhibit cyclo-oxygenase had protective effects. The response induced by localized PDT appears to mimic that of a classical traumatic shock syndrome and may be limited to PDT in small animals such as mice.

Safety of a novel botanical extract formula for ameliorating allergic rhinitis.

PubMed

Amit, A; Saxena, V S; Pratibha, N; Bagchi, M; Bagchi, D; Stohs, S J

2003-01-01

Allergic rhinitis (also known as hay fever) is the most commonly occurring immunological disorder, and it affects 40 million men, women, and children in the United States. Symptomatically, it is an inflammation and irritation of the mucous membranes that line the nose. Allergy is defined as a state of hypersensitivity or hyperimmunity caused by exposure to a particular antigen (allergen) that results in increased reactivity upon subsequent exposure. A novel botanical formulation, Aller-7/NR-A2, was developed for the treatment of allergic rhinitis; it is a combination of medicinal plant extracts from Phyllanthus emblica, Terminalia chebula, Terminalia bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale, and Piper longum. This novel formulation has demonstrated potent antihistaminic, anti-inflammatory, antispasmodic, antioxidant, and mast-cell-stabilization activities. All of the doses for these toxicity studies were selected according to the guidelines of the Organization for Economic Cooperation and Development, the World Health Organization, and the Environmental Protection Agency. Acute toxicity of Aller-7 was evaluated in Swiss Albino mice at doses of 125, 250, 500, 1000, and 1500 mg/kg. After 15 days of treatment, the animals were sacrificed. No histopathological changes were observed in major vital organs. A similar study was conducted in Albino Wistar rats, which were sacrificed at the end of 15 days. No histopathological changes or toxicity was observed at up to 2 g/kg body weight. Subacute toxicity was conducted in Albino Wistar rats at a dose of 90 mg/kg body weight for 3 days, then at 180 mg/kg for the next 3 days, and then at 270 mg/kg for 3 weeks. After 28 days, the animals were sacrificed and tested; no toxicity was observed. In a subchronic toxicity study, there was no observed adverse effect level at 1 g/kg body weight in rats. In a teratological assay, at doses of 3.0 g/kg (20 times the recommended dose) and 1.8 g/kg, respectively, no visceral or skeletal anomalies were observed in the fetuses. No maternal changes were observed when Aller-7 was administered during gestation and lactation. No evidence of mutagenicity was observed at doses up to 5000 mug per plate of Aller-7 in Salmonella typhimurium cells. The present study evaluated the safety of Aller-7 by conducting several in vitro and in vivo studies. Further studies of the 90-day chronic toxicity of Aller-7 are currently in progress.

Abortifacient potential of methanolic extract of Anthocephalus cadamba stem bark in mice.

PubMed

Shaikh, Muhammad Vaseem; Kala, Manika; Ravat, Nirav; Nivsarkar, Manish

2015-09-15

Medicinal plants possessing abortifacient activity have been used traditionally for a long time in folk medicine. Anthocephalus cadamba, is one such herb that has been known to possess abortifacient potential in ethnobotanical literature, but has not been validated scientifically. The methanolic extract of Anthocephalus cadamba stem bark (MEAC) was prepared and tested for abortifacient, estrogenic and uterotrophic activity. Pregnant Swiss albino mice were randomized into 5 groups (1-5). Group 1 (negative control) received 0.2% w/v agar, group 2-4 (received extract at the dose of 500, 1000 and 1500mg/kg b.w.) and group 5 received mifepristone at a dose of 5.86mg/kg b.w. respectively, by oral route from 10(th) to 18(th) day post-coitum daily, and various parameters recorded. The uterotrophic bioassay was performed in bilaterally ovariectomized mice dosed from 9(th) to 15(th) day of ovariectomy and change in uterotrophic parameters was observed. Preliminary phytochemical screening revealed presence of glycosides, alkaloids, steroids, saponins, triterpenoids, flavonoids and tannins. No signs of clinical toxicity were observed at any time during the period of treatment. The extract significantly reduced (P<0.05) the number of live fetus, weight and survival ratio of the fetus, number of corpora lutea, progesterone, estradiol and luteinizing hormone whereas the number of dead fetus, number of mice that aborted, percentage vaginal opening and post-implantation loss increased significantly (P<0.05). The estrogenicity experiments showed increase in uterine weight (P<0.05), ballooning of uterus, uterine glucose (P<0.05) and ALP (P<0.001) in extract treated group dose dependently. In addition, the extract also induced vaginal bleeding preceding parturition. This study has substantiated the abortifacient potential of the methanolic extract of Anthocephalus cadamba stem bark. The activity was more marked in 1000 and 1500mg/kg b.w. of the extract and was comparable to that of mifepristone. The mechanism of abortion could possibly be through changes in the uterine mileu, altered hormone levels, luteolysis and partly, estrogenicity. This study thus justifies the ethnobotanical claim of MEAC as an abortifacient. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of the neuroprotective potential of Mucuna pruriens seed extract with estrogen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model.

PubMed

Yadav, Satyndra Kumar; Prakash, Jay; Chouhan, Shikha; Westfall, Susan; Verma, Mradul; Singh, Tryambak Deo; Singh, Surya Pratap

2014-01-01

Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In Ayurveda, Mucuna pruriens (Mp), a leguminous plant, is used as an anti-inflammatory drug. In this study, the neuroprotective effect of an ethanolic extract of Mp seed is evaluated in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and compared to estrogen, a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+Mp and MPTP+estrogen. The behavioural recovery in both Mp and estrogen treated mice was investigated using the rotarod, foot printing and hanging tests. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by tyrosine hydroxylase (TH), immunostaining. Additionally inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) immunoreactivity was evaluated to assess the level of oxidative damage and glial activation respectively. The levels of dopamine and its metabolite in the nigrostriatal region were measured by HPLC. Mp treatment restored all the deficits induced by MPTP more effectively than estrogen. Mp treatment recovered the number of TH-positive cells in both the SN region and the striatum while reducing the expression of iNOS and GFAP in the SN. Treatment with Mp significantly increased the levels of dopamine, DOPAC and homovanillic acid compared to MPTP intoxicated mice. Notably, the effect of Mp was greater than that elicited by estrogen. Mp down regulates NO production, neuroinflammation and microglial activation and all of these actions contribute to Mp's neuroprotective activity. These results suggest that Mp can be an effective treatment for neurodegenerative diseases, especially PD by decreasing oxidative stress and possibly by implementing neuronal and glial cell crosstalk. Copyright © 2013 Elsevier Ltd. All rights reserved.

Whole body protection against lethal ionizing radiation in mice by REC-2001: a semi-purified fraction of Podophyllum hexandrum.

PubMed

Lata, M; Prasad, J; Singh, S; Kumar, R; Singh, L; Chaudhary, P; Arora, R; Chawla, R; Tyagi, S; Soni, N L; Sagar, R K; Devi, M; Sharma, R K; Puri, S C; Tripathi, R P

2009-01-01

The current study has concentrated on assessment of the radioprotective potential of REC-2001, a semi-purified fraction of rhizomes of Podophyllum hexandrum, in Swiss albino Strain 'A' mice exposed to 10 Gy whole-body gamma radiation. Animals were treated with 10 and 15 mg/kg b wt (i.p.) of REC-2001 1h prior to exposure to a lethal dose of gamma-radiation (10 Gy) and observed upto 30 days. For analysis of maximum tolerable dose (MTD), LD(50) and acute toxic dose, different concentrations of the extract were administered to animals and their mortality and morbidity status was observed upto 72 h and one week, respectively. Dose reduction factor (DRF) was determined by exposing REC-2001 pre-treated mice to supra-lethal doses of gamma-radiation. Endogenous spleen colony forming units (CFU), DNA strand breaks in thymocytes (alkaline halo assay) and lipid degradation was studied to understand the mechanism of radioprotection. A single dose of REC-2001 (10 and 15 mg/kg b wt i.p.) exhibited >90% survival in the pre-treated irradiated group versus no survival in radiation control group. Single doses of upto 75 mg/kg b wt (i.p.) did not cause any mortality (MTD) in mice. REC-2001, a dose of 90 mg/kg b wt, resulted in 50% mortality (LD(50)), while the LD(100) was 115 mg/kg b wt REC-2001 exhibited a DRF of 1.62. CFU counts in the REC-2001 treated group were found significantly high (5.33/spleen) as compared to controls. Exposure of thymocytes to 10 Gy radiation resulted in increased halo diameter (45+/-3 microm) in comparison to untreated controls (8+/-1 microm). REC-2001 administration (500 microg/ml) decreased the halo diameter to 15+/-2 microm. Radiation-induced lipid degradation was also inhibited by REC-2001. The present study has revealed that REC-2001 is a promising radioprotective fraction that can be effectively used against lethal doses of gamma-radiation after further investigations in higher animal models.

Protective effect of unsymmetrical dichalcogenide, a novel antioxidant agent, in vitro and an in vivo model of brain oxidative damage.

PubMed

Prigol, Marina; Wilhelm, Ethel A; Schneider, Caroline C; Nogueira, Cristina W

2008-11-25

Unsymmetrical dichalcogenides, a class of organoselenium compounds, were screened for antioxidant activity in rat brain homogenates in vitro. Unsymmetrical dichalcogenides (1-3) were tested against lipid peroxidation induced by sodium nitroprusside (SNP) or malonate, and reactive species (RS) production induced by sodium azide in rat brain homogenates. Compounds 1 (without a substituent at the phenyl group), 2 (chloro substituent at the phenyl group bounded to the sulfur atom) and 3 (chloro substituent at the phenyl group bounded to the selenium atom) protected against lipid peroxidation induced by SNP. The IC50 values followed the order 3<2<1. Lipid peroxidation induced by malonate was also reduced by dichalcogenides 1, 2 and 3. The IC50 values were 3

Assessment of the genotoxic/clastogenic potential of coumarin derivative 6,7-dihydroxycoumarin (aesculetin) in multiple mouse organs.

PubMed

Marques, Eduardo de Souza; Salles, Daiane Bernardoni; Maistro, Edson Luis

2015-01-01

6,7-Dihydroxycoumarin (6,7-HC) (aesculetin) is a natural and synthetic coumarin derivative of great interest for use by humans due to their potent antioxidant properties. Considering that there are no reports that assess the in vivo genetic toxicity of 6,7-HC, the aim of the present study was to investigate its genotoxic potential in terms of DNA damage in peripheral blood, liver, bone marrow and testicular cells of Swiss albino mice by the comet assay, and its clastogenic/aneugenic potential in bone marrow cells using the micronucleus test. In addition, the ability of 6,7-HC to modulate the genotoxic effects induced by doxorubicin (DXR) was also preliminarily evaluated. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes' ratio. The test compound was administered orally at doses of 25, 50 and 500 mg kg -1 isolated and also simultaneously to DXR (80 mg kg -1 ). The results showed that 6,7-HC did not induce significant DNA damage in any of the analyzed cells, and also did not show any significant increase in micronucleated PCE at the three tested doses. The PCE/NCE ratio indicated no cytotoxicity. Moreover, the extent of DNA damage induced by DXR decreased significantly only in peripheral blood and testicular cells, and only at the lowest dose of 6,7-HC.

Dextran based herbal nanobiocomposite membranes for scar free wound healing.

PubMed

Singh, Surabhi; Gupta, Amlan; Sharma, Deepika; Gupta, Bhuvanesh

2018-07-01

Dextran based bionanocomposite membranes encapsulating clove oil (CO) and sandalwood oil (SO) that are capable of preventing infection due to their inherent virtue of antibacterial activity and modifying the wound healing cascade for accelerated scar free healing, were developed. A facile solvent casting technique was used to fabricate dextran/nanosoy/glycerol/chitosan (DNG/Ch) nanocomposite membranes followed by subsequent addition of CO and SO to obtain DNG/Ch/CO and DNG/Ch/SO herbal nanodressings. Dressings exhibited >98% antibacterial activity against both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) at extremely low loadings of 5% and 10% for CO and SO, respectively. This encapsulation strategy allowed controlled diffusion of EO over a period of 72h which was measured in terms of drug efficacy using bacterial reduction count test and serial plate transfer disk diffusion test (SPTDDT). Swelling behavior and mechanical properties were also examined. Bacterial adherence study was performed to demonstrate the efficiency of dressings for arresting microbial invasion. In vivo wound healing studies were conducted using male swiss albino mice of BALB/c strain and DNG/Ch/CO dressings exhibited complete healing within 14days with remarkable efficacy in scar prevention. Histological analysis revealed that CO and SO treatment led to deposition of ordered collagen along with fibroblast migration. Copyright © 2018 Elsevier B.V. All rights reserved.

Pomegranate fruit as a rich source of biologically active compounds.

PubMed

Sreekumar, Sreeja; Sithul, Hima; Muraleedharan, Parvathy; Azeez, Juberiya Mohammed; Sreeharshan, Sreeja

2014-01-01

Pomegranate is a widely used plant having medicinal properties. In this review, we have mainly focused on the already published data from our laboratory pertaining to the effect of methanol extract of pericarp of pomegranate (PME) and have compared it with other relevant literatures on Punica. Earlier, we had shown its antiproliferative effect using human breast (MCF-7, MDA MB-231), and endometrial (HEC-1A), cervical (SiHa, HeLa), and ovarian (SKOV3) cancer cell lines, and normal breast fibroblasts (MCF-10A) at concentration of 20-320 μg/mL. The expressions of selected estrogen responsive genes (PR, pS2, and C-Myc) were downregulated by PME. Unlike estradiol, PME did not increase the uterine weight and proliferation in bilaterally ovariectomized Swiss-Albino mice models and its cardioprotective effects were comparable to that of 17 β -estradiol. We had further assessed the protective role of PME on skeletal system, using MC3T3-E1 cells. The results indicated that PME (80 μg/mL) significantly increased ALP (Alkaline Phosphatase) activity, supporting its suggested role in modulating osteoblastic cell differentiation. The antiosteoporotic potential of PME was also evaluated in ovariectomized (OVX) rodent model. The results from our studies and from various other studies support the fact that pomegranate fruit is indeed a source of biologically active compounds.

Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid.

PubMed

Patra, Kartick; Bose, Samadrita; Sarkar, Shehnaz; Rakshit, Jyotirmoy; Jana, Samarjit; Mukherjee, Avik; Roy, Abhishek; Mandal, Deba Prasad; Bhattacharjee, Shamee

2012-02-05

Cinnamic acid (C9H8O2), is a major constituent of the oriental Ayurvedic plant Cinnamomum cassia (Family: Lauraceae). This phenolic acid has been reported to possess various pharmacological properties of which its antioxidant activity is a prime one. Therefore it is rational to hypothesize that it may ameliorate myelosuppression and oxidative stress induced by cyclophosphamide, a widely used chemotherapeutic agent. Commercial cyclophosphamide, Endoxan, was administered intraperitoneally to Swiss albino mice (50mg/kg) pretreated with 15, 30 and 60mg/kg doses of cinnamic acid orally at alternate days for 15days. Cinnamic acid pre-treatment was found to reduce cyclophosphamide induced hypocellularity in the bone marrow and spleen. This recovery was also reflected in the peripheral blood count. Amelioration of hypocellularity could be correlated with the modulation of cell cycle phase distribution. Cinnamic acid pre-treatment reduced bone marrow and hepatic oxidative stress as evident by lipid peroxidation and activity assays of antioxidant enzymes such as superoxide dismutase, catalase and glutathione-S-transferase. The present study indicates that cinnamic acid pretreatment has protective influence on the myelosuppression and oxidative stress induced by cyclophosphamide. This investigation is an attempt and is the first of its kind to establish cinnamic acid as an agent whose consumption provides protection to normal cells from the toxic effects of a widely used anti-cancer drug. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Two different approaches in skin cancer therapy: using a photosensitizer/a natural product

NASA Astrophysics Data System (ADS)

Abraham, Annie; Gayathri, Devi D.; Cibin, T. R.; Ramaiah, D.

2010-02-01

This paper deals with two potential modes for the treatment of skin cancer-one a novel approach using a squaraine dye and the other using a natural product- the flavonoid fraction of Saraca asoka. Squaraine dye is a photosensitizing agent, which is preferentially taken up and retained by the tumor cells and when irradiated with high power visible light results in the selective destruction of the tumor cells by photodynamic therapy. The uniqueness of this mode of treatment lies in the selective destruction of tumor cells without affecting the neighbouring normal cells, which is much advantageous over radiation therapy now frequently used. The chemopreventive and therapeutic effects of the plant component are explored as well. The experimental models were Swiss albino mice in which skin tumor was induced by DMBA. Marked reduction in tumor volume and burden in the treated groups were observed. The reversal of biochemical enzyme markers like rhodanese, myeloperoxidase, β-D glucuronidase, lactate dehydrogenase, hexokinase and sialic acid to near normal levels were observed in the PDT and flavonoid fraction treated groups. The live photographs of the experimental animals and histopathological data further support the obtained results. The study assumes importance as it combines a traditional treatment mode and a novel aspect in cancer therapy using the same experimental models. Also this is the first report on PDT using a squaraine dye for skin cancer therapy in vivo.

Ethanolic extract of Moringa oleifera Lam. leaves protect the pre-pubertal spermatogonial cells from cyclophosphamide-induced damage.

PubMed

Nayak, Guruprasad; Honguntikar, Sachin D; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Mutalik, Srinivas; Setty, Manjunath M; Kalyankumar, Raksha; Krishnamurthy, Hanumanthappa; Kalthur, Guruprasad; Adiga, Satish Kumar

2016-04-22

Moringa oleifera Lam. is widely cultivated in Asian and African countries for its medicinal and dietary significance. The leaves are highly nutritious and are known to possess various biological activities. Pre-pubertal Swiss albino male mice were injected with single dose of cyclophosphamide (CP, 200mg/kg body weight) or ethanolic extract of Moringa oleifera leaves (MOE, 100mg/kg body weight) intraperitoneally. In combination group, MOE was administered 24h prior to CP injection. CP induced a significant decrease in testicular weight (p<0.01) and depletion of germ cells (p<0.001) and higher level of DNA damage (p<0.001) compared to control. The expression of P53, Bax, Cytochrome C (Cyt C) was increased while there was a decrease in the expression of Bcl2, c-Kit and Oct4. Administration of MOE 24h prior to CP treatment ameliorated the depletion (p<0.001), DNA damage (p<0.001) and apoptosis (p<0.01) of germ cells induced by CP. The mitigating effect of MOE appears to be mediated by up-regulating the expression of c-Kit and Oct4 transcripts in P53-independent manner. MOE protects the spermatogonial cells from CP-induced damage by modulating the apoptotic response elicited by CP and therefore can be considered as an efficient method of male fertility preservation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Intraspecific Variation of Centruroides Edwardsii Venom from Two Regions of Colombia

PubMed Central

Estrada-Gómez, Sebastián; Cupitra, Nelson Ivan; Arango, Walter Murillo; Vargas Muñoz, Leidy Johana

2014-01-01

We report the first description studies, partial characterization, and intraspecific difference of Centruroides edwardsii, Gervais 1843, venom. C. edwardsii from two Colombian regions (Antioquia and Tolima) were evaluated. Both venoms showed hemolytic activity, possibly dependent of enzymatic active phospholipases, and neither coagulant nor proteolytic activities were observed. Venom electrophoretic profile showed significant differences between C. edwardsii venom from both regions. A high concentration of proteins with molecular masses between 31 kDa and 97.4 kDa, and an important concentration close or below 14.4 kDa were detected. RP-HPLC retention times between 38.2 min and 42.1 min, showed bands close to 14.4 kDa, which may correspond to phospholipases. RP-HPLC venom profile showed a well conserved region in both venoms between 7 and 17 min, after this, significant differences were detected. From Tolima region venom, 50 well-defined peaks were detected, while in the Antioquia region venom, 55 well-defined peaks were detected. Larvicidal activity was only detected in the C. edwardsii venom from Antioquia. No antimicrobial activity was observed using complete venom or RP-HPLC collected fractions of both venoms. Lethally activity (carried out on female albino swiss mice) was detected at doses over 19.2 mg/kg of crude venom. Toxic effects included distress, excitability, eye irritation and secretions, hyperventilation, ataxia, paralysis, and salivation. PMID:25025710

In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments.

PubMed

Kasinathan, Narayanan; Amirthalingam, Muthukumar; Reddy, Neetinkumar D; Jagani, Hitesh V; Volety, Subrahmanyam M; Rao, Josyula Venkata

2016-01-01

Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes. To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN). In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer. The effect of independent variables was studied in two stages. First, the effect of drug-polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500 nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release. This implant could be further evaluated for pharmacological activities.

TNF-α inhibits SCF, ghrelin, and substance P expressions through the NF-κB pathway activation in interstitial cells of Cajal.

PubMed

Ren, Keyu; Yong, Chunming; Yuan, Hao; Cao, Bin; Zhao, Kun; Wang, Jin

2018-01-01

Ulcerative colitis is a chronic inflammatory disease of the colon where intestinal motility is disturbed. Interstitial cells of Cajal (ICC) are required to maintain normal intestinal motility. In the present study, we assessed the effect of tumor necrosis factor-alpha (TNF-α) on viability and apoptosis of ICC, as well as on the expression of stem cell factor (SCF), ghrelin, and substance P. ICC were derived from the small intestines of Swiss albino mice. Cell viability and apoptosis were measured using CCK-8 assay and flow cytometry, respectively. ELISA was used to measure the concentrations of IL-1β, IL-6, ghrelin, substance P, and endothelin-1. Quantitative RT-PCR was used to measure the expression of SCF. Western blotting was used to measure the expression of apoptosis-related proteins, interleukins, SCF, and NF-κB signaling pathway proteins. TNF-α induced inflammatory injury in ICC by decreasing cell viability and increasing apoptosis and levels of IL-1β and IL-6. TNF-α decreased the levels of SCF, ghrelin, and substance P, but had no effect on endothelin-1. TNF-α down-regulated expressions of SCF, ghrelin, and substance P by activating the NF-κB pathway in ICC. In conclusion, TNF-α down-regulated the expressions of SCF, ghrelin, and substance P via the activation of the NF-κB pathway in ICC.

Superparamagnetic Iron Oxide-Loaded Lipid Nanocarriers Incorporated in Thermosensitive In Situ Gel for Magnetic Brain Targeting of Clonazepam.

PubMed

Abbas, Haidy; Refai, Hanan; El Sayed, Nesrine

2018-04-14

The objective of the study was to target clonazepam to the brain through the intranasal olfactory mucosa using nanolipid carriers loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to allow nanocarrier guidance and retention with an external magnetic field. For improved delivery, the nanolipid carriers were incorporated in a thermosensitive mucoadhesive in situ gel. Different nanolipid carriers including solid lipid nanoparticles and nanostructured lipid carriers (NLC) were prepared and characterized with respect to particle size, zeta potential, entrapment efficiency, and in vitro release. The NLC composed of 3 solid lipids (Compritol ® 888, stearic acid, and glyceryl monostearate) and 2 liquid oils (oleic acid and glyceryl monooleate) showed the most satisfactory characteristics and was loaded with SPION (NLC/SPION). Both formulae (NLC and NLC/SPION) were incorporated in an optimized thermosensitive mucoadhesive in situ system composed of 15% pluronic 127 and 0.75% sodium alginate and evaluated for the anticonvulsant action in chemically induced convulsive Swiss Albino mice. The treatment of animals with NLC/SPION significantly prolonged the onset times for convulsion and considerably protected the animals from death. One can thus hope for the emergence of a new intranasal treatment of epilepsy with consequent decrease in peripheral side effects of clonazepam. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Ganoderma lucidum total triterpenes induce apoptosis in MCF-7 cells and attenuate DMBA induced mammary and skin carcinomas in experimental animals.

PubMed

Smina, T P; Nitha, B; Devasagayam, T P A; Janardhanan, K K

2017-01-01

Ganoderma lucidum total triterpenes were evaluated for its apoptosis-inducing and anti-cancer activities. Cytotoxicity and pro-apoptotic effect of total triterpenes were evaluated in human breast adenocarcinoma (MCF-7) cell line using MTT assay and DNA fragmentation analysis. Total triterpenes induced apoptosis in MCF-7 cells by down-regulating the levels of cyclin D1, Bcl-2, Bcl-xL and also by up-regulating the levels of Bax and caspase-9. Anti-carcinogenicity of total triterpenes was analysed using dimethyl benz [a] anthracene (DMBA) induced skin papilloma and mammary adenocarcinoma in Swiss albino mice and Wistar rats respectively. Topical application of 5mg, 10mg and 20mg total triterpenes reduced the incidence of skin papilloma by 62.5, 37.5 and 12.5% respectively. Incidence of the mammary tumour was also reduced significantly by 33.33, 66.67 and 16.67% in 10, 50 and 100mg/kg b.wt. total triterpenes treated animals respectively. Total triterpenes were also found to reduce the average number of tumours per animal and extended the tumour latency period in both the models. The results indicate the potential cytotoxicity and anti-cancerous activity of total triterpenes, there by opens up a path to the development of a safe and successive chemo preventive agent of natural origin. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of novel wound care systems based on nanosilver nanohydrogels of polymethacrylic acid with Aloe vera and curcumin.

PubMed

Anjum, Sadiya; Gupta, Amlan; Sharma, Deepika; Gautam, Deepti; Bhan, Surya; Sharma, Anupama; Kapil, Arti; Gupta, Bhuvanesh

2016-07-01

This study is aimed at the development of a composite material for wound dressing containing nanosilver nanohydrogels (nSnH) along with Aloe vera and curcumin that promote antimicrobial nature, wound healing and infection control. Nanosliver nanohydrogels were synthesized by nanoemulsion polymerization of methacrylic acid (MAA) followed by subsequent crosslinking and silver reduction under irradiation. Both the polymerization and irradiation time had significant influence on the nanoparticle shape, size and its formation. Polyvinyl alcohol/polyethylene oxide/carboxymethyl cellulose matrix was used as gel system to blend with nSnH, A. vera, curcumin and coat it on the hydrolysed PET fabric to develop antimicrobial dressings. The cumulative release of silver from the dressing was found to be ~42% of the total loading after 48h. The antimicrobial activity of the dressings was studied against both Staphylococcus aureus and Escherichia coli. In vivo wound healing studies were carried out over a period of 16d on full-thickness skin wounds created on Swiss albino mice. Fast healing was observed in Gel/nSnH/Aloe treated wounds with minimum scarring, as compared to other groups. The histological studies showed A. vera based dressings to be the most optimum one. These results suggest that nSnH along with A. vera based dressing material could be promising candidates for wound dressings. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of prenatal exposure to mobile phone on pyramidal cell numbers in the mouse hippocampus: a stereological study.

PubMed

Rağbetli, Murat Cetin; Aydinlioğlu, Atif; Koyun, Necat; Rağbetli, Cennet; Karayel, Metin

2009-01-01

Because of the possible risk factor for the health, World Health Organization (WHO) recommended the study with animals on the developing nervous system concerning the exposure to radiofrequency (RF) field. A few studies related to hippocampal exposure are available, which indicate the impact of RF field in some parameters. The present study investigated the effect of exposure to mobile phone on developing hippocampus. Male and female Swiss albino mice were housed as control and mobile phone exposed groups. The pregnant animals in tested group were exposed to the effects of mobile phone in a room possessing the exposure system. The left hemispheres of the brains were processed by frozen microtome. The sections obtained were stained with Hematoxylin & Eosin. For cell counting by the optical fractionator method, a pilot study was first performed. Hippocampal areas were analyzed using Axiovision software running on a personal computer. The optical dissector, systematically and randomly spaced, was focused to the widest profile of the pyramidal cell nucleus. No significant difference in pyramidal cell number of total Cornu Ammonis (CA) sectors of hippocampus was found between the control and the mobile phone exposed groups (p > .05). It was concluded that further study is needed in this field due to popular use of mobile telephones and relatively high exposure to the developing brain.

Pomegranate Fruit as a Rich Source of Biologically Active Compounds

PubMed Central

Sreekumar, Sreeja; Sithul, Hima; Muraleedharan, Parvathy; Azeez, Juberiya Mohammed; Sreeharshan, Sreeja

2014-01-01

Pomegranate is a widely used plant having medicinal properties. In this review, we have mainly focused on the already published data from our laboratory pertaining to the effect of methanol extract of pericarp of pomegranate (PME) and have compared it with other relevant literatures on Punica. Earlier, we had shown its antiproliferative effect using human breast (MCF-7, MDA MB-231), and endometrial (HEC-1A), cervical (SiHa, HeLa), and ovarian (SKOV3) cancer cell lines, and normal breast fibroblasts (MCF-10A) at concentration of 20–320 μg/mL. The expressions of selected estrogen responsive genes (PR, pS2, and C-Myc) were downregulated by PME. Unlike estradiol, PME did not increase the uterine weight and proliferation in bilaterally ovariectomized Swiss-Albino mice models and its cardioprotective effects were comparable to that of 17β-estradiol. We had further assessed the protective role of PME on skeletal system, using MC3T3-E1 cells. The results indicated that PME (80 μg/mL) significantly increased ALP (Alkaline Phosphatase) activity, supporting its suggested role in modulating osteoblastic cell differentiation. The antiosteoporotic potential of PME was also evaluated in ovariectomized (OVX) rodent model. The results from our studies and from various other studies support the fact that pomegranate fruit is indeed a source of biologically active compounds. PMID:24818149

Combinatorial drug delivery strategy employing nano-curcumin and nano-MiADMSA for the treatment of arsenic intoxication in mouse.

PubMed

Kushwaha, Pramod; Yadav, Abhishek; Samim, M; Flora, S J S

2018-04-25

Chelation therapy is the mainstream treatment for heavy metal poisoning. Apart from this, therapy using antioxidant/herbal extracts are the other strategies now commonly being tried for the treatment. We have previously reported individual beneficial efficacy of nanoparticle mediated administration of an antioxidant like 'curcumin' and an arsenic chelator 'monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)' for the treatment of arsenic toxicity compared to bulk drugs. The present paper investigates our hypothesis that a combination drug delivery therapy employing two nanosystems, a chelator and a strong antioxidant, may produce more pronounced therapeutic effects compared to individual effects in the treatment of arsenic toxicity. An in-vivo study was conducted wherein arsenic as sodium arsenite (100 ppm) was administered in drinking water for 5 months to Swiss albino mice. This was followed by a treatment protocol comprising of curcumin encapsulated chitosan nanoparticles (nano-curcumin, 15 mg/kg, orally for 1 month) either alone or in combination with MiADMSA encapsulated polymeric nanoparticles (nano-MiADMSA, 50 mg/kg for last 5 days) to evaluate the therapeutic potential of the combination treatment. Our results demonstrated that co-treatment with nano-curcumin and nano-MiADMSA provided beneficial effects in a synergistic way on the adverse changes in oxidative stress parameters and metal status induced by arsenic. Copyright © 2018 Elsevier B.V. All rights reserved.

Antiinflammatory, Diuretic and Antimicrobial Activities of Rungia pectinata Linn. and Rungia repens Nees

PubMed Central

Swain, S. R.; Sinha, B. N.; Murthy, P. N.

2008-01-01

The hydroalcoholic extracts prepared from leaves of Rungia pectinata and Rungia repens were investigated for antiinflammatory and diuretic activity in wistar rats. The results obtained were compared with that of standard drug aspirin and frusemide for their antiinflammatory and diuretic activity respectively. The acute toxicity study was also carried out using adult swiss albino mice of either sex which indicates the safety of the extracts even at a dose of 4000 mg/kg. R. pectinata showed better anti-inflammatory activity than R. repens. In the present study, it was demonstrated that hydroalcoholic extracts of both R. repens and R. pectinata produce diuretic effect by increasing the excretion of Na+, K+ and Cl−. Results showed that R. repens is most effective in increasing urinary electrolyte concentration of Na+ and K+ ions. The antimicrobial potency of the aerial parts of Rungia pectinata and Rungia repens have been studied using the petroleum ether, benzene, chloroform, acetone and ethanol extract against a wide number of bacteria and fungi by disc diffusion method. The ethanol extract at a concentration of 30 to 60 μg/disc showed significant activity against the bacteria and fungus investigated. All the extracts of R. pectinata and R. repens have got moderate action but chloroform and acetone extracts of R. repens and ethanol extract of R. pectinata have got significant activity against Trichophyton mentagrophytes. PMID:21394276

Genetically inbred Balb/c mice differ from outbred Swiss Webster mice on discrete measures of sociability: relevance to a genetic mouse model of autism spectrum disorders.

PubMed

Jacome, Luis F; Burket, Jessica A; Herndon, Amy L; Deutsch, Stephen I

2011-12-01

The Balb/c mouse is proposed as a model of human disorders with prominent deficits of sociability, such as autism spectrum disorders (ASDs) that may involve pathophysiological disruption of NMDA receptor-mediated neurotransmission. A standard procedure was used to measure sociability in 8-week-old male genetically inbred Balb/c and outbred Swiss Webster mice. Moreover, because impaired sociability may influence the social behavior of stimulus mice, we also measured the proportion of total episodes of social approach made by the stimulus mouse while test and stimulus mice were allowed to interact freely. Three raters with good inter-rater agreement evaluated operationally defined measures of sociability chosen because of their descriptive similarity to deficits of social behavior reported in persons with ASDs. The data support previous reports that the Balb/c mouse is a genetic mouse model of impaired sociability. The data also show that the behavior of the social stimulus mouse is influenced by the impaired sociability of the Balb/c strain. Interestingly, operationally defined measures of sociability did not necessarily correlate with each other within mouse strain and the profile of correlated measures differed between strains. Finally, "stereotypic" behaviors (i.e. rearing, grooming and wall climbing) recorded during the session of free interaction between the test and social stimulus mice were more intensely displayed by Swiss Webster than Balb/c mice, suggesting that the domains of sociability and "restricted repetitive and stereotyped patterns of behavior" are independent of each other in the Balb/c strain. Copyright © 2011, International Society for Autism Research, Wiley-Liss, Inc.

Sensory irritation structure-activity study of inhaled aldehydes in B6C3F1 and Swiss-Webster mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinhagen, W.H.; Barrow, C.S.

1984-03-15

The sensory irritation potential of a series of saturated and unsaturated aliphatic and cyclic aldehydes was investigated in B6C3F1 and Swiss-Webster mice. With the reflex decrease in respiratory rate as the endpoint response, alpha, beta-unsaturated aliphatic aldehydes yielded RD/sub 50/ values (concentration which elicits a 50% decrease in respiratory rate) ranging from 1 to 5 ppm while saturated aliphatic aldehydes with two or more carbons produced RD/sub 50/ values from 750 to 4200 ppm. Cyclic aldehydes produced intermediate RD/sub 50/ values which ranged from 60 to 400 ppm. No statistically significant differences were found between concentration-response curves of B6C3F1 andmore » Swiss-Webster mice. Saturated aliphatic aldehydes with two or more carbons were nearly 1000 times less potent than formaldehyde. Although the mechanisms responsible for stimulation of trigeminal nerve endings by airborne chemicals are poorly understood, several hypotheses may help to explain the differences seen in this study. For example, the sensory irritation potency of the saturated aliphatic aldehydes diminished with their reported dehydration constants which may determine the degree to which these aldehydes crosslink with receptor proteins. The sensory irritation potency of acrolein and crotonaldehyde was probably due to 1,2 or 1,4 addition reactions. Additionally, molecular conformation and a recently published physical mechanism may contribute to sensory irritation responses, particularly for the less reactive aldehydes. Tentative threshold limit values (TLVs), based upon prevention of sensory irritation, were extrapolated from the RD/sub 50/ values of Swiss-Webster mice. With the exception of crotonaldehyde, good agreement was found with currently published TLVs.« less

Mammalian Toxicological Evaluation of p-Chlorophenyl Methyl Sulfide, p-Chlorophenyl Methyl Sulfoxide, and p-Chlorophenyl Methyl Sulfone.

DTIC Science & Technology

1979-07-01

albino guinea pigs (Charles River Breeding Laboratories, Wilmington, Massachusetts) weighing 300-500 grams were used in the skin sensitization tests...mice weighing 17-21 g used in the studies were supplied by Charles River Breeding Laboratories. Rats and mice were individually housed in...cornea, and conjunctivae (the anterior chamber). All rat eye exams were done by a trained and experienced veterinary ophthalmologist . Hematologr and

Effects of type of light on mouse circadian behaviour and stress levels.

PubMed

Alves-Simoes, Marta; Coleman, Georgia; Canal, Maria Mercè

2016-02-01

Light is the principal synchronizing environmental factor for the biological clock. Light quantity (intensity), and light quality (type of light source) can have different effects. The aim of this study was to determine the effects of the type of light experienced from the time of birth on mouse growth, circadian behaviour and stress levels. We raised pigmented and albino mice under 24 h light-dark cycles of either fluorescent or white light-emitting diode (LED) light source during the suckling stage, and the animals were then exposed to various light environments after weaning and their growth rate, locomotor activity and plasma corticosterone concentration were measured. We found that the type of light the animals were exposed to did not affect the animals' growth rates or stress levels. However, we observed significant effects on the expression of the locomotor activity rhythm under low contrast light-dark cycles in pigmented mice, and under constant light in both albino and pigmented mice. These results highlight the importance of environmental light quality (light source) on circadian behavioural rhythms, and the need for close monitoring of light environments in animal facilities. © The Author(s) 2015.

Histopathological evaluation of gastro protective effect of Berberis vulgaris (Zereshk) seeds against aspirin induced ulcer in albino mice.

PubMed

Majeed, Wafa; Aslam, Bilal; Javed, Ijaz; Khaliq, Tanweer; Muhammad, Faqir; Ali, Asghar; Raza, Ahmed

2015-11-01

The present study was carried out to investigate the antiulcer activity of Berberis vulgaris (Zereshk) seeds in albino mice. After acclimatization, animals were divided into six equal groups. Aspirin 150 mg/kg was used to induce gastric ulcer in all groups except normal control. Omeprazole 20mg/kg was used as synthetic anti ulcer drug in study. Three dose levels of B. vulgaris seed powder 300 mg/kg, 600 mg/kg and 900 mg/kg were used respectively orally. Histopathological analysis was carried out to evaluate the gastroprotective activity of B. vulgaris seed powder. Results of the study showed that in case of aspirin treated mice gastric luminal mucosa villi were decreased in height or were absent. In the glandular region there was connective tissue proliferation and also infiltration of cells. Similar infiltration of cells was present on muscularis mucosa. In esophageal region tumor cells were present. However three dose levels of B. vulgaris significantly reduced the tissue proliferation, infiltration of cells and sloughing induced by aspirin. Highest dose of B. vulgaris (900 mg/kg) showed similar results as synthetic antiulcer drug omeprazole.

Multiagent vaccines vectored by Venezuelan equine encephalitis virus replicon elicits immune responses to Marburg virus and protection against anthrax and botulinum neurotoxin in mice.

PubMed

Lee, John S; Groebner, Jennifer L; Hadjipanayis, Angela G; Negley, Diane L; Schmaljohn, Alan L; Welkos, Susan L; Smith, Leonard A; Smith, Jonathan F

2006-11-17

The development of multiagent vaccines offers the advantage of eliciting protection against multiple diseases with minimal inoculations over a shorter time span. We report here the results of using formulations of individual Venezuelan equine encephalitis (VEE) virus replicon-vectored vaccines against a bacterial disease, anthrax; a viral disease, Marburg fever; and against a toxin-mediated disease, botulism. The individual VEE replicon particles (VRP) expressed mature 83-kDa protective antigen (MAT-PA) from Bacillus anthracis, the glycoprotein (GP) from Marburg virus (MBGV), or the H(C) fragment from botulinum neurotoxin (BoNT H(C)). CBA/J mice inoculated with a mixture of VRP expressing BoNT H(C) serotype C (BoNT/C H(C)) and MAT-PA were 80% protected from a B. anthracis (Sterne strain) challenge and then 100% protected from a sequential BoNT/C challenge. Swiss mice inoculated with individual VRP or with mixtures of VRP vaccines expressing BoNT H(C) serotype A (BoNT/A H(C)), MAT-PA, and MBGV-GP produced antibody responses specific to the corresponding replicon-expressed protein. Combination of the different VRP vaccines did not diminish the antibody responses measured for Swiss mice inoculated with formulations of two or three VRP vaccines as compared to mice that received only one VRP vaccine. Swiss mice inoculated with VRP expressing BoNT/A H(C) alone or in combination with VRP expressing MAT-PA and MBGV GP, were completely protected from a BoNT/A challenge. These studies demonstrate the utility of combining individual VRP vaccines into multiagent formulations for eliciting protective immune responses to various types of diseases.

Urtica dioica leaves modulates hippocampal smoothened-glioma associated oncogene-1 pathway and cognitive dysfunction in chronically stressed mice.

PubMed

Patel, Sita Sharan; Mahindroo, Neeraj; Udayabanu, Malairaman

2016-10-01

The present study was aimed to evaluate the effect of Urtica dioica (UD) extract against chronic unpredictable stress (CUS)-induced associative memory dysfunction and attempted to explore the possible mechanism. Male Swiss albino mice (25-30g) were divided into six groups, viz. group-I received 0.3% carboxymethyl cellulose and served as control (CTRL), group II was exposed to CUS (21days) and received vehicle (CUS), group III was subjected to CUS and received Hypericum perforatum extract (350mg/kg, p.o.) (CUS+HYP), group IV received Hypericum perforatum extract (350mg/kg, p.o.) (CTRL+HYP); group V was subjected to CUS and received UD extract (50mg/kg, p.o.) (CUS+UD), group VI received UD extract (50mg/kg, p.o.) (CTRL+UD). CUS significantly induced body weight loss (p<0.05) and associative memory impairment in step down task (p<0.05) as compared to control mice. CUS significantly downregulated Smo (p<0.05), Gli1 (p<0.01), cyclin D1 (p<0.05), BDNF (p<0.01), TrKB (p<0.01) and MAPK1 (p<0.01) mRNA expression in hippocampus as compared to control mice. CUS significantly increased the levels of TBARS (p<0.01) and nitric oxide (p<0.001), and decreased catalase (p<0.001) and total thiol (p<0.01) in plasma resulting in oxidative stress and inflammation. Chronic UD administration significantly reverted CUS mediated body weight loss (p<0.05) and cognitive impairment (p<0.05). UD administration significantly decreased the levels of TBARS (p<0.01) and nitric oxide (p<0.05), and increased the levels of catalase (p<0.01) and total thiol (p<0.05) in plasma. Chronic UD administration significantly upregulated hippocampal Smo (p<0.05), Gli1 (p<0.001), cyclin D1 (p<0.05), BDNF (p<0.05), TrKB (p<0.05) and MAPK1 (p<0.05) in stressed mice. Further, UD extract did not reverse cyclopamine induced downregulation of Gli1 and Ptch1 mRNA in hippocampal slices. UD modulated Smo-Gli1 pathway in the hippocampus as well as exerted anti-inflammatory and antioxidant effects. UD extract might prove to be effective for stress mediated neurological disorders. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Effects of raloxifene against letrozole-induced bone loss in chemically-induced model of menopause in mice.

PubMed

Kalam, Abul; Talegaonkar, Sushama; Vohora, Divya

2017-01-15

The deleterious effects of letrozole, an aromatase inhibitor, used in the adjuvant treatment of breast cancer in postmenopausal women, on bone are well-documented and represent a major drawback to its clinical use. Raloxifene, a selective estrogen receptor modulator and a clinically approved anti-osteoporotic drug, has been recently demonstrated to be efficacious in women with breast cancer. The present study evaluated the effects of preventive and curative treatment with raloxifene on letrozole-induced alterations of bone microarchitecture and turnover markers in a chemically-induced menopause model in mice. Swiss strain albino female mice were made menopausal by inducing ovotoxicity using vinyl cyclohexene di epoxide (VCD, 160 mg/kg for 15 days followed by 30 days drug-free period) confirmed by ovarian histology and serum estradiol levels. Effects on femoral and lumbar bones were evaluated by micro CT determination of bone volume, trabecular number, separation, thickness, connective density and trabecular pattern factor and bone turnover markers including ALP, TRAP5b, hydroxyproline and RANKL. In addition to these, markers of Wnt signaling (sclerostin and dickkopf-1) were also evaluated. To rule out the involvement of pharmacokinetic interaction, plasma levels of letrozole and raloxifene were measured following drugs alone and in combination. Though bone loss was observed in VCD treated mice (as indicated by micro CT measurements), it was further enhanced with letrozole administration (1 mg/kg) for one month particularly in epiphysis of femoral bones. Raloxifene (15 mg/kg), whether administered concurrently or post-letrozole was able to revert the structural alterations and changes in turnover markers caused by letrozole to varying degrees (p < 0.01 or p < 0.001). Further, estrogen deficiency following letrozole treatment in ovotoxic mice was associated with significant increase in sclerostin and dickkopf-1 in both lumbar and femur bones (p < 0.001) which was attenuated with preventive and curative treatment with raloxifene (p < 0.05). The plasma levels of letrozole remained unaffected by raloxifene administration and vice versa. Our study indicates the potential of raloxifene in preventing and attenuating letrozole-induced bone loss. Further, these effects were found to be independent of a pharmacokinetic interaction between the two drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In vivo antimalarial activity of crude extracts and solvent fractions of leaves of Strychnos mitis in Plasmodium berghei infected mice.

PubMed

Fentahun, Selamawit; Makonnen, Eyasu; Awas, Tesfaye; Giday, Mirutse

2017-01-05

Malaria is a major public health problem in the world which is responsible for death of millions particularly in sub-Saharan Africa. Today, the control of malaria has become gradually more complex due to the spread of drug-resistant parasites. Medicinal plants are the unquestionable source of effective antimalarials. The present study aimed to evaluate antiplasmodial activity and acute toxicity of the plant Strychnos mitis in Plasmodium berghei infected mice. Standard procedures were employed to investigate acute toxicity and 4-day suppressive effect of crude aqueous and hydro-methanolic extracts of the leaves of Strychnos mitis against P. berghei in Swiss albino mice. Water, n-hexane and chloroform fractions, obtained from crude hydro-methanolic extract, were also tested for their suppressive effect against P. berghei. All crude extracts revealed no obvious acute toxicity in mice up to the highest dose administered (2000 mg/kg). All crude and solvent fractions of the leaves of Strychnos mitis inhibited parasitaemia significantly (p < 0.01). At the highest dose of 600 mg/kg, both aqueous and hydro-methanolic extracts demonstrated higher performance with 95.5 and 93.97% parasitaemia suppression, respectively. All doses of crude extracts and fractions of leaves of Strychnos mitis prolonged survival time of infected mice dose dependently. The highest two doses of the crude aqueous and hydro-methanolic extracts, and chloroform and aqueous fractions prevented weight loss in a dose dependent manner. Whereas, all doses of n-hexane fraction prevented loss of body weight but not in a dose dependent manner. The crude aqueous extract at the doses of 400 mg/kg and 600 mg/kg and hydro-methanolic extract at all dose levels significantly (p < 0.01) prevented packed cell volume reduction. Crude aqueous extract at a dose of 600 mg/kg and hydro-methanolic extract at all dose levels significantly prevented temperature reduction. Phytochemical screening of the crude aqueous and hydro-methanolic extracts revealed the presence of alkaloids, anthraquinones, glycosides, terpenoids, saponins, tannins and phenols. The results of this study provide support the traditional therapeutic use of Strychnos mitis for treatment of malaria. However, further in-depth study is needed to evaluate the potential of the plant towards the development of new antimalarial agent.

Behavioral Assessment of NIH Swiss Mice Acutely Intoxicated with Tetramethylenedisulfotetramine

PubMed Central

Flannery, Brenna M.; Silverman, Jill L.; Bruun, Donald A.; Puhger, Kyle R.; McCoy, Mark R.; Hammock, Bruce D.; Crawley, Jacqueline N.; Lein, Pamela J.

2014-01-01

Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison that is thought to trigger seizures by inhibiting the function of the type A gamma-aminobutyric acid receptor (GABAAR). Acute intoxication with TETS can cause vomiting, convulsions, status epilepticus (SE) and even death. Clinical case reports indicate that individuals who survive poisoning may exhibit long-term neuropsychological issues and cognitive deficits. Therefore, the objective of this research was to determine whether a recently described mouse model of acute TETS intoxication exhibits persistent behavioral deficits. Young adult male NIH Swiss mice received a seizure-inducing dose of TETS (0.15 mg/kg, ip) and then were rescued from lethality by administration of diazepam (5 mg/kg, ip) approximately 20 min post-TETS-exposure. TETS-intoxicated mice typically exhibited 2 clonic seizures prior to administration of diazepam with no subsequent seizures post-diazepam injection as assessed using behavioral criteria. Seizures lasted an average of 72 seconds. Locomotor activity, anxiety-like and depression-relevant behaviors and cognition were assessed at 1 week, 1 month and 2 months post-TETS exposure using open field, elevated-plus maze, light↔dark transitions, tail suspension, forced swim and novel object recognition tasks. Interestingly, preliminary validation tests indicated that NIH Swiss mice do not respond to the shock in fear conditioning tasks. Subsequent evaluation of hot plate and tail flick nociception tasks revealed that this strain exhibits significantly decreased pain sensitivity relative to age- and sex-matched C57BL/6J mice, which displayed normal contextual fear conditioning. NIH Swiss mice acutely intoxicated with TETS exhibited no significant anxiety-related, depression-relevant, learning or memory deficits relative to vehicle controls at any of the time points assessed with the exception of significantly increased locomotor activity at 2 months post-TETS intoxication. The general absence of long-term behavioral deficits in TETS-intoxicated mice on these six assays suggests that the neurobehavioral consequences of TETS exposure described in human survivors of acute TETS intoxication are likely due to sustained seizure activity, rather than a direct effect of the chemical itself. Future research efforts are directed towards developing an animal model that better recapitulates the SE and seizure duration reported in humans acutely intoxicated with TETS. PMID:25446016

Toxicological studies of stem bark extract from Schefflera barteri Harms (Araliaceae).

PubMed

Atsafack, Serge Secco; Kuiate, Jules-Roger; Mouokeu, Raymond Simplice; Koanga Mogtomo, Martin Luther; Tchinda, Alembert Tiabou; De Dieu, Tamokou Jean; Magnifouet Nana, Huguette; Ebelle Etame, Rébecca Madeleine; Biyiti, Lucie; Ngono Ngane, Rosalie Annie

2015-03-07

The use of herbal medicines as complements or alternatives to orthodox medicines has been on the increase. There has been the erroneous belief that these medicines are free from adverse effects. Schefflera barteri is popularly used in the West region of Cameroon for the treatment of various diseases such as diarrhea, spasm, pneumonia and animals bite. Considering the ethnopharmacological relevance of this plant, this study was designed to investigate the possible toxic effects of the stem bark extract of S. barteri. The extract was prepared by maceration of stem bark dry powder in methylene chloride/methanol mixture. Phytochemical analysis was performed by chemical reaction method. Oral acute toxicity study was carried out by administering single geometric increasing doses (2 to 16 g/kg body weight) of plant extract to Swiss albino mice. For sub-acute toxicity study, repeated doses (100, 200, 400 and 800 mg/kg bw) of plant extract were given to Wistar albino rats for 28 consecutive days by oral route. At the end of the treatment period, hematological and biochemical parameters were assessed, as well as histopathological studies. Phytochemical analysis of stem bark extract of S. barteri revealed the presence of anthocyanins, anthraquinons and saponins. Acute toxicity results showed that the LD50 was greater than 16000 mg/kg. Sub-acute treatment significantly (P < 0.05) increased the level of serum transaminase, proteins and HDL cholesterol. On the other hand, the extract significantly (P < 0.05) reduced the level of leucocytes as well as neutrophils, basophils and monocytes in female. No significant variation of serum creatinine, LDL cholesterol, serum triglycerides as well as liver, spleen, testicles and ovaries proteins was noted. Histopathological analysis of organs showed vascular congestion, inflammation of peri-portal and vacuolization of hepatocytes at the level of the liver. Leucocytes infiltration of peri-portal veins were noticed on lungs and liver cells as well as inflammatory peri-bronchial and basal membranes seminar tube merely joined on lungs and testis respectively. The results suggest that acute administration of the stem bark extract of S. barteri is associated with signs of toxicity, administration over a long duration provokes hepatotoxicity, testes and lungs toxicities.

Effects of day-length variations on emotional responses towards unfamiliarity in Swiss mice.

PubMed

Kopp, C; Misslin, R; Vogel, E; Rettori, M C; Delagrange, P; Guardiola-Lemaitre, B

1997-11-01

Pineal melatonin secretion occurs at night in all vertebrates and the duration of its secretion is negatively correlated with day length. As an anxiolytic activity of melatonin has been shown in rats and mice, this study examined possible changes of emotional reactivity in response to day length variations in Swiss mice. Three groups of mice were observed in a free-exploratory test: a group submitted to a short-day exposure (6:18 h light-dark cycle) for 2 weeks, a group submitted to a long-day exposure (18:6 h light-dark cycle) for 2 weeks and a control group which was maintained in housing 12:12 h light-dark cycle. The short-day exposed group of mice exhibited significantly fewer attempts to enter into the unfamiliar enclosure, spent significantly more time in it and presented significantly more rears than controls whereas the long-day exposed group of mice made more attempts than controls. These results suggest a decreased emotional level in short-day exposed mice and an increased level in long-day exposed mice. This could be interpreted as confirming the idea of anxiolytic-like properties of melatonin; however, the specific role of this hormone in the changes of anxiety related to day length must be assessed by further measures of potential variations of circulating melatonin.

Maternal Weight Gain as a Predictor of Litter Size in Swiss Webster, C57BL/6J, and BALB/cJ mice.

PubMed

Finlay, James B; Liu, Xueli; Ermel, Richard W; Adamson, Trinka W

2015-11-01

An important task facing both researchers and animal core facilities is producing sufficient mice for a given project. The inherent biologic variability of mouse reproduction and litter size further challenges effective research planning. A lack of precision in project planning contributes to the high cost of animal research, overproduction (thus waste) of animals, and inappropriate allocation of facility resources. To examine the extent daily prepartum maternal weight gain predicts litter size in 2 commonly used mouse strains (BALB/cJ and C57BL/6J) and one mouse stock (Swiss Webster), we weighed ≥ 25 pregnant dams of each strain or stock daily from the morning on which a vaginal plug (day 0) was present. On the morning when dams delivered their pups, we recorded the weight of the dam, the weight of the litter itself, and the number of pups. Litter sizes ranged from 1 to 7 pups for BALB/cJ, 2 to 13 for Swiss Webster, and 5 to 11 for C57BL/6J mice. Linear regression models (based on weight change from day 0) demonstrated that maternal weight gain at day 9 (BALB/cJ), day 11 (Swiss Webster), or day 14 (C57BL/6J) was a significant predictor of litter size. When tested prospectively, the linear regression model for each strain or stock was found to be accurate. These data indicate that the number of pups that will be born can be estimated accurately by using maternal weight gain at specific or stock-specific time points.

Effect of tranquilizers on animal resistance to the adequate stimuli of the vestibular apparatus

NASA Technical Reports Server (NTRS)

Maksimovich, Y. B.; Khinchikashvili, N. V.

1980-01-01

The effect of tranquilizers on vestibulospinal reflexes and motor activity was studied in 900 centrifuged albino mice. Actometric studies have shown that the tranquilizers have a group capacity for increasing animal resistance to the action of adequate stimuli to the vestibular apparatus.

[The accumulation of lipid peroxidation products in the eye structures of mice under whole-body x-ray irradiation].

PubMed

Sakina, N L; Dontsov, A E; Afanas'ev, G G; Ostrovski, M A; Pelevina, I I

1990-01-01

In studying the effect of whole-body X-irradiation on the accumulation of lipid peroxidation products (conjugated dienes, TBA-active products, and Schiff bases) in retina and retinal pigmented epithelium of pigmented and nonpigmented mice it was shown that irradiation of dark-pigmented mice does not cause even a slight accumulation of lipid peroxidation products as compared to that in the controls. Albino mice exhibited a marked increase in the level of lipid peroxidation products which was manifested soon after irradiation and persisted for at least 3 months after irradiation. Melanine is suggested to participate in protecting eye structures against pro-oxidizing action of ionizing radiation.

Reduction of alcohol induced sleep time in albino mice by potentized Nux vomica prepared with 90% ethanol.

PubMed

Sukul, A; Sinhabau, S P; Sukul, N C

1999-04-01

Male adult albino mice were administered potentized Nux vomica 30 c (Nux v). The drug was mixed with sterile distilled water at 0.05 ml/2 ml water and given at 0.05 ml/individual. Control consisted of blank ethanol solution. Ethanolic extract from the seeds of Strychnos nuxvomica L was mixed with 90% ethanol 1:100 and sonicated for 30 s at 20 KHz. This was further diluted and sonicated in 30 steps to produce Nux v 30 c. Six hours after treatment, mice were given 25% ethanol i.p. at 4 g/kg body wt. The duration of sleep time starting from the loss of righting reflex until its restoration was recorded for each mouse. The duration of sleep time with ethanol was recorded in four sessions for the same group of mice with an interval of 10 d between sessions. session 1 with control solution, 2 with Nux v (oral), 3 with control solution and 4 with Nux v (i.p.). Nux v (oral) produced the shortest sleep time as compared to other treatments which did not differ from each other significantly with respect to sleep time. In another experiment Nux v 30 c was prepared with distilled water and pure absolute ethanol by the above process of successive dilution and sonication. These two preparations together with Nux v 30 c, prepared with 90% ethanol, were tested on mice for their effect on alcohol-induced sleep time. Only Nux v 30 c prepared with 90% ethanol was effective in reducing the sleep time in mice. It is concluded that the solution structure of ethanol/water mixture carries the specificity of the Nux v at ultra high dilution. It is further concluded that the effect is mediated through oral receptors.

Optical properties of mice skin for optical therapy relevant wavelengths: influence of gender and pigmentation

NASA Astrophysics Data System (ADS)

Sabino, C. P.; Deana, A. M.; Silva, D. F. T.; França, C. M.; Yoshimura, T. M.; Ribeiro, M. S.

2015-03-01

Red and near-infrared light have been widely employed in optical therapies. Skin is the most common optical barrier in non-invasive techniques and in many cases it is the target tissue itself. Consequently, to optimize the outcomes brought by lightbased therapies, the optical properties of skin tissue must be very well elucidated. In the present study, we evaluated the dorsal skin optical properties of albino (BALB/c) and pigmented (C57BL/6) mice using the Kubelka-Munk photon transport model. We evaluated samples from male and female young mice of both strains. Analysis was performed for wavelengths at 630, 660, 780, 810 and 905 nm due to their prevalent use in optical therapies, such as low-level light (or laser) and photodynamic therapies. Spectrophotometric measurements of diffuse transmittance and reflectance were performed using a single integrating sphere coupled to a proper spectrophotometer. Statistic analysis was made by two-way ANOVA, with Tukey as post-test and Levenne and Shapiro-Wilks as pre-tests. Statistical significance was considered when p<0.05. Our results show only a slight transmittance increment (<10 %) as wavelengths are increased from 630 to 905 nm, and no statistical significance was observed. Albino male mice present reduced transmittance levels for all wavelengths. The organization and abundance of skin composing tissues significantly influence its scattering optical properties although absorption remains constant. We conclude that factors such as subcutaneous adiposity and connective tissue structure can have statistically significant influence on mice skin optical properties and these factors have relevant variations among different gender and strains.

Identification of multi-targeted anti-migraine potential of nystatin and development of its brain targeted chitosan nanoformulation.

PubMed

Girotra, Priti; Thakur, Aman; Kumar, Ajay; Singh, Shailendra Kumar

2017-03-01

The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (β 2 adrenoceptor, Dopamine D 3 , 5HT 1B , TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), β 2 adrenoceptor (3NYA) and Dopamine D 3 (3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

Bioactivity guided isolation of antipsychotic constituents from the leaves of Rauwolfia tetraphylla L.

PubMed

Gupta, Shikha; Khanna, Vinay Kumar; Maurya, Anupam; Bawankule, Dnyaneshwar Umrao; Shukla, Rajendra Kumar; Pal, Anirban; Srivastava, Santosh Kumar

2012-09-01

This study was undertaken to ascertain the antipsychotic properties of Rauwolfia tetraphylla L. leaves and to isolate and characterize the antipsychotic constituents. Among the MeOH extract and some alkaloidal fractions at different pHs, the alkaloidal CHCl(3) fraction at pH-9 (2C) showed the highest antipsychotic activity against dopaminergic (DA-D(2)) and serotonergic (5-HT(2A)) receptors in-vitro and amphetamine induced hyperactive mouse model in-vivo. The activity guided isolation of CHCl(3) fraction (2C) afforded six indole alkaloids: 10-methoxytetrahydroalstonine (1), isoreserpiline (2), an isomeric mixture of 11-demethoxyreserpiline (3) and 10-demethoxyreserpiline (4), α-yohimbine (5) and reserpiline (6). Given orally, alkaloids 3-6 showed significant antipsychotic activity in a dose dependent manner. None of the extract, alkaloidal fractions or alkaloids showed any extra pyramidal symptoms at the tested doses. It was also observed that MeOH extract was behaving similar to other clinically used novel atypical antipsychotics in having 5-HT(2A) occupancy greater than the DA-D(2) receptor at the tested doses. Further toxicity and safety evaluation studies of MeOH extracts of R. tetraphylla leaves at different doses (10, 100, 300 and 2000 mg/kg) on female Swiss albino mice showed that MeOH extract is non toxic. The isolated alkaloids, 3-6 could serve as a promising lead structure for drug development of treating psychotic conditions in human. Copyright © 2012 Elsevier B.V. All rights reserved.

Curculigo orchioides Gaertn Effectively Ameliorates the Uro- and Nephrotoxicities Induced by Cyclophosphamide Administration in Experimental Animals

PubMed Central

Murali, Vishnu Priya; Kuttan, Girija

2015-01-01

Background. Curculigo orchioides Gaertn is an ancient medicinal plant (Family: Amaryllidaceae), well known for its immunomodulatory and rejuvenating effects. Cyclophosphamide (CPA) is an alkylating agent widely used for treating a variety of human malignancies, but associated with different toxicities too. Our previous reports regarding the hemoprotective and hepatoprotective effects of the plant against CPA toxicities provide the background for the present study, which is designed to analyze the ameliorative effect of the methanolic extract of C orchioides on the urotoxicity and nephrotoxicity induced by CPA. Methods. CPA was administered to male Swiss albino mice at a single dose of 1.5 mmol/kg body weight to induce urotoxicity after 5 days of prophylactic treatment with C orchioides extract (20 mg/kg body weight). Mesna (2-mercaptoethanesulfonate) was used as a control drug. Serum, tissue, and urine levels of kidney function markers and antioxidant levels were checked along with the serum cytokine levels. Results. The plant extract was found to be effective in ameliorating the urotoxic and nephrotoxic side effects of CPA. Upregulation of serum interferon-γ and interleukin-2 levels were observed with C orchioides treatment, which was decreased by CPA administration. Besides these, serum tumor necrosis factor-α level was also downregulated by C orchioides treatment. Conclusion. Curculigo orchioides was found to be effective against the CPA-induced bladder and renal toxicities by its antioxidant capability and also by regulating the pro-inflammatory cytokine levels. PMID:26424815

Time course pathogenesis of sulphur mustard-induced skin lesions in mouse model.

PubMed

Lomash, Vinay; Jadhav, Sunil E; Vijayaraghavan, Rajagopalan; Pant, Satish C

2013-08-01

Sulphur mustard (SM) is a bifunctional alkylating agent that causes cutaneous blistering in humans and animals. In this study, we have presented closer views on pathogenesis of SM-induced skin injury in a mouse model. SM diluted in acetone was applied once dermally at a dose of 5 or 10 mg/kg to Swiss albino mice. Skin was dissected out at 0, 1, 3, 6, 12, 24, 48, 72 and 168 hours, post-SM exposure for studying histopathological changes and immunohistochemistry of inflammatory-reparative biomarkers, namely, transforming growth factor alpha (TGF-α), fibroblast growth factor (FGF), endothelial nitric oxide synthase (eNOS) and interlukin 6 (IL-6). Histopathological changes were similar to other mammalian species and basal cell damage resembled the histopathological signs observed with vesication in human skin. Inflammatory cell recruitment at the site of injury was supported by differential expressions of IL-6 at various stages. Time-dependent expressions of eNOS played pivotal roles in all the events of wound healing of SM-induced skin lesions. TGF-α and FGF were strongly associated with keratinocyte migration, re-epithelialisation, angiogenesis, fibroblast proliferation and cell differentiation. Furthermore, quantification of the tissue leukocytosis and DNA damage along with semiquantitative estimation of re-epithelialisation, fibroplasia and neovascularisation on histomorphologic scale could be efficiently used for screening the efficacy of orphan drugs against SM-induced skin injury. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

In vivo evaluation of cetuximab-conjugated poly(γ-glutamic acid)-docetaxel nanomedicines in EGFR-overexpressing gastric cancer xenografts.

PubMed

Sreeranganathan, Maya; Uthaman, Saji; Sarmento, Bruno; Mohan, Chethampadi Gopi; Park, In-Kyu; Jayakumar, Rangasamy

2017-01-01

Epidermal growth factor receptor (EGFR), upregulated in gastric cancer patients, is an oncogene of interest in the development of targeted cancer nanomedicines. This study demonstrates in silico modeling of monoclonal antibody cetuximab (CET MAb)-conjugated docetaxel (DOCT)-loaded poly(γ-glutamic acid) (γ-PGA) nanoparticles (Nps) and evaluates the in vitro/in vivo effects on EGFR-overexpressing gastric cancer cells (MKN-28). Nontargeted DOCT-γ-PGA Nps (NT Nps: 110±40 nm) and targeted CET MAb-DOCT-γ-PGA Nps (T Nps: 200±20 nm) were prepared using ionic gelation followed by 1-Ethyl-3-(3-dimethyl aminopropyl)carbodiimide-N-Hydoxysuccinimide (EDC-NSH) chemistry. Increased uptake correlated with enhanced cytotoxicity induced by targeted Nps to EGFR +ve MKN-28 compared with nontargeted Nps as evident from MTT and flow cytometric assays. Nanoformulated DOCT showed a superior pharmacokinetic profile to that of free DOCT in Swiss albino mice, indicating the possibility of improved therapeutic effect in the disease model. Qualitative in vivo imaging showed early and enhanced tumor targeted accumulation of CET MAb-DOCT-γ-PGA Nps in EGFR +ve MKN-28-based gastric cancer xenograft, which exhibited efficient arrest of tumor growth compared with nontargeted Nps and free DOCT. Thus, actively targeted CET MAb-DOCT-γ-PGA Nps could be developed as a substitute to conventional nonspecific chemotherapy, and hence could become a feasible strategy for cancer therapy for EGFR-overexpressing gastric tumors.

Role of Ferulic Acid in the Amelioration of Ionizing Radiation Induced Inflammation: A Murine Model

PubMed Central

Das, Ujjal; Manna, Krishnendu; Sinha, Mahuya; Datta, Sanjukta; Das, Dipesh Kr; Chakraborty, Anindita; Ghosh, Mahua; Saha, Krishna Das; Dey, Sanjit

2014-01-01

Ionizing radiation is responsible for oxidative stress by generating reactive oxygen species (ROS), which alters the cellular redox potential. This change activates several redox sensitive enzymes which are crucial in activating signaling pathways at molecular level and can lead to oxidative stress induced inflammation. Therefore, the present study was intended to assess the anti-inflammatory role of ferulic acid (FA), a plant flavonoid, against radiation-induced oxidative stress with a novel mechanistic viewpoint. FA was administered (50 mg/kg body wt) to Swiss albino mice for five consecutive days prior to exposing them to a single dose of 10 Gy 60Co γ-irradiation. The dose of FA was optimized from the survival experiment and 50 mg/kg body wt dose showed optimum effect. FA significantly ameliorated the radiation induced inflammatory response such as phosphorylation of IKKα/β and IκBα and consequent nuclear translocation of nuclear factor kappa B (NF-κB). FA also prevented the increase of cycloxygenase-2 (Cox-2) protein, inducible nitric oxide synthase-2 (iNOS-2) gene expression, lipid peroxidation in liver and the increase of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in serum. It was observed that exposure to radiation results in decreased activity of superoxide dismutase (SOD), catalase (CAT) and the pool of reduced glutathione (GSH) content. However, FA treatment prior to irradiation increased the activities of the same endogenous antioxidants. Thus, pretreatment with FA offers protection against gamma radiation induced inflammation. PMID:24854039

Interleukin-6-driven inflammatory response induces retinal pathology in a model of ocular toxoplasmosis reactivation.

PubMed

Rochet, Élise; Brunet, Julie; Sabou, Marcela; Marcellin, Luc; Bourcier, Tristan; Candolfi, Ermanno; Pfaff, Alexander W

2015-05-01

Ocular inflammation is one of the consequences of infection with the protozoan parasite Toxoplasma gondii. Even if lesions are self-healing in immunocompetent persons, they pose a lifetime risk of reactivation and are a serious threat to vision. As there are virtually no immunological data on reactivating ocular toxoplasmosis, we established a model of direct intravitreal injection of parasites in previously infected mice with a homologous type II strain. Two different mouse strains with variable ability to control retinal infection were studied in order to describe protective and deleterious reaction patterns. In Swiss-Webster mice, which are already relatively resistant to primary infection, no peak of parasite load was observed upon reinfection. In contrast, the susceptible inbred strain C57BL/6 showed high parasite loads after 7 days, as well as marked deterioration of retinal architecture. Both parameters were back to normal on day 21. C57BL/6 mice also reacted with a strong local production of inflammatory and Th1-type cytokines, like interleukin-6 (IL-6), IL-17A, and gamma interferon (IFN-γ), while Swiss-Webster mice showed only moderate expression of the Th2 cytokine IL-31. Interestingly, rapid intraocular production of anti-Toxoplasma antibodies was observed in Swiss-Webster but not in C57BL/6 mice. We then localized the cellular source of different immune mediators within the retina by immunofluorescence. Finally, neutralization experiments of IFN-γ or IL-6 demonstrated the respective protective and deleterious roles of these cytokines for parasite control and retinal integrity during reinfection. In conclusion, we developed and immunologically characterized a promising mouse model of reactivating ocular toxoplasmosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Neonatal transection of the corpus callosum affects paw preference lateralization of adult Swiss mice.

PubMed

Manhães, Alex C; Krahe, Thomas E; Caparelli-Dáquer, Egas; Ribeiro-Carvalho, Anderson; Schmidt, Sergio L; Filgueiras, Cláudio C

2003-09-11

In the present work, the hypothesis that the ontogenetic development of the corpus callosum (CC) affects the establishment of behavioral lateralization was tested by studying paw preference performance in adult Swiss mice that were subjected to mid-sagittal transection of the CC on the first postnatal day. Magnitude and direction of laterality were evaluated independently. No significant differences between groups were found for the magnitude of paw preference. On the other hand, the transected group presented a significant populational bias favoring the left paw that was not present in the control groups. These results lend support to the hypothesis that the development of the CC plays a role in the establishment of the normal pattern of behavioral lateralization.

Early Deposition of Ceroid in Kupffer Cells of Mice Fed Hepatic Necrogenic Diets

PubMed Central

Porta, Eduardo A.; Hartroft, W. Stanley

1963-01-01

Experiments were undertaken to study the prenecrotic morphologic changes in liver of mice that were fed diets deficient in vitamin E and selenium. When these diets were fed to male albino mice the accumulation of ceroid pigment in Kupffer cells was observed within seven days of commencing the diets, long before any evidence of necrosis was observed. In later stages of the experiment the ceroid pigment deposited in Kupffer cells was so abundant that it appeared possible that interference with hepatic sinusoidal blood flow and impairment of physiologic activity of the reticuloendothelial system had resulted. ImagesFig. 1Fig. 2 PMID:20327568

Radical Scavenging Activities of Lagerstroemia speciosa (L.) Pers. Petal Extracts and its hepato-protection in CCl4-intoxicated mice.

PubMed

Tiwary, Bipransh Kumar; Dutta, Somit; Dey, Priyankar; Hossain, Mossaraf; Kumar, Anoop; Bihani, Sony; Nanda, Ashis Kumar; Chaudhuri, Tapas Kumar; Chakraborty, Ranadhir

2017-01-18

Lagerstroemia speciosa (L.) Pers. has medicinal importance. Bioactive phytochemicals isolated from different parts of L. speciosa, have revealed hypoglycemic, antibacterial, anti-inflammatory, antioxidant and hepato protective properties. Despite one report from Philippines detailing the use of L. speciosa as curative for fever and as well as diuretic, there is no experimental evidence about the hepatoprotective activity of the flower extracts. Several spectroscopic methods, including GC-MS, were used to characterize phytochemicals present in the petal extract of L. speciosa. Ethanol extract of petals was evaluated for anti-oxidant and free radical scavenging properties by using methods related to hydrogen atom transfer, single electron transfer, reducing power, and metal chelation. This study has also revealed the in vitro antioxidant and in vivo hepatoprotective properties of petal extract against carbon tetra chloride (CCl 4 )-induced liver toxicity in Swiss albino mice. Hepatoprotection in CCl 4 -intoxicated mice was studied with the aid of histology and different enzymatic and non-enzymatic markers of liver damage. Cytotoxicity tests were done using murein spleenocytes and cancareous cell lines, MCF7 and HepG2. GCMS of the extract has revealed the presence of several potential antioxidant compounds, of them γ-Sitosterol and 1,2,3-Benzenetriol (Pyrogallol) were the predominant ones. The antioxidants activities of the flower-extract were significantly higher than curcumin (in terms of Nitric oxide scavenging activity; p = 0.0028) or ascorbic acid (in terms of 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) assay; p = 0.0022). The damage control by the flower extract can be attributed to the reduction in lipid peroxidation and restoration of catalase activity. In vitro cytotoxicity tests have shown that the flower extract did not affect growth and survivability of the cell lines. It left beyond doubt that a flower of L. speciosa is a reservoir of antioxidant and hepatoprotective agents capable of reversing the damage inflicted by CCl 4 -intoxication. Results from the present study may be used in developing a potential hepato-protective health drink enriched with antioxidants from Lagerstroemia speciosa (L.) Pers.

In vivo antiplasmodial and toxicological effect of crude ethanol extract of Echinops kebericho traditionally used in treatment of malaria in Ethiopia.

PubMed

Toma, Alemayehu; Deyno, Serawit; Fikru, Abrham; Eyado, Amalework; Beale, Andrew

2015-05-10

Medicinal plants have contributed significantly to current malaria treatment. Emergence of resistance to currently available drugs has necessitated the search for new plant-based anti-malarial agents and several plant-based, pharmacologically active anti-malarial compounds have been isolated. This study was conducted to validate the traditional usage of Echinops kebericho for treating malaria in the traditional health care system of Ethiopia. The roots of E. kebericho were collected from Masha Woreda, Sheka Zone. After collection, the plant materials were identified by a taxonomist, dried under shade and crushed to powder for extraction. The powdered roots were extracted by maceration using 70 % ethanol. Acute toxicity study of the crude extract was carried out in Swiss albino mice. The in vivo anti-malarial activity of plant extract (200, 350 and 500 mg/kg) of E. kebericho roots against a chloroquine (CQ) sensitive strain of Plasmodium berghei strain ANKA was assessed using the four-day suppressive test procedure. Parameters such as parasitaemia, packed cell volume, body weight and survival time were then determined using standard tests. Oral administration of the ethanol extract showed significant (P<0.001) parasitaemia suppression at dose levels of 350 and 500 mg/kg in dose-related manner compared with the negative control. Five hundred mg/kg showed the highest (57.29±1.76 %) parasitaemia suppression. The survival times of P. berghei-infected mice were also increased in a dose-dependent manner but the test material did not prevent weight loss associated with increased parasitaemia. The result also showed the plant material prevented the loss in packed cell volume associated with increased parasitaemia. Its oral LD50 was found to be greater than 5,000 mg/kg, indicating its wider safety margin in mice. The result revealed the ethanol extract of E. kebericho roots has anti-malarial activity against P. berghei in an animal model and lends support to the use of the plant to combat malaria in Ethiopian folk medicine. Further work is necessary to isolate, identify and characterize the active principles from the plant material.

Pharmacologic investigations on the role of Sirt-1 in neuroprotective mechanism of postconditioning in mice.

PubMed

Kaur, Harpreet; Kumar, Amit; Jaggi, Amteshwar S; Singh, Nirmal

2015-07-01

Cerebral ischemia-reperfusion (I-R) injury is one of the primary causes of ischemic stroke. Ischemic postconditioning (iPoCo) is evolving as an important adaptive technique to contain I-R injury. Some recent studies have shown neuroprotective effects of iPoCo. However, the neuroprotective mechanism of iPoCo is not clear. So, the present study has been undertaken to investigate the possible role of Sirtinol, a selective class III histone deacetylase (HDAC) inhibitor in the neuroprotective mechanism of iPoCo in mice. Bilateral carotid artery occlusion (BCAO) for 12 min followed by reperfusion for 24 h was used to produce I-R-induced cerebral injury in Swiss albino mice. iPoCo involving three episodes of 10-s carotid artery occlusion and reperfusion instituted immediately after BCAO just before prolonged reperfusion of 24 h. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using a Morris water maze test. Rotarod test, inclined beam-walking test, and neurologic severity score (NSS) were used to assess motor incoordination. Acetylcholine esterase levels, brain thiobarbituric acid reactive species (TBARS), and glutathione level were also estimated. BCAO for 12 min followed by reperfusion for 24 h produced a significant rise in cerebral infarct size and NSS along with impairment of memory and motor coordination and biochemical alteration (↑acetylcholine esterase, ↓glutathione, and ↑TBARS). iPoCo, involving three episodes of 10-s carotid artery occlusion with intermittent reperfusion of 10 s applied just after ischemic insult of 12 min produced a significant decrease in cerebral infarct size and NSS along with the reversal of I-R-induced impairment of memory and motor coordination. iPoCo-induced neuroprotective effects were significantly abolished by pretreatment with selective SIRT 1 (class III HDAC) blocker Sirtinol (10 mg/kg intraperitoneal). It may be concluded that the neuroprotective effect of iPoCo probably involves activation of SIRT 1 (class III HDAC) enzyme. Copyright © 2015 Elsevier Inc. All rights reserved.

Donkey milk kefir induces apoptosis and suppresses proliferation of Ehrlich ascites carcinoma by decreasing iNOS in mice.

PubMed

Esener, Obb; Balkan, B M; Armutak, E I; Uvez, A; Yildiz, G; Hafizoglu, M; Yilmazer, N; Gurel-Gurevin, E

2018-04-12

Donkey milk and donkey milk kefir exhibit antiproliferative, antimutagenic and antibacterial effects. We investigated the effects of donkey milk and donkey milk kefir on oxidative stress, apoptosis and proliferation in Ehrlich ascites carcinoma (EAC) in mice. Thirty-four adult male Swiss albino mice were divided into four groups as follows: group 1, administered 0.5 ml water; group 2, administered 0.5 ml water + EAC cells; group 3, administered 0.5 ml donkey milk + EAC cells; group 4, administered 0.5 ml donkey milk kefir + EAC cells. We introduced 2.5 x 10 6 EAC cells into each animal by subcutaneous injection. Tap water, donkey milk and donkey milk kefir were administered by gavage for 10 days. Animals were sacrificed on day 11. After measuring the short and long diameters of the tumors, tissues were processed for histology. To determine oxidative stress, cell death and proliferation iNOS and eNOS, active caspase-3 and proliferating cell nuclear antigen were assessed using immunohistochemistry. A TUNEL assay also was used to detect apoptosis. Tumor volume decreased in the donkey milk kefir group compared to the control and donkey milk groups. Tumor volume increased in the donkey milk group compared to the control group. Proliferating cell nuclear antigen levels were higher in the donkey milk kefir group compared to the control and donkey milk groups. The number of apoptotic cells was less in the donkey milk group, compared to the control, whereas it was highest in the donkey milk kefir group. Donkey milk administration increased eNOS levels and decreased iNOS levels, compared to the control group. In the donkey milk kefir group, iNOS levels were significantly lower than those of the control and donkey milk groups, while eNOS levels were similar to the control group. Donkey milk kefir induced apoptosis, suppressed proliferation and decreased co-expression of iNOS and eNOS. Donkey milk promoted development of the tumors. Therefore, donkey milk kefir appears to be more beneficial for treating breast cancer than donkey milk.

Experimental infection with Cryptosporidium parvum IIaA21G1R1 subtype in immunosuppressed mice

USDA-ARS?s Scientific Manuscript database

Cryptosporidium parvum subtype IIaA21G1R1 oocysts were used to infect dexamethasone immunosuppressed N: NIH Swiss mice. Histology showed developmental stages in the duodenum, proximal and distal jejunum, ileum, cecum and colon, with the small intestine remaining infected until day 35 post infection....

Evaluation of Antiulcer Properties of Ethanolic and Hot Aqueous Stem Extracts of Synclisia scabrida on Experimentally Induced Ulcer Models in Albino Mice

PubMed Central

Onwudiwe, TC; Ughachukwu, PO; Unekwe, PC; Ogamba, JO

2012-01-01

Background: The treatment of peptic ulcer disease poses therapeutic challenges to both patients and physicians alike because of the tendency of ulcers to relapse. Drugs used in the treatment of this disease are either costly or are associated with high incidence of adverse effects. Synclisia scabrida is a plant used in ethnomedicine for the treatment of various forms of stomach disorders and menstrual pains. The medicinal properties of the plants are claimed to reside in the roots, stems, and the leaves. Aim: This study, therefore, is to verify this claim and elucidate the probable mechanism of action by using crude stem extracts of this plant on drug- and stress-induced ulcer models in albino mice. Materials and Methods: Crude ethanol and hot water extracts, EE and HWE respectively, of the stem were prepared. These extracts were fractionated and separated by chromatographic methods and the fractions pooled together as fractions (PF-1, PF-2, PF-3 respectively) based on their chromatographic mobility and color reactions. Phytochemical analysis was done on the extracts. Ulcer models were induced in albino mice by means of indomethacin, histamine, and stress after prior cytoprotection with orally administered crude extracts and control (cimetidine). Results: Phytochemical analysis of the crude extracts and their fractions revealed the presence of cardiac glycosides (+++), tannins (+++), saponins (+), flavonoids (++), carbohydrates (++) and alkaloids (+++). Acute toxicity study on the crude extracts and their fractions revealed relative safety at the dose of 5000 mg/kg. The crude extracts (EE and HWE) and their fractions (PF-1, PF-2, PF-3) significantly (P = 0.001) protected against indomethacin-, histamine- and stress-induced ulcers. The decrease in GIT motility produced by these extracts was comparable to that produced by atropine sulfate. Conclusion: The findings suggest that these extracts of Synclisia scabrida possess antiulcer and antispasmodic properties, which justify the claims for its use in the treatment of various forms of stomach disorders. PMID:23440331

Bacterial infection causes stress-induced memory dysfunction in mice.

PubMed

Gareau, Mélanie G; Wine, Eytan; Rodrigues, David M; Cho, Joon Ho; Whary, Mark T; Philpott, Dana J; Macqueen, Glenda; Sherman, Philip M

2011-03-01

The brain-gut axis is a key regulator of normal intestinal physiology; for example, psychological stress is linked to altered gut barrier function, development of food allergies and changes in behaviour. Whether intestinal events, such as enteric bacterial infections and bacterial colonisation, exert a reciprocal effect on stress-associated behaviour is not well established. To determine the effects of either acute enteric infection or absence of gut microbiota on behaviour, including anxiety and non-spatial memory formation. Behaviour was assessed following infection with the non-invasive enteric pathogen, Citrobacter rodentium in both C57BL/6 mice and germ-free Swiss-Webster mice, in the presence or absence of acute water avoidance stress. Whether daily treatment with probiotics normalised behaviour was assessed, and potential mechanisms of action evaluated. No behavioural abnormalities were observed, either at the height of infection (10 days) or following bacterial clearance (30 days), in C rodentium-infected C57BL/6 mice. When infected mice were exposed to acute stress, however, memory dysfunction was apparent after infection (10 days and 30 days). Memory dysfunction was prevented by daily treatment of infected mice with probiotics. Memory was impaired in germ-free mice, with or without exposure to stress, in contrast to conventionally reared, control Swiss-Webster mice with an intact intestinal microbiota. The intestinal microbiota influences the ability to form memory. Memory dysfunction occurs in infected mice exposed to acute stress, while in the germ-free setting memory is altered at baseline.

Immune Dysfunctions and Abrogation of the Inflammatory Response by Environmental Chemicals.

DTIC Science & Technology

1981-08-01

vitro effects in cats, mice, and humans. Materials and Methods: Animals: Mice: Young adult Swiss outbred mice and C57BL/6 (for skin graft donors) were...was used to determine significant differences between control (untreated) and MNU-treated cell cultures or animal groups. Results: Skin grafts : The...MNU-treated mice showed a dose-related increase in skin graft retention time, which was significant at 25 and 50 mg/kg MNU (p<.001). This is compared

In vivo effect of Commiphora swynnertonii ethanolic extracts on Trypanosoma congolense and selected immunological components in mice.

PubMed

Nagagi, Yakob P; Silayo, Richard S; Luziga, Claudius; Kweka, Eliningaya J

2017-05-23

The search for alternative trypanocidal compounds which can be available at affordable price is of paramount importance for control of trypanosomosis in human and animals. The current study evaluates the in vivo activity of ethanolic stem bark extracts on Trypanosoma congolense and selected immunological components in an inbred Swiss albino mouse model. Groups of mice infected with T. congolense were treated with the stem bark extracts at a rate of 1000 mg/kg, 1500 mg/kg, and 2000 mg/kg, twice a day in one set and thrice a day in another setting for three days consecutively. Negative (infected and untreated) and positive (infected treated with diminazene diaceturate at 3.5 mg/kg) control groups were used. Levels of parasitaemia were monitored daily for the first 10 days and thereafter 2-3 times per week to the end of experiment. In the other setting, uninfected mice, randomized in groups were treated with the extract but categorized as: thorough mixed extract (TME) and supernatant extract (SE) each at 500 mg/kg and 1500 mg/kg, in 8 hourly intervals respectively for three days consecutively. Control group was administered with phosphate buffered saline with glucose at 0.1 ml/10 g in a similar manner as for the extract. Whole blood and spleen were taken 24 h after the last treatment for hematological and histopathological analysis. The groups that received the extracts at 8 hourly intervals drastically reduced the parasitaemia. The higher dose of SE significantly reduced the percentage of lymphocytes (P < 0.05). Both high and low dose of TME significantly reduced lymphocytes percent (P < 0.05) while percent of neutrophils and monocytes increased significantly (P < 0.05). Histopathological changes of the spleen in the mice treated with higher concentrations of the extract of C. swynnertonii were suggestive of lymphocytes toxicity. The current study has provided evidence that, in vivo trypanocidal activity of ethanolic bark extracts of C. swynnertonii is probably affected by its negative effect on humoral mediated immune response. Further studies are recommended to determine its potential as an alternative source of lead compounds for trypanocidal drug discovery.

Role of estrogen and levodopa in 1-methyl-4-pheny-l-1, 2, 3, 6-tetrahydropyridine (mptp)-induced cognitive deficit in Parkinsonian ovariectomized mice model: A comparative study.

PubMed

Yadav, Satyndra Kumar; Pandey, Shivani; Singh, Babita

2017-11-01

Parkinson's disease (PD) is one of the most common neurodegenerative disease found in the aging population. Currently, many studies are being conducted to find a suitable and effective cure for PD, with an emphasis on the use of herbal plants. In this study, the neuroprotective effects of estrogen was evaluated in the 1-methyl-4-phe-nyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD with cognitive deficit and compared to Levodopa (LD), a well reported neuroprotective agent used for treating PD. Twenty-four Swiss albino mice were randomly divided into four groups: Control, MPTP, MPTP+LD and MPTP+estrogen. The behavioral recovery in both LD and estrogen treated mice were investigated using the rotarod, foot printing, narrow beam walking test and hanging tests. Non-motor behavioral recovery in both LD and estrogen treated were investigated using the Y-maze and Morris water maze. Furthermore, we performed the biochemical test i.e. catalase, lipid and nitrite in prefrontal cortex as well as nigrostriatal region of mouse brain. We also performed the acetylcholine esterase activity in prefrontal cortex and nigrostriatal region of mice brain. The recovery of dopamine neurons in the substantia nigra (SN) region was estimated by immunostaining of tyrosine hydroxylase (TH). Estrogen treatment restored all the deficits induced by MPTP more effectively than levodopa. Estrogen treatment recovered the number of TH-positive cells in both the SN region. Treatment with Estrogen significantly increased the levels of catalase, decreased the level of lipid and nitite in both region SN as well as prefrontal cortex region. Notably, the effect of estrogen was greater than that elicited by levodopa. Acetylcholine esterase activity was significantly increased in MPTP and it was found to be decreased by the treatment of estrogen as well as levodopa, although decrease in the activity was highly significant in estrogen treated group. Our result suggested that estrogen treatment significantly reduced the MPTP induced neurotoxicity as evident by decrease in oxidative damage, physiological abnormalities and immunohistochemical changes in the Parkinsonian mouse with cognitive deficit as compared to levodopa treatment. Copyright © 2017. Published by Elsevier B.V.

Antigenotoxic and anticytotoxic effect of camel milk in mice treated with cisplatin

PubMed Central

Salwa, M. Quita; Lina, A.F. Kurdi

2010-01-01

Camel milk (CM) has good nutritive value, in addition to its antigenotoxic and anticytotoxic effects. Therefore the aim of this investigation was to evaluate the capacity of CM to inhibit the micronucleated polychromatic erythrocytes (MnPCEs) in the bone marrow and improve the mitotic activity produced by cisplatin. Cisplatin is one of the most widely used antineoplastic drugs in the treatment of cancer. The 70 adult male Swiss albino mice were divided into seven groups:Gr. I: treated with distilled water and considered as a control group.Gr. II: treated with camel milk (33 ml/kg, b.w).Gr. III: treated previously with cisplatin (0.5 mg/kg, b.w).Gr. IV: treated with camel milk and followed after 2 h. with cisplatin (33 ml/kg → 0.5 mg/kg, b.w).Gr. V: treated with camel milk and cisplatin at the same time (33 ml/kg + 0.5 mg/kg, b.w).Gr. VI: treated with an acute single dose of cisplatin (2.5 mg/kg, b.w).Gr. VII: treated with camel milk prior and followed with an acute single dose of cisplatin (33 ml/kg → 2.5 mg /kg, b.w). The animals were sacrificed 24 h after cisplatin injection. The pretreatment with CM dose caused a significant decrease (P < 0.001) in the frequency of MnPCEs and increase (P < 0.001) in the mitotic index (MI) induced by cisplatin when compared with the groups treated with cisplatin alone. The possible explanation for the antigenotoxic and anticytotoxic effects observed in the pretreatment with CM is ascribed to its contents. In conclusion, from the findings we suggest that this milk has some antioxidant effect, and the antigenotoxic mechanism of this milk needs to be explored further before their use during cisplatin chemotherapy. PMID:23961073

Enhanced anti-tumor efficacy of paclitaxel with PEGylated lipidic nanocapsules in presence of curcumin and poloxamer: In vitro and in vivo studies.

PubMed

Anwar, Mohammed; Akhter, Sohail; Mallick, Neha; Mohapatra, Sharmistha; Zafar, Sobiya; Rizvi, M Moshahid A; Ali, Asgar; Ahmad, Farhan J

2016-11-01

Cancer chemotherapeutic drug containing PEGylated lipidic nanocapsules (D-LNCs) were formulated by the controlled addition of organic phase (combined solution of paclitaxel and curcumin in a mixture of oleic acid and MPEG 2000 -DSPE (90:2.5 molar ratio) in acetone) to the aqueous phase (consist of Poloxamer 407 as emulsifying agents and glycerol as a co-solvent) at a temperature of 55-60°C followed by evaporation of organic solvent. The obtained pre-colloidal dispersion of D-LNCs was processed through high pressure homogenization to get more uniformly and nano-sized particles. Effect of concentration of emulsifying agent and process variables of high pressure homogenization (pressure and number of cycles) on average particle size and entrapment efficiency was further investigated by constructing Box-Behnken experimental design to achieve the optimum manufacturing process. D-LNCs were characterized by dynamic light scattering, scanning and transmission electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. In vitro release studies showed a sustained release pattern of drug from the PEGylated D-LNCs, whereas in vivo pharmacokinetic studies after a single-dose intravenous (i.v.) administration of paclitaxel (15mg/kg) in Ehrlich ascites tumor (EAT)-bearing female Swiss albino mice showed a prolonged circulation time and slower elimination of paclitaxel from D-LNCs as compared with marketed formulation (Paclitec ® ). From the plasma concentration vs. time profile, i.v. bioavailability (AUC 0-∞ ) of paclitaxel from D-LNCs was found to be increased approximately 2.91-fold (P<0.001) as compared to Paclitec ® . In vitro cell viability assay against MCF-7 and MCF-7/ADR cell lines, in vivo biodistribution studies and tumor inhibition study in EAT-bearing mice, all together prove its significantly improved potency towards cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibition of Group IIA Secretory Phospholipase A2 and its Inflammatory Reactions in Mice by Ethanolic Extract of Andrographis paniculata, a Well-known Medicinal Food

PubMed Central

Kishore, V.; Yarla, N. S.; Zameer, F.; Nagendra Prasad, M. N.; Santosh, M. S.; More, S. S.; Rao, D. G.; Dhananjaya, Bhadrapura Lakkappa

2016-01-01

Andrographis paniculata Nees is an important medicinal plant found in the tropical regions of the world, which has been traditionally used in Indian and Chinese medicinal systems. It is also used as medicinal food. A. paniculata is found to exhibit anti-inflammatory activities; however, its inhibitory potential on inflammatory Group IIA phospholipases A2 (PLA2) and its associated inflammatory reactions are not clearly understood. The aim of the present study is to evaluate the inhibitory/neutralizing potential of ethanolic extract of A. paniculata on the isolated inflammatory PLA2 (VRV-PL-VIIIa) from Daboii rusellii pulchella (belonging to Group IIA inflammatory secretory PLA2 [sPLA2]) and its associated edema-induced activities in Swiss albino mice. A. paniculata extract dose dependently inhibited the Group IIA sPLA2 enzymatic activity with an IC50 value of 10.3 ± 0.5 μg/ml. Further, the extract dose dependently inhibited the edema formation, when co-injected with enzyme indicating that a strong correlation exists between lipolytic and pro-inflammatory activities of the enzyme. In conclusion, results of this study shows that the ethanolic extract of A. paniculata effectively inhibits Group IIA sPLA2 and its associated inflammatory activities, which substantiate its anti-inflammatory properties. The results of the present study warranted further studies to develop bioactive compound (s) in ethanolic extract of A. paniculata as potent therapeutic agent (s) for inflammatory diseases. SUMMARY This study emphasis the anti-inflammatory effect of A. paniculata by inhibiting the inflammatory Group IIA sPLA2 and its associated inflammatory activities such as edema. It was found that there is a strong correlation between lipolytic activity and pro-inflammatory activity inhibition. Therefore, the study suggests that the extract processes potent anti-inflammatory agents, which could be developed as a potential therapeutic agent against inflammatory and related diseases. PMID:27365993

An Antioxidant Extract of the Insectivorous Plant Drosera burmannii Vahl. Alleviates Iron-Induced Oxidative Stress and Hepatic Injury in Mice

PubMed Central

Das, Abhishek; Panja, Sourav; Mandal, Nripendranath

2015-01-01

Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME) was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 μg/ml) and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 μg) were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls’ staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38) cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a treatment for iron overload diseases. PMID:26010614

Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaballah, Hanaa H., E-mail: hanaahibishy@hotmail.c

Background: Although 5- Fluorouracil (5-FU) has exhibited effectiveness against cancer, novel therapeutic strategies are needed to enhance its antitumor efficiency and modulate its cytotoxity. Apigenin, a flavonoid present in fruits and vegetables, is a potent dietary phytochemical effective in cancer chemoprevention. Aim: This study was undertaken to investigate the potential synergistic antitumor activity of apigenin and 5-FU on Solid Ehrlich carcinoma (SEC). Methods: Eighty Swiss albino male mice were divided into four equal groups: vehicle treated control SEC, SEC + 5-FU, SEC + apigenin, SEC + 5-FU + apigenin. Beclin-1 and caspases 3, 9 and JNK activities were estimated bymore » ELISA; mRNA expression levels of the antiapoptotic gene Mcl-1 were estimated using quantitative real-time RT-PCR, while tissue malondialdehyde (MDA), glutathione peroxidase and total antioxidant capacity were evaluated spectrophotometrically. A part of the tumor was examined for histopathological and Ki-67 immunohistochemistry analysis. Results: 5-FU and/or apigenin caused significant increase in tissue levels of Beclin-1, caspases 3, 9 and JNK activities, MDA with significant decrease in tumor volume, Mcl-1expression, tissue glutathione peroxidase and total antioxidant capacity and alleviated the histopathological changes with significant decrease of Ki-67 proliferation index compared to vehicle treated SEC control group. In conclusion: The combination of 5-FU and apigenin had a greater effect than each of 5-FU or apigenin alone against solid Ehrlich carcinoma in mice. - Highlights: • Apigenin potentiated 5-FU cytotoxicity in EAC solid tumor models in vivo. • It acted via autophagy stimulation, downregulating MCL-1 and Ki-67 expression. • It caused JNK activation and ROS accumulation; resulted in tumor growth inhibition. • Apigenin can be used as a co-adjuvant agent in cancer therapy.« less

Methionine-supplemented diet affects the expression of cardiovascular disease-related genes and increases inflammatory cytokines in mice heart and liver.

PubMed

Aissa, Alexandre Ferro; Amaral, Catia Lira do; Venancio, Vinicius Paula; Machado, Carla da Silva; Hernandes, Lívia Cristina; Santos, Patrick Wellington da Silva; Curi, Rui; Bianchi, Maria de Lourdes Pires; Antunes, Lusânia Maria Greggi

2017-01-01

Some important environmental factors that influence the development of cardiovascular diseases (CVD) include tobacco, excess alcohol, and unhealthy diet. Methionine obtained from the diet participates in the synthesis of DNA, proteins, lipids and affects homocysteine levels, which is associated with the elevated risk for CVD development. Therefore, the aim of this study was to investigate the manner in which dietary methionine might affect cellular mechanisms underlying CVD occurrence. Swiss albino mice were fed either control (0.3% DL-methionine), methionine-supplemented (2% DL-methionine), or a methionine-deprived diet (0% DL-methionine) over a 10-week period. The parameters measured included plasma homocysteine concentrations, oxidative stress by reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, levels of inflammatory cytokines IL-1ß, TNF-α, and IL-6, as well as expression of genes associated with CVD. The levels of apolipoprotein A5 (APOA5), a regulator of plasma triglycerides, were measured. The methionine-supplemented diet increased oxidative stress by lowering the GSH/GSSG ratio in heart tissues and decreased expression of the genes Apob, Ctgf, Serpinb2, Spp1, Il1b, and Sell, but elevated expression of Thbs4, Tgfb2, Ccr1, and Vegfa. Methionine-deprived diet reduced expression of Col3a1, Cdh5, Fabp3, Bax, and Hbegf and increased expression of Sell, Ccl5, Itga2, Birc3, Msr1, Bcl2a1a, Il1r2, and Selp. Methionine-deprived diet exerted pro-inflammatory consequences as evidenced by elevated levels of cytokines IL-1ß, TNF-α, and IL-6 noted in liver. Methionine-supplemented diet increased hepatic IL-6 and cardiac TNF-α. Both methionine supplementation and deprivation lowered hepatic levels of APOA5. In conclusion, data demonstrated that a methionine-supplemented diet modulated important biological processes associated with high risk of CVD development.

Consequences of continuous social defeat stress on anxiety- and depressive-like behaviors and ethanol reward in mice.

PubMed

Macedo, Giovana Camila; Morita, Gleice Midori; Domingues, Liz Paola; Favoretto, Cristiane Aparecida; Suchecki, Deborah; Quadros, Isabel Marian Hartmann

2018-01-01

This study employed the intruder-resident paradigm to evaluate the effects of continuous social defeat on depressive- and anxiety-like behaviors and the reinforcing and motivational actions of ethanol in male Swiss mice. Male Swiss mice were exposed to a 10-day social defeat protocol, while control mice cohabitated with a non-aggressive animal. Continuous defeat stress consisted of episodes of defeat, followed by 24h or 48h cohabitation with the aggressor until the following defeat. Mice were assessed for sucrose drinking (anhedonia), social investigation test, elevated plus-maze, conditioned place preference to ethanol, and locomotor response to ethanol. Plasma corticosterone was measured prior to, after the first and the final defeat, and 10days after the end of defeat. Defeated mice exhibited a depressive-like phenotype as indicated by social inhibition and reduced sucrose preference, relative to non-defeated controls. Defeated mice also displayed anxiety-like behavior when tested in the elevated plus-maze. Stressed animals failed to present ethanol-induced locomotor stimulation, but showed increased sensitivity for ethanol-induced conditioned place preference. Corticosterone response to defeat was the highest after the first defeat, but was still elevated after the last defeat (day 10) when compared to non-stressed controls. Baseline corticosterone levels were unchanged 10days after the final defeat. These data suggest that social defeat stress increased depressive- and anxiety-like behavior as well increased vulnerability to ethanol reward in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Patulin in apple juice and its risk assessments on albino mice.

PubMed

Al-Hazmi, Mansour A

2014-07-01

The contamination of apple juice with patulin mycotoxin is a major risk factor in food safety. This study focuses to assess the biochemical and histopathological effects of patulin in apple juice samples collected from different outlets retailing in Jeddah, Kingdom of Saudi Arabia. On the basis of the selected dose level, 152.5 ppb patulin/ml was administered daily orally for up to 6 weeks to male albino mice. The exposure to contaminated samples revealed significant elevation of all the studied blood parameters (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities as well as creatinine, urea and uric acid contents). On the other hand, and with regard to the accumulated neuronal toxicity of the tested dose level, the toxic signs were recorded as significant increase in the aggressive and locomotor behavioral changes. In addition, the brain areas monoamines concentration revealed variable increased changes. The potential maximal changes in norepinephrine, dopamine and serotonin5-hydroxytryptamine levels attained in cortex, hypothalamus, striatum, hippocampus, midbrain and pons and medulla were assessed. Moreover, the histological examination revealed degeneration and necrosis in liver tissues and degenerated glomeruli and hemorrhage between the tubules of the cortical region in kidney tissues. The study declared that patulin-contaminated (152.5 ppb) apple juice exhibited liver, kidney and neurotoxicological effects in 6 weeks orally administered mice. © The Author(s) 2012.

The effects of compound 48/80, morphine, and mast cell depletion on electroshock seizure in mice.

PubMed

Yillar, D O; Küçükhüseyin, C

2008-01-01

The effects of compound 48/80 (C48/80), morphine, and mast cell depletion on maximal electroshock seizure (MES) were studied in Swiss albino mice. An electrical current (60Hz, 0.2 msec) inducing convulsions in 50% of the animals (CC50) was assessed as 46 mA. Compound 48/80 (5 mg/kg) and morphine (100mg/kg) were administered subcutaneously. CC50 was applied separately to electroshock-unexposed animal groups at 15, 30, 60, 120, and 240 min after the onset of the experiment. In untreated controls, the percent of seizure induced by CC50 and percent of death among mice having convulsions were 50 and 20, respectively. After C48/80, a significant increase in rates of seizure at 60th and 120th min and death beyond 60th min (p < .0001) indicates a pro-convulsive action of the drug, probably caused by a reduction in MES threshold. In contrast, rate of seizure tended to decrease following mast-cell depletion, which was readily reversed by C48/80 at the 60th min (p < .0001). Mast-cell depletion, alone or plus morphine, significantly increased the death percentage of convulsions. Morphine alone reduced the percentage of seizure induced by the application of CC50 in the mast-cell depleted animals (anticonvulsive action) but increased the percent of dying animals by as much as 100% at the 30th and 60th min (p < .0001). Combined morphine + C48/80 not only augmented the anticonvulsive effect of morphine at the 30th min but also nullified the rate of death among mice having convulsions. We concluded that compound 48/80 (1) penetrates into the central nervous system to produce a central effect; (2) acts as pro-convulsive, and (3) paradoxically augments the anticonvulsive action of morphine, likely caused by the ability of the compound to increase the permeability of blood-brain barrier for morphine or by the release of histamine from mast cells in the brain, acting as anticonvulsant through the stimulation of H1 receptors or both. The precise mechanism of the increased death rate by C48/80 or morphine in intact and in mast-cell-depleted mice appears to involve pro-convulsive effects, cardiovascular impairment, and respiratory depression. The nullification of morphine-induced lethal toxicity by C48/80 could be due to the antagonistic interaction of the drug with opiate receptors in the brain.

NASA Rodent Foodbar: Long Term Effects in Swiss Webster Mice

NASA Technical Reports Server (NTRS)

Santiago, D. L.; Yu, D. S.; Naficy, N. H.; Roghani, P. M.; Dalton, B. P.; Barrett, J. E.; Dalton, Bonnie (Technical Monitor)

2001-01-01

Swiss Webster male and female mice (150 of each) were fed NASA Rodent Foodbar for more than 110 days to test the diet's nutritional adequacy for use in future long-term studies aboard the International Space Station. Mice were grouped three to a cage (one cage = one sample) and cages were assigned to either Foodbar or Purina Chow #5001 (control) diet groups. Body weights, food intake, and water intake were obtained throughout the study. There were no significant differences in body weights between male Foodbar fed and Chow fed males (p=0.58), and at 15 weeks into the female mouse study there appear to be no significant body weight differences. Both male and female Foodbar fed groups consumed more food and less water than their Chow controls, both factors thought to be attributable to the high moisture content of the Foodbars (26% versus 10% for Chow). All differences in gross food and water consumption had p-values of less than 0.01. When food and water intake were adjusted for the moisture content in the food, both male and female Foodbar fed animals consumed less food, but still had a lower water intake rate than their controls. (p is less than 0.01). Preliminary analysis on blood samples from male and female halfway point dissections suggests differences in glucose and fat metabolism. In both male and female Foodbar fed animals, blood glucose values were significantly lower (p is less than 0.01) but there were no significant differences in cholesterol levels (p=0.51). In Foodbar fed females, triglycerides were significantly higher (p is less than 0.01). These data suggest that Foodbars allow for normal growth in Swiss Webster mice, but affect some blood chemistry parameters.

Acute oral toxicity of 3-MCPD mono- and di-palmitic esters in Swiss mice and their cytotoxicity in NRK-52E rat kidney cells.

PubMed

Liu, Man; Gao, Bo-Yan; Qin, Fang; Wu, Ping-Ping; Shi, Hai-Ming; Luo, Wei; Ma, Ai-Niu; Jiang, Yuan-Rong; Xu, Xue-Bing; Yu, Liang-Li Lucy

2012-10-01

The acute oral toxicity of 1-palmitoyl-3-chloropropanediol (3-MCPD 1-monopalmitate) and 1,2-bis-palmitoyl-3-chloropropanediol (3-MCPD dipalmitate) in Swiss mice were examined, along with their cytotoxicity in NRK-52E rat kidney cells. LD50 (median lethal dose) value of 3-MCPD 1-monopalmitate was determined 2676.81 mg/kg body weight (BW). The results showed that 3-MCPD 1-monopalmitate dose-dependently decreased the mean body weight, and caused significant increase of serum urea nitrogen and creatinine in dead mice compared to the control and survived mice. Major histopathological changes in mice fed 3-MCPD 1-monopalmitate were renal tubular necrosis, protein casts and spermatids decrease in the seminiferous tubules. According to the limit test for 3-MCPD dipalmitate, LD50 value of 3-MCPD dipalmitate was presumed to be greater than 5000 mg/kg BW. Obvious changes were not observed on mean body weight, absolute and relative organ weight or serum urea nitrogen and creatinine levels in mice fed 3-MCPD dipalmitate. However, renal tubular necrosis, protein casts and spermatids decrease were also observed in the dead mice. In addition, MTT and LDH assay results only showed the cytotoxicity of 3-MCPD 1-monopalmitate in NRK-52E rat kidney cells in a dose-dependent manner. Together, the results indicated a greater toxicity of 3-MCPD 1-monopalmitate compared to 3-MCPD dipalmitate. Copyright © 2012 Elsevier Ltd. All rights reserved.

Anti-inflammatory, analgesic and anti-pyretic activities of standardized root extract of Jasminum sambac.

PubMed

Sengar, Nidhi; Joshi, Apurva; Prasad, Satyendra K; Hemalatha, S

2015-02-03

The plant Jasminum sambac L. (Oleaceae) is cultivated throughout India. The leaves and roots of the plant are used traditionally in the treatment of inflammation, fever and pain. The leaves of the plant have been reported to posses significant anti-inflammatory and analgesic activities. To scientifically validate anti-inflammatory, analgesic and anti-pyretic activities of roots from Jasminum sambac. Ethanol root extract of Jasminum sambac (EJS) was standardized using HPTLC and was subjected to acute oral toxicity study. Further, analgesic activity of EJS at 100, 200 and 400mg/kg, p.o. was evaluated using writhing test on Swiss albino mice and tail-flick test on Charles Foster albino rats. Anti-inflammatory activity of EJS was assessed by carrageenan-induced rat paw edema, cotton pellet-induced granuloma and Freund׳s adjuvant-induced arthritis models, while antipyretic activity was evaluated using Brewer׳s yeast induced pyrexia. In addition, biochemical parameters such as alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) in blood serum and edematous tissue of rats exposed to acute (carrageenan) and granulomatous tissue in sub-chronic (cotton pellet granuloma) inflammation models were also evaluated. Phytochemical analysis of EJS revealed the presence of flavonoids, phenols, saponins, tannins and carbohydrates in major quantities, while the quantity of hesperidin in EJS (using HPTLC) was found to be 4.25%w/w. EJS at 400mg/kg, p.o. reduced writhing count up to 49.21%, whereas in tail-flick test, EJS in a dose dependent manner increased latency in flicking tail. EJS at 400mg/kg, p.o. showed significant anti-inflammatory activity after 2nd, 3rd, 4th and 6thh of treatment in carrageenan-induced edema, while a 33.58% inhibition in cotton pellet induced granuloma formation was observed at same dose level. EJS significantly (p<0.001) inhibited adjuvant-induced arthritis and also showed significant antipyretic activity. Further, a significant reversal in alterations of all the biochemical parameters (except ALP) in tissues was also observed. The study confirms the anti-inflammatory, analgesic and antipyretic activity of EJS which may be attributed to the presence of various phytoconstituents quantified especially hesperidin which have already been reported for its significant role in the treatment of inflammation and associated problems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evidence of functional cross talk between the Notch and NF-κB pathways in nonneoplastic hyperproliferating colonic epithelium.

PubMed

Ahmed, Ishfaq; Roy, Badal; Chandrakesan, Parthasarathy; Venugopal, Anand; Xia, Lijun; Jensen, Roy; Anant, Shrikant; Umar, Shahid

2013-02-15

The Notch and NF-κB signaling pathways regulate stem cell function and inflammation in the gut, respectively. We investigate whether a functional cross talk exists between the two pathways during transmissible murine colonic hyperplasia (TMCH) caused by Citrobacter rodentium (CR). During TMCH, NF-κB activity and subunit phosphorylation in colonic crypts of NIH Swiss mice at days 6 and 12 were associated with increases in downstream target CXC chemokine ligand (CXCL)-1/keratinocyte-derived chemokine (KC) expression. Blocking Notch signaling acutely for 5 days with the Notch blocker dibenzazepine (DBZ) failed to inhibit crypt NF-κB activity or CXCL-1/KC expression. Chronic DBZ administration for 10 days, however, blocked Notch and NF-κB signaling in the crypts and abrogated hyperplasia. Intriguingly, chronic Notch inhibition was associated with significant increases in IL-1α, granulocyte colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 2, and KC in the crypt-denuded lamina propria or whole distal colon, with concomitant increases in myeloperoxidase activity. In core-3(-/-) mice, which are defective in intestinal mucin, DBZ administration replicated the results of NIH Swiss mice; in Apc(Min/+) mice, which are associated with CR-induced elevation of NF-κB-p65(276) expression, DBZ reversed the increase in NF-κB-p65(276), which may have blocked rapid proliferation of the mutated crypts. DBZ further blocked reporter activities involving the NF-κB-luciferase reporter plasmid or the Toll-like receptor 4/NF-κB/SEAPorter HEK-293 reporter cell line, while ectopic expression of Notch-N(ICD) reversed the inhibitory effect. Dietary bael (Aegle marmelos) extract (4%) and curcumin (4%) restored Notch and NF-κB cross talk in NIH Swiss mice, inhibited CR/DBZ-induced apoptosis in the crypts, and promoted crypt regeneration. Thus functional cross talk between the Notch and NF-κB pathways during TMCH regulates hyperplasia and/or inflammation in response to CR infection.

Hippocampal CA1 local field potential oscillations induced by olfactory cue of liked food.

PubMed

Samerphob, Nifareeda; Cheaha, Dania; Chatpun, Surapong; Kumarnsit, Ekkasit

2017-07-01

Eating motivation is induced not only by negative energy balance but also food related cues. However, neural processing for acquisition of learned food preference remains to be established. This study aimed to identify hippocampal neural signaling in response to olfactory cue (chocolate scent) after completion of repetitive chocolate sessions. Male Swiss albino mice implanted with intracranial electrode into the hippocampus were used for local field potential (LFP) recording. Animals were given chocolate sessions (a piece of 2g chocolate per each mouse to eat on day 1, 3, 5 and 7). Hippocampal CA1 LFP signals and exploratory behavior of animals receiving chocolate scent were analyzed before and after chocolate sessions. The experiment was performed in a place preference-like apparatus with the zones of normal food pellet and chocolate (both kept in a small perforated cup for smell dispersion) at the opposite ends. Following chocolate sessions, time spent in a chocolate zone and CA1 LFP patterns were analyzed in comparison to control levels. Two-way ANOVA revealed significant increase in time spent seeking for chocolate. Frequency analysis of LFP power spectra revealed significant increases in delta and theta powers. Phase-amplitude analysis showed significant increase in maximal modulation index and decrease in frequency for phase of theta-high gamma coupling. Taken together, neural signaling in the hippocampus was sensitive to chocolate olfactory cue that might underlie learning process in response to repeated chocolate consumptions that primed intense food approaching behavior. Ultimately, these LFP patterns might reflect motivation to eat and predict feeding probability. Copyright © 2017 Elsevier Inc. All rights reserved.

Genotoxic assessment of Rubus imperialis (Rosaceae) extract in vivo and its potential chemoprevention against cyclophosphamide-induced DNA damage.

PubMed

Alves, Ana Beatriz Costa Rodrigues; dos Santos, Rafaella Souza; Calil, Susana de Santana; Niero, Rivaldo; Lopes, Jhonny da Silva; Perazzo, Fábio F; Rosa, Paulo César Pires; Andrade, Sérgio Faloni; Cechinel-Filho, Valdir; Maistro, Edson Luis

2014-05-14

Rubus imperialis Cham. Schl. (Rosaceae) is frequently used in traditional medicine as hypoglycemic, antinociceptive and antiviral remedy. Swiss albino mice were distributed in eight groups for acute treatment with Rubus imperialis extract (24 h). The extract doses selected were 50, 250 and 500 mg/kg b.w. administered by gavage alone or plus to CPA (50 mg/kg b.w.) administered by intraperitoneal injection. Control groups were treated in a similar way. Analyses were performed using the comet assay, on leukocytes (collected 4 and 24h after treatment) and liver (collected 24 h after treatment), and using the micronucleus test (MN) in bone marrow cells. Cytotoxicity was assessed by scoring 200 consecutive polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). The main compounds identified in the Rubus imperialis extract were saponins and steroidal compounds, with niga-ichigoside and tormentic acid being the major compounds. Tested doses of Rubus imperialis extract showed no genotoxic effects on leukocytes from peripheral blood or liver cells by the comet assay. However, the MN test showed an increase in the frequency of micronucleated cells at the two higher doses tested, indicating that this extract has clastogenic/aneugenic effects on bone marrow cells at higher doses. On the other hand, for all cells evaluated, the three tested doses of the Rubus imperialis extract promoted inhibition of DNA damage induced by CPA. Despite the chemoprevention observed, the clastogenicity/aneugenicity observed suggested caution about either continuous or high-dose usage of Rubus imperialis aerial parts extract by humans. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Novel Fish Oil-based Bigel System for Controlled Drug Delivery and its Influence on Immunomodulatory Activity of Imiquimod Against Skin Cancer.

PubMed

Rehman, Khurram; Zulfakar, Mohd Hanif

2017-01-01

To characterize bigel system as a topical drug delivery vehicle and to establish the immunomodulatory role of imiquimod-fish oil combination against skin cancer and inflammation resulting from chemical carcinogenesis. Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model. Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer. Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.

Apoptotic role of natural isothiocyanate from broccoli (Brassica oleracea italica) in experimental chemical lung carcinogenesis.

PubMed

Kalpana Deepa Priya, D; Gayathri, R; Gunassekaran, G R; Murugan, S; Sakthisekaran, D

2013-05-01

Sulforaphane (SFN) [1-isothiocyanato-4-(methylsulfinyl)butane] is a naturally occurring isothiocyanate found in cruciferous vegetables such as broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)]. Since it is among the most potent bioactive components with antioxidant and antitumor properties, it has received intense attention in the recent years for its chemopreventive properties. The present work determined the rehabilitating role in alleviating the oxidative damage caused by benzo(a)pyrene [B(a)P] to biomolecules and the apoptotic cascade mediated by orally administered isothiocyanate-SFN (9 µmol/mouse/day) against B(a)P (100 mg/kg body weight, i.p.) induced pulmonary carcinogenesis in Swiss albino mice. Oxidative damage was assessed by measuring lipid peroxidation, 8-hydroxydeoxyguanosine, hydrogen peroxide (H2O2) production, glycoprotein components, protein carbonyl levels and DNA-protein crosslinks. DNA fragmentation by agarose gel electrophoresis and caspase-3 activity by ELISA proved apoptotic induction by SFN along with the protein expression of Bcl-2, Bax and Cyt c. SFN treatment was found to decrease the H2O2 production (p < 0.001) in cancer induced animals, proving its antioxidant potential. Apoptosis was induced by increasing the release of Cyt c (p < 0.001) from mitochondria, decreasing and increasing the expression of Bcl-2 (p < 0.01) and Bax (p < 0.001), respectively. Caspase-3 activity was also enhanced (p < 0.001) which leads to DNA fragmentation in SFN treated groups. Our results reflect the rehabilitating role of SFN in B(a)P induced lung carcinogenesis.

A novel decontaminant and wound healant formulation of N,N'-dichloro-bis[2,4,6-trichlorophenyl]urea against sulfur mustard-induced skin injury.

PubMed

Lomash, Vinay; Pant, Satish C

2014-01-01

Sulfur mustard (SM)-induced dermatotoxicity can be prevented by an immediate use of decontamination agents. However, practically due to the time lapse between decontamination and exposure, there is always a possibility of wound formation. In view of this, a hydrophilic decontamination formulation of CC-2 (DRDE/WH-03) was fortified with Aloe vera gel and betaine (DRDE/WH-01) for improving its wound healing ability. Swiss albino mice were exposed to SM percutaneously (5 mg/kg) once, and after 24 hours, DRDE/WH-01, DRDE/WH-03, framycetin, and aloe gel were applied topically, daily for 7 days. Skin sections were subjected to histopathology, histomorphologic grading, tissue leukocytosis, and immunohistochemistry of inflammatory-reparative biomarkers on 3 and 7 days, respectively. DRDE/WH-01, framycetin, and aloe gel showed better reepithelialization, angiogenesis, and fibroplasia compared with DRDE/WH-03 and SM control. On the basis of histomorphologic scale, DRDE/WH-01, framycetin, and aloe gel were found to be equally efficacious. Up-regulation of interleukin-6 and infiltrating leukocytes, endothelial nitric oxide synthase and angiogenesis, fibroblast growth factor, and transforming growth factor-alpha with fibroplasia and reepithelialization were well correlated at various stages of the healing process. DRDE/WH-01 was equally effective as framycetin and has shown improved wound healing efficacy compared with DRDE/WH-03. Thus, DRDE/WH-01 can be recommended as a universal decontaminant and wound healant against vesicant-induced skin injury. © 2014 by the Wound Healing Society.

Anti-cancer activity of bromelain nanoparticles by oral administration.

PubMed

Bhatnagar, Priyanka; Patnaik, Soma; Srivastava, Amit K; Mudiam, Mohan K R; Shukla, Yogeshwer; Panda, Amulya K; Pant, Aditya B; Kumar, Pradeep; Gupta, Kailash C

2014-12-01

Oral administration of anti-cancer drugs is an effective alternative to improve their efficacy and reduce undesired toxicity. Bromelain (BL) is known as an effective anti-cancer phyto-therapeutic agent, however, its activity is reduced upon oral administration. In addressing the issue, BL was encapsulated in Poly(lactic-co-glycolic acid) (PLGA) to formulate nanoparticles (NPs). Further, the NPs were coated with Eudragit L30D polymer to introduce stability against the gastric acidic conditions. The resultant coated NPs were characterized for BL entrapment, proteolytic activity and mean particle size. The stability and release pattern of NPs were evaluated under simulated gastrointestinal tract (GIT) pH conditions. Cytotoxicity studies carried out in human cell lines of diverse origin have shown significant dose advantage (-7-10 folds) with NPs in reducing the IC50 values compared with free BL. The cellular uptake of NPs in MCF-7, HeLa and Caco-2 cells monolayer was significantly enhanced several folds as compared to free BL. Altered expression of marker proteins associated with apoptosis and cell death (P53, P21, Bcl2, Bax) also confirmed the enhanced anti-carcinogenic potential of formulated NPs. Oral administration of NPs reduced the tumor burden of Ehrlich ascites carcinoma (EAC) in Swiss albino mice and also increased their life-span (160.0 ± 5.8%) when compared with free BL (24 ± 3.2%). The generation of reactive oxygen species, induction of apoptosis and impaired mitochondrial membrane potential in EAC cells treated with NPs confirmed the suitability of Eudragit coated BL-NPs as a promising candidate for oral chemotherapy.

Evaluation of oleoresin capsicum of Capsicum frutescenes var. Nagahari containing various percentages of capsaicinoids following inhalation as an active ingredient for tear gas munitions.

PubMed

Kumar, Pravin; Deb, Utsab; Kaushik, M P

2012-08-01

Comparative efficacy as peripheral sensory irritant, oral and inhalation exposure studies were carried out on oleoresin capsicum (OC) of Capsicum frutescence var. Nagahari containing various percentages of capsaicinoids and two synthetic isomers of capsaicin in Swiss albino male mouse model to come up with a suitable active ingredient from natural source for tear gas munitions. The compounds screened were OC having varying percentages of capsaicinoids (20, 40 and 80%, respectively) and synthetic isomers (E and Z) of capsaicin (8-methyl-N-vanillyl-6-nonenamide). Mice were exposed to pyrotechnically generated smoke of the compounds in an all glass static exposure chamber for 15 min to determine acute inhalation toxicity (LC₅₀) and quantitative sensory irritation potential (RD₅₀). Acute oral median lethal dose (LD₅₀) was also evaluated. Safety index of tear gas (SITG), a ratio of lethal concentration 50% (LC₅₀) and the concentration which depresses respiration by 50% (RD₅₀) due to peripheral sensory irritation is also proposed. The compound having highest SITG is considered as the most suitable to be used for tear gas munitions. The study revealed that oleoresin capsicum containing 40% capsaicinoids had the highest SITG among the compounds studied. The oral dosage versus mortality pattern of some compounds did not follow a true dose-response curve (DRC); however, following inhalation, all the compounds followed DRC. It was concluded that oleoresin capsicum (40% capsaicinoids) may be considered as the most suitable and environmental friendly compound from natural source to be used as an active ingredient for tear gas munitions.

Chemopreventive effect of Lagenaria siceraria in two stages DMBA plus croton oil induced skin papillomagenesis.

PubMed

Kumar, Navneet; Kale, Raosaheb K; Tiku, Ashu B

2013-01-01

Cancer chemoprevention is a dietary or therapeutic strategy to prevent, suppress, or delay carcinogenesis either at initiation or progression level with nontoxic agents. Use of natural dietary compounds has been a major chemopreventive approach to modulate tumorigenic pathways. In the present study, we have evaluated Lagenaria siceraria (bottle gourd), a common vegetable of Indian household for its chemomodulatory potential. The fruit has been used in traditional medicine for a very long time for health benefits and to cure pain, ulcers, fever, cough, asthma, and other bronchial disorders. However, despite its reported beneficial effect the chemo modulatory potential of this plant has not been reported. Therefore chemopreventive effect of bottle gourd juice (BGJ) was studied against 7,12-dimethylbenz(a)anthracene (DMBA) plus croton oil induced skin papillomagenesis in Swiss albino mice. The effect was studied both at antiinitiation and antiinitiation/promotion level followed by histopathological study. A dose of 2.5% and 5% given in drinking water showed significant decrease in papilloma number, papilloma incidence, papilloma multiplicity, papilloma latency, papilloma volume, and papilloma size in different size range. Histopathological study showed chemopreventive effect by minimizing loss of stratification, a decrease in number of epithelial layers, reducing dermal infiltration and protection for various cytoplasmic changes. Higher dose of BGJ was found to be more effective than lower dose and the chemopreventive effect was maximum for antiinitiation/promotion treatment. Altogether, this study reports the chemopreventive effect of Lagenaria siceraria on skin papillomagenesis for the first time and suggests that its consumption may help in suppression of skin cancer.

[Formation of endogenous pyrogen by mononuclear phagocytes].

PubMed

Agasarov, L G

1980-03-01

Incubation of alveolar macrophages of rabbits and peritoneal macrophages of the abdominal cavity washing of albino mice does not lead to endogenous pyrogen release. Peritoneal macrophages obtained after peritoneal administration to mice of thioglycollate, glycogen or heterologous blood cells do not discharge pyrogen either during incubation without additional stimulation. Macrophages isolated after intraperitoneal administration of heterologous blood cells do not exhibit pyrogenic activity possibly because of a long period of time elapsed after phagocytosis of foreign agents. The triggering of pyrogen formation by macrophages can be effected by means of in vitro phagocytosis of corpuscular particles: staphylococci or heterologous blood cells.

In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract.

PubMed

Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

2016-01-01

Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae . The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. The LD 50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant ( P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant ( P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant ( P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. Anxiety is implicated in the number of psychiatric disorders In vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening test in mice and Rota-.rod test.The GABAergic system plays a significant role in CNS depressant and muscle relaxant effects.The study proves the traditional claims of the plant used in the treatment of phobia, panic, stress, anxiety and it is as well used in producing a calming effect on the nerves. Abbreviations Used : WHO: World Health Organization; CNS: Central nervous system; GGSME: Galphimia glauca stem methanol extract; IAEC: Institutional Animal Ethics Committee; OECD: The Organization for Economic Co-operation and Development; PTZ: Pentylenetetrazole; REM: Rapid eye movement; GABA: γ-aminobutyric acid; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; b.w: Body weight; i.p: Intraperitoneal; p.o: per oral.

In vivo Study on Depressant Effects and Muscle Coordination Activity of Galphimia glauca Stem Methanol Extract

PubMed Central

Garige, Baba Shankar Rao; Keshetti, Srisailam; Vattikuti, Uma Maheshwara Rao

2016-01-01

Background: Galphimia glauca is an evergreen shrub found across peninsular India, belonging to family Malpighiaceae. Objective: The objective of this study was to assess the in vivo depressant effects and muscle coordination activity of G. glauca stem methanol extract (GGSME). Materials and Methods: The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test. Results: The LD50 of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (P ≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (P ≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (P ≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice. Conclusion: The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs. SUMMARY Anxiety is implicated in the number of psychiatric disordersIn vivo depressant activity is studied employing animal models like Sodium pentobarbital-.induced sleep test, Hole-board test, Open field test, Pentylenetetrazole induced convulsions and Picrotoxin-induced convulsions tests.Muscle coordination activity is studied employing animal models like Grip strengthening test in mice and Rota-.rod test.The GABAergic system plays a significant role in CNS depressant and muscle relaxant effects.The study proves the traditional claims of the plant used in the treatment of phobia, panic, stress, anxiety and it is as well used in producing a calming effect on the nerves. Abbreviations Used: WHO: World Health Organization; CNS: Central nervous system; GGSME: Galphimia glauca stem methanol extract; IAEC: Institutional Animal Ethics Committee; OECD: The Organization for Economic Co-operation and Development; PTZ: Pentylenetetrazole; REM: Rapid eye movement; GABA: γ-aminobutyric acid; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; b.w: Body weight; i.p: Intraperitoneal; p.o: per oral PMID:27695258

Nootropic activity of Albizzia lebbeck in mice.

PubMed

Chintawar, S D; Somani, R S; Kasture, Veena S; Kasture, S B

2002-08-01

The effect of saponin containing n-butanolic fraction (BF) extracted from dried leaves of Albizzia lebbeck on learning and memory was studied in albino mice using passive shock avoidance paradigm and the elevated plus maze. Significant improvement was observed in the retention ability of the normal and amnesic mice as compared to their respective controls. We have also studied the effects of BF on the behavior influenced by serotonin (5-HT), noradrenaline and dopamine. The brain levels of serotonin, gamma-aminobutyric acid (GABA) and dopamine were also estimated to correlate the behavior with neurotransmitter levels. The brain concentrations of GABA and dopamine were decreased, whereas the 5-HT level was increased. The data indicate the involvement of monoamine neurotransmitters in the nootropic action of BF of A. lebbeck.

Effects of natural enrichment materials on stress, memory and exploratory behavior in mice.

PubMed

Acklin, Casey J; Gault, Ruth A

2015-07-01

Environmental enrichment is an essential component of laboratory animal housing that allows animals to engage in natural behaviors in an otherwise artificial setting. Previous research by the authors suggested that, compared with synthetic enrichment materials, natural materials were associated with lower stress levels in mice. Here, the authors compare the effects of different enrichment materials on stress, memory and exploratory behavior in Swiss Webster mice. Mice that were provided with natural enrichment materials had lower stress levels, better memory and greater exploratory behavior than did mice provided with synthetic enrichment materials or with no enrichment materials. These findings suggest that provision of natural enrichment materials can improve well-being of laboratory mice.

Aflatoxin-induced biochemical changes in liver of mice and its mitigation by black tea extract.

PubMed

Jha, Anamika; Shah, Komal; Verma, Ramtej J

2012-01-01

Aflatoxin belongs to the class of naturally occurring mycotoxins, food contaminants having potent carcinogenicity. We have evaluated the ameliorative role of black tea extract on aflatoxin-induced biochemical changes in the liver of albino male mice. Adult male mice were orally administered with 750 and 1500 pg of aflatoxin in 0.2 mL olive oil/kg b.w./day for 30 days. Oral administration of aflatoxin caused, as compared with controls, significant, dose-dependent reduction in DNA, RNA, protein and glycogen contents; however, cholesterol content and phsphorylase activity were significantly increased. Black tea is one of the most potent antioxidants containing numerous bioactive phytonurtients having therapeutic applications. Aflatoxin-induced changes in the liver of mice were significantly ameliorated on co-treatment of black tea extract (2% infusion in water).

Long-term effects of intragastic instillations of BDNPF:BDNPA in male Sprague-Dawley rats and female Swiss-Webster mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, D.M.; Drake, G.A.; London, J.E.

1981-07-01

Young male Sprague-Dawley rats were given a single dose of 1.3 g/kg body weight (BW) bis-dinitro-propyl-formal:bisdinitro-propyl-acetal (BDNPF:BDNPA) intragastrically (IG) and young female Swiss-Webster mice were given BDNPF:BDNPA either as a single dose (800 mg/kg/Bw) IG or a dose (500 mg/kg/BW) IG on each of 5 consecutive days. All animals were then maintained for the durations of their life spans and autopsied at death. The incidence of testicular Leydig cell tumors and subcutaneous fibrosarcomas in rats receiving the material was significantly elevated compared to controls, though treated animals' life spans were not significantly different from those of control animals. No significantmore » effects were seen in any of the mice receiving either a single dose or multiple doses of BDNPF:BDNPA compared to control animals. We suggest that another species of male Laboratory animals be treated with BDNPF:BDNPA to see if these findings can be replicated.« less

Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

PubMed Central

Farook, Justin M.; Krazem, Ali; Littleton, John M.; Barron, Susan

2008-01-01

In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg) + methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1mg/kg (p’s < 0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300mg/kg (p’s < 0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence. PMID:18577392

Antigenotoxic and antimutagenic effects of Schinus terebinthifolius Raddi in Allium cepa and Swiss mice: a comparative study.

PubMed

Fedel-Miyasato, L E S; Formagio, A S N; Auharek, S A; Kassuya, C A L; Navarro, S D; Cunha-Laura, A L; Monreal, A C D; Vieira, M C; Oliveira, R J

2014-04-30

It is estimated that 60% of anticancer drugs are derived directly or indirectly from medicinal plants. Schinus terebinthifolius Raddi (Anacardiaceae) is traditionally used in Brazilian medicine to treat inflammation, ulcers, and tumors. Because of the need to identify new antimutagenic agents and to determine their mechanism of action, this study evaluated the chemopreventive activity of the methanolic extract from leaves of S. terebinthifolius (MEST) in Allium cepa cells and in Swiss mice analyzing different protocols of MEST in association with DNA-damaging agents. The antigenotoxic and antimutagenic aspects in peripheral blood were evaluated using the comet and micronucleus assays, respectively. The percentage of damage reduction was used to compare the A. cepa and mice results. Our results showed for the first time that MEST can act as a chemopreventive compound that promotes cellular genome integrity by desmutagenic and bioantimutagenic activities in vegetal and animal models. This finding may therefore have therapeutic applications that can indirectly correlate to the prevention and/or treatment of the degenerative diseases such as cancer.

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas.

PubMed

Fortes, Paula Madeira; Albrechet-Souza, Lucas; Vasconcelos, Mailton; Ascoli, Bruna Maria; Menegolla, Ana Paula; de Almeida, Rosa Maria M

2017-01-01

Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Low- and high-frequency transcutaneous electrical nerve stimulation have no deleterious or teratogenic effects on pregnant mice.

PubMed

Yokoyama, L M; Pires, L A; Ferreira, E A Gonçalves; Casarotto, R A

2015-06-01

To evaluate the effects of application of transcutaneous electrical nerve stimulation (TENS) at low and high frequencies to the abdomens of Swiss mice throughout pregnancy. Experimental animal study. Research laboratory. Thirty Swiss mice received TENS throughout pregnancy. They were divided into three groups (n=10): placebo, low-frequency TENS (LF group) and high-frequency TENS (HF group). In the placebo group, the electrodes were applied to the abdominal region without any electrical current. In the LF group, the frequency was 10 Hz, pulse duration was 200 μs and intensity started at 2 mA. In the HF group, the same parameters were applied and the frequency was 150 Hz. All stimulation protocols were applied for 20 min/day from Day 0 until Day 20. The pregnant mice were weighed on Days 0, 7, 14 and 20 to verify weekly weight gain by two-way analysis of variance. The numbers of fetuses, placentas, implantations, resorptions and major external fetal malformations on Day 20 were analysed using the Kruskal-Wallis test. No significant differences were found between the placebo and TENS groups (P>0.05). Application of low- and high-frequency TENS to the abdomens of pregnant mice did not cause any deleterious or major teratogenic effects. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Development and Persistence of Methamphetamine Conditioned Hyperactivity in Swiss-Webster Mice

PubMed Central

Rauhut, Anthony S.; Bialecki, Victoria

2011-01-01

The present experiments examined the development and persistence of methamphetamine conditioned hyperactivity in Swiss-Webster mice. Experiments 1 and 2 examined the development of conditioned hyperactivity, varying the methamphetamine dose (0.25 – 2.0 mg/kg), the temporal injection parameters (continuous; Experiment 1 or intermittent; Experiment 2), and the comparison control group (saline; Experiment 1 or unpaired; Experiment 2). Experiment 3 examined the persistence of methamphetamine conditioned hyperactivity by comparing mice 1 (Immediate) or 28 (Delay) days after drug withdrawal. In each experiment, several behavioral measures (vertical counts, distance travelled and velocity) were recorded and temporal analyses conducted to assess methamphetamine conditioned hyperactivity. In Experiments 1 and 2, it was found that methamphetamine conditioned hyperactivity was 1) dose-dependent, 2) detected early in the session, 3) detected by a behavioral measure indicative of general activity (i.e., distance travelled), and 4) varied as a function of the number of conditioning sessions. In Experiment 3, it was found that conditioned hyperactivity persisted for 28 days, though was weakened by non-associative factors, following methamphetamine withdrawal. Collectively, these results suggest that conditioned hyperactivity to methamphetamine is robust and persists following prolonged periods of drug withdrawal in mice. Furthermore, these results are consistent with an excitatory classical conditioning interpretation of conditioned hyperactivity. PMID:21448061

Repeated-Doses Toxicity Study of the Essential Oil of Hyptis martiusii Benth. (Lamiaceae) in Swiss Mice

PubMed Central

Freire Rocha Caldas, Germana; Araújo, Alice Valença; Albuquerque, Giwellington Silva; Silva-Neto, Jacinto da Costa; Costa-Silva, João Henrique; de Menezes, Irwin Rose Alencar; Leite, Ana Cristina Lima; da Costa, José Galberto Martins; Wanderley, Almir Gonçalves

2013-01-01

Hyptis martiusii Benth. (Lamiaceae) is found in abundance in Northeastern Brazil where it is used in traditional medicine to treat gastric disorders. Since there are no studies reporting the toxicity and safety profile of this species, we investigated repeated-doses toxicity of the essential oil of Hyptis martiusii (EOHM). Swiss mice of both sexes were orally treated with EOHM (100 and 500 mg/kg) for 30 days, and biochemical, hematological, and morphological parameters were determined. No toxicity signs or deaths were recorded during the treatment with EOHM. The body weight gain was not affected, but there was an occasional variation in water and food consumption among mice of both sexes treated with both doses. The hematological and biochemical profiles did not show significant differences except for a decrease in the MCV and an increase in albumin, but these variations are within the limits described for the species. The microscopic analysis showed changes in liver, kidneys, lungs, and spleen; however, these changes do not have clinical relevance since they varied among the groups, including the control group. The results indicate that the treatment of repeated-doses with the essential oil of Hyptis martiusii showed low toxicity in mice. PMID:24151521

Myocarditis in mice and guinea pigs experimentally infected with a canine-origin Borrelia isolate from Florida.

PubMed

Breitschwerdt, E B; Geoly, F J; Meuten, D J; Levine, J F; Howard, P; Hegarty, B C; Stafford, L C

1996-04-01

To characterize the pathogenic potential of a unique Borrelia isolate obtained from a dog from Florida (FCB isolate). Prospective experimental infection. 32 preweanling Swiss Webster mice and 12 adult male Hartley guinea pigs were injected intraperitoneally with 10(5) spirochetes. Mice were used as controls and blood recipients, and at 3- to 4-day intervals, 1 control mouse and 2 infected mice were necropsied, tissues were cultured, and a recipient mouse was inoculated with blood. Guinea pigs were randomized to 4 groups and inoculated intradermally with 10(0), 10(2), 10(3), or 10(4) spirochetes. For 48 days, clinical, hematologic, serologic, and microbiologic tests were performed on them, after which they were necropsied. In mice, spirochetemia was detectable between postinoculation days (PID) 3 and 13, and seroreactivity to homologous antigen was detectable during PID 10 through 31. Compared with control mice, infected mouse spleens were 2 to 3 times larger. Histologic lesions included lymphoid hyperplasia, neutrophilic panniculitis, epicarditis, and myocarditis, with intralesional spirochetes detected from PID 3 through 6. During PID 10 through 31, nonsuppurative epicarditis developed. Signs of illness and hematologic abnormalities were not observed in guinea pigs, despite isolating spirochetes from blood during PID 7 to 27. When necropsied on PID 48, histologic lesions included lymphoid hyperplasia and lymphocytic plasmacytic epicarditis. The FCB isolate causes spirochetemia, lymphoid hyperplasia, dermatitis, and myocardial injury in Swiss Webster mice and can be transmitted by blood inoculation. In Hartley guinea pigs, the isolate causes spirochetemia, lymphoid hyperplasia, and epicarditis. Documentation of disease in mice, guinea pigs, and, presumably, dogs raises the level of concern that the FCB isolate might be pathogenic for man and other animal species.

Genetic variation within and between strains of outbred Swiss mice.

PubMed

Cui, S; Chesson, C; Hope, R

1993-04-01

The aim of this survey was to measure levels of genetic variation within and between 5 different strains of outbred Swiss mice. Ten to 15 animals from each strain (NIH, Q(S), ARC, IMVS and STUD) were typed, using allozyme electrophoresis, at 10 gene loci: Mod-1, Idh-1, Gpi-I, Es-1, Es-3, Hbb, Pep-3, Gr-1, Got-2 and Pgm-1. Polymorphic variation in at least one of the 5 strains was detected at all 10 loci. The proportion of polymorphic loci ranged from 0.3 (NIH) to 0.8 (IMVS) with a mean of 0.52. Average expected heterozygosities ranged from 0.08 (NIH) to 0.37 (IMVS) with a mean of 0.21. The inbred strain SWR was, as expected, homozygous at all 10 loci. The amount of allelic substitution between pairs of strains was quantified using Nei's genetic distance, and a dendrogram based on these genetic distances showed a close overall similarity in its branching pattern to the known genealogy of the strains. This survey showed that a considerable degree of genetic variation persists in the 5 strains examined, a level of variation similar to that previously detected by Rice and O'Brien (1980) in 3 other outbred Swiss strains.

Mutations in GPR143/OA1 and ABCA4 Inform Interpretations of Short-Wavelength and Near-Infrared Fundus Autofluorescence

PubMed Central

Paavo, Maarjaliis; Zhao, Jin; Kim, Hye Jin; Lee, Winston; Zernant, Jana; Cai, Carolyn; Allikmets, Rando; Tsang, Stephen H.; Sparrow, Janet R.

2018-01-01

Purpose We sought to advance interpretations and quantification of short-wavelength fundus autofluorescence (SW-AF) emitted from bisretinoid lipofuscin and near-infrared autofluoresence (NIR-AF) originating from melanin. Methods Carriers of mutations in X-linked GPR143/OA1, a common form of ocular albinism; patients with confirmed mutations in ABCA4 conferring increased SW-AF; and subjects with healthy eyes were studied. SW-AF (488 nm excitation, 500–680 nm emission) and NIR-AF (excitation 787 nm, emission >830 nm) images were acquired with a confocal scanning laser ophthalmoscope. SW-AF images were analyzed for quantitative autofluoresence (qAF). Analogous methods of image acquisition and analysis were performed in albino and pigmented Abca4−/− mice and wild-type mice. Results Quantitation of SW-AF (qAF), construction of qAF color-coded maps, and examination of NIR-AF images from GPR143/OA1 carriers revealed mosaics in which patches of fundus exhibiting NIR-AF signal had qAF levels within normal limits whereas the hypopigmented areas in the NIR-AF image corresponded to foci of elevated qAF. qAF also was increased in albino versus pigmented mice. Although melanin contributes to fundus infrared reflectance, the latter appeared to be uniform in en face reflectance images of GPR143/OA1-carriers. In patients diagnosed with ABCA4-associated disease, NIR-AF increased in tandem with increased qAF originating in bisretinoid lipofuscin. Similarly in Abca4−/− mice having increased SW-AF, NIR-AF was more pronounced than in wild-type mice. Conclusions These studies corroborate RPE melanin as the major source of NIR-AF but also indicate that bisretinoid lipofuscin, when present at sufficient concentrations, contributes to the NIR-AF signal. Ocular melanin attenuates the SW-AF signal.

Epidemiology of intestinal helminthiasis among school children with emphasis on Schistosoma mansoni infection in Wolaita zone, Southern Ethiopia.

PubMed

Alemayehu, Bereket; Tomass, Zewdneh; Wadilo, Fiseha; Leja, Dawit; Liang, Song; Erko, Berhanu

2017-06-20

Intestinal helminth infections are major parasitic diseases causing public health problems in Ethiopia. Although the epidemiology of these infections are well documented in Ethiopia, new transmission foci for schistosomiasis are being reported in different parts of the country. The objective of this study was to assess the prevalence of Schistosoma mansoni and other intestinal helminth infections among school children and determine the endemicity of schistosomiasis in Wolaita Zone, southern Ethiopia. Cross-sectional parasitological and malacological surveys were conducted by collecting stool samples for microscopic examination and snails for intermediate host identification. Stool samples were collected from 503 children and processed for microscopic examination using Kato-Katz and formalin-ether concentration methods. Snails collected from aquatic environments in the study area were identified to species level and Biomphalaria pfeifferi snails, the intermediate host of S. mansoni,, were individually exposed to artificial light in order to induce cercariae shedding. Cercariae shed from snails were used to infect laboratory-bred Swiss albino mice in order to identify the schistosome to species level. The overall prevalence of intestinal helminth infections was 72.2% among school children. S. mansoni infection prevalence was 58.6%. The prevalence and intensity of S. mansoni infections varied among schools and sex of children. Swimming was the only factor reported to be significantly associated with S. mansoni infection (AOR = 2.954, 95% CI:1.962-4.449). Other intestinal helminth species identified were hookworms (27.6%), Ascaris lumbricoides (8.7%), E. vermicularis (2.8%), Taenia species (2.6%), T. trichiura (1.2%) and H. nana (0.6%). Only B. pfeifferi snails collected from streams shed schistosome cercariae and 792 adult S. mansoni worms were harvested from mice exposed to cercariae shed from B. pfeifferi on the 6th week post-exposure. The present study found high level of intestinal helminth infections in the study area. The study also confirmed autochthonous transmission and endemicity of S. mansoni as evidenced by both parasitological and malacological findings as well as by further establishing infections in lab-bred mice. Therefore, there is a need to include the area in the control programs with anti-helminth drugs and also consider other complementary measures including sanitation, provision of clean water supply, and snail control.

Chemomodulatory effect of Moringa oleifera, Lam, on hepatic carcinogen metabolising enzymes, antioxidant parameters and skin papillomagenesis in mice.

PubMed

Bharali, Rupjyoti; Tabassum, Jawahira; Azad, Mohammed Rekibul Haque

2003-01-01

The modulatory effects of a hydro-alcoholic extract of drumsticks of Moringa oliefera Lam at doses of 125 mg/kg bodyweight and 250 mg/ kg body weight for 7 and 14 days, respectively, were investigated with reference to drug metabolising Phase I (Cytochrome b(5) and Cytochrome p(450) ) and Phase II (Glutathione-S- transferase) enzymes, anti-oxidant enzymes, glutathione content and lipid peroxidation in the liver of 6-8 week old female Swiss albino mice. Further, the chemopreventive efficacy of the extract was evaluated in a two stage model of 7,12 - dimethylbenz(a)anthracene induced skin papillomagenesis. Significant increase (p<0.05 to p<0.01) in the activities of hepatic cytochrome b(5), cytochrome p(450), catalase, glutathione peroxidase ( GPx ), glutathione reductase (GR), acid soluble sulfhydryl content (-SH ) and a significant decrease ( p<0.01 ) in the hepatic MDA level were observed at both dose levels of treatment when compared with the control values. Glutathione-S- transferase ( GST )activity was found to be significantly increased (p<0.01 ) only at the higher dose level. Butylated hydroxyanisol (BHA ) fed at a dose of 0.75% in the diet for 7 and 14 days (positive control ) caused a significant increase (p<0.05 to p<0.01) in the levels of hepatic phase I and phase II enzymes, anti- oxidant enzymes, glutathione content and a decrease in lipid peroxidation. The skin papillomagenesis studies demonstrated a significant decrease (p<0.05 ) in the percentage of mice with papillomas, average number of papillomas per mouse and papillomas per papilloma bearing mouse when the animals received a topical application of the extract at a dose of 5mg/ kg body weight in the peri-initiation phase 7 days before and 7 days after DMBA application, Group II ), promotional phase (from the day of croton oil application and continued till the end of the experiment, Group III ) and both peri and post initiation stages (from 7 days prior to DMBA application and continued till the end of the experiment, Group IV) compared to the control group (Group I ). The percentage inhibition of tumor multiplicity has been recorded to be 27, 72, and 81 in Groups II, III, and IV, respectively. These findings are suggestive of a possible chemopreventive potential of Moringa oliefera drumstick extract against chemical carcinogenesis.

Ethnopharmacological investigation of the aerial part of Phragmites karka (Poaceae).

PubMed

Sultan, Ramiz Ahmed; Kabir, Mohammad Shah Hafez; Uddin, Mir Muhammad Nasir; Uddin, Mohi; Mahmud, Zobaer Al; Raihan, Sheikh Zahir; Qais, Nazmul

2017-05-01

In this ethnopharmacological study, methanolic extract of the aerial plant parts of Phragmites karka (Family: Poaceae) and its petroleum ether and carbon tetrachloride fractions were investigated for bioactivities in Swiss-albino mice, namely, analgesic, central nervous system (CNS) depressant, hypoglycemic, and antidiarrheal activity. The cold methanolic extract of the aerial plant parts of Phragmites karka (MEPK) was first prepared, and it was then further fractionated as petroleum ether (PEFMEPK) and carbon tetrachloride (CTFMEPK) fractions. Analgesic activity was performed employing acidic acid-induced writhing test, central analgesic effect by radiant heat tail-flick method. CNS depressant activity was evaluated by phenobarbitone-induced sleeping time test. Hypoglycemic activity was tested by glucose tolerance test (GTT). Antidiarrheal activity was evaluated by castor oil-induced diarrhea method. For all in vivo tests, doses of 200 and 400 mg/kg body weight were used. In the mice model, the MEPK, PEFMEPK, and CTFMEPK fractions showed significant peripheral analgesic activity at a dose of 400 mg/kg body weight with percentage of inhibition of acetic acid-induced writhing 77.67 (p<0.001), 33.50 (p<0.001), and 40.29 (p<0.001), respectively, compared to the standard dichlofenac (60.68%, p<0.001) group. The hypoglycemic properties of MEPK, PEFMEPK, and CTFMEPK extracts were evaluated in normoglycemic mice where the reduction of blood glucose level after 30 min of glucose load were 69.85%, 78.91%, and 72.73%, respectively, and for standard glibenclamide, the reduction was 72.85%. All results were significant (p<0.05). In the case of the CNS depressant activity by phenobarbitone-induced sleeping time test, the crude ME significantly reduced sleep latency by 57.14% and increased the duration of sleep by 63.29% compared to the control, which were comparable to that of standard diazepam (65.71% and 77.62%, respectively). Among all the extract and fractions, methanolic extract showed the maximum antidiarrheal effect. The methanolic extract at 200 mg/kg dose induced a significant decrease in the total number of defecation in 4 h (69.05% of inhibition, p<0.001) and at 400 mg/kg dose showed 76.19% of inhibition (p<0.001). In light of the available literature, these findings represent the first experimental investigation of biological activities of P. karka in the perspective of their traditional use.

Prevalence of intestinal helminth infection among school children in Maksegnit and Enfranz Towns, northwestern Ethiopia, with emphasis on Schistosoma mansoni infection.

PubMed

Gashaw, Fikru; Aemero, Mulugeta; Legesse, Mengistu; Petros, Beyene; Teklehaimanot, Tilahun; Medhin, Girmay; Berhe, Nega; Mekonnen, Yalemtsehay; Erko, Berhanu

2015-10-31

Schistosomiasis is endemic in Ethiopia and previously unknown transmission foci have been reported from time to time in different parts of the country. Further surveys are required in areas where endemicity of the disease is not known to cover them with control program if transmission is taking place. This study, therefore, aims to assess the magnitude of schistosomiasis mansoni and soil-transmitted helminthiasis in Maksegnit and Enfranz Towns, northwestern Ethiopia. Cross-sectional parasitological and malacological surveys were conducted in three schools found in Maksegnit and Enfranz Towns. Stool specimens were collected from 550 randomly selected school children (age range 5 to 17 years) and processed for microscopic examination using Kato-Katz method (single smear per stool sample). Malacological survey was conducted in Gumara and Garno Rivers found in the study areas. Biomphalaria pfeifferi snails collected from the two rivers were individually exposed to artificial light in order to induce cercarial shedding. Laboratory-bred Swiss albino mice were exposed to the cercariae and definite identification of the schistosome species was made based on morphology. The overall prevalence of S. mansoni infection was found to be 49%; however, it varied by schools, with Selam having 60.7%, and Maksegnit Number 1 and 2 having 45.8 and 39.6%, respectively. The respective mean intensity of S. mansoni infection among school children in Selam, Maksegnit Number 1 and Maksegnit Number 2 Schools were 243, 194 and 183 eggs per gram of stool (epg). In all the study areas there was no difference in prevalence of S. mansoni infection in relation to age, however, the prevalence varied by sex, with males having highest prevalence (54.5% vs 44.1%) (p = 0.012). Adult S. mansoni worms were harvested from mice exposed to cercariae shed from B. pfeifferi on the 6(th) week post-exposure. The prevalence of Ascaris lumbricoides single infection was 16.5% while its co-infection with S. mansoni was 18.2%. Infections of young children, findings of schistosome infected snails, establishment of mice infection and harvesting adult worms from the lab-bred mice confirm that autochthonous transmission is taking place in the study areas. Hence, preventive chemotherapy with praziquantel should be put in place, complemented with other measures such as provision of sanitary facilities and health education, to control morbidity and transmission of schistosomiasis and soil-transmitted helminthiasis in the study areas.

Evaluation of antinociceptive activity of aqueous extract of bark of psidium guajava in albino rats and albino mice.

PubMed

Sekhar, N Chandra; Jayasree, T; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

2014-09-01

Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. AEPG antinociceptive activity involves activation of the peripheral and central mechanisms.

TNT Metabolites in Animal Tissues

DTIC Science & Technology

1991-06-01

bonded to the silica surface contained both a C18 (reversed-phase function) and a secondary amine (anioni exchange function) incorporated into a single ...contains both a C18, (reversed-phase function) and a secondary amine, (anion exchange function) incorporated into a single ligand in a 1:1 ratio. The...and store at 4°C. 4. Dosing of Mice with [14CITNT Young adult mice (Swiss Webster outbred strain) of both sexes weighing approximately 30 grams each

The lymphatic drainage of the epididymis and of the ductus deferens of the rat, with reference to the immune response to vasectomy.

PubMed Central

McDonald, S W; Scothorne, R J

1988-01-01

The lymphatic drainage of the testis, epididymis and ductus deferens was determined in unoperated and in unilaterally vasectomised Albino Swiss rats. In the vasectomised animals, the lymphatic drainage of epididymal and vasal sperm granulomas was also investigated. The normal epididymis, and sperm granulomas which develop in it after vasectomy, drain to the regional testicular lymph node via the inferior epididymal trunk; vasectomy does not interfere with this route. There is a lymphatic watershed within the middle one third of the scrotal ductus deferens; lymph may drain caudally, to enter the inferior epididymal trunk and/or rostrally to the iliac node. Lymphatics draining granulomas at the vasectomy site, may, therefore, be interrupted by vasectomy. This would contribute to, but does not fully explain, the variable immune response of the regional testicular node following vasectomy. PMID:3225225

Effect of Biodegradable Shape-Memory Polymers on Proliferation of 3T3 Cells

NASA Astrophysics Data System (ADS)

Xu, Shuo-Gui; Zhang, Peng; Zhu, Guang-Ming; Jiang, Ying-Ming

2011-07-01

This article evaluates the in vitro biocompatibility for biodegradable shape-memory polymers (BSMP) invented by the authors. 3T3 cells (3T3-Swiss albino GNM 9) of primary and passaged cultures were inoculated into two kinds of carriers: the BSMP carrier and the control group carrier. Viability, proliferation, and DNA synthesis (the major biocompatibility parameters), were measured and evaluated for both the BSMP and naked carrier via cell growth curve analysis, MTT colorimetry and addition of 3H-TdR to culture media. The results showed that there was no difference between the BSMP carrier and the control dish in terms of viability, proliferation, and metabolism of the 3T3 cells. Overall, the BSMP carrier provides good biocompatibility and low toxicity to cells in vitro, and could indicate future potential for this medium as a biological material for implants in vivo.

Combined effects of treatment with vitamin C, vitamin E and selenium on the skin of diabetic rats.

PubMed

Sokmen, B B; Basaraner, H; Yanardag, R

2013-04-01

The aim of this study was to investigate the effects of vitamin C, vitamin E and selenium (Se) on the skin tissue of streptozotocin-induced diabetic rats. Swiss albino rats were divided into four groups: control, control + antioxidants, diabetic, diabetic + antioxidants groups. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin. Vitamin C (250 mg/kg), vitamin E (250 mg/kg) and Se (0.2 mg/kg) were given by gavage technique to rats of one diabetic and one control group for 30 days. In the diabetic group, the levels of serum urea and creatinine, skin lipid peroxidation and nonenzymatic glycosylation levels increased, but skin glutathione levels decreased. Treatment with vitamin C, vitamin E and Se reversed these effects. The present study showed that vitamin C, vitamin E and Se exerted antioxidant effects and consequently may prevent skin damage caused by streptozotocin-induced diabetes.

Comparative pathogenicity in Swiss mice of Trypanosoma cruzi IV from northern Brazil and Trypanosoma cruzi II from southern Brazil.

PubMed

Meza, Sheila Karina Lüders; Kaneshima, Edilson Nobuyoshi; Silva, Sueli de Oliveira; Gabriel, Maristela; de Araújo, Silvana Marques; Gomes, Mônica Lúcia; Monteiro, Wuelton Marcelo; Barbosa, Maria das Graças Vale; Toledo, Max Jean de Ornelas

2014-11-01

The geographical heterogeneity of Chagas disease (ChD) is mainly caused by genetic variability of the etiological agent Trypanosoma cruzi. Our hypothesis was that the pathogenicity for mice may vary with the genetic lineage (or Discrete Typing Unit - DTU) of the parasite. To test this hypothesis, parasitological and histopathological evaluations were performed in mice inoculated with strains belonging to the DTU T. cruzi IV (TcIV) from the State of Amazonas (northern Brazil), or the DTU T. cruzi II (TcII) from the State of Paraná (southern Brazil). Groups of 10 Swiss mice were inoculated with eight strains of TcIV obtained from acute cases (7) from two outbreaks of orally acquired ChD, and from the triatomine Rhodnius robustus (1) from Amazonas; and three strains of TcII obtained from chronic patients in Paraná. We evaluated the pre-patent period, patent period, maximum peak of parasitemia, day of maximum peak of parasitemia, area under the parasitemia curve, inflammatory process, and tissue parasitism in the acute phase. TcIV was less virulent than TcII, and showed significantly (p < 0.005) lower parasitemia levels. Although the levels of tissue parasitism did not differ statistically, mice infected with TcIV displayed significantly (p < 0.001) fewer inflammatory processes than mice infected with TcII. This supported the working hypothesis, since TcIV from Amazonas was less pathogenic than TcII from Paraná; and agreed with the lower severity of human cases of ChD in the Amazon region. Copyright © 2014 Elsevier Inc. All rights reserved.

The Effects of Ochratoxin A on the Immune Response of Swiss Mice

PubMed Central

Prior, M.G.; Sisodia, C.S.

1982-01-01

The acute intraperitoneal toxicity of ochratoxin A (OA) for adult female Swiss mice is presented. The seven-day LD50 was calculated to be 48 ± 3.2 mg/kg. Daily intraperitoneal administrations of 10 mg OA/kg resulted in 50% mortality by the tenth day of injection. Clinical symptoms included depression, huddling, roughened hair coats, humped backs and reduced weight gains. Mice injected intraperitoneally daily for 50 days with 5 mg OA/kg had a significantly (P<0.01) depressed antibody response to killed Brucella abortus. In contrast, oral administrations of OA at 4 ppm in feed for 50 days did not depress titre levels. Ochratoxin A also significantly (P<0.01 intraperitoneal; P<0.05 oral administrations) reduced body weight gain over the period of the trials. Neither oral nor intraperitoneal administration of OA for 50 days affected the response of mice to sheep red blood cells although both the number of antibody-forming cells and the number of cells per spleen were significantly lowered (P<0.01) by cyclophosphamide. Both spleen and body weights were significantly lowered (P<0.05) in the groups given OA. There was a significant depression of blast transformation (P<0.01) in mice treated intraperitoneally with either OA or cyclophosphamide and stimulated with concanavalin A; oral administration of OA did not depress blast transformation. It would appear that lower levels of exposure, e.g. 4 ppm OA in feed, do not cause depression of the immune response of mice. The depressive effect seen at much higher levels may be a result of a nonselective toxic effect. PMID:6804072

Complex effects of mGluR5 antagonism on sociability and stereotypic behaviors in mice: possible implications for the pharmacotherapy of autism spectrum disorders.

PubMed

Burket, Jessica A; Herndon, Amy L; Winebarger, Erin E; Jacome, Luis F; Deutsch, Stephen I

2011-10-10

Balb/c mice display deficits of sociability; for example, they show reduced locomotor activity in the presence of an enclosed or freely-moving social stimulus mouse. Transgenic mice with defective or diminished expression of NMDA receptors manifest impaired sociability, while a partial and full agonist of the obligatory glycine co-agonist binding site on the NMDA receptor improved sociability in the Balb/c mouse strain. Because 2-methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor (mGluR), reduced self-grooming behavior in BTBR T+tfJ (BTBR) mice, another inbred genetic mouse model of autism spectrum disorders (ASDs), and mGluR5 antagonism is emerging as an experimental treatment for the 'fragile X syndrome," which has a high prevalence of co-morbid ASDs, we examined the effects of MPEP on sociability and stereotypic behaviors in Balb/c and Swiss Webster mice in a standard paradigm. MPEP had complex effects on sociability, impairing some measures of sociability in both strains, while it reduced the intensity of some spontaneous measures of stereotypic behaviors emerging during free social interaction in Swiss Webster mice. Conceivably, mGluR5 antagonism exacerbates diminished endogenous tone of NMDA receptor-mediated neurotransmission in neural circuits relevant to at least some measures of sociability in Balb/c mice; the mGluR5 receptor contributes to regulation of the phosphorylation status of the NMDA receptor. In any event, although stereotypies are an important therapeutic target in ASDs, medication strategies to attenuate their severity via antagonism of mGluR5 receptors must be pursued cautiously because of their potential to worsen at least some measures of sociability. Copyright © 2011 Elsevier Inc. All rights reserved.

Inhalation reproductive toxicology studies: Male dominant lethal study of n-hexane in Swiss (CD-1) mice: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mast, T.J.; Rommereim, R.L.; Evanoff, J.J.

The straight-chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent routinely used in industrial environments; consequently, the opportunity for industrial, environmental or accidental exposure to hexane vapors is significant. Although myelinated nerve tissue is the primary target organ of hexane, the testes have also been identified as being sensitive to hexacarbon exposure. The objective of this study was to evaluate male dominant lethal effects in Swiss (CD-1) mice after exposure to 0, 200, 1000, or 5000 ppM n-hexane, 20 h/day for 5 consecutive days. Each exposure concentration consisted of 30 randomly selected, proven male breeders; 4 groups. The mice were weighedmore » just prior to the first day of exposure and at weekly intervals until sacrifice. Ten males in each dose group were sacrificed one day after the cessation of exposure, and their testes and epididymides were removed for evaluation of the germinal epithelium. The remaining male mice, 20 per group, were individually housed in hanging wire-mesh breeding cages where they were mated with unexposed, virgin females for eight weekly intervals; new females were provided each week. The mated females were sacrificed 12 days after the last day of cohabitation and their reproductive status and the number and viability of the implants were recorded. The appearance and behavior of the male mice were unremarkable throughout the study period and no evidence of n-hexane toxicity was observed. 18 refs., 3 figs., 11 tabs.« less

Clinical and serological tests for arboviruses in free-living domestic pigeons (Columba livia).

PubMed

Ramos, Bruna Alves; Chiang, Jannifer Oliveira; Martins, Lívia Carício; Chagas, Liliane Leal das; Silva, Franko de Arruda E; Ferreira, Milene Silveira; Freitas, Maria Nazaré Oliveira; Alcantara, Bianca Nascimento de; Silva, Sandro Patroca da; Miranda, Stefânia Araújo; Sepulvreda, Barbara Alves; Corrêa, Layna Thayssa Guimarães; Negrão, Andréa Maria Góes; Vasconcelos, Pedro Fernando da Costa; Casseb, Alexandre do Rosário

2017-08-01

In this study, we evaluated the role of free-living domestic pigeons (Columba livia) as a reservoir of arboviruses in the city of Belém, state of Pará, Brazil. We investigated the presence of antibodies against the most prevalent arboviruses. This study was aimed at evaluating some clinical and physical parameters of domestic pigeons, including the presence of antibodies to Amazon-endemic arboviruses. Eighty-five healthy pigeons were captured in Mangal das Garças Park, in Belém, and were bled. Upon capture, the birds were subjected to a clinical examination in search of alterations that could indicate the presence of arboviruses. Blood samples were converted to serum and tested using the haemagglutination inhibition (HI) technique with a panel of 19 antigens of arboviruses circulating in the Amazon. The confirmation assay for the positive reactions to the viral species tested by HI was a neutralisation test in new-born Swiss albino mice (Mus musculus) [mouse neutralisation test (MNT)]. A total of 10 (11.8%) serum samples tested positive for antiflavivirus antibodies by HI. All the samples positive for the HI test were subjected to MNT for detection of viruses and yielded negative results (logarithmic neutralisation index < 1.7). The results represent the first serological detection of antiarbovirus antibodies in domestic pigeons as potential hosts of arboviruses in Brazil. The detection of haemagglutination-inhibiting antibodies against genus Flavivirus indicated that there was recent contact between the analysed domestic pigeons and these arboviruses. Further studies are needed to evaluate the role of free-living pigeons in the maintenance cycle and spread of arboviruses in the Amazon.

Clinical and serological tests for arboviruses in free-living domestic pigeons (Columba livia)

PubMed Central

Ramos, Bruna Alves; Chiang, Jannifer Oliveira; Martins, Lívia Carício; Chagas, Liliane Leal das; Silva, Franko de Arruda e; Ferreira, Milene Silveira; Freitas, Maria Nazaré Oliveira; de Alcantara, Bianca Nascimento; da Silva, Sandro Patroca; Miranda, Stefânia Araújo; Sepulvreda, Barbara Alves; Corrêa, Layna Thayssa Guimarães; Negrão, Andréa Maria Góes; Vasconcelos, Pedro Fernando da Costa; Casseb, Alexandre do Rosário

2017-01-01

BACKGROUND In this study, we evaluated the role of free-living domestic pigeons (Columba livia) as a reservoir of arboviruses in the city of Belém, state of Pará, Brazil. We investigated the presence of antibodies against the most prevalent arboviruses. OBJECTIVES This study was aimed at evaluating some clinical and physical parameters of domestic pigeons, including the presence of antibodies to Amazon-endemic arboviruses. METHODS Eighty-five healthy pigeons were captured in Mangal das Garças Park, in Belém, and were bled. Upon capture, the birds were subjected to a clinical examination in search of alterations that could indicate the presence of arboviruses. Blood samples were converted to serum and tested using the haemagglutination inhibition (HI) technique with a panel of 19 antigens of arboviruses circulating in the Amazon. The confirmation assay for the positive reactions to the viral species tested by HI was a neutralisation test in new-born Swiss albino mice (Mus musculus) [mouse neutralisation test (MNT)]. FINDINGS A total of 10 (11.8%) serum samples tested positive for antiflavivirus antibodies by HI. All the samples positive for the HI test were subjected to MNT for detection of viruses and yielded negative results (logarithmic neutralisation index < 1.7). MAIN CONCLUSION The results represent the first serological detection of antiarbovirus antibodies in domestic pigeons as potential hosts of arboviruses in Brazil. The detection of haemagglutination-inhibiting antibodies against genus Flavivirus indicated that there was recent contact between the analysed domestic pigeons and these arboviruses. Further studies are needed to evaluate the role of free-living pigeons in the maintenance cycle and spread of arboviruses in the Amazon. PMID:28767977

Chemical composition, antimicrobial properties and toxicity evaluation of the essential oil of Cupressus lusitanica Mill. leaves from Cameroon.

PubMed

Teke, Gerald Ngo; Elisée, Kemadjou Nana; Roger, Kuiate Jules

2013-06-13

The leaves of Cupressus lusitanica Mill. are used in the western highlands of Cameroon for their medicinal property. The leaves of this species were collected in the West Region of Cameroon in August 2010 and subjected to hydrodistillation to obtain the essential oil. The oil was fractionated using adsorption column chromatography. The chemical composition of this oil and its fractions was analysed by gas chromatography-mass spectrometry (GC-MS). The essential oil and fractions were tested for antimicrobial activity against eight bacterial species and six species of Candida by the agar diffusion method. Macrodilution method was used to determine the minimum inhibition concentrations (MICs) and minimum bactericidal and/or fungicidal concentrations (MBCs and MFCs). The toxicity profile of the oil was studied using Swiss mice and Wistar albino rats. Forty-nine compounds were identified in the essential oil. The main components were germacrene D (18.5%), epi-zonarene (8.2%), cis-calamenene (8.2%), terpinen-4-ol (6.3%), linalool (6.0%) and umbellulone (6.0%). Enterococcus faecalis, Proteus mirabilis and Candida albicans were most susceptible to the oil (MICs of 1.25 and 0.16% for bacteria and fungi respectively). The estimated oral LD50 was 6.33 g/kg. There was an increase in sera ALT and AST activities while the blood cells and protein levels decreased in treated animals. The results obtained from this study support the ethnomedicinal use of C. lusitanica leaf oil in the treatment of whooping cough and skin infections though it should be used with care. This plant oil could be useful in the standardisation of phytomedicine.

In vivo tissue distribution and efficacy studies for cyclosporin A loaded nano-decorated subconjunctival implants.

PubMed

Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Kaffashi, Abbas; Çalamak, Semih; Ulubayram, Kezban; Palaska, Erhan; Çakmak, Hasan Basri; Ünlü, Nurşen

2016-11-01

Biodegradable implants are promising drug delivery systems for sustained release ocular drug delivery with the benefits such as minimum systemic side effects, constant drug concentration at the target site and getting cleared without surgical removal. Dry eye syndrome (DES) is a common disease characterized with the changes in ocular epithelia surface and results in inflammatory reaction that might lead to blindness. Cyclosporin A (CsA) is a cyclic peptide that is frequently employed for the treatment of DES and it needs to be applied several times a day in tear drops form. The aim of this study was to evaluate in vivo behavior and efficacy of the developed nano-decorated subconjunctival implant systems for sustained release CsA delivery. Biodegradable Poly-ɛ-caprolactone (PCL) implant or micro-fiber implants containing CsA loaded poly-lactide-co-glycolide (85:15) (PLGA) or PCL nanoparticles were prepared in order to achieve sustained release. Two of the formulations PCL-PLGA-NP-F and PCL-PCL-NP-I were selected for in vivo evaluation based on their in vitro characteristics determined in our previous study. In this study, formulations were implanted to Swiss Albino mice with induced dry eye syndrome to investigate the ocular distribution of CsA following subconjunctival implantation and to evaluate the efficacy. Tissue distribution study indicated that CsA was present in ocular tissues such as cornea, sclera and lens even 90 days after the application and blood CsA levels were found lower than ocular tissues. Efficacy studies also showed that application of CsA-loaded fiber implant formulation resulted in faster recovery based on their staining scores.

Anticholinesterase, antioxidant, analgesic and anti-inflammatory activity assessment of Xeranthemum annuum L. and isolation of two cyanogenic compounds.

PubMed

Orhan, Ilkay Erdogan; Gulyurdu, Fulya; Kupeli Akkol, Esra; Senol, Fatma Sezer; Arabaci Anul, Serap; Tatli, Iffet Irem

2016-11-01

Xeranthemum annuum L. (Asteraceae) (XA) is an ornamental and medicinal species with limited bioactivity and phytochemical data. Identification of anticholinesterase, antioxidant, anti-inflammatory and analgesic effects of the flower and root-stem (R-S) extracts of XA. Anticholinesterase (at 100 μg mL -1 ) and antioxidant (at 1000 μg mL -1 ) effects of various extracts were evaluated via microtiter assays, while anti-inflammatory and analgesic effects of the R-S extracts were tested using carrageenan-induced hind paw oedema (100 and 200 mg kg -1 ) and p-benzoquinone (PBQ) writhing models (200 mg kg -1 ) in male Swiss albino mice. The R-S ethanol extract of XA was subjected to isolation studies using conventional chromatographic methods. Most of the extracts showed inhibition over 85% against butyrylcholinesterase and no inhibition towards acetylcholinesterase. The flower chloroform and the R-S ethyl acetate extracts were most effective (97.85 ± 0.94% and 96.89 ± 1.09%, respectively). The R-S ethanol extract displayed a remarkable scavenging activity against DPPH (77.33 ± 1.99%) and in FRAP assay, while the hexane extract of the R-S parts possessed the highest metal-chelating capacity (72.79 ± 0.33%). The chloroform extract of the R-S caused a significant analgesic effect (24.4%) in PBQ writhing model. No anti-inflammatory effect was observed. Isolation of zierin and zierin xyloside, which were inactive in anticholinesterase assays, was achieved from the R-S ethanol extract. This is the first report of anticholinesterase, antioxidant, analgesic and anti-inflammatory activities and isolation of zierin and zierin xyloside from XA. Therefore, XA seems to contain antioxidant and BChE-inhibiting compounds.

Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice.

PubMed

Bhattacharjee, Arin; Basu, Abhishek; Biswas, Jaydip; Bhattacharya, Sudin

2015-07-01

Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid peroxidation as evident by increased in reactive oxygen species, nitric oxide level, and malondialdehyde (MDA) formation with decreased in level of antioxidants such as reduced glutathione, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase, and catalase. Furthermore, CP at a dose of 25 mg/kg b.w. increased pulmonary DNA damage ('comet tail') and triggered DNA fragmentation and apoptosis in mouse bone marrow cells. On the other hand, Nano-Se at a dose of 2 mg Se/kg b.w., significantly inhibited CP-induced DNA damage in bronchoalveolar lavage cells, and decreased the apoptosis and percentage of DNA fragmentation in bone marrow cells and also antagonized the reduction of the activities of antioxidant enzymes and the increase level of MDA. Thus, our results suggest that Nano-Se in pre- and co-administration may serve as a promising preventive strategy against CP-induced pulmonary toxicity.

Efficacy of multiple exposure with low level He-Ne laser dose on acute wound healing: a pre-clinical study

NASA Astrophysics Data System (ADS)

Prabhu, Vijendra; Rao, Bola Sadashiva S.; Mahato, Krishna Kishore

2014-02-01

Investigations on the use of Low Level Laser Therapy (LLLT) for wound healing especially with the red laser light have demonstrated its pro-healing potential on a variety of pre-clinical and surgical wounds. However, until now, in LLLT the effect of multiple exposure of low dose laser irradiation on acute wound healing on well-designed pre-clinical model is not much explored. The present study aimed to investigate the effect of multiple exposure of low dose Helium Neon laser on healing progression of full thickness excision wounds in Swiss albino mice. Further, the efficacy of the multiple exposure of low dose laser irradiation was compared with the single exposure of optimum dose. Full thickness excision wounds (circular) of 15 mm diameter were created, and subsequently illuminated with the multiple exposures (1, 2, 3, 4 and 5 exposure/ week until healing) of He-Ne (632.8 nm, 4.02 mWcm-2) laser at 0.5 Jcm-2 along with single exposure of optimum laser dose (2 J/cm-2) and un-illuminated controls. Classical biophysical parameters such as contraction kinetics, area under the curve and the mean healing time were documented as the assessment parameters to examine the efficacy of multiple exposures with low level laser dose. Experimental findings substantiated that either single or multiple exposures of 0.5 J/cm2 failed to produce any detectable alterations on wound contraction, area under the curve and mean healing time compared to single exposure of optimum dose (2 Jcm-2) and un-illuminated controls. Single exposure of optimum, laser dose was found to be ideal for acute wound healing.

Analgesic, anti-inflammatory and anti-pyretic activities of Caesalpinia decapetala

PubMed Central

Parveen, Amna; Sajid Hamid Akash, Muhammad; Rehman, Kanwal; Mahmood, Qaisar; Qadir, Muhammad Imran

2014-01-01

Introduction: In many pathological conditions, pain, inflammation and fever are interdependent to each other. Due to the use of synthetic drugs, many unwanted effects usually appear. Various studies have been conducted on Caesalpinia decapetala (C. decapetala) to evaluate its effects in the treatment of various diseases but no sufficient scientific literature is available online to prove its analgesic, anti-inflammatory and anti-pyretic activities. Methods: The analgesic, anti-inflammatory and anti-pyretic activities of 70% aqueous methanolic and n-hexane extracts of C. decapetala was evaluated using Swiss albino mice (20-30 g). Results: The results showed that aqueous methanolic extract of C. decapetala at the dose of 100 mg/kg exhibited significant (p< 0.05) activities in various pain models including acetic acid-induced writhing (18.4 ± 0.53), formalin-induced licking (275 ± 4.18) and hot plate method (2.3 ± 0.0328); whereas,  n-hexane extract showed its effects in acetic acid-induced writhing (20 ± 0.31), formalin-induced licking (293 ± 1.20) and hot plate method (2.224 ± 0.029) compared to the effects observed in control group animals. Similarly, the aqueous methanolic extract of C. decapetala after 2 h of treatment exhibited more significant anti-inflammatory (0.66 ± 0.06) and anti-pyretic (38.81 ± 0.05) activities compared to the control group animals. Conclusion: From the findings of our present study, we concluded that the aqueous methanolic extract of C. decapetala has stronger analgesic, anti-inflammatory and anti-pyretic effects than its n-hexane extract. Further studies are required to investigate the active constituents of C. decapetala that exhibit analgesic, anti-inflammatory and anti-pyretic activities. PMID:24790898

Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression.

PubMed

Fogaça, Manoela Viar; Cândido-Bacani, Priscila de Matos; Benicio, Lucas Milanez; Zapata, Lara Martinelli; Cardoso, Priscilla de Freitas; de Oliveira, Marcelo Tempesta; Calvo, Tamara Regina; Varanda, Eliana Aparecida; Vilegas, Wagner; de Syllos Cólus, Ilce Mara

2017-12-01

Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN- and ISA-induced expression of ERCC1 or BAX genes. HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 μM) or ISA (0.5 to 50 μM). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD 50 - 1 g/kg b.w.) and submitted to comet assay in vivo. IRN reduced the viability of CHO-K1 (24 h; 5 to 200 μM) and HeLa cells (10 to 200 μM), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 μM; HeLa: 5 and 10 μM). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations.

Chemoprevention of chemical-induced skin cancer by Panax ginseng root extract.

PubMed

Sharma, Jyoti; Goyal, Pradeep K

2015-07-01

Cancer has emerged as a major health problem globally as a consequence to the increased longevity of the population, changing the environment and life style. Chemoprevention is a new and promising strategy for reducing cancer burden. Recently, some natural products have been identified for their chemopreventive activity to reduce the cancer incidence. Ginseng is known for its potential to treat various ailments in human beings. The present study was designed to explore the anticancer and antioxidative potential of Panax ginseng against chemical-induced skin carcinogenesis in mammals. Skin tumors were induced in Swiss albino mice by a single topical application of 7,12-dimethylbenz(a)anthracene (100 μg/100 μL acetone) and, 2 wks later, promoted by repeated applications of croton oil (thrice in a wk in 1% acetone) till the end of the experiment (i.e., 16 wk). Hydroalcoholic ginseng root extract at a dose of 25 mg/kg body weight/d was orally administered at the peri-initiation, postinitiation, and peri-post-initiation stages. Ginseng root extract treatment caused a significant reduction in tumor incidence, cumulative number of tumors, tumor yield, and tumor burden, as compared to the 7,12-dimethylbenz(a)anthracene-croton oil-treated control group. Further, biochemical assays revealed a significant enhancement in the levels of reduced glutathione, superoxide dismutase, catalase, vitamin C, and total proteins but a significant reduction in lipid peroxidation levels in both the liver and skin with ginseng root extract treatment, as compared to carcinogen-treated control group. These results suggest that P. ginseng has the potential to become a pivotal chemopreventive agent that can reduce cancer in mammals.

PASS-predicted design, synthesis and biological evaluation of cyclic nitrones as nootropics.

PubMed

Marwaha, Alka; Goel, R K; Mahajan, Mohinder P

2007-09-15

Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compounds acting as cognition enhancers have been provided, which can be further exploited in search of such New Chemical Entities (NCEs).

Topiramate (Topamax) reduces conditioned abstinence behaviours and handling-induced convulsions (HIC) after chronic administration of alcohol in Swiss-Webster mice.

PubMed

Farook, Justin M; Morrell, Dennis J; Lewis, Ben; Littleton, John M; Barron, Susan

2007-01-01

Topiramate has emerged as one of the promising drugs for the treatment of alcoholism and alcohol addiction. Recent studies have shown that topiramate reduces harmful drinking and initiates abstinence in humans, but little is known as to why this drug is effective. In the present study, we examined the effects of topiramate in reducing convulsions during alcohol withdrawal using a procedure called the handling-induced convulsion (HIC) test in male Swiss-Webster mice. In addition, we examined the ability of topiramate to reduce alcohol conditioned and anxiety related behaviours during conditioned abstinence using the elevated plus maze (EPM) test. HICs were examined 10 h after the 3rd daily alcohol (2.5 g/kg; 20% w/v)+4 methylpyrazole (4MP) (9 mg/kg) intraperitoneal (i.p.) injection with topiramate (0, 10 or 20 mg/kg ip) administered 30 min before testing. In the EPM, alcohol (1.75 g/kg; 20%, i.p.) or saline was administered daily for 9 days and subjects were immediately placed on the maze. Anxiety related behaviours included the amount of time spent and number of entries in the open or closed arms and grooming bouts, and conditioned behaviours including the stretched-attend posture were examined 24 h after the last day of alcohol injection. Topiramate (10 and 20 mg/kg) significantly reduced HIC scores (P<0.05) compared to the alcohol/saline group. In the EPM, topiramate (20 mg/kg) reduced the stretched-attend postures (P<0.001) compared to the alcohol/saline group. These findings suggest that topiramate reduces HICs during alcohol withdrawal and alcohol-conditioned behaviours during conditioned abstinence in Swiss-Webster mice.

Protective effects of polyphenol-rich infusions from carob (Ceratonia siliqua) leaves and cladodes of Opuntia ficus-indica against inflammation associated with diet-induced obesity and DSS-induced colitis in Swiss mice.

PubMed

Aboura, Ikram; Nani, Abdelhafid; Belarbi, Meriem; Murtaza, Babar; Fluckiger, Aurélie; Dumont, Adélie; Benammar, Chahid; Tounsi, Moufida Saidani; Ghiringhelli, François; Rialland, Mickaël; Khan, Naim Akhtar; Hichami, Aziz

2017-12-01

In the present study, we have investigated the effects of polyphenol-rich infusions from carob leaves and OFI-cladodes on inflammation associated with obesity and dextran sulfate sodium (DSS)-induced ulcerative colitis in Swiss mice. In vitro studies revealed that aqueous extracts of carob leaves and OFI-cladodes exhibited anti-inflammatory properties marked by the inhibition of IL-6, TNF-α and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells concomitant with NF-κβ nucleus translocation inhibition. For in vivo investigations, Swiss male mice were subjected to control or high fat diet (HFD). At the 8th week after the start of study, animals received or not 1% infusion of either carob leaves or OFI-cladode for 4 weeks and were subjected to 2% DSS administration in drinking water over last 7 days. After sacrifice, pro-inflammatory cytokines levels in plasma and their mRNA expression in different organs were determined. Results showed that carob leaf and OFI-cladode infusions reduced inflammation severity associated with HFD-induced obesity and DSS-induced acute colitis indicated by decrease in pro-inflammatory cytokines expression (as such TNF-α, IL1b and IL-6) in colon, adipose tissue and spleen. In addition, plasma levels of IL-6 and TNF-α were also curtailed in response to infusions treatment. Thus, carob leaf and OFI-cladode infusions prevented intestinal permeability through the restoration of tight junction proteins (Zo1, occludins) and immune homeostasis. Hence, the anti-inflammatory effect of carob leaves and OFI-cladodes could be attributed to their polyphenols which might alleviate inflammation severity associated with obesity and colitis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Baicalein inhibits pulmonary carcinogenesis-associated inflammation and interferes with COX-2, MMP-2 and MMP-9 expressions in-vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chandrashekar, Naveenkumar; Selvamani, Asokkumar; Subramanian, Raghunandhakumar

2012-05-15

The objective of the present study is to investigate the therapeutic efficacy of baicalein (BE) on inflammatory cytokines, which is in line with tumor invasion factors and antioxidant defensive system during benzo(a)pyrene [B(a)P] (50 mg/kg body weight) induced pulmonary carcinogenesis in Swiss albino mice. After experimental period, increased levels of total and differential cell count in bronchoalveolar lavage fluid were observed. Accompanied by marked increase in immature mast cell by toluidine blue staining and mature mast cell by safranin–alcian blue staining in B(a)P-induced lung cancer bearing animals. Protein expression levels studied by immunohistochemistry and immunoblot analysis of cytokines such asmore » tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were also found to be significantly increased in lung cancer bearing animals. B(a)P-exposed mice lung exhibits activated expression of nuclear transcription factor kappa-B as confirmed by immunofluorescence and immunoblot analysis. Administration of BE (12 mg/kg body weight) significantly counteracted all the above deleterious changes. Moreover, assessment of tumor invasion factors on protein levels by immunoblot and mRNA expression levels by RT-PCR revealed that BE treatment effectively negates B(a)P-induced upregulated expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and cyclo-oxygenase-2. Further analysis of lipid peroxidation markers such as thiobarbituric acid reactive substances, hydro-peroxides and antioxidants such as glutathione-S-transferase and reduced glutathione in lung tissue was carried out to substantiate the antioxidant effect of BE. The chemotherapeutic effect observed in the present study is attributed to the potent anti-inflammatory and antioxidant potential by BE against pulmonary carcinogenesis. -- Highlights: ► BE treatment protects from inflammatory cells and mast-cells accumulation in lungs. ► BE altered the expressions of TNF-α, IL-1β, i-NOS and NF-κBp65 at protein levels. ► BE modulates the expressions of MMP-2, MMP-9 and COX-2 at protein and mRNA levels. ► BE decreases LPO levels and enhances antioxidant status.« less

Toxicity and mutagenicity of hymenoxon, sequiterpene lactone.

PubMed

Jones, D H; Kim, H L

1981-12-01

The oral LD50 of hymenoxon in Swiss white mice was found to be 241 +/- 37 mg/kg. No significant sex differences were observed. Pretreatment of male mice for 3 days using doses of 50 and 100 mg/kg hymenoxon failed to alter significantly pentobarbital sleeping time. Hymenoxon was found to be a direct-acting mutagen in the Salmonella/mammalian microsome test. Urine samples obtained from hymenoxon-treated mice were found to be negative activity when tested directly and when incubated with beta-glucuronidase. Hymenoxon did not produce lethal DNA damage as measured in the Escherichia coli polA or Bacillus subtilis recombinational assays.

Behavioral and biochemical effects of ketamine and dextromethorphan relative to its antidepressant-like effects in Swiss Webster mice

PubMed Central

Nguyen, Linda; Lucke-Wold, Brandon P.; Logsdon, Aric F.; Scandinaro, Anna L.; Huber, Jason D.; Matsumoto, Rae R.

2016-01-01

Ketamine has been shown to produce rapid and robust antidepressant effects in depressed individuals, however its abuse potential and adverse psychotomimetic effects limit its widespread use. Dextromethorphan may serve as a safer alternative based on pharmacodynamic similarities to ketamine. In this proof of concept study, behavioral and biochemical analyses were undertaken to evaluate the potential involvement of brain derived neurotrophic factor (BDNF) in the antidepressant-like effects of dextromethorphan in mice, with comparisons to ketamine and imipramine. Male Swiss, Webster mice were injected with dextromethorphan, ketamine or imipramine and their behaviors evaluated in the forced swim test (FST) and open field test. Western blots were used to measure brain derived neurotrophic factor (BDNF) and its precursor, pro-BDNF, protein expression in the hippocampus and frontal cortex of these mice. Our results show dextromethorphan and imipramine each reduced immobility time in the FST without affecting locomotor activity, whereas ketamine reduced immobility time and increased locomotor activity. Ketamine also rapidly (within 40 min) increased pro-BDNF expression in an AMPA receptor-dependent manner in the hippocampus, while DM and imipramine did not alter pro-BDNF or BDNF levels in either the hippocampus or frontal cortex within this timeframe. These data demonstrate that dextromethorphan shares some features with both ketamine and imipramine. Additional studies looking at dextromethorphan may aid in the development of more rapid, safe, and efficacious antidepressant treatment. PMID:27580401

Pyrrolidine-Acridine hybrid in Artemisinin-based combination: a pharmacodynamic study.

PubMed

Pandey, Swaroop Kumar; Biswas, Subhasish; Gunjan, Sarika; Chauhan, Bhavana Singh; Singh, Sunil Kumar; Srivastava, Kumkum; Singh, Sarika; Batra, Sanjay; Tripathi, Renu

2016-09-01

Aiming to develop new artemisinin-based combination therapy (ACT) for malaria, antimalarial effect of a new series of pyrrolidine-acridine hybrid in combination with artemisinin derivatives was investigated. Synthesis, antimalarial and cytotoxic evaluation of a series of hybrid of 2-(3-(substitutedbenzyl)pyrrolidin-1-yl)alkanamines and acridine were performed and mode of action of the lead compound was investigated. In vivo pharmacodynamic properties (parasite clearance time, parasite reduction ratio, dose and regimen determination) against multidrug resistant (MDR) rodent malaria parasite and toxicological parameters (median lethal dose, liver function test, kidney function test) were also investigated. 6-Chloro-N-(4-(3-(3,4-dimethoxybenzyl)pyrrolidin-1-yl)butyl)-2-methoxyacridin-9-amine (15c) has shown a dose dependent haem bio-mineralization inhibition and was found to be the most effective and safe compound against MDR malaria parasite in Swiss mice model. It displayed best antimalarial potential with artemether (AM) in vitro as well as in vivo. The combination also showed favourable pharmacodynamic properties and therapeutic response in mice with established MDR malaria infection and all mice were cured at the determined doses. The combination did not show toxicity at the doses administered to the Swiss mice. Taken together, our findings suggest that compound 15c is a potential partner with AM for the ACT and could be explored for further development.

Microbiota is an essential element for mice to initiate a protective immunity against Vaccinia virus.

PubMed

Lima, Maurício T; Andrade, Ana C S P; Oliveira, Graziele P; Calixto, Rafael S; Oliveira, Danilo B; Souza, Éricka L S; Trindade, Giliane S; Nicoli, Jacques R; Kroon, Erna G; Martins, Flaviano S; Abrahão, Jônatas S

2016-02-01

The gastrointestinal tract of vertebrates harbors one of the most complex ecosystems known in microbial ecology and this indigenous microbiota almost always has a profound influence on host-parasite relationships, which can enhance or reduce the pathology of the infection. In this context, the impact of the microbiota during the infection of several viral groups remains poorly studied, including the family Poxviridae. Vaccinia virus (VACV) is a member of this family and is the causative agent of bovine vaccinia, responsible for outbreaks that affect bovines and humans. To determine the influence of the microbiota in the development of the disease caused by VACV, a comparative study using a murine model was performed. Germ-free and conventional, 6- to 7-week-old Swiss NIH mice were infected by tail scarification and intranasally with VACV. Moreover, immunosuppression and microbiota reposition were performed, to establish the interactions among the host's immune system, microbiota and VACV. The data demonstrate that the microbiota is essential for the effective immune response of mice against VACV in intranasal inoculation and to control the virus at the primary site of infection. Furthermore, this study is the first to show that Swiss conventional mice are refractory to the intranasal infection of VACV. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sucralose administered in feed, beginning prenatally through lifespan, induces hematopoietic neoplasias in male swiss mice

PubMed Central

M., Soffritti; M., Padovani; E., Tibaldi; L., Falcioni; F., Manservisi; M., Lauriola; L., Bua; M., Manservigi; F., Belpoggi

2016-01-01

Background Sucralose is an organochlorine artificial sweetener approximately 600 times sweeter than sucrose and used in over 4,500 products. Long-term carcinogenicity bioassays on rats and mice conducted on behalf of the manufacturer have failed to show the evidence of carcinogenic effects. Objective The aim of this study was to evaluate the carcinogenic effect of sucralose in mice, using a sensitive experimental design. Methods Five groups of male (total n = 457) and five groups female (total n = 396) Swiss mice were treated from 12 days of gestation through the lifespan with sucralose in their feed at concentrations of 0, 500, 2,000, 8,000, and 16,000 ppm. Results We found a significant dose-related increased incidence of males bearing malignant tumors (p < 0.05) and a significant dose-related increased incidence (p < 0.01) of hematopoietic neoplasias in males, in particular at the dose levels of 2,000 ppm (p < 0.01) and 16,000 ppm (p < 0.01). Conclusions These findings do not support previous data that sucralose is biologically inert. More studies are necessary to show the safety of sucralose, including new and more adequate carcinogenic bioassay on rats. Considering that millions of people are likely exposed, follow-up studies are urgent. PMID:27078173

Sucralose administered in feed, beginning prenatally through lifespan, induces hematopoietic neoplasias in male swiss mice.

PubMed

M, Soffritti; M, Padovani; E, Tibaldi; L, Falcioni; F, Manservisi; M, Lauriola; L, Bua; M, Manservigi; F, Belpoggi

2016-01-01

Sucralose is an organochlorine artificial sweetener approximately 600 times sweeter than sucrose and used in over 4,500 products. Long-term carcinogenicity bioassays on rats and mice conducted on behalf of the manufacturer have failed to show the evidence of carcinogenic effects. The aim of this study was to evaluate the carcinogenic effect of sucralose in mice, using a sensitive experimental design. Five groups of male (total n = 457) and five groups female (total n = 396) Swiss mice were treated from 12 days of gestation through the lifespan with sucralose in their feed at concentrations of 0, 500, 2,000, 8,000, and 16,000 ppm. We found a significant dose-related increased incidence of males bearing malignant tumors (p < 0.05) and a significant dose-related increased incidence (p < 0.01) of hematopoietic neoplasias in males, in particular at the dose levels of 2,000 ppm (p < 0.01) and 16,000 ppm (p < 0.01). These findings do not support previous data that sucralose is biologically inert. More studies are necessary to show the safety of sucralose, including new and more adequate carcinogenic bioassay on rats. Considering that millions of people are likely exposed, follow-up studies are urgent.

Amelioration effects against N-nitrosodiethylamine and CCl4-induced hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes aspera

PubMed Central

Kartik, R.; Rao, Ch. V.; Trivedi, S.P.; Pushpangadan, P.; Reddy, G.D.

2010-01-01

Objective: The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis. Materials and Methods: The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl4), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl4, treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups. Results: The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl4 -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were decreased after treatment with AAE in comparison to positive control group. The architecture of hepatic tissue was normalized upon treatment with extract at different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive control group. Conclusion: These results suggest that A. aspera significantly alleviate hepatic diagnostic and oxidative stress markers which signify its protective effect against NDEA and CCl4-induced two-stage hepatocarcinogenesis. PMID:21189908

Amelioration effects against N-nitrosodiethylamine and CCl(4)-induced hepatocarcinogenesis in Swiss albino rats by whole plant extract of Achyranthes aspera.

PubMed

Kartik, R; Rao, Ch V; Trivedi, S P; Pushpangadan, P; Reddy, G D

2010-12-01

The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis. The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl(4)), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl(4), treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups. The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl(4) -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were decreased after treatment with AAE in comparison to positive control group. The architecture of hepatic tissue was normalized upon treatment with extract at different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive control group. These results suggest that A. aspera significantly alleviate hepatic diagnostic and oxidative stress markers which signify its protective effect against NDEA and CCl(4)-induced two-stage hepatocarcinogenesis.

Antipyretic and analgesic activities of Caesalpinia bonducella seed kernel extract.

PubMed

Archana, P; Tandan, S K; Chandra, S; Lal, J

2005-05-01

Ethanolic extract (70%) of Caesalpinia bonducella seed kernel has been subjected for its antipyretic and antinociceptive activities in adult albino rats or mice of either sex at 30, 100 and 300 mg/kg orally. The extract demonstrated marked antipyretic activity against Brewer's yeast-induced pyrexia in rats. The extract had significant central analgesic activity in hot plate and tail flick methods. It also exhibited marked peripheral analgesic effect in both acetic acid-induced writhing test in mice and Randall-Selitto assay in rats. It also significantly inhibited the formalin-induced hind paw licking in mice. In conclusion, the present study suggests that the ethanolic extract of Caesalpinia bonducella seed kernel possesses potent antipyretic and antinociceptive activities and thus, validates its use in the treatment of pain and pyretic disorders. Copyright (c) 2005 John Wiley & Sons, Ltd.

Toxic Hazards Research Unit Annual Technical Report: 1975

DTIC Science & Technology

1975-10-01

by different sampling rates 160 21 Particle size distribution curves 167 22 Effect of 03 or N02 concentrations on rat lung weight 177 23 Relationship...previously, consisted of female C57 black/6 mice obtained from Jackson Laboratories, male CDF (Fischer 344 derived) albino rats from Charles River...the exposure phase of the study but made at the conclusion of the 5 ppm and 0. 5 ppm experiments were: Blood urea nitrogen SGOT Chloride Prothrombin

Evaluation of Antinociceptive Activity of Aqueous Extract of Bark of Psidium Guajava in Albino Rats and Albino Mice

PubMed Central

Jayasree, T.; Ubedulla, Shaikh; Dixit, Rohit; V S, Manohar; J, Shankar

2014-01-01

Background: Psidium guajava is commonly known as guava. Psidium guajava is a medium sized tree belonging to the family Myrtaceae found throughout the tropics. All the parts of the plant, the leaves, followed by the fruits, bark and the roots are used in traditional medicine. The traditional uses of the plant are Antidiarrheal, Antimicrobial Activity, Antimalarial/Antiparasitic Activity, Antitussive and antihyperglycaemic. Leaves are used as Anti-inflammatory, Analgesic and Antinociceptive effects. Aim: To evaluate the antinociceptive activity of aqueous extract of bark of Psidium guajava in albino rats with that of control and standard analgesic drugs aspirin and tramadol. Materials and Methods: Mechanical (Tail clip method) and thermal (Tail flick method using Analgesiometer), 0.6% solution of acetic acid writhing models of nociception were used to evaluate the extract antinociceptive activity. Six groups of animals, each consists of 10 animals, first one as control, second and third as standard drugs, Aspirin and Tramadol, fourth, fifth and sixth groups as text received the extract (100, 200, and 400 mg/ kg) orally 60 min prior to subjection to the respective test. Results: The results obtained demonstrated that aqueous extract of bark of Psidium guajava produced significant antinociceptive response in all the mechanical and thermal-induced nociception models. Conclusion: AEPG antinociceptive activity involves activation of the peripheral and central mechanisms. PMID:25386462

L-arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male Swiss mice subjected to physical exercise under environmental heat stress.

PubMed

Costa, Kátia Anunciação; Soares, Anne Danieli Nascimento; Wanner, Samuel Penna; Santos, Rosana das Graças Carvalho dos; Fernandes, Simone Odília Antunes; Martins, Flaviano dos Santos; Nicoli, Jacques Robert; Coimbra, Cândido Celso; Cardoso, Valbert Nascimento

2014-02-01

Dietary supplementation with l-arginine has been shown to improve the intestinal barrier in many experimental models. This study investigated the effects of arginine supplementation on the intestinal permeability and bacterial translocation (BT) induced by prolonged physical exercise under heat stress. Under anesthesia, male Swiss mice (5-wk-old) were implanted with an abdominal sensor to record their core body temperature (T(core)). After recovering from surgery, the mice were divided into 3 groups: a non-supplemented group that was fed the standard diet formulated by the American Institute of Nutrition (AIN-93G; control), a non-supplemented group that was fed the AIN-93G diet and subjected to exertional hyperthermia (H-NS), and a group supplemented with l-arginine at 2% and subjected to exertional hyperthermia (H-Arg). After 7 d of treatment, the H-NS and H-Arg mice were forced to run on a treadmill (60 min, 8 m/min) in a warm environment (34°C). The control mice remained at 24°C. Thirty min before the exercise or control trials, the mice received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with technetium-99m ((99m)Tc-DTPA) or (99m)Tc-Escherichia coli by gavage to assess intestinal permeability and BT, respectively. The H-NS mice terminated the exercise with T(core) values of ∼40°C, and, 4 h later, presented a 12-fold increase in the blood uptake of (99m)Tc-DTPA and higher bacterial contents in the blood and liver than the control mice. Although supplementation with arginine did not change the exercise-induced increase in T(core), it prevented the increases in intestinal permeability and BT caused by exertional hyperthermia. Our results indicate that dietary l-arginine supplementation preserves the integrity of the intestinal epithelium during exercise under heat stress, acting through mechanisms that are independent of T(core) regulation.

Effect of NR-ANX-C (a polyherbal formulation) on haloperidol induced catalepsy in albino mice.

PubMed

Nair, Vinod; Arjuman, Albina; Dorababu, P; Gopalakrishna, H N; Chakradhar Rao, U; Mohan, Lalit

2007-11-01

Use of typical antipsychotics like haloperidol in treatment of schizophrenia is associated with a high incidence of extrapyramidal side effects. In rodents, administration of haloperidol leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we evaluated the anticataleptic efficacy of NR-ANX-C, a polyherbal formulation containing bioactives of Withania somnifera, Ocimum sanctum, Camellia sinensis, triphala and shilajit in haloperidol induced catalepsy in mice. Five groups (n = 6) of male albino mice were used in the study. Catalepsy was induced by ip administration of haloperidol (1mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of NR-ANX-C (10, 25 and 50 mg/kg) with scopolamine (1 mg/kg). The superoxide dismutase (SOD) level in brain tissue was also estimated to correlate the levels of oxidative stress and degree of catalepsy in the animal. Significant (P<0.01) reduction in the cataleptic scores was observed in all NR-ANX-C treated groups and maximum reduction was observed in the NR-ANX-C (25 mg/kg) treated group. Significant (P<0.05) reduction in SOD activity was observed in NR-ANX-C (25 and 50 mg/kg) treated groups and maximum reduction was observed in NR-ANX-C (25mg/kg) treated group. In our study, maximum reduction in cataleptic score was observed in NR-ANX-C (25 mg/kg) treated group. The maximum reduction in SOD activity was also observed in the same group. These findings suggest a possible involvement of the antioxidant potential of NRANX- C in alleviating haloperidol induced catalepsy.

Species-associated differences in the inhibition of propofol glucuronidation by magnolol.

PubMed

Yang, Lu; Zhu, Liangliang; Ge, Guangbo; Xiao, Ling; Wu, Yan; Liang, Sicheng; Cao, Yunfeng; Yang, Ling; Wang, Dong

2014-07-01

Magnolol, a major active constituent in herbal medicine, potently inhibits propofol glucuronidation in human liver microsomes, with inhibition constants in the nanomolar range. This study was conducted to investigate magnolol-induced inhibition of propofol glucuronidation in liver microsomes from Swiss-Hauschka mice, Sprague-Dawley rats, Chinese Bama pigs, and cynomolgus macaques. Results indicated that magnolol (10 μM) inhibited propofol glucuronidation in liver microsomes from Bama pigs and cynomolgus macaques but not in those from mice or rats. Data from liver microsomes from Bama pigs indicated a competitive inhibition mechanism, with a Ki of 1.7 μM. In contrast to that of pig liver microsomes, the inhibition of microsomes from cynomolgus macaques followed a noncompetitive mechanism, with a Ki of 3.4 μM. In summary, this study indicates that magnolol-induced inhibition of propofol glucuronidation varies substantially among species, and the Ki values determined by using liver microsomes from various experimental animal species far exceed that for human liver microsomes. The inhibition of propofol glucuronidation by magnolol in liver microsomes from all animal species tested was significantly lower than the inhibition previously demonstrated in human liver microsomes. Hepatic microsomes from Swiss-Hauschka mice, Sprague-Dawley rats, Chinese Bama pigs, and cynomolgus macaques are not effective models of the inhibition of glucuronidation induced by magnolol in humans.

In vivo screening of candidate pretreatment compounds against cyanide using mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kiser, R.C.; Olson, C.T.; Menton, R.G.

1993-05-13

An in vivo screening procedure was established at Battelle's Medical Research and Evaluation Facility (MREF) to evaluate the efficacy of candidate pretreatment compounds in mice challenged with the blood agent, sodium cyanide (NaCN). Male albino mice of ICR outbred stock weighing between 22.5 and 27.5 g are challenged by intramuscular (i.m.) injection, at a volume of 0.5 mL/kg, of a dose of NaCN twice the LD50 of untreated mice as determined on that day of testing. Candidate drugs are tested at fractions of their LD50 or their limit of solubility in the most optimum vehicle and given intraperitoneally (i.p.) tomore » separate groups of mice at either 60 or 15 min prior to NaCN challenge. Sodium thiosulfate (1000 mg/kg)/sodium nitrite (100 mg/kg) controls are injected i.p. only at 60 min prior to challenge. A test compound is deemed effective if, at any of three concentrations tested, or at either pretreatment time, it is statistically more efficacious in preventing lethality than is a negative control substance (candidate compound vehicle).« less

Behavioral and biochemical effects of ketamine and dextromethorphan relative to its antidepressant-like effects in Swiss Webster mice.

PubMed

Nguyen, Linda; Lucke-Wold, Brandon P; Logsdon, Aric F; Scandinaro, Anna L; Huber, Jason D; Matsumoto, Rae R

2016-09-28

Ketamine has been shown to produce rapid and robust antidepressant effects in depressed individuals; however, its abuse potential and adverse psychotomimetic effects limit its widespread use. Dextromethorphan (DM) may serve as a safer alternative on the basis of pharmacodynamic similarities to ketamine. In this proof-of-concept study, behavioral and biochemical analyses were carried out to evaluate the potential involvement of brain-derived neurotrophic factor (BDNF) in the antidepressant-like effects of DM in mice, with comparisons to ketamine and imipramine. Male Swiss, Webster mice were injected with DM, ketamine, or imipramine and their behaviors were evaluated in the forced-swim test and the open-field test. Western blots were used to measure BDNF and its precursor, pro-BDNF, protein expression in the hippocampus and the frontal cortex of these mice. Our results show that both DM and imipramine reduced immobility time in the forced-swim test without affecting locomotor activity, whereas ketamine reduced immobility time and increased locomotor activity. Ketamine also rapidly (within 40 min) increased pro-BDNF expression in an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-dependent manner in the hippocampus, whereas DM and imipramine did not alter pro-BDNF or BDNF levels in either the hippocampus or the frontal cortex within this timeframe. These data show that DM shares some features with both ketamine and imipramine. Additional studies examining DM may aid in the development of more rapid, safe, and efficacious antidepressant treatments.

Papaver Rhoeas L. Hydroalcoholic Extract Exacerbates Forced Swimming Test-Induced Depression in Mice.

PubMed

Osanloo, Naser; Najafi-Abedi, Akram; Jafari, Fatemeh; Javid, Farshid; Pirpiran, Mohsen; Memar Jafari, Mohammad-Reza; Mousavi Khosravi, Seyed Ali; Rahimzadeh Behzadi, Mohammad; Ranjbaran, Mina; Sahraei, Hedayat

2016-07-01

Depression is one of the most frequent psychiatric disorders in the world with occurs with higher incidence in women. In the present study, the effect of water-alcoholic extract of Papaver rhoeas L. on forced swimming test (FST) in Swiss-Webster mice were examined. We used Swiss-Webster mice (20-25 g) to execute FST on them. The plant extract (1, 10, 30, and 100 mg/kg) was injected to the animals 30 minutes before each session. Fluoxetine (20 mg/kg) was used as standard antidepressant drug. In another group of animals, 30 minutes after extract administration, blood samples were taken from retro-orbital sinus for corticosterone assay. Yet in third group, the drugs were injected to the animals and 30 minutes later, their activities were tested in an open field apparatus. Our experiments showed that the extract efficiently reduced FST time both in male and female mice dose-dependently. This effect was comparable with fluoxetine. In addition, corticosterone assay indicated that plasma corticosterone in animals which received extract was higher than those amounts in fluoxetine and saline controls. Moreover, the animals did not show any motor activity deficit in all doses of the extract and fluoxetine compared to saline control. The extract of Papaver rhoeas can reduce immobility time which is comparable to the effect of fluoxetine. Also the effect of the extract is contrary to its effects on plasma corticosterone level and or animals' activity.

Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson's Disease.

PubMed

Kurowska, Zuzanna; Jewett, Michael; Brattås, Per Ludvik; Jimenez-Ferrer, Itzia; Kenéz, Xuyian; Björklund, Tomas; Nordström, Ulrika; Brundin, Patrik; Swanberg, Maria

2016-08-23

Motor symptoms in Parkinson's disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/- mouse strain. In contrast, C57Bl/6-En1+/- mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/- and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/- 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson's disease-like damage in rodent disease models and considered in clinical association studies in PD.

Tick-borne typhus fever of northern Asia: some characteristics of the pathogenesis.

PubMed

Nelyubov, M V

2002-09-01

Morphological changes in the viscera of albino mice were studied over the course of North Asia typhus fever. In general, the microcirculatory bed in the studied organs (brain, liver, spleen, peritoneum, and testicle) corresponded to angioparalytical capillary and venular hyperemia. Macrophagic reaction (proliferation of stellate macrophages) transformed into granulomatous reaction in the course of the experiment. Macrophagic reaction of the spleen was characterized by blurred follicular pattern. In the testes a tendency to the loss of normal spermatogenesis was observed.

[Chemotherapeutic effectiveness of a new derivative of 5-alkyl-3N-furanones in experimental staphylococcal infection].

PubMed

Tomnikov, A Iu; Shub, G M

1990-02-01

High chemotherapeutic efficacy of the compound 1929, a new derivative of 5-alkyl-3H-furanones was shown in albino mice with experimental staphylococcal infection caused by intraperitoneal administration to the animals. The efficacy was found to be higher than that of furagin used for comparison. The average therapeutic dose (AD50) of the compound for intraperitoneal administration amounted to 40 mg/kg while the average lethal dose (LD50) was 3000 mg/kg.

Colorimetry provides a rapid objective measurement of de novo hair growth rate in mice.

PubMed

Tzung, Tien-Yi; Yang, Chia-Yi; Huang, Yung-Chang; Kao, Fu-Jen

2009-11-01

Depilated mice have been used as a test platform for hair growth-regulating agents. However, currently available assessment tools for hair growth in mice are less than ideal. Tristimulus colorimetry of the fur color of depilated agouti, albino, and black mice with L*, a*, and b* values were performed daily until the full growth of pelage. Using light-emitting diode (LED) irradiation (650 and 890 nm) with a daily dose of 3.5 J/cm(2) as hair growth regulators, the hair growth rates observed by the global assessment were compared with those derived from colorimetry. In contrast to a* and b* values, L* values changed more drastically over time in the anagen phase regardless of fur color. Unlike the inhibitory effect of 650 nm irradiation, LED of 890 nm promoted de novo hair regrowth in mice. The difference in hair growth rates detected by colorimetry paralleled the observation made by the global assessment. The L* value of fur color obtained by tristimulus colorimetry was a sensitive yet quantitative indicator of de novo hair growth, and could be used to project the hair growth rate in mice.

Behavioral effects of β-phenylethylamine and various monomethylated and monohalogenated analogs in mice are mediated by catecholaminergic mechanisms.

PubMed

Mosnaim, Aron D; Hudzik, Thomas; Wolf, Marion E

2015-01-01

The effects of the administration [intraperitoneally, 15 and 75 mg/kg, except α-MePEA (amphetamine, AMPH) at 5 and 10 mg/kg] of β-phenylethylamine (PEA), its methylated (o-Me-, p-Me-, α-Me-, β-Me-, N-Me-, p-OMe-, N,N-di-Me-, and 3,4-diOH-N-Me-), para-halogenated (Br-, Cl-, F-, and I-), and other derivatives for example, p-OHPEA (p-tyramine), on Swiss male albino mice caged behavior fall into 3 broad categories. (1) N,N-diMe-, 3,4-diOH-N-Me-, and o-MePEA tend to reduce the behavioral activity, (2) p-OH and p-IPEA were without noticeable effects, and (3) the remaining compounds increased locomotor activity, produced hyperexcitability and fighting, jumping and vocalization, and convulsion in a graded manner (listed in increasing order p-OMe-, β-Me-, p-Cl-, p-Br-, p-F-, p-Me-, and N-MePEA, PEA itself and α-MePEA). The latter compound (amphetamine) being the most potent among them; equieffective but with lower potency were p-MePEA, N-MePEA, and PEA itself. The effects of PEAs upon group cage behavior were increased by pretreatment with pargyline (1.5 hours; 15 mg/kg) and decreased after reserpine or haloperidol [4 hours and/or 24 hours (2.5 and/or 2.5 mg/kg) and 1 hour (1 mg/kg), respectively], reaching full suppression with the double-dose regimen of reserpine and single dose of haloperidol. As expected, none of these substances by themselves were noticeable changed group mice activity or stereotypic behavior. The effects of test amines and catecholamine-modulating agents on stereotypy were assessed by rating the sequentially occurring behaviors: increased exploratory behavior with increased sniffing; occasional side-to-side head weaving; paw-licking and other grooming; gnawing, fighting and continuous side-to-side head weaving, and periodic episodes of "popcorn" behavior, during which all mice in the cage ran, jumped, and vocalized. In general, rank efficacy in eliciting stereotype aligned with rank efficacy in affecting group cage behavior. Our results show that a number of as yet little studied monomethylated and monohalogenated PEA analogs share a similar behavioral profile with PEA and AMPH. Behavioral changes observed appear to be, at least in part, mediated by catecholaminergic mechanism as they are modulated by drugs known to influence catecholamine activity. PEA analogs provide a large number of clinically useful drugs; whether further studies on these novel amines will lead to the rational design of newer, safer, and effective PEA-class drugs remains to be seen.

Rodent malaria: BCG-induced protection and immunosuppression. [Mice, gamma radiation, Plasmodium berghei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smrkovski, L.L.; Strickland, G.T.

1978-10-01

One dose of 10/sup 7/ viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10/sup 4/ thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites onlymore » if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge.« less

5-AZA-2'-DEOXYCYTIDINE INDUCED CYTOTOXICITY AND LONG BONE REDUCTION DEFECTS IN THE MURINE LIMB

EPA Science Inventory

The antineoplastic drug 5-aza-2'-deoxycytidine (dAZA) is a DNA hypomethylating agent that can be used to induce hind limb phocomelia in the offspring of CD-1 Swiss Webster mice. Previously, our laboratory investigated the possibility that dAZA induced alterations in gene express...

Elimination of the tremorgenic toxin of Ipomoea asarifolia by milk

USDA-ARS?s Scientific Manuscript database

With the aim to determine if the tremorgenic toxin of Ipomoea asarifolia is eliminated in milk, three groups of Swiss female mice received, immediately after giving birth until weaning, a ration containing 20% or 30% of dry I. asarifolia. All the offspring of the females that received 20% or 30% I. ...

Quantitative anti-F1 and anti-V IgG ELISAs as serological correlates of protection against plague in female Swiss Webster mice.

PubMed

Little, S F; Webster, W M; Wilhelm, H; Fisher, D; Norris, S L W; Powell, B S; Enama, J; Adamovicz, J J

2010-01-22

A recombinant fusion protein composed of Yersinia pestis fraction 1 capsule (F1) and virulence-associated V antigen (V) (F1-V) has been developed as the next-generation vaccine against plague. In this study, female Swiss Webster mice received a single intramuscular vaccination with one of eight doses of the F1-V vaccine and exposed 4 weeks later to either Y. pestis CO92 or C12 organisms by the subcutaneous or aerosol routes of infection. Quantitative anti-F1 and anti-V immunoglobulin G (IgG) ELISAs were used to examine the relationship between survival outcome and antibody titers to F1 and V. Results suggested that each 1log(10) increase in week 4 quantitative anti-F1 and anti-V IgG ELISA titers were associated with a 1.7-fold (p=0.0051) and 2.5-fold (p=0.0054) increase in odds of survival, respectively, against either bubonic or pneumonic plague and may serve as serological correlates of protection.

Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice.

PubMed

Soffritti, Morando; Belpoggi, Fiorella; Manservigi, Marco; Tibaldi, Eva; Lauriola, Michelina; Falcioni, Laura; Bua, Luciano

2010-12-01

Aspartame (APM) is a well-known intense artificial sweetener used in more than 6,000 products. Among the major users of aspartame are children and women of childbearing age. In previous lifespan experiments conducted on Sprague-Dawley rats we have shown that APM is a carcinogenic agent in multiple sites and that its effects are increased when exposure starts from prenatal life. The aim of this study is to evaluate the potential of APM to induce carcinogenic effects in mice. Six groups of 62-122 male and female Swiss mice were treated with APM in feed at doses of 32,000, 16,000, 8,000, 2,000, or 0  ppm from prenatal life (12 days of gestation) until death. At death each animal underwent complete necropsy and all tissues and organs of all animals in the experiment were microscopically examined. APM in our experimental conditions induces in males a significant dose-related increased incidence of hepatocellular carcinomas (P < 0.01), and a significant increase at the dose levels of 32,000  ppm (P < 0.01) and 16,000  ppm (P < 0.05). Moreover, the results show a significant dose-related increased incidence of alveolar/bronchiolar carcinomas in males (P < 0.05), and a significant increase at 32,000  ppm (P < 0.05). The results of the present study confirm that APM is a carcinogenic agent in multiple sites in rodents, and that this effect is induced in two species, rats (males and females) and mice (males). No carcinogenic effects were observed in female mice. Am. J. Ind. Med. 53:1197-1206, 2010. © 2010 Wiley-Liss, Inc.

Chronic inhalation study of mice subjected to diethylhydroxylamine, nitroethane, and diethylamine hydrogen sulfite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heicklen, J.; Lundgard, R.; Partymiller, K.

1982-04-01

Institute of Cancer Research Swiss strain mice were subjected to the inhalation of 10.3 +/- 3.7 ppm diethylhydroxylamine, 10.1 +/- 4.1 ppm nitroethane, and the vapor of diethylamine hydrogen sulfite for over 2 years. Histopathologic evaluation of all organs indicated only a few significant findings. The incidence of all tumors, as well as subcutaneous tumors (principally fibrosarcomas), increased in exposed males with marginal statistical significance (P = 0.12 and 0.048, respectively). The incidence of all tumors in exposed females decreased with marked statistical significance (P < 0.0005).

Adhesion and proliferation of fibroblasts on RF plasma-deposited nanostructured fluorocarbon coatings: evidence of FAK activation.

PubMed

Rosso, Francesco; Marino, Gerardo; Muscariello, Livio; Cafiero, Gennaro; Favia, Pietro; D'Aloia, Erica; d'Agostino, Riccardo; Barbarisi, Alfonso

2006-06-01

We used combined plasma-deposition process to deposit smooth and nanostructured fluorocarbon coatings on polyethylenethereftalate (PET) substrates, to obtain surfaces with identical chemical composition and different roughness, and investigate the effect of surface nanostructures on adhesion and proliferation of 3T3 Swiss Albino Mouse fibroblasts. Untreated PET and polystyrene (PS) were used as controls for cell culture. We have found that the statistically significant increase of cell proliferation rate and FAK (a nonreceptor tyrosine kinase) activation detected on ROUGH fluorocarbon surfaces is due to the presence of nanostructures. Changes in cytoskeletal organization and phospho FAK (tyr 397) localization were evident after 60 min on cells adhering to ROUGH surfaces. This change was characterized by the formation of actin stress fibers along lamellar membrane protrusion instead of usual focal contacts. Also the morphology of the adhering fibroblasts (60 min) adhering on ROUGH surfaces was found quite different compared to cells adhering on smooth ones. Copyright 2006 Wiley-Liss, Inc.

Chemical Composition of Pinus roxburghii Bark Volatile Oil and Validation of Its Anti-Inflammatory Activity Using Molecular Modelling and Bleomycin-Induced Inflammation in Albino Mice.

PubMed

Labib, Rola M; Youssef, Fadia S; Ashour, Mohamed L; Abdel-Daim, Mohamed M; Ross, Samir A

2017-08-29

The chemical composition of Pinus roxburghii bark essential oil (PRO) was qualitatively and quantitatively determined using GC/FID and GC/MS. The anti-inflammatory activity was assessed in vitro by evaluating the binding percentages on the cannabinoids and opioids receptors. Bleomycin (BLM)-induced pulmonary inflammation in albino mice was adopted to assess PRO anti-inflammatory efficacy in vivo. In silico molecular modelling of its major components was performed on human glucocorticoids receptor (GR). Seventy-five components were identified in which longifolene (33.13%) and palmitic acid (9.34%) constituted the predominant components. No binding was observed on cannabinoid receptor type 1 (CB1), whereas mild binding was observed on cannabinoid receptor type 2 (CB2), delta , kappa , and mu receptors accounting for 2.9%, 6.9%, 10.9% and 22% binding. A significant in vivo activity was evidenced by reduction of the elevated malondialdehyde (MDA), nitric oxide (NO), myeloperoxidase (MPO), interleukin-6 (IL-6), and tumor necrosis factor- α (TNF- α ) levels by 55.56%, 55.66%, 64.64%, 58.85% and 77.78% with concomitant elevation of superoxide dismutase (SOD) and catalase (CAT) activities comparable to BLM-treated group at 100 mg/kg body weight. In silico studies showed that palmitic acid exerted the fittest binding. PRO could serve as a potent anti-inflammatory natural candidate that should be supported by further clinical trials.

Enhanced hepatic and kidney cytochrome p-450 activities in nandrolone decanoate treated albino mice.

PubMed

Acharjee, B K; Mahanta, R

2009-04-01

Anabolic androgenic steroids are the xenobiotic substrates that are metabolized in the body by the protective enzyme systems. Mixed function oxygenase enzymes include a group of enzymes which play an essential role in the metabolism of a broad range of xenobiotics including endogenous and exogenous substrates. Cytochrome P-450, a member of mixed function oxygenase enzymes, plays an important role in oxidative metabolism of drugs and xenobiotics entering human body. Various anabolic steroids are found either to increase or decrease the activity of cytochrome P-450. However, effect of nandrolone decanoate, most commonly abused anabolic steroid, on cytochrome P-450 activity is still fragmentary. In the present study, albino mice were administered intramuscular 2.5 mg of nandrolone decanoate injection at 15 days interval. Cytochrome P-450 activity is determined by following the method of Omura and Sato (1964) in liver and kidney tissues of both normal and experimental groups upto 90 days. Investigation shows a significant (p <0.01) increase of cytochrome P-450 (nmol/mg) activity in liver tissue as compared to that of kidney tissues. A tissue specific and dose specific increase of cytochrome P-450 activity is observed. Mean cytochrome P-450 is found highest in liver tissue on 45(th) day whereas the activity in kidney tissue is noticed on 90(th) day of treatment. From the above observation, nandrolone decanoate can be suggested as a potent inducer of cytochrome P-450 activity like other anabolic steroids.

Effect of Administration of Nandrolone Decanoate upon Aldosterone Concentration and Serum Na+/K+ Levels in Albino Mice.

PubMed

Chowdhury, Parmita; Mahanta, Rita

2017-01-01

This article is a study of adverse effects associated with the abuse of recreational drugs such as anabolic androgenic steroids. Nandrolone decanoate is one such drug often abused by athletes and bodybuilders seeking enhanced physical strength or appearance. The use of such steroids has increased dramatically over the years. The present study was conducted to investigate the impact of nandrolone decanoate when consumed at an abused dose, upon serum aldosterone concentration in albino mice. Sodium and potassium ion concentrations were also monitored with the same experimental dosage. 0.1ml of 25 mg Nandrolone decanoate was administered to the animals twice a week for a period of 90 days. Blood samples for obtaining the serum from both normal and treated group of animals were collected at an interval of 15 days upto the 90th day. The present investigation revealed a significant increase (p<0.01) in the serum aldosterone and sodium ion concentrations in the treated group of animals compared to that in the normal group. Potassium ion concentration in the treated group did not exhibit a significant alteration when compared with the untreated animals. From the above observation, nandrolone decanoate abuse could be suggested as one of the causes of aldosterone and electrolyte imbalance in the body that could possibly be a serious risk factor for cardiovascular related disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Oxygen-induced retinopathy in mice with retinal photoreceptor cell degeneration.

PubMed

Zhang, Qian; Zhang, Zuo-Ming

2014-04-25

It is reported that retinal neovascularization seems to rarely co-exist with retinitis pigmentosa in patients and in some mouse models; however, it is not widely acknowledged as a universal phenomenon in all strains of all animal species. We aimed to further explore this phenomenon with an oxygen-induced retinopathy model in mice with retinal photoreceptor cell degeneration. Oxygen-induced retinopathy of colored and albino mice with rapid retinal degeneration were compared to homologous wild-type mice. The retinas were analyzed using high-molecular-weight FITC-dextran stained flat-mount preparation, hematoxylin and eosin (H&E) stained cross-sections, an immunohistochemical test for vascular endothelial growth factor (VEGF) distribution and Western blotting for VEGF expression after exposure to hyperoxia between postnatal days 17 (P17) and 21. Leakage and areas of non-perfusion of the retinal blood vessels were alleviated in the retinal degeneration mice. The number of preretinal vascular endothelial cell nuclei in the retinal degeneration mice was smaller than that in the homologous wild-type mice after exposure to hyperoxia (P<0.01). The degree of oxygen-induced retinopathy was positively correlated with the VEGF expression level. However, the VEGF expression level was lower in the retinal degeneration mice. Proliferative retinopathy occurred in mice with rapid retinal degeneration, but retinal photoreceptor cell degeneration could partially restrain the retinal neovascularization in this rapid retinal degeneration mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

Psychological aspects of albinism: an exploratory study with Nigerian (Igbo) albino subjects.

PubMed

Ezeilo, B N

1989-01-01

This paper reviews some studies done on the psychological aspects of albinism. Studies on the intellectual ability of albinos produce equivocal results. Results from personality studies seem more consistent and show albinos to be more emotionally unstable than non-albinos. This paper also reports a study by the author which examines the phenomenon of albinism from the albino's viewpoint. It examined the responses of three undergraduate albino subjects--one female and two males--to the author's request for each to write an essay on the merits and demerits of being an albino based on personal experiences. All consider being an albino to be more of a demerit than a merit. The demerits include conspicuous colour, delicate skin which blisters under the sun, defective sight, interpersonal, especially heterosexual, problems and society's unkind attitude. The paper ends with a discussion of possible future research in the area and a recommendation of the need for psychological rehabilitation as part of the management programme for albinos.

Short-term social memory deficits in adult female mice exposed to tannery effluent and possible mechanism of action.

PubMed

Estrela, Fernanda Neves; Rabelo, Letícia Martins; Vaz, Boniek Gontijo; de Oliveira Costa, Denys Ribeiro; Pereira, Igor; de Lima Rodrigues, Aline Sueli; Malafaia, Guilherme

2017-10-01

The accumulated organic residues in tannery-plant courtyards are an eating attraction to small rodents; however, the contact of these animals with these residues may change their social behavior. Thus, the aim of the present study is to investigate whether the exposure to tannery effluent (TE) can damage the social recognition memory of female Swiss mice, as well as to assess whether vitamin C supplementation could provide information about how TE constituents can damage these animals' memory. We have observed that resident females exposed to TE (without vitamin supplementation) did not explore the anogenital region, their body or chased intruding females for shorter time or with lower frequency during the retest session of the social recognition test, fact that indicates social recognition memory deficit in these animals. Such finding is reinforced by the confirmation that there was no change in the animals' olfactory function during the buried food test, or locomotor changes in females exposed to the pollutant. Since no behavioral change was observed in the females exposed to TE and treated with vitamin C (before or after the exposure), it is possible saying that these social cognitive impairments seem to be directly related to the imbalance between the cellular production of reactive oxygen species and the counteracting antioxidant mechanisms (oxidative stress) in female mice exposed to the pollutant (without vitamin supplementation). Therefore, the present study evidences that the direct contact with tannery effluent, even for a short period-of-time, may cause short-term social memory deficits in adult female Swiss mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of Multiple QTLs Linked to Neuropathology in the Engrailed-1 Heterozygous Mouse Model of Parkinson’s Disease

PubMed Central

Kurowska, Zuzanna; Jewett, Michael; Brattås, Per Ludvik; Jimenez-Ferrer, Itzia; Kenéz, Xuyian; Björklund, Tomas; Nordström, Ulrika; Brundin, Patrik; Swanberg, Maria

2016-01-01

Motor symptoms in Parkinson’s disease are attributed to degeneration of midbrain dopaminergic neurons (DNs). Heterozygosity for Engrailed-1 (En1), one of the key factors for programming and maintenance of DNs, results in a parkinsonian phenotype featuring progressive degeneration of DNs in substantia nigra pars compacta (SNpc), decreased striatal dopamine levels and swellings of nigro-striatal axons in the SwissOF1-En1+/− mouse strain. In contrast, C57Bl/6-En1+/− mice do not display this neurodegenerative phenotype, suggesting that susceptibility to En1 heterozygosity is genetically regulated. Our goal was to identify quantitative trait loci (QTLs) that regulate the susceptibility to PD-like neurodegenerative changes in response to loss of one En1 allele. We intercrossed SwissOF1-En1+/− and C57Bl/6 mice to obtain F2 mice with mixed genomes and analyzed number of DNs in SNpc and striatal axonal swellings in 120 F2-En1+/− 17 week-old male mice. Linkage analyses revealed 8 QTLs linked to number of DNs (p = 2.4e-09, variance explained = 74%), 7 QTLs linked to load of axonal swellings (p = 1.7e-12, variance explained = 80%) and 8 QTLs linked to size of axonal swellings (p = 7.0e-11, variance explained = 74%). These loci should be of prime interest for studies of susceptibility to Parkinson’s disease-like damage in rodent disease models and considered in clinical association studies in PD. PMID:27550741

Evaluation of anti-inflammatory and gastric anti-ulcer activity of Phyllanthus niruri L. (Euphorbiaceae) leaves in experimental rats.

PubMed

Mostofa, Ronia; Ahmed, Shanta; Begum, Mst Marium; Sohanur Rahman, Md; Begum, Taslima; Ahmed, Siraj Uddin; Tuhin, Riazul Haque; Das, Munny; Hossain, Amir; Sharma, Manju; Begum, Rayhana

2017-05-16

The medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analogue in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcer and inflammation. In this project we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. The anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20 mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats - keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa. P. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and 69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed good protective effect against ethanol-acid induced gastric mucosal injury in the rats. Administration of the extract's doses (100, 200 and 400 mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/kg) resulted in better inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20 mg/kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of mucosal layer and significantly prevented the formation of hemorrhage and edema. The investigation suggests that methanolic extract of P. niruri leaf possess anti-inflammatory activity and promotes ulcer protection as ascertained by regeneration of mucosal layer and substantial prevention of the formation of hemorrhage and edema.

Effect of Tribulus terrestris on Haloperidol-induced Catalepsy in Mice.

PubMed

Nishchal, B S; Rai, S; Prabhu, M N; Ullal, Sheetal D; Rajeswari, S; Gopalakrishna, H N

2014-01-01

Haloperidol, an antipsychotic drug, leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we have attempted to evaluate the anticataleptic effect of Tribulus terrestris on haloperidol-induced catalepsy in albino mice. Mice were allocated to four groups, each group containing six animals. Both, the test drug, Tribulus terrestris and the standard drug trihexyphenidyl were uniformly suspended in 1% gum acacia solution. Catalepsy was induced in mice with haloperidol (1.0 mg/kg, intraperitoneally). The first group received the vehicle (10 ml/kg, orally), the second group received trihexyphenidyl (10 mg/kg, orally) and the remaining two groups received Tribulus terrestris (100, 200 mg/kg, orally). The animals were assessed after single and repeated dose administration for ten days, 30 min prior to haloperidol, using standard bar test. The result of the present study demonstrates Tribulus terrestris has a protective effect against haloperidol-induced catalepsy, which is comparable to the standard drug used for the same purpose. Our study indicates Tribulus terrestris can be used to prevent haloperidol-induced extrapyramidal side effects.

Distribution of (/sup 14/C)acrylamide in male and pregnant Swiss-Webster mice studied by whole-body autoradiography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marlowe, C.; Clark, M.J.; Mast, R.W.

1986-12-01

Male and 13.5- and 17.5-day pregnant Swiss-Webster mice were administered 120 mg/kg (2,3-14C)acrylamide orally. The male mice were frozen 0.33, 1, 3, 9, 24, 72, and 216 hr later, and the pregnant mice at each gestational period were frozen at 3 and 24 hr. Whole-body autoradiographs from the male mice at early time intervals revealed accumulation of radioactivity in the contents of the gastrointestinal tract, liver, pancreas, testis, brain and gallbladder, and epithelia of oral cavity, esophagus, and bronchi. The distribution appears to be similar in the male and pregnant mice. Absorption from the stomach was virtually complete by 3more » hr; renal and hepatic elimination was essentially complete at 24 hr. Radioactivity in the male reproductive tract appeared in the parenchyma of the testis at 1 hr, moved to the seminiferous tubules and head of the epididymis at 9 hr, and by 9 days remained only in the tail of the epididymis and the crypts of the epithelium of the glans penis. This movement parallels that of spermatids. The 13.5-day fetuses were uniformly labeled except for a slightly increased uptake in fetal brain. The distribution of radioactivity in the 17.5-day fetal tissues resembled that in maternal tissues; the remarkable exception was an intense accumulation in fetal skin. This study indicates that acrylamide is efficiently absorbed from the stomach and eliminated by the liver, kidney, and possibly the pancreas. A previously unrecognized affinity of acrylamide or a metabolic product was demonstrated for fetal skin in late gestation and for adult epithelia of oral cavity, esophagus, forestomach, and bronchi. Also, acrylamide or a metabolite appears to bind to spermatids at a specific stage near maturation.« less