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Sample records for rata sprague dawley

  1. IMMUNOTOXICITY OF INDIVIDUAL ORGANOTIN COMPOUNDS IN SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Organotins, used as stabilizers for polyvinyl chloride pipe, leach into drinking water from supply pipes and may cause multisystem toxicity, including immunotoxicity. We assessed immune function in Sprague-Dawley rats exposed to dibutyltin dichloride (DBTC) or dimethyltin dichlor...

  2. Spontaneous complex odontoma in a Sprague-Dawley rat.

    PubMed

    Jang, Dong Deuk; Kim, Chuel-Kyu; Ahn, Byeongwoo; Kang, Jin Seok; Nam, Ki Tack; Kim, Dae Joong; Han, Dong Un; Jung, Kwonil; Chung, Han-Kook; Ha, Seung-Kwon; Choi, Changsun; Cho, Wan-Seob; Kim, Junghyun; Chae, Chanhee

    2002-03-01

    Complex odontoma from a female Sprague-Dawley rat is described histopathologically. Necropsy revealed a hard (bony), white mass (3.0 x 3.0 x 2.1 cm) on the left mandible. Microscopically, the mass consisted of islands or nests of epithelial and mesenchymal elements that formed abortive tooth structures. In other areas, tooth formation consisted of a pulp cavity lined by layers of odontoblasts, dentin, enamel, and ameloblasts. Concerning all features of normal tooth formation which was differentiated and mineralized yet completely disorganized, the diagnosis of complex odontoma was recommended.

  3. Keishibukuryogan is not carcinogenic in Sprague-Dawley rats

    PubMed Central

    Kanitani, Masanao; Nishimura, Nobuo; Edamoto, Hiroshi; Kase, Yoshio

    2016-01-01

    Keishibukuryogan is a traditional Japanese medicine widely administered to patients with menopausal symptoms. Because humans use it on a long-term basis, we believed that a carcinogenicity study was warranted. We orally administered keishibukuryogan (TJ-25) extract powder to 6-week-old Sprague-Dawley rats [Crl:CD(SD)], which were divided into four dosage groups-0 (water for injection), 100, 500 and 2,500 mg/kg/day for 24 months. We found that TJ-25 did not affect the survival rate of either sex. Furthermore, it did not affect the clinical condition of the rats, number of superficial tumors found by palpation, body weight, food consumption, hematology, or gross pathological findings. The severity of degeneration of muscle fiber in the femoral skeletal muscle increased slightly in males and females in the 2,500 mg/kg/day group, but TJ-25 did not increase the number of tumors found on histopathological examination. In our study, oral administration of TJ-25 extract powder in rats for 24 months was not associated with an increased incidence of tumors. PMID:27182114

  4. Oral toxicity evaluation of thiodiglycol in Sprague-Dawley rats.

    PubMed

    Angerhofer, Richard A; Michie, Mark W; Leach, Glenn J; Johnson, Mark S; Reddy, Gunda

    2014-01-01

    Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly. At termination of the experiment, urine, blood, and tissue samples were collected. Rats displayed significant decreased body weight with no effect on food consumption following administration of TDG at 5000 mg/kg/d. Both male and female rats showed significant increased kidney weights at 5000 mg/kg/d. The organ to body weight ratios increased significantly for liver, kidneys, testes, and brain in males and adrenals in females for 5000 mg/kg/d. At all doses of TDG, hematological and clinical parameters and tissue histopathology remained unaltered. The no observed adverse effect level (NOAEL) for oral subchronic toxicity was 500 mg/kg/d. Benchmark dose (BMD) was derived from the decreased gain in body weight that was seen in male rats. A BMD based on a 10% decrease in body weight was 1704 mg/kg/d, and the lower confidence limit on the dose BMD, the BMDL, was 372 mg/kg/d.

  5. Respiratory tract lung geometry and dosimetry model for male Sprague-Dawley rats.

    SciTech Connect

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2014-08-26

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague- Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  6. Respiratory Tract Lung Geometry and Dosimetry Model for Male Sprague-Dawley Rats

    SciTech Connect

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2015-07-24

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  7. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN DEVELOPING SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...

  8. DEVELOPMENTAL ATRAZINE EXPOSURE SUPPRESSES IMMUNE FUNCTION IN MALE, BUT NOT FEMALE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Developmental Atrazine Exposure Suppresses Immune Function in Male, but not Female Sprague-Dawley Rats

    Andrew A. Rooney,*,1 Raymond A. Matulka,? and Robert Luebke?

    *College of Veterinary Medicine, Anatomy, Physiological Sciences and Radiology, NCSU, Raleigh, North...

  9. Maternal Copper Deficiency Perpetuates Altered Vascular Function in Sprague-Dawley Rat Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known about the consequences of maternal Cu (Cu) deficiency on the vascular function of offspring or on perpetuation of vascular effects to a second generation. We examined vascular functional responses in mesenteric arteries from Cu-deficient Sprague-Dawley rat dams and from offspring dir...

  10. DEVELOPMENTAL EXPOSURE TO A THYROID DISRUPTING CHEMICAL STIMULATES PHAGOCYTOSIS IN JUVENILE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Developmental Exposure to a Thyroid Disrupting Chemical Stimulates Phagocytosis in Juvenile Sprague-Dawley Rats.
    AA Rooney1, R Matulka2, and R Luebke3. 1NCSU/US EPA CVM, Department of Anatomy, Physiological Sciences and Radiology, Raleigh, NC;2UNC Department of Toxicology, Cha...

  11. PERINATAL EXPOSURE TO THE PESTICIDE HEPTACHLOR PRODUCES ALTERATIONS IN IMMUNE FUNCTION PARAMETERS IN SPRAGUE DAWLEY RATS

    EPA Science Inventory

    PERINATAL EXPOSURE TO THE PESTICIDE HEPTACHLOR PRODUCES ALTERATIONS IN IMMUNE FUNCTION PARAMETERS IN SPRAGUE DAWLEY RATS. R A Matulka1, AA Rooney3, W Williams2, CB Copeland2, and R J Smialowicz2. 1Curriculum in Toxicology, UNC, Chapel Hill, NC, USA; 2US EPA, ITB, ETD, NHEERL, RT...

  12. PERIPUBERTAL DEHP EXPOSURE INHIBITS ANDROGEN-DEPENDENT DEVELOPMENT IN SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Peripubertal DEHP exposure inhibits androgen-dependent development in Sprague-Dawley rats.

    N.C. Noriega, J. Furr, C. Lambright, V.S. Wilson and L.E. Gray.

    noriega.nigel@epa.gov

    US EPA, MD-72 RTD, NHEERL, ORD, RTP, NC 27711

    The plasticizer Di (2-ethylhe...

  13. THE DEVELOPMENTAL IMMUNOTOXICITY OF DIBUTYLTIN DICHLORIDE IN SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Methyl- and butyltin compounds used as stabilizers in polyvinyl chloride (PVC) pipe production are of concern as they leach from supply pipes into drinking water and have been associated with multisystem toxicity. This study assessed immune function in Sprague-Dawley (CD) rats d...

  14. Beacon-like immunoreactivity in the hypothalamus of Sprague-Dawley rats.

    PubMed

    Brailoiu, G Cristina; Dun, Siok L; Yang, Jun; Chang, Jaw Kang; Castellino, Sonya; Dun, Nae J

    2002-01-14

    Distribution of the novel peptide beacon in the hypothalamus of Sprague-Dawley rats was examined by immunohistochemical methods. Beacon-immunoreactive (irBC) neurons were found in the paraventricular, supraoptic, and accessory neurosecretory nuclei, and intensely labeled fibers in the median eminence and infundibulo-pituitary stalk. Scattered cells and/or fibers were noted in the suprachiasmatic nucleus, arcuate nucleus, retrochiasmatic area, lateral and medial preoptic area, as well as anterior and lateral hypothalamic area. The wide distribution of irBC in the hypothalamus of Sprague-Dawley rats suggests that the peptide may influence, in addition to a proposed role in feeding, a multitude of biological activities associated with the hypothalamic-pituitary axis.

  15. Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats.

    PubMed

    Zelzer, Sieglinde; Mangge, Harald; Pailer, Sabine; Ainoedhofer, Herwig; Kieslinger, Petra; Stojakovic, Tatjana; Scharnagl, Hubert; Prüller, Florian; Weghuber, Daniel; Datz, Christian; Haybaeck, Johannes; Obermayer-Pietsch, Barbara; Trummer, Christian; Gostner, Johanna; Gruber, Hans-Jürgen

    2015-01-01

    Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats. PMID:26006242

  16. Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats

    PubMed Central

    Zelzer, Sieglinde; Mangge, Harald; Pailer, Sabine; Ainoedhofer, Herwig; Kieslinger, Petra; Stojakovic, Tatjana; Scharnagl, Hubert; Prüller, Florian; Weghuber, Daniel; Datz, Christian; Haybaeck, Johannes; Obermayer-Pietsch, Barbara; Trummer, Christian; Gostner, Johanna; Gruber, Hans-Jürgen

    2015-01-01

    Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats. PMID:26006242

  17. Pharmacokinetics and anesthetic activity of eugenol in male Sprague-Dawley rats.

    PubMed

    Guenette, S A; Beaudry, F; Marier, J F; Vachon, P

    2006-08-01

    Eugenol, the principle chemical constituent of clove oil, has recently been evaluated for its anesthetic and analgesic properties in fish and amphibians. The objective of this study was to determine the pharmacokinetic (PK) and anesthetic activity of eugenol in rats. Male Sprague-Dawley rats received single i.v. doses of eugenol (0, 5, 10, 20, 40 and 60 mg/kg) and anesthetic level was evaluated with the withdrawal reflex. For the 20 mg/kg dose level, blood and urinary samples were collected over 1 h for the PK assessment. Plasma and blood concentrations of eugenol, as well as metabolite identification in urine, were determined using a novel dansyl chloride derivatization method with liquid chromatography mass spectrometry (LC/MS/MS). PK parameters were calculated using noncompartmental methods. Eugenol-induced loss of consciousness in a dose-dependent manner, with mean (+/-SEM) recovery in reflex time of 167 +/- 42 sec observed at the highest dose level. Mean systemic clearance (Cl) in plasma and blood were 157 and 204 mL/min/kg, respectively. Glucuronide and sulfate conjugates were identified in urine. Overall, eugenol produced a reversible, dose-dependent anesthesia in male Sprague-Dawley rats. PMID:16846463

  18. Safety Assessment of Zigbir®: A Polyherbal Formulation in Sprague-Dawley Rats

    PubMed Central

    Allan, Joseph Joshua; Bhide, Ranjit Madhukar; Agarwal, Amit

    2012-01-01

    The safety of Zigbir®, a polyherbal formulation intended for use as food supplement, was evaluated in Sprague-Dawley rats treated orally at the dose of 2000 mg/kg in acute and at 250, 500, and 1000 mg/kg for 90 days in subchronic toxicity study. The median lethal dose of Zigbir® was found to be more than 2000 mg/kg, and fourteen-day repeated dose toxicity study revealed it to be safe up to 1000 mg/kg. The subchronic study did not show any mortality or treatment-related adverse clinical signs. The treated animals exhibited normal feed intake and comparable body weight gain except for a decrease in females of 500 and 1000 mg/kg groups. Ocular examination revealed no abnormalities. Further, Zigbir® administration in rats did not induce any major changes in urinalysis, hematological, and biochemical evaluations except for minor alterations in few parameters at different dose levels. Gross and histopathological findings did not show any lesions attributable to Zigbir® administration. The no observed effect level of Zigbir® was found to be 500 and 250 mg/kg in male and female Sprague-Dawley rats. PMID:23125854

  19. Chemopreventive Properties and Toxicity of Kelulut Honey in Sprague Dawley Rats Induced with Azoxymethane.

    PubMed

    Saiful Yazan, Latifah; Muhamad Zali, Muhamad Firdaus Shyfiq; Mohd Ali, Razana; Zainal, Nurul Amira; Esa, Nurulaidah; Sapuan, Sarah; Ong, Yong Sze; Tor, Yin Sim; Gopalsamy, Banulata; Voon, Fui Ling; Syed Alwi, Sharifah Sakinah

    2016-01-01

    Ethnopharmacological Relevance. Colon cancer has been a major problem worldwide. Kelulut honey (KH) is produced by the stingless bees from Trigona species and has strong antioxidant activities that could be one of the potential chemopreventive agents from natural resources. Aim of This Study. This study investigated the chemopreventive properties and toxicity of KH in Sprague Dawley rats induced with azoxymethane (AOM). Material and Method. Twenty-four male Sprague Dawley rats aged 5 weeks were divided into 4 groups: (G1) untreated group not induced with AOM, (G2) untreated group induced with AOM, (G3) treated group induced with AOM, and (G4) treated group not induced with AOM. Injection of AOM (15 mg/kg) was via intraperitoneal route once a week for two subsequent weeks. The treatment groups were given oral administration of KH (1183 mg/kg body weight) twice daily for 8 weeks. Results. Treatment with KH significantly reduced the total number of aberrant crypt foci (ACF) and aberrant crypts (AC) and crypt multiplicity. KH was not toxic to the animals since the level of blood profile parameters, liver enzymes, and kidney functions was in normal range. Conclusions. The current finding shows that KH has chemopreventive properties in rats induced with colorectal cancer and also was found not toxic towards the animals. PMID:27525267

  20. Chemopreventive Properties and Toxicity of Kelulut Honey in Sprague Dawley Rats Induced with Azoxymethane

    PubMed Central

    Muhamad Zali, Muhamad Firdaus Shyfiq; Mohd Ali, Razana; Zainal, Nurul Amira; Sapuan, Sarah; Tor, Yin Sim; Gopalsamy, Banulata; Syed Alwi, Sharifah Sakinah

    2016-01-01

    Ethnopharmacological Relevance. Colon cancer has been a major problem worldwide. Kelulut honey (KH) is produced by the stingless bees from Trigona species and has strong antioxidant activities that could be one of the potential chemopreventive agents from natural resources. Aim of This Study. This study investigated the chemopreventive properties and toxicity of KH in Sprague Dawley rats induced with azoxymethane (AOM). Material and Method. Twenty-four male Sprague Dawley rats aged 5 weeks were divided into 4 groups: (G1) untreated group not induced with AOM, (G2) untreated group induced with AOM, (G3) treated group induced with AOM, and (G4) treated group not induced with AOM. Injection of AOM (15 mg/kg) was via intraperitoneal route once a week for two subsequent weeks. The treatment groups were given oral administration of KH (1183 mg/kg body weight) twice daily for 8 weeks. Results. Treatment with KH significantly reduced the total number of aberrant crypt foci (ACF) and aberrant crypts (AC) and crypt multiplicity. KH was not toxic to the animals since the level of blood profile parameters, liver enzymes, and kidney functions was in normal range. Conclusions. The current finding shows that KH has chemopreventive properties in rats induced with colorectal cancer and also was found not toxic towards the animals. PMID:27525267

  1. Effect of green tea supplementation on insulin sensitivity in Sprague-Dawley rats.

    PubMed

    Wu, Liang-Yi; Juan, Chi-Chang; Ho, Low-Tone; Hsu, Yung-Pei; Hwang, Lucy Sun

    2004-02-11

    Epidemiological observations and laboratory studies have shown that green tea has a variety of health effects, including antitumor, antioxidative, and hypolipidemic activities. The aim of this study was to examine whether it had an effect on glucose tolerance and insulin sensitivity in Sprague-Dawley rats. In experiment 1 (in vivo study), rats were divided into two groups: a control group fed standard chow and deionized distilled water and a "green tea" group fed the same chow diet but with green tea instead of water (0.5 g of lyophilized green tea powder dissolved in 100 mL of deionized distilled water). After 12 weeks of green tea supplementation, the green tea group had lower fasting plasma levels of glucose, insulin, triglyceride, and free fatty acid than the control rats. Insulin-stimulated glucose uptake of, and insulin binding to, adipocytes were significantly increased in the green tea group. In experiment 2 (in vitro study), a tea polyphenol extract was used to determine its effect on insulin activity in vitro. Green tea polyphenols (0.075%) significantly increased basal and insulin-stimulated glucose uptake of adipocytes. Results demonstrated that green tea increases insulin sensitivity in Sprague-Dawley rats and that green tea polyphenol is one of the active components.

  2. Strain differences in toxic effects of long-lasting isoflurane anaesthesia between Wistar rats and Sprague Dawley rats.

    PubMed

    Siller-Matula, J M; Jilma, B

    2008-11-01

    We investigated if long-lasting (5 h) anaesthesia with isoflurane has different pharmacological effects in two different rat strains: Wistar and Sprague Dawley. The mean blood pressure was 34% higher in Sprague Dawley rats as compared to the Wistar rats (p = 0.04). In Wistar rats, the pH value decreased to 7.1, lactate increased by 53%, creatinine increased 2.7-fold, alanine amino transferase and aspartate amino transferase increased more than 4-fold and lactate dehydrogenase increased 9-fold (p < 0.05). There were no changes in laboratory parameters in Sprague Dawley rats. This indicates that the Wistar rats were more sensitive to a 5 h anaesthesia with isoflurane after a premedication with ketamin/xylazine in the described study design.

  3. The effects of strontium ranelate treatment on ovariectomized Sprague-Dawley rat tibia

    NASA Astrophysics Data System (ADS)

    Zheng, Y.; Jin, W.; Wang, C.; Yang, M.; Shen, H.; Eisa, M. H.; Mi, Y.

    2009-06-01

    Micro Proton Induced X-ray Emission (micro-PIXE) technique was used to study the effect of strontium ranelate on osteoporosis resulted from estrogen deficiency. The contents of calcium and strontium in tibia, as well as calcium distribution for structural determination were investigated. Three groups of tibia samples were respectively taken from three groups of female Sprague-Dawley (S.D.) rats, i.e. control, ovariectomized and ovariectomized followed strontium ranelate treatment. It was found that the strontium content was decreasing in the bone from ovariectomized rat compared with that in control, but significantly increasing in the bone from strontium ranelate treated ovariectomized rat. Our study showed that strontium content is a feasible parameter for the diagnosis of osteoporosis caused by estrogen deficiency. Strontium ranelate is an effective antiosteoporosis chemical to rebuild the bone structure and prevent deterioration of bone strength as well.

  4. Cytogenetic evaluation of malathion-induced toxicity in Sprague-Dawley rats

    PubMed Central

    Moore, Pamela D.; Patlolla, Anita K.; Tchounwou, Paul B.

    2011-01-01

    Malathion is a well known pesticide and is commonly used in many agricultural and non-agricultural settings. Its toxicity has been attributed primarily to the accumulation of acetylcholine (Ach) at nerve junctions, due to inhibition of acetylcholinesterase (AChE), and consequently overstimulation of the nicotinic and muscarinic receptors. However, the genotoxicity of malathion has not been adequately studied; published studies suggest a weak interaction with the genetic material. In the present study, we investigated the genotoxic potential of malathion in bone marrow cells and peripheral blood obtained from Sprague-Dawley rats; using chromosomal aberrations (CA), mitotic index (MI), and DNA damage as toxicological endpoints. Four groups of four male rats each, weighing approximately 60 ± 2 g, were injected intraperitoneally (i.p.) once a day for five days with doses of 2.5, 5, 10, and 20 mg/kg body weight (BW) of malathion dissolved in 1% DMSO. The control group was made up of four animals injected with 1% DMSO. All the animals were sacrificed 24 h after the fifth day treatment. Chromosome preparations were obtained from bone marrow cells following standard protocols. DNA damage in peripheral blood leukocytes was determined using alkaline single-cell gel electrophoresis (comet assay). Malathion exposure significantly increased the number of structural chromosomal aberrations (CA) and the percentages of DNA damage, and decreased the mitotic index (MI) in treated groups when compared with the control group. Our results demonstrate that malathion has a clastogenic/genotoxic potential as measured by the bone marrow CA and comet assay in Sprague-Dawley rats. PMID:21835262

  5. Flor-Essence? Herbal Tonic Promotes Mammary Tumor Development in Sprague Dawley Rats

    SciTech Connect

    Bennett, L; Montgomery, J; Steinberg, S; Kulp, K

    2004-01-28

    Background: Women who are diagnosed with breast cancer often self-administer complementary and alternative medicines to augment their conventional treatments, improve health, or prevent recurrence. Flor-Essence{reg_sign} Tonic is a complex mixture of herbal extracts used by cancer patients because of anecdotal evidence that it can treat or prevent disease. Methods: Female Sprague Dawley rats were given water or exposed to 3% or 6% Flor-Essence{reg_sign} beginning at one day of age. Mammary tumors were induced with a single oral 40 mg/kg/bw dose of dimethylbenz(a)anthracene at 50 days of age and sacrificed at 23 weeks. Rats were maintained on AIN-76A diet. Results: Control rats had palpable mammary tumor incidence of 51.0% at 19 weeks of age compared to 65.0% and 59.4% for the 3% and 6% Flor-Essence{reg_sign} groups respectively. Overall, no significant difference in time until first palpable tumor was detected among any of the groups. At necropsy, mammary tumor incidence was 82.5% for controls compared to 90.0% and 97.3% for rats consuming 3% and 6% Flor-Essence{reg_sign}, respectively. Mean mammary tumor multiplicity ({+-}SES) for the controls was 2.8 ({+-} 0.5) and statistically different from the 3% or 6% Flor- Essence{reg_sign} groups with 5.2 ({+-} 0.7), and 4.8 ({+-} 0.6), respectively (p{<=}0.01). As expected, the majority of isolated tumors were diagnosed as adenocarcinomas. Conclusions: Flor-Essence{reg_sign} can promote mammary tumor development in the Sprague Dawley rat model. This observation is contrary to widely available anecdotal evidence as well as the desire of the consumer that this commercially available herbal tonic will suppress and/or inhibit tumor growth.

  6. Restraint Stress Impairs Glucose Homeostasis Through Altered Insulin Signalling in Sprague-Dawley Rat.

    PubMed

    Morakinyo, Ayodele O; Ajiboye, Kolawole I; Oludare, Gabriel O; Samuel, Titilola A

    2016-01-01

    The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the rats were exposed to one of the four different restraint stressors; 1 h, twice daily for a period of 7 days (S7D), 14 days (S14D) and 28 days (S28D). Glucose tolerance and insulin sensitivity were evaluated following the final stress exposure. ELISA were performed to assess the level of insulin and adiponectin as well as expression of INSR and GLUT4 protein in skeletal muscle. Plasma corticosterone level was also determined as a marker of stress exposure. Restraint stress for 7 days caused transient glucose intolerance, while S14D rats demonstrated increased glucose intolerance and insulin insensitivity. However, restraint stress for 28 days had no effect on glucose tolerance, but did cause an increase in glucose response to insulin challenge. The serum level of adiponectin was significantly (p< 0.05) lower compared with the control value while insulin remained unchanged except at in S28D rats that had a significant (p<0.05) increase. The expression of INSR and GLUT4 receptors were significantly (p< 0.05) decreased in the skeletal muscle of restraint stress exposed rats. There was a significant (p< 0.05) increase in the plasma corticosterone level of the stress rats compared with their control counterparts. Restraint stress caused glucose intolerance and insulin insensitivity in male Sprague-Dawley rats, which becomes accommodated with prolonged exposure and was likely related to the blunted insulin signalling in skeletal muscle. PMID:27574760

  7. Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats

    PubMed Central

    Patlolla, Anita K.; Todorov, Todor I.; Tchounwou, Paul B.; van der Voet, Gijsbert; Centeno, Jose A.

    2012-01-01

    Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg bw of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p<0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p<0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels. PMID:23175155

  8. Serum acetyl cholinesterase as a biomarker of arsenic induced neurotoxicity in sprague-dawley rats.

    PubMed

    Patlolla, Anita K; Tchounwou, Paul B

    2005-04-01

    Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 +/- 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW), one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 +/- 822, 5697 +/- 468, 5069 +/- 624, 4054 +/- 980, and 3158 +/- 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

  9. Mammary gland development and response to prenatal atrazine exposure in the Sprague Dawley and Long-Evans rats.

    EPA Science Inventory

    Mammary gland (MG) tumor development in Sprague Dawley (SD) rats is increased by longterm dietary exposure to the chlorotriazine herbicide atrazine (ATR). ATR is proposed to cause these changes in the adult SD rat by altering hormonally-regulated estrous cyclicity. In Long-Evans...

  10. PERINATAL EXPOSURE TO ATRAZINE SUPPRESSES JUVENILE IMMUNE FUNCTION IN MALE, BUT NOT FEMALE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    PERINATAL EXPOSURE TO ATRAZINE SUPPRESSES JUVENILE IMMUNE FUNCTION IN MALE, BUT NOT FEMALE SPRAGUE-DAWLEY RATS. AA Rooney1 and RW Luebke2. 1NCSU/USEPA CVM, Department of Anatomy, Physiological Sciences, and Radiology, Raleigh, NC;2USEPA, NHEERL, RTP, NC.
    The ability of the ...

  11. DEVELOPMENT OF A PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR DELTAMETHRIN IN ADULT AND DEVELOPING SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    This work describes the development of a physiologically based pharmacokinetic (PBPK) model of deltamethrin, a type II pyrethroid, in the developing male Sprague-Dawley rat. Generalized Michaelis-Menten equations were used to calculate metabolic rate constants and organ weights ...

  12. PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

    Nigel Noriega, Jonathan Furr, Christy Lambright, Vickie Wilson, L. Earl Gray Jr.

    The plasticizer Di (2-ethylhexyl) phtha...

  13. INVESTIGATION OF THE ABILITY OF DIISONONYL PHTHALATE (DINP) TO ALTER ANDROGEN-DEPENDENT TISSUE DEVELOPMENT IN SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Title: INVESTIGATION OF THE ABILITY OF DIISONONYL PHTHALATE (DINP) TO ALTER ANDROGEN-DEPENDENT TISSUE DEVELOPMENT IN SPRAGUE-DAWLEY RATS.
    Authors: J S Ostby 1 , A K Hotchkiss 2 , J R Furr 1 and L E Gray Jr. 1
    Sponsor: L Gray Jr.
    Institutions: 1. USEPA, NH...

  14. PRENATAL WINDOW OF SUSCEPTIBILITY TO PERFLUOROOCTANE SULFONATE-INDUCED NEONATAL MORTALITY IN THE SPRAGUE-DAWLEY RAT

    EPA Science Inventory

    Abstract
    The critical period for increased neonatal mortality induced by PFOS exposure was evaluated in the rat . Timed-pregnant Sprague-Dawley rats were treated by oral gavage with 25 mg/kg/d PFOS/K+ on four consecutive days during gestation (gestation days (GD) 2-5, 6-9, 1...

  15. EFFECTS OF INDUCED RESPIRATORY CHANGES ON CARDIAC, VENTILATORY, AND THERMOREGULATORY PARAMETERS IN HEALTHY SPRAGUE-DAWLEY RATS

    EPA Science Inventory


    EFFECTS OF INDUCED RESPIRATORY CHANGES ON CARDIAC, VENTILATORY, AND THERMOREGULATORY PARAMETERS IN HEALTHY SPRAGUE-DAWLEY RATS. LB Wichers1, WH Rowan2, DL Costa2, MJ Campen3 and WP Watkinson2 1UNC SPH, Chapel Hill, NC, USA; 2USEPA, ORD/NHEERL/ETD/PTB, RTP, NC, USA; 3LRRI, A...

  16. Polychlorinated Biphenyls Induce Oxidative DNA Adducts in Female Sprague-Dawley Rats.

    PubMed

    Mutlu, Esra; Gao, Lina; Collins, Leonard B; Walker, Nigel J; Hartwell, Hadley J; Olson, James R; Sun, Wei; Gold, Avram; Ball, Louise M; Swenberg, James A

    2016-08-15

    Polychlorinated biphenyls (PCBs) are organic chemicals that were traditionally produced and widely used in industry as mixtures and are presently formed as byproducts of pigment and dye manufacturing. They are known to persist and bioaccumulate in the environment. Some have been shown to induce liver cancer in rodents. Although the mechanism of the toxicity of PCBs is unknown, it has been shown that they increase oxidative stress, including lipid peroxidation. We hypothesized that oxidative stress-induced DNA damage could be a contributor for PCB carcinogenesis and analyzed several DNA adducts in female Sprague-Dawley rats exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB 126), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), and a binary mixture (PCB 126 + 153) for 14, 31, and 53 wks. Eight adducts were measured to profile oxidative DNA lesions, including 8-oxo-deoxyguanosine (8-oxo-dG), 1,N(6)-ethenodeoxyadenosine (1,N(6)-εdA), N(2),3-ethenoguanine (N(2),3-εG), 1,N(2)-ethenodeoxyguanosine (1,N(2)-εdG), as well as malondialdehyde (M1dG), acrolein (AcrdG), crotonaldehyde (CrdG), and 4-hydroxynonenal-derived dG adducts (HNEdG) by LC-MS/MS analysis. Statistically significant increases were observed for 8-oxo-dG and 1,N(6)-εdA concentrations in hepatic DNA of female rats exposed to the binary mixture (1000 ng/kg/day + 1000 μg/kg/day) but not in rats exposed to PCB 126 (1000 ng/kg/day) or PCB 153 (1000 μg/kg/day) for 14 and 31 wks. However, exposure to PCB 126 (1000 ng/kg/day) for 53 wks significantly increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, and M1dG. Exposure to PCB 153 (1000 μg/kg/day) for 53 wks increased 8-oxo-dG, and 1,N(6)-εdA. Exposure to the binary mixture for 53 wks increased 8-oxo-dG, 1,N(6)-εdA, AcrdG, 1,N(2)-εdG, and N(2),3-εG significantly above control groups. Increased hepatic oxidative DNA adducts following exposure to PCB 126, PCB 153, or the binary mixture shows that an increase in DNA damage may play an important role in hepatic toxicity and

  17. A study of the mechanism of butachlor-associated gastric neoplasms in Sprague-Dawley rats.

    PubMed

    Thake, D C; Iatropoulos, M J; Hard, G C; Hotz, K J; Wang, C X; Williams, G M; Wilson, A G

    1995-05-01

    Long term administration of butachlor to Sprague-Dawley rats in a previous bioassay, resulted in the induction of gastric neoplasms which occurred only in the highest dose group (3000 ppm in the diet), primarily in females and specifically in the fundic region. The tumors were a composite of highly undifferentiated enterochromaffin-like (ECL) cells and mucus producing cells with morphologic characteristics unlike those previously described in the rat stomach. Mucosal atrophy of marked intensity was a consistent feature of the gastric mucosa in animals from the highest dose group. An additional long term study was conducted in female Sprague-Dawley rats at dietary levels of 0, 100, 1000 and 3000 ppm to explore the mechanism(s) involved in the formation of these neoplasms. Cell proliferation was evaluated in both fundic and pyloric regions of the stomachs of rats at multiple time periods from 14 days to 26 months. Mucosal thickness was determined in the fundic region at the same time intervals as were used for cell proliferation studies. Gastric pH and gastric acid production were measured after approximately 21 months of exposure. Serum gastrin levels were analyzed at 14, 60, and 120 days and at 6, 18 and 20 months. Cholecystokinin (CCK)/gastrin receptor binding studies were conducted on samples of four tumors and pooled fundic mucosa from five animals in the control group. Cell proliferation was increased in both the neck and base regions of the fundic mucosa at nearly all time points measured from 14 days to 26 months. The magnitude of the changes in the base region were substantially greater than those in the neck region. Fundic mucosal thickness was decreased beginning at the 30-day time point and continued at all intervals, being less than one half that of controls at 20 and 26 months. Gastric pH in rats from the highest dose was elevated to nearly twice control levels at 21 months. Gastric acid secretion was dramatically decreased in animals from the 3000 ppm

  18. Histologic Features of Postnatal Development of Immune System Organs in the Sprague-Dawley Rat.

    PubMed

    Parker, George A; Picut, Catherine A; Swanson, Cynthia; Toot, Jonathan D

    2015-08-01

    The immune system of the rat undergoes substantial functional and morphological development during the postnatal period. Some aspects of this development are genetically predetermined, while other aspects depend on environmental influences. Detailed information on postnatal development is important in the interpretation of histopathologic findings in juvenile toxicology and pubertal assay studies, as well as other studies conducted in juvenile rats. Studies were conducted to provide detailed characterization of histologic features of the major functional compartments of immune system organs in male and female Sprague-Dawley rats at weekly intervals from the day of birth through postnatal day (PND) 42. Maturation of the individual immune system organs occurred across a range of ages, with histologic maturation of T-cell-related compartments typically occurring prior to maturation of B-cell-related compartments. The sequence of histologic maturation was bone marrow and thymus on PND 14, mesenteric lymph node on PND 21, Peyer's patches and bronchus-associated lymphoid tissue on PND 28, mandibular lymph node, nasopharynx-associated lymphoid tissue, and diffuse mucosal mononuclear cell population of small intestine on PND 35, and spleen on PND 42. An estimation of functional maturation can be made based on the morphological indications of maturity of each compartment of immune system organs, but histologic indications of maturity do not confirm functional immunocompetence.

  19. Hypolipidemic effect of bamboo shoot oil (P. pubescens) in Sprague-Dawley rats.

    PubMed

    Lu, Baiyi; Xia, Daozhong; Huang, Weisu; Wu, Xiaoqin; Zhang, Ying; Yao, Yiyuan

    2010-08-01

    Atherosclerosis and its related complications are the leading causes of death in the West and in many developed countries. This study aims to investigate the hypolipidemic effect of bamboo shoot oil (BSO) in Sprague-Dawley rats. A group of rats had induced hyperlipidemia, hypercholesterolemia, and fatty liver by being fed with a high-fat, high-cholesterol diet for 4 wk. The control group was administered 10 mL distilled water per kg body weight, while the other groups were, respectively, administered 250 mg beta-sitosterol, 250 mg BSO, 500 mg BSO, and 1000 mg BSO per kg body weight by oral gavage. The results demonstrated that BSO could significantly decrease the levels of total cholesterol, triacylglycerol, low-density lipoprotein-cholesterol, phytosterol, lipoprotein lipase, hepatic lipase, and atherogenic index in serum, and increase the levels of cholesterol in feces. It could also significantly decrease the level of relative liver weight and liver lipids. The pronounced hypolipidemic effects of BSO might be attributed to its ability to inhibit cholesterol absorption and increase cholesterol excretion. These results suggest that consuming BSO may provide benefits in managing hypercholesterolemia. Therefore, BSO may be a good candidate for development as a functional food and nutraceutical. PMID:20722933

  20. Single Intramuscular-dose Toxicity of Samgihwalryeok-Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

    Kim, Sung-Chul; Ahn, Seong-Hun

    2014-01-01

    Objectives: This study was performed to examine the single-dose toxicity of Samgihwalryeok pharmacopuncture. Methods: Forty six-week-old Sprague-Dawley (SD) rats were divided into four groups of 10 rats each; each group was then sub-divided into two smaller groups, one of five males and the other of five females. Group 1 (G1, control) received 1.0 mL of normal saline solution, while group 2 (G2, low-dose group), group 3 (G3, mid-does group, and group 4 (G4, high-dose group) received 0.1, 0.5, and 1.0 mL of Samgihwalryeok pharmacopuncture, respectively. Results: No mortalities or clinical signs were observed in the four groups. Also, no significant changes in body weights were observed among the group, and no significant differences in hematology/biochemistry, necropsy, or histopathology results were noted. Conclusion: The above findings suggest that treatment with Samgihwalryeok pharmacopuncture is relatively safe. Further studies on this subject are needed. PMID:25780699

  1. Magnetic resonance histology of age-related nephropathy in the Sprague Dawley rat.

    PubMed

    Xie, Luke; Cianciolo, Rachel E; Hulette, Brian; Lee, Ha Won; Qi, Yi; Cofer, Gary; Johnson, G Allan

    2012-07-01

    Magnetic resonance histology (MRH) has become a valuable tool in evaluating drug-induced toxicity in preclinical models. However, its application in renal injury has been limited. This study tested the hypothesis that MRH could detect image-based biomarkers of chronic disease, inflammation, or age-related degeneration in the kidney, laying the foundation for more extensive use in evaluating drug toxicity. We examined the entire intact kidney in a spontaneous model of chronic progressive nephropathy. Kidneys from male Sprague Dawley rats were imaged at 8 weeks (n = 4) and 52 weeks (n =4) on a 9.4 T system dedicated to MR microscopy. Several potential contrast mechanisms were explored to optimize the scanning protocols. Full coverage of the entire kidney was achieved with isotropic spatial resolution at 31 microns (voxel volume = 30 pL) using a gradient recalled echo sequence. Isotropic spatial resolution of 15 microns (voxel volume < 4 pL) was achieved in a biopsy core specimen. Qualitative age-related structural changes, such as renal cortical microvasculature, tubular dilation, interstitial fibrosis, and glomerular architecture, were apparent. The nondestructive 3D images allowed measurement of quantitative differences of kidney volume, pelvis volume, main vessel volume, glomerular size, as well as thickness of the cortex, outer medulla, and inner medulla.

  2. Regulation of paraoxonase 1 (PON1) in PCB 126-exposed male Sprague Dawley rats

    PubMed Central

    Shen, Hua; Robertson, Larry W.; Ludewig, Gabriele

    2012-01-01

    3,3′,4,4′,5-Pentachlorobiphenyl (PCB 126), an aryl hydrocarbon receptor (AhR) agonist and most potent dioxin-like PCB congener, significantly alters gene expression, lipid metabolism, and oxidative stress in the liver. PON1, an antioxidant and anti-atherogenic enzyme, is produced in the liver and secreted into the blood where it is incorporated into high density lipoprotein (HDL) and protects LDL and cellular membranes against lipid peroxidation. To explore the regulation of PON1, male Sprague-Dawley rats were treated with ip injections of 0, 1 or 5 μmol/kg PCB 126 and euthanized up to two weeks afterwards. Serum total and HDL-cholesterol were increased by low dose and decreased by high dose exposure, while LDL-cholesterol was unchanged. PCB 126 significantly increased hepatic PON1 gene expression and liver and serum PON1 activities. Liver and serum thiobarbituric acid reactive substances levels were not elevated except for high dose and long exposure times. Serum antioxidant capacity was unchanged across all exposure doses and time points. This study, the first describing the regulation of gene expression of PON1 by a PCB congener, raises interesting questions whether elevated PON1 is able to ameliorate PCB 126-induced lipid peroxidation and whether serum PON1 levels may serve as a new biomarker of exposure to dioxin-like compounds. PMID:22266287

  3. Advantame sweetener preference in C57BL/6J mice and Sprague-Dawley rats.

    PubMed

    Sclafani, Anthony; Ackroff, Karen

    2015-03-01

    Advantame is a new ultrahigh-intensity noncaloric sweetener derived from aspartame and approved for human use. Rats and mice are not attracted to the taste of aspartame and this study determined their preference for advantame. In 24-h choice tests with water, C57BL/6J mice and Sprague-Dawley rats were indifferent to advantame at concentrations of 0.01, 0.03, and 0.1mM but significantly preferred 0.3 and 1mM advantame to water. Both species also preferred 1mM advantame to 1mM saccharin in direct choice tests, but preferred 10mM saccharin to 1mM advantame, which is near the solubility limit for this sweetener. Mice also preferred 1mM advantame to 1mM sucralose or acesulfame K, but preferred both sweeteners at 10mM to 1mM advantame. In addition, mice preferred 1mM advantame to 1 and 10mM aspartame. Thus, advantame is a potent sweetener for rodents but, because of limited solubility, is not an effective alternative to saccharin, sucralose, or acesulfame K at higher concentrations. PMID:25560795

  4. Variations in lead isotopic abundances in Sprague-Dawley rat tissues: possible reason of formation.

    PubMed

    Liu, Duojian; Wu, Jing; Ouyang, Li; Wang, Jingyu

    2014-01-01

    It has been reported in previous research that the lead isotopic composition of blood, urine and feces samples statistically differed from the given lead sources in Sprague-Dawley (SD) rats. However, the reason for this phenomenon is still unclear. An animal experiment was performed to investigate the lead isotope fractionation in diverse biological samples (i.e., lungs, liver, kidneys, bone) and to explore the possible reasons. SD rats were intratracheally instilled with lead acetate at the concentrations of 0, 0.02, 0.2, and 2 mg/kg body weight. Biological samples were collected for lead isotope analysis using an inductively coupled plasma mass spectrometry (ICP-MS). Significant differences are observed in lead isotope abundances among the diverse biological samples. The lead isotope abundances ((206)Pb, (207)Pb and (208)Pb) in diverse biological samples show different degrees and directions of departure from the given lead source. The results suggest that differences in enrichment or depletion capacity for each lead isotope in the various tissues might lead to the variation in lead isotopic abundances in tissues. Moreover, a nonlinear relationship between the blood lead level and the lead isotope abundances in liver and bone is observed. When the whole-blood level is higher than 50 ng/mL, the lead isotopic compositions of biological samples tend to be the same. Thus, the data support the speculation of a fractionation functional threshold.

  5. Subchronic toxicity study of standardized methanolic extract of Mitragyna speciosa Korth in Sprague-Dawley Rats

    PubMed Central

    Ilmie, Mohd U.; Jaafar, Hasnan; Mansor, Sharif M.; Abdullah, Jafri M.

    2015-01-01

    Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days). Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardized methanolic extract of ketum (SMEMS) in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for hematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals. PMID:26136645

  6. Effects of dietary supplements on space radiation-induced oxidative stress in Sprague-Dawley rats.

    PubMed

    Guan, Jun; Wan, X Steven; Zhou, Zhaozong; Ware, Jeffrey; Donahue, Jeremiah J; Biaglow, John E; Kennedy, Ann R

    2004-11-01

    Of particular concern for the health of astronauts during space travel is radiation from protons and high-mass, high-atomic-number (Z), and high-energy particles (HZE particles). Space radiation is known to induce oxidative stress in astronauts after extended space flight. In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by gamma rays, protons and HZE-particle radiation. The results demonstrate that the plasma level of total antioxidants in Sprague-Dawley rats was significantly decreased (P < 0.01) in a dose-dependent manner within 4 h after exposure to gamma rays. Exposure to protons and HZE-particle radiation also significantly decreased the serum or plasma level of total antioxidants in the irradiated animals. Diet supplementation with L-selenomethionine alone or a combination of selected antioxidant agents was shown to partially or completely prevent the decrease in the serum or plasma levels of total antioxidants in animals exposed to gamma rays, protons or HZE particles. These findings suggest that exposure to space radiation may compromise the capacity of the host antioxidant defense and that this adverse biological effect can be prevented at least partially by dietary supplementation with L-selenomethionine and antioxidants.

  7. Classical and instrumental conditioning of eyeblink responses in Wistar-Kyoto and Sprague-Dawley rats.

    PubMed

    Ricart, Thomas M; Jiao, Xilu; Pang, Kevin C H; Beck, Kevin D; Servatius, Richard J

    2011-01-01

    Wistar-Kyoto (WKY) rats, an animal model of anxiety vulnerability, acquire lever-press avoidance faster than outbred Sprague-Dawley (SD) rats. Faster avoidance acquisition may reflect an inherent ability to acquire cue-outcome associations, response-outcome associations or both. To evaluate cue-outcome learning, acquisition of classically conditioned eyeblink response was compared in SD and WKY rats using a delay-type paradigm (500-ms conditioned stimulus (CS) coterminating with a 10-ms unconditional stimulus (US)). WKY rats demonstrated enhanced classical conditioning, with both faster acquisition and greater asymptotic performance in delay-type training than SD rats. To evaluate response-outcome learning, separate SD and WKY rats were given control over US delivery through imposition of an omission contingency into delay-type training (emitting a conditioned response (CR) prevented delivery of the US). The schedule of US delivery derived by these rats became the training regimen for a separate group of SD and WKY rats, yoked within strain. In SD rats, no differences in acquisition were detected between those given control over US delivery and those trained with the same partial reinforcement schedule. Acquisition rates of those WKY rats with control exceeded those trained with a yoked-schedule of US presentation. Collectively, WKY rats exhibit enhanced classical conditioning and sensitivity to schedules of reinforcement compared to outbred SD rats. Anxiety vulnerability, in particular inhibited temperament, may be traced to active processes in the prediction and control of aversive events.

  8. Comparative analysis of growth characteristics of Sprague Dawley rats obtained from different sources

    PubMed Central

    Brower, Marcia; Grace, Martha; Kotz, Catherine M.

    2015-01-01

    Genetic background in animal models is an intrinsic research variable in biomedical research. Although inbred strains offer genetic uniformity, the outbred stocks, known for genetic variability are often used to develop animal models of human disease. The genetic variability is considered to be even higher when outbred stocks are obtained from different sources. In order to examine the degree of variability of an outbred stock obtained from various sources, Sprague Dawley (SD) rat lines obtained from two sources were evaluated for their growth characteristics. The SD rats from Charles River laboratories (CRL) and Harlan Laboratories (HAR) were monitored for weight gain from the age of 6 weeks to 24 weeks. Food intake was monitored between 13 and 24 weeks. Body composition, organ weights, tibial lengths and blood parameters were measured. There was no difference observed in food intake per 100 gram body weight at most of the time points. CRL rats showed higher body fat mass (49.6%), higher gross liver weights (22.2%), lower testicular weights (30.8%) and lower cholesterol levels (25.4%) than HAR rats. Phenotypic differences may be attributed to genetic heterogeneity of the SD outbred stock between the two sources and represent a significant research variable impacting studies especially related to metabolic diseases. Therefore, in order the minimize research variables for those studies where genetic diversity is not a basis for experimental design, the use of single source genetically uniform inbred animal models is highly recommended over the use of outbred stocks. PMID:26755919

  9. Inhalation toxicity and carcinogenicity of 1,3-butadiene in Sprague-Dawley rats.

    PubMed Central

    Owen, P E; Glaister, J R

    1990-01-01

    A 2-year inhalation study was conducted in Sprague-Dawley rats with 1,3-butadiene. Groups of 110 male and 110 female rats inhaled 1,3-butadiene at 0, 1000, or 8000 ppm for 6hr/day, 5 days/week. Interim clinical pathology, neuromuscular, and histopathology investigations were carried out. The study terminated at 20 to 25% survival (105 weeks for females, 111 weeks for males). Following exposure to 1,3-butadiene there were no effects on hematology, blood chemistry, urine analysis, and neuromuscular function that definitely could be associated with treatment. Treatment was associated with changes in clinical condition, suppression of body weight gain, reduced survival, and increases in certain organ weights and in both common and uncommon tumor types. Although the biological interpretation of the significance of some of the tumor types is equivocal, the evidence suggests that the test article is an oncogen to the rat under the conditions of exposure used in this study, and the mechanism is more likely to be an indirect effect through the endocrine system, rather than a direct effect through the production of reactive metabolites. PMID:2401255

  10. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition.

    PubMed

    Engler-Chiurazzi, Elizabeth B; Stapleton, Phoebe A; Stalnaker, Jessica J; Ren, Xuefang; Hu, Heng; Nurkiewicz, Timothy R; McBride, Carroll R; Yi, Jinghai; Engels, Kevin; Simpkins, James W

    2016-01-01

    It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole-body nanoparticle inhalation facility, pregnant Sprague-Dawley rats (gestational day [GD] 7) were exposed 4 d/wk to either filtered air (control) or nano-titanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9 ± 6.4 nm, 10.4 ± 0.4 mg/m(3), 5 h/d) for 7.8 ± 0.5 d of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9 ± 0.5 µg. Subsequently, at 5 mo of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats.

  11. Sex differences in MDMA-induced toxicity in Sprague-Dawley rats.

    PubMed

    Soleimani Asl, Sara; Mehdizadeh, Mehdi; Hamedi Shahraki, Soudabeh; Artimani, Tayebeh; Joghataei, Mohammad Taghi

    2015-01-01

    Recent evidence demonstrates that female subjects show exaggerated responses to 3,4-methylenedioxymethamphetamine (MDMA) compared with males. The aim of our study was to evaluate sex differences and the role of endogenous gonadal hormones on the effects of MDMA. Fifty-six intact and gonadectomized male and female Sprague-Dawley rats were randomly assigned to either MDMA (5 mg/kg) or saline treatment. Learning and memory were assessed using the Morris water maze (MWM). The expression of Bax and Bcl-2 in the hippocampus was detected by Western blotting. Behavioral analysis showed that MDMA led to memory impairment in both male and female rats. The female rats showed more sensitivity to impairment than the males, as assessed using all the memory parameters in the MWM. Ovariectomy attenuated the MDMA-induced memory impairment. By contrast, orchiectomized rats showed more impairment than MDMA-treated intact male rats. Bcl-2 and Bax were down-regulated and up-regulated in MDMA-treated male and female rats, respectively. MDMA treatment in the orchiectomized rats led to upregulation of Bax and down-regulation of Bcl-2. Ovariectomy attenuated the MDMA-induced up-regulation of Bax and caused more expression of Bcl-2 compared with what was observed in the MDMA-treated intact female rats. In summary, female rats showed exaggerated responses to the effects of MDMA and this may be explained by endogenous gonadal hormones. PMID:26415786

  12. Pathophysiological differences between paired and communal breeding of male and female Sprague-Dawley rats.

    PubMed

    Wexler, B C; Greenberg, B P

    1978-01-01

    Sexually mature, male and female Sprague-Dawley rats were housed in large communal breeding cages or in smaller paired breeding cages. Virgin control rats of the same age were housed similarly but segregated by sex. Breeders became obese, developed a fatty liver, and showed elevated levels of triglycerides, free fatty acids, and cholesterol. Breeders had high blood pressure, enlarged hearts, hyperglycemia, and islet beta cell degranulation. Serum enzymes, creatine phosphokinase, serum glutamic oxalo-pyruvic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, and blood urea nitrogen levels were elevated in breeder rats. The adrenal glands of male breeders appeared hyperactive; the adrenal glands of female breeders were thrombosed and appeared to be hypoactive. Male breeder rats developed microscopic aortic lesions only; female breeders developed advanced calcific aortic sclerosis. Male breeders kept in active stud service manifested the most abnormal metabolic and pathophysiological changes. Female breeders developed similar pathophysiological changes after four pregnancies, irrespective of their paired or communal breeding environment. Virgin rats were normal regardless of housing conditions. Our findings suggest that repeated breeding in male and female rats causes resetting of the hypothalamic-pituitary-adrenal-gonadal axis. This may lead to disturbed hormonal and metabolic changes which culminate with the development of accelerated cardiovascular degenerative changes.

  13. Cyclocarya paliurus prevents high fat diet induced hyperlipidemia and obesity in Sprague-Dawley rats.

    PubMed

    Yao, Xiaoming; Lin, Zi; Jiang, Cuihua; Gao, Meng; Wang, Qingqing; Yao, Nan; Ma, Yonglan; Li, Yue; Fang, Shengzuo; Shang, Xulan; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2015-08-01

    Cyclocarya paliurus (CP; qing qian liu), which is used as an herbal tea in China, has been confirmed to have therapeutic effects on hyperlipidemia and obesity, and therefore it is widely consumed to prevent metabolic diseases such as hyperlipidemia and diabetes. In this study, we investigated the preventive effects of CP on obesity and hyperlipidemia, as well as the underlying mechanisms involved in intestinal secretion of apolipoprotein (apo) B48. Sprague-Dawley rats were fed a high-fat diet (HFD) and with or without various concentrations of an ethanol extract of CP (CPE; 2, 4, or 8 g·(kg body mass)(-1)) administered by gavage for 8 weeks. From the results we see that CPE dose-dependently blocked increases in body mass, and decreased food utilization as well as visceral fat mass. Decreased serum levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol, and elevated levels of high density lipoprotein cholesterol, as well as lowered levels of total cholesterol and triglycerides in the liver were also noticed in CPE-treated rats. Magnetic resonance images indicated that the abnormal fat storage induced by the HFD was obviously suppressed by CPE. In addition, ELISA analysis showed reduced fasting serum apoB48 in the CPE treatment groups. Based on the above results, CPE shows a promising preventive effect on obesity and hyperlipidemia, partially through suppressing intestinal apoB48 overproduction.

  14. Sub-acute toxicity studies of acetaminophen in Sprague Dawley rats.

    PubMed

    Venkatesan, Pachaiyappan Sampath; Deecaraman, Munuswamy; Vijayalakshmi, Melanathuru; Sakthivelan, Sigamany Masilamani

    2014-01-01

    The aim of the present study was to evaluate the sub-acute oral toxicity of acetaminophen in Sprague Dawley (SD) rats at 250 to 1000 mg/kg body weight (b.wt.). The following observations were noticed during the study. No mortality in male and female rats, at and up to the dose of 1000 mg/kg b.wt. There were abnormal clinical signs observed on female animals at 1000 mg/kg b.wt. dose level. There were no difference in body weight gain and no effect on the daily feed consumption. No toxicologically significant effect on the haematological parameters but liver and kidney related biochemical parameter showed significant difference at 1000 mg/kg b.wt. in females. No toxicologically significant effect on the urinalysis parameters, absolute and relative organ weights and gross pathological alterations; whereas histopathological alterations were observed in female liver at dose level of 1000 mg/kg b.wt. were observed. Based on the findings of this study, the No Observed Adverse Effect Level (NOAEL) of acetaminophen in SD rats, following oral administration at the doses of 250, 500 and 1000 mg/kg on daily basis was found to be 500 mg/kg b.wt.

  15. Cyclocarya paliurus prevents high fat diet induced hyperlipidemia and obesity in Sprague-Dawley rats.

    PubMed

    Yao, Xiaoming; Lin, Zi; Jiang, Cuihua; Gao, Meng; Wang, Qingqing; Yao, Nan; Ma, Yonglan; Li, Yue; Fang, Shengzuo; Shang, Xulan; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2015-08-01

    Cyclocarya paliurus (CP; qing qian liu), which is used as an herbal tea in China, has been confirmed to have therapeutic effects on hyperlipidemia and obesity, and therefore it is widely consumed to prevent metabolic diseases such as hyperlipidemia and diabetes. In this study, we investigated the preventive effects of CP on obesity and hyperlipidemia, as well as the underlying mechanisms involved in intestinal secretion of apolipoprotein (apo) B48. Sprague-Dawley rats were fed a high-fat diet (HFD) and with or without various concentrations of an ethanol extract of CP (CPE; 2, 4, or 8 g·(kg body mass)(-1)) administered by gavage for 8 weeks. From the results we see that CPE dose-dependently blocked increases in body mass, and decreased food utilization as well as visceral fat mass. Decreased serum levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol, and elevated levels of high density lipoprotein cholesterol, as well as lowered levels of total cholesterol and triglycerides in the liver were also noticed in CPE-treated rats. Magnetic resonance images indicated that the abnormal fat storage induced by the HFD was obviously suppressed by CPE. In addition, ELISA analysis showed reduced fasting serum apoB48 in the CPE treatment groups. Based on the above results, CPE shows a promising preventive effect on obesity and hyperlipidemia, partially through suppressing intestinal apoB48 overproduction. PMID:26203820

  16. Single dose toxicity study of IRDye 800CW in Sprague-Dawley rats

    NASA Astrophysics Data System (ADS)

    Marshall, Milton V.; Draney, Daniel; Sevick-Muraca, Eva M.; Olive, D. Michael

    2010-02-01

    Fluorophore-labeled contrast imaging agents are moving toward clinical use as aids in nodal staging and intraoperative resection of tumors. Near-infrared fluorophores with defined toxicity properties will be needed before these agents can be translated to the clinic. The near-infrared dye IRDye 800CW is frequently used in its N-hydroxysuccinamide (NHS) ester form for labeling these agents. Following conjugation or breakdown of a labeled ligand, excess NHS ester is converted to the carboxylate form. We report here the results of a preliminary toxicity study on IRDye 800CW carboxylate in preparation for its use as a labeling moiety for targeted contrast agents. Male and female Sprague Dawley rats were given a single intravenous or intradermal administration of IRDye 800CW carboxylate; indocyanine green was used as a comparative control. Following administration of varying doses of either the dyes or saline, animals were observed for up to fourteen days during which time, hematological, clinical chemistry, enzymological, and histological testing was performed on animal subgroups. Under the conditions tested, a single administration of IRDye 800CW carboxylate intravenously at dose levels of 1, 5 and 20 mg/kg or 20 mg/kg intradermally produced no pathological evidence of toxicity. A dose of 20 mg/kg was identified as the NOAEL (no observed adverse effect level) following IV or ID routes of administration of IRDye 800CW.

  17. Immunotoxicological effects of benzene inhalation in male Sprague-Dawley rats.

    PubMed

    Robinson, S N; Shah, R; Wong, B A; Wong, V A; Farris, G M

    1997-05-16

    The inhalation of benzene is toxic to various components of the immunologic system in rodents. Spleen and thymus weights, total spleen and femur marrow cell counts, enumeration of spleen B- and T-lymphocytes, and an assessment of humoral immunocompetence, were used to evaluate the immunotoxicity of benzene in male Sprague-Dawley rats. Rats were exposed to 0, 30, 200 or 400 ppm benzene for 6 h/day, 5 days/week for 2 or 4 weeks. An early indicator of immunotoxicity was a reduction in the number of B-lymphocytes after 2 weeks of 400 ppm. After 4 weeks of 400 ppm, there was a reduction in thymus weight and spleen B-, CD4+/CD5+ and CD5+ T-lymphocytes. Rats exposed to 30, 200 or 400 ppm benzene for 2 or 4 weeks and challenged with sheep red blood cells developed a humoral response comparable to that of the control (0 ppm) animals. Enumeration of spleen T- and B-lymphocytes in rats exposed to benzene and challenged with SRBC showed only a transient reduction in spleen B-lymphocytes after 2 weeks of exposure to 400 ppm. These data suggest that there are no immunotoxicological effects of exposure to 200 ppm benzene or less, in rats exposed for 6 h/day, 5 days/week for 2 or 4 weeks.

  18. In vivo mammary tumourigenesis in the Sprague-Dawley rat and microdosimetric correlates.

    PubMed

    Dicello, J F; Christian, A; Cucinotta, F A; Gridley, D S; Kathirithamby, R; Mann, J; Markham, A R; Moyers, M F; Novak, G R; Piantadosi, S; Ricart-Arbona, R; Simonson, D M; Strandberg, J D; Vazquez, M; Williams, J R; Zhang, Y; Zhou, H; Huso, D

    2004-08-21

    Standard methods for risk assessments resulting from human exposures to mixed radiation fields in Space consisting of different particle types and energies rely upon quality factors. These are generally defined as a function of linear energy transfer (LET) and are assumed to be proportional to the risk. In this approach, it is further assumed that the risks for single exposures from each of the radiation types add linearly. Although risks of cancer from acute exposures to photon radiations have been measured in humans, quality factors for protons and ions of heavier atomic mass are generally inferred from animal and/or cellular data. Because only a small amount of data exists for such particles, this group has been examining tumourigenesis initiated by energetic protons and iron ions. In this study, 741 female Sprague-Dawley rats were irradiated or sham irradiated at approximately 60 days of age with 250 MeV protons, 1 GeV/nucleon iron ions or both protons and iron ions. The results suggest that the risk of mammary tumours in the rats sequentially irradiated with 1 GeV/nucleon 56Fe ions and 250 MeV protons is less than additive. These data in conjunction with earlier results further suggest that risk assessments in terms of only mean LETs of the primary cosmic rays may be insufficient to accurately evaluate the relative risks of each type of particle in a radiation field of mixed radiation qualities. PMID:15446807

  19. Developmental neurotoxicity of polybrominated diphenyl ethers mixture de71 in Sprague-Dawley rats.

    PubMed

    Gill, Santokh; Hou, Yangxun; Li, Nanqin; Pulido, Olga; Bowers, Wayne

    2016-01-01

    Polybrominated diphenyl ethers (PBDE) are a class of brominated flame retardants that are recognized as global environmental contaminants and a potential adverse health risk. The objective of this study was to evaluate the developmental impacts on rat Sprague-Dawley (SD) pups at postnatal day (PND) 11, 21, 50, 105, and 250 after perinatal exposure to a DE71 mixture. These PNDs corresponded to juveniles, young, and mature adults, respectively. The analysis included histopathological, transcriptional evaluation, and Western blots in both hippocampus and midbrain. There were no marked histopathological changes, but significant transcriptional alterations were observed at PND 21 and 250 in midbrain. These changes occurred in a number of the markers of the cholinergic system, including acetylcholinesterase, muscarinic and nicotinic receptors, and structural gene,s including those of neurofilaments, cell adhesion molecules including N-cadherin and CAMKII, and cytokines. The markers were upregulated at least twofold or greater at PND 21. These biomarkers were predominantly altered in males at low dose (0.3 mg/kg), whereas females were affected only at high concentration (30 mg/kg). At PND 250 both males and females showed downregulation of markers in both intermediate- and high-dose groups. Our results support the findings that in utero and lactational exposure to DE71 mixture leads to transcriptional alterations in midbrain of adult SD rats. PMID:27294297

  20. Differences in performance between Sprague-Dawley and Fischer 344 rats in positive reinforcement tasks.

    PubMed

    Rodriguez, Jesse S; Boctor, Sherin Y; Phelix, Clyde F; Martinez, Joe L

    2008-03-01

    This experimental investigation tested two different strains of rat, Sprague-Dawley (SD) and Fischer 344 (F344), in their ability to learn lever pressing for food (autoshaping) or intracranial self-administration (ICSA) of dextroamphetamine (AMPH) into the nucleus accumbens (NAcc). Additionally, a unique method of intracranial drug delivery was utilized, via reverse dialysis, by the use of a microdiaylsis probe. The experiments revealed definite behavioral differences between SD and F344 animals. The autoshaping data indicated that SD rats, on average, acquired lever pressing for food in fewer training days than F344 rats. Also, the ICSA experiment revealed that SD rats self-administered AMPH at a 30 mug/mul concentration. Lever pressing was significantly greater in those SD rats receiving AMPH than in the F344 drug group. Furthermore, the F344 rats never acquired lever pressing for intra-NAcc delivery of AMPH under our testing regime. These data reveal differences in performance of positively reinforced operant tasks between the inbred F344 rats as compared to the outbred SD strain.

  1. Evidence of thyroxine formation following iodine administration in Sprague-Dawley rats

    NASA Technical Reports Server (NTRS)

    Thrall, K. D.; Sauer, R. L.; Bull, R. J.

    1992-01-01

    Iodine (I2) has been proposed to be used as a water disinfectant on the manned space station. Previous work has shown that subchronic administration of I2 to Sprague-Dawley rats in drinking water significantly increases plasma thyroxine/triiodothyronine (T4/T3) levels. This is not observed with iodide (I-) treatment. The present study addresses the possibility that I2 reacts with deiodinated T4 metabolites in the gastrointestinal tract to resynthesize T4. Incubation of diiodothyronine (T2), T3, or reverse T3 with I2 in phosphate-buffered saline resulted in the formation of T4 as measured by radioimmunoassay. Washes from the initial segments of the small intestine of the rat show that substrates are present that react with I2 to produce T4. Single oral doses of I2 to rats produced significant dose-related increases in serum T4 and decreases in T3 concentrations after 2 h. Administration of an equivalent dose of I- did not alter significantly plasma T4 concentrations. Higher concentrations of a radioactive substance that bound a T4-specific antibody are present in plasma of animals treated with 125I2 compared to 125I-. These data support the hypothesis that I2 reacts with metabolites of thyroid hormone in the gastrointestinal tract to resynthesize T4 and elevate its levels in blood.

  2. Effects of dietary supplements on space radiation-induced oxidative stress in Sprague-Dawley rats.

    PubMed

    Guan, Jun; Wan, X Steven; Zhou, Zhaozong; Ware, Jeffrey; Donahue, Jeremiah J; Biaglow, John E; Kennedy, Ann R

    2004-11-01

    Of particular concern for the health of astronauts during space travel is radiation from protons and high-mass, high-atomic-number (Z), and high-energy particles (HZE particles). Space radiation is known to induce oxidative stress in astronauts after extended space flight. In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by gamma rays, protons and HZE-particle radiation. The results demonstrate that the plasma level of total antioxidants in Sprague-Dawley rats was significantly decreased (P < 0.01) in a dose-dependent manner within 4 h after exposure to gamma rays. Exposure to protons and HZE-particle radiation also significantly decreased the serum or plasma level of total antioxidants in the irradiated animals. Diet supplementation with L-selenomethionine alone or a combination of selected antioxidant agents was shown to partially or completely prevent the decrease in the serum or plasma levels of total antioxidants in animals exposed to gamma rays, protons or HZE particles. These findings suggest that exposure to space radiation may compromise the capacity of the host antioxidant defense and that this adverse biological effect can be prevented at least partially by dietary supplementation with L-selenomethionine and antioxidants. PMID:15624312

  3. Sex differences in MDMA-induced toxicity in Sprague-Dawley rats.

    PubMed

    Soleimani Asl, Sara; Mehdizadeh, Mehdi; Hamedi Shahraki, Soudabeh; Artimani, Tayebeh; Joghataei, Mohammad Taghi

    2015-01-01

    Recent evidence demonstrates that female subjects show exaggerated responses to 3,4-methylenedioxymethamphetamine (MDMA) compared with males. The aim of our study was to evaluate sex differences and the role of endogenous gonadal hormones on the effects of MDMA. Fifty-six intact and gonadectomized male and female Sprague-Dawley rats were randomly assigned to either MDMA (5 mg/kg) or saline treatment. Learning and memory were assessed using the Morris water maze (MWM). The expression of Bax and Bcl-2 in the hippocampus was detected by Western blotting. Behavioral analysis showed that MDMA led to memory impairment in both male and female rats. The female rats showed more sensitivity to impairment than the males, as assessed using all the memory parameters in the MWM. Ovariectomy attenuated the MDMA-induced memory impairment. By contrast, orchiectomized rats showed more impairment than MDMA-treated intact male rats. Bcl-2 and Bax were down-regulated and up-regulated in MDMA-treated male and female rats, respectively. MDMA treatment in the orchiectomized rats led to upregulation of Bax and down-regulation of Bcl-2. Ovariectomy attenuated the MDMA-induced up-regulation of Bax and caused more expression of Bcl-2 compared with what was observed in the MDMA-treated intact female rats. In summary, female rats showed exaggerated responses to the effects of MDMA and this may be explained by endogenous gonadal hormones.

  4. Prenatal developmental toxicity studies on diundecyl and ditridecyl phthalates in Sprague-Dawley rats.

    PubMed

    Saillenfait, Anne-Marie; Gallissot, Frédéric; Sabaté, Jean-Philippe; Remy, Aurélie

    2013-06-01

    This study evaluates the developmental toxicity of two high molecular weight dialkyl phthalate esters, diundecyl phthalate (DUDP) and ditridecyl phthalate (DTDP). Sprague-Dawley rats were administered 0, 0.25, 0.50, or 1g/kg/day of DUDP or DTDP, by gavage, on gestation days 6-20. DUDP and DTDP had no adverse effects on maternal body weight and food consumption. The number of live fetuses, percent of post-implantation loss and of resorptions, fetal sex, and fetal body weights were not affected by either phthalate. There was no evidence of teratogenicity, whatever treatment. Small decreases in the anogenital distance of male fetuses were noted at 0.5 and 1g DUDP/kg/day. The incidence of fetuses with supernumerary lumbar ribs was significantly higher than control at 0.5 and 1g DUDP/kg/day. Thus, DTDP was not developmentally toxic up to 1g/kg/day and there were signs of DUDP-induced fetal effects at 0.5 and 1g/kg/day.

  5. Niacin (nicotinic acid) in non-physiological doses causes hyperhomocysteineaemia in Sprague-Dawley rats.

    PubMed

    Basu, Tapan K; Makhani, Neelam; Sedgwick, Gary

    2002-02-01

    Niacin (nicotinic acid) in its non-physiological dose level is known to be an effective lipid-lowering agent; its potential risk as a therapeutic agent, however, has not been critically considered. Since niacin is excreted predominantly as methylated pyridones, requiring methionine as a methyl donor, the present study was undertaken to examine whether metabolism of the amino acid is altered in the presence of large doses of niacin. Male Sprague-Dawley rats were given a nutritionally adequate, semi-synthetic diet containing niacin at a level of either 400 or 1000mg/kg diet (compared to 30mg/kg in the control diet) for up to 3 months. Supplementation with niacin (1,000 mg/kg diet) for 3 months resulted in a significant increase in plasma and urinary total homocysteine levels; this increase was further accentuated in the presence of a high methionine diet. The hyperhomocysteineaemia was accompanied by a significant decrease in plasma concentrations of vitamins B6 and B12, which are cofactors for the metabolism of homocysteine. The homocysteine-raising action of niacin, in particular, has an important toxicological implication, as hyperhomocysteineaemia is considered to be an independent risk factor for arterial occlusive disease. The niacin-associated change in homocysteine status may be an important limiting factor in the use of this vitamin as a lipid-lowering agent.

  6. Red Palm Oil Attenuates Lead Acetate Induced Testicular Damage in Adult Male Sprague-Dawley Rats.

    PubMed

    Jegede, A I; Offor, U; Azu, O O; Akinloye, O

    2015-01-01

    To study the protective effect of Red Palm Oil (RPO) on testicular damage induced by administration of lead acetate on male Sprague-Dawley rats, 28 rats divided into four groups of 7 animals each were used. They were administered orally with RPO (1 mL and 2 mL) and lead acetate (i.p.) 6 mg/kg body weight/day, respectively. Treatment was conducted for 8 weeks, and 24 hrs after the last treatment the rats were sacrificed using cervical dislocation. Sperms collected from epididymis were used for seminal fluid analyses; while the testes sample was used for ROS and oxidative enzyme activities assessment. Statistical analysis was carried out using GraphPad Prism 5.02 statistical analysis package. Administration of lead acetate increased generation of reactive oxygen species (ROS) significantly (p < 0.05) as evidenced by the elevated value of H2O2 and LPO and decreased GSH level. Also there was reduced epididymal sperm count, poor grade of sperm motility, and lower percentage of normal sperm morphology significantly. Coadministration with RPO, however, has a protective effect against lead toxicity by decreasing H2O2 production, increased GSH level, and increased sperm qualities especially. This shows that RPO has a potential to attenuate the toxic effect of lead on testicular cells preventing possible resultant male infertility. PMID:26516332

  7. Red Palm Oil Attenuates Lead Acetate Induced Testicular Damage in Adult Male Sprague-Dawley Rats

    PubMed Central

    Jegede, A. I.; Offor, U.; Azu, O. O.; Akinloye, O.

    2015-01-01

    To study the protective effect of Red Palm Oil (RPO) on testicular damage induced by administration of lead acetate on male Sprague-Dawley rats, 28 rats divided into four groups of 7 animals each were used. They were administered orally with RPO (1 mL and 2 mL) and lead acetate (i.p.) 6 mg/kg body weight/day, respectively. Treatment was conducted for 8 weeks, and 24 hrs after the last treatment the rats were sacrificed using cervical dislocation. Sperms collected from epididymis were used for seminal fluid analyses; while the testes sample was used for ROS and oxidative enzyme activities assessment. Statistical analysis was carried out using GraphPad Prism 5.02 statistical analysis package. Administration of lead acetate increased generation of reactive oxygen species (ROS) significantly (p < 0.05) as evidenced by the elevated value of H2O2 and LPO and decreased GSH level. Also there was reduced epididymal sperm count, poor grade of sperm motility, and lower percentage of normal sperm morphology significantly. Coadministration with RPO, however, has a protective effect against lead toxicity by decreasing H2O2 production, increased GSH level, and increased sperm qualities especially. This shows that RPO has a potential to attenuate the toxic effect of lead on testicular cells preventing possible resultant male infertility. PMID:26516332

  8. Histopathological evaluation of liver, pancreas, spleen, and heart from iron-overloaded Sprague-Dawley rats.

    PubMed

    Whittaker, P; Hines, F A; Robl, M G; Dunkel, V C

    1996-01-01

    The effects of increasing dietary levels of Fe on the histopathology of liver, pancreas, spleen, and heart were examined in a rat model for iron overload. Sprague-Dawley rats were fed diets containing 35, 350, 3,500, or 20,000 micrograms Fe/g, and, after 12 wk, there was a direct correlation between increased liver nonheme Fe and lipid peroxidation measured by the lipid-conjugated diene assay. Histopathological examination of tissues revealed the following: (a) hepatocellular hemosiderosis in all groups of rats, with a dose-related accumulation of cytoplasmic Fe-positive material predominantly in hepatocytes located in the periportal region (Zone 1), (b) myocardial degeneration and necrosis (cardiomyopathy) with hemosiderin in interstitial macrophages or in myocardial fibers of animals with heart damage, (c) splenic lymphoid atrophy affecting the marginal zone of the white pulp and hemosiderin deposition in the sinusoidal macrophages, and (d) pancreatic atrophy with loss of both the endocrine and exocrine pancreatic tissue in those animals receiving 3,500 and 20,000 micrograms Fe/g of diet. The toxic effects of Fe overload in this rat model include cellular apoptosis or necrosis in heart, spleen, and pancreas and, when coupled with the findings on lipid peroxidation, suggests that oxidative stress is involved in the pathogenesis of the lesions.

  9. Developmental atrazine exposure suppresses immune function in male, but not female Sprague-Dawley rats.

    PubMed

    Rooney, Andrew A; Matulka, Raymond A; Luebke, Robert W

    2003-12-01

    Each year, 75 million pounds of the broadleaf herbicide atrazine (ATR) are applied to crops in the United States. Despite limited solubility, ATR is common in ground and surface water, making it of regulatory concern. ATR suppresses the immunomodulatory hormones prolactin (PRL) and the thyroid hormones (THs), with developmental exposure to ATR permanently disrupting PRL regulation. We hypothesized that ATR may cause developmental immunotoxicity through its disruption of PRL or THs. To test this hypothesis, pregnant Sprague-Dawley (SD) rats were exposed to 35-mg ATR/kg/d from gestational day (GD) 10 through postnatal day (PND) 23. Separate groups were exposed to bromocryptine (BCR) at 0.2 mg/kg/2x/day to induce hypoprolactinemia or to propylthiouracil (PTU) at 2 mg/kg/day to induce hypothyroidism. After the offspring reached immunologic maturity (at least 7 weeks old), the following immune functions were evaluated: natural killer (NK) cell function; delayed-type hypersensitivity (DTH) responses; phagocytic activity of peritoneal macrophages; and antibody response to sheep erythrocytes (SRBC). ATR decreased the primary antibody and DTH responses in male offspring only. Neither PTU nor BCR caused immunosuppression in any measured variable, although PTU increased phagocytosis by peritoneal macrophages. These results demonstrate that developmental exposure to ATR produced gender-specific changes in immune function in adult rats and suggest that immune changes associated with ATR are not mediated through the suppression of PRL or THs.

  10. Pharmacological mechanisms underlying gastroprotective activities of the fractions obtained from Polygonum minus in Sprague Dawley rats.

    PubMed

    Qader, Suhailah Wasman; Abdulla, Mahmood Ameen; Chua, Lee Suan; Sirat, Hasnah Mohd; Hamdan, Salehhuddin

    2012-01-01

    The leaves of Polygonum minus were fractionated using an eluting solvent to evaluate the pharmacological mechanisms underlying the anti-ulcerogenic activity of P. minus. Different P. minus fractions were obtained and evaluated for their ulcer preventing capabilities using the ethanol induction method. In this study, Sprague Dawley rats weighing 150-200 g were used. Different parameters were estimated to identify the active fraction underlying the mechanism of the gastroprotective action of P. minus: the gastric mucus barrier, as well as superoxide dismutase, total hexosamine, and prostaglandin synthesis. Amongst the five fractions from the ethanolic extract of P. minus, the ethyl acetate:methanol 1:1 v/v fraction (F2) significantly (p < 0.005) exhibited better inhibition of ulcer lesions in a dose-dependent manner. In addition, rats pre-treated with F2 showed a significant elevation in superoxide dismutase (SOD), hexosamine and PGE2 levels in the stomach wall mucosa in a dose-dependent matter. Based on these results, the ethyl acetate:methanol 1:1 v/v fraction was considered to be the best fraction for mucous protection in the ethanol induction model. The mechanisms underlying this protection were attributed to the synthesis of antioxidants and PGE2. PMID:22408403

  11. Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats

    PubMed Central

    Nalabotu, Siva K; Kolli, Madhukar B; Triest, William E; Ma, Jane Y; Manne, Nandini DPK; Katta, Anjaiah; Addagarla, Hari S; Rice, Kevin M; Blough, Eric R

    2011-01-01

    Background Cerium oxide (CeO2) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. Methods and results Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO2 nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO2 nanoparticles. Conclusion Taken together, these data suggest that intratracheal instillation of CeO2 nanoparticles can result in liver damage. PMID:22072870

  12. Impacts of prenatal nanomaterial exposure on male adult Sprague-Dawley rat behavior and cognition.

    PubMed

    Engler-Chiurazzi, Elizabeth B; Stapleton, Phoebe A; Stalnaker, Jessica J; Ren, Xuefang; Hu, Heng; Nurkiewicz, Timothy R; McBride, Carroll R; Yi, Jinghai; Engels, Kevin; Simpkins, James W

    2016-01-01

    It is generally accepted that gestational xenobiotic exposures result in systemic consequences in the adult F1 generation. However, data on detailed behavioral and cognitive consequences remain limited. Using our whole-body nanoparticle inhalation facility, pregnant Sprague-Dawley rats (gestational day [GD] 7) were exposed 4 d/wk to either filtered air (control) or nano-titanium dioxide aerosols (nano-TiO2; count median aerodynamic diameter of 170.9 ± 6.4 nm, 10.4 ± 0.4 mg/m(3), 5 h/d) for 7.8 ± 0.5 d of the remaining gestational period. All rats received their final exposure on GD 20 prior to delivery. The calculated daily maternal deposition was 13.9 ± 0.5 µg. Subsequently, at 5 mo of age, behavior and cognitive functions of these pups were evaluated employing a standard battery of locomotion, learning, and anxiety tests. These assessments revealed significant working impairments, especially under maximal mnemonic challenge, and possible deficits in initial motivation in male F1 adults. Evidence indicates that maternal engineered nanomaterial exposure during gestation produces psychological deficits that persist into adulthood in male rats. PMID:27092594

  13. Single-dose Intramuscular Toxicity of Neutral Natured Blood Stasis Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

    Yeo, In Ho; Lee, Eun Yong

    2014-01-01

    Objectives: This study was performed to analyze the single-dose toxicity of neutral natured blood stasis pharmacopuncture extracts. Methods: All experiments were conducted at Biotoxtech, an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP). Sprague-Dawley rats were chosen for the pilot study. Doses of neutral natured blood stasis pharmacopuncture extracts, 0.1, 0.5 and 1.0 mL, were administered to the experimental group, and the same doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: In all 4 groups, no deaths occurred, and the neutral natured blood stasis pharmacopuncture extracts administered by intramuscular (IM) injection was over 1.0 mL/animal. No significant changes in the body weights between the control group and the experimental group were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any organs or tissues. Conclusion: The above findings suggest that treatment with neutral natured blood stasis pharmacopuncture extracts is relatively safe. Further studies on this subject should be conducted to yield more concrete evidence. PMID:25780698

  14. Macro- and Microelemental Composition and Toxicity of Unsweetened Natural Cocoa Powder in Sprague-Dawley Rats

    PubMed Central

    Frimpong-Manso, Samuel; Abdulai Seidu, Mahmood; Osei-Prempeh, Paul; Kwaku Boamah, Daniel

    2016-01-01

    Unsweetened natural cocoa powder (UNCP) is a pulverized high-grade powder of compressed solid blocks which remains after extraction. Little scientific data is available concerning its safety despite the presence of potential toxic elements. Elemental composition in UNCP was analyzed with ED-XRF spectroscopy. Single oral high dose toxicity study was conducted on adult male Sprague-Dawley rats (150 g) by the limit test method. One group received water and the test group 2000 mg/kg UNCP. All animals were observed for 14 days and then euthanized for haematological, biochemical, and histopathological examinations. Thirty-eight (38) elements were found in UNCP. There was an increase in HDL cholesterol (p < 0.05), reduction in LDL cholesterol (p > 0.05), alkaline phosphatase (p < 0.05), and creatinine levels, and slight increase in urea levels (p > 0.05). Haematological changes were not significant. Histopathological analysis showed no toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Intestinal erosion was observed in the test group. UNCP appears to be relatively safe when taken as a single oral high dose of 2000 mg/kg b.w.t. in rats. Caution should however be exercised at high doses due to the high elemental content of copper and high possibility of intestinal lining erosion.

  15. Teratogenicity study of N-methylpyrrolidone after dermal application to Sprague-Dawley rats.

    PubMed

    Becci, P J; Knickerbocker, M J; Reagan, E L; Parent, R A; Burnette, L W

    1982-01-01

    Teratogenicity studies were performed in rats given N-methylpyrrolidone, a solvent used in chemical processing. Dosages of 75,237 and 750 mg of N-methylpyrrolidone/kg body weight/day were administered dermally to groups of 25 pregnant Sprague-Dawley rats on days 6 through 15 of gestation. Additionally, the study used a positive dermal control. Hexafluoroacetone, was chosen based on its dermal teratogenic activity. An oral positive control, aspirin, was included in order to add significance to the data generated in the experimental positive dermal control group. All animals were killed and subjected to uterine examination on day 20 of gestation. Maternal toxicity was indicated at 750 mg of N-methylpyrrolidone/kg by reduced body weight gain during gestation. Treatment with N-methylpyrrolidone resulted in dose-dependent brightly colored yellow urine and dry skin. Treatment at the high dosage level resulted in fewer live fetuses per dam, an increase in the percentage of resorption sites and skeletal abnormalities. These effects could be the result of maternal toxicity. There was no evidence of teratogenic effects nor effects on the dams at 75 and 237 mg/kg of body weight.

  16. Macro- and Microelemental Composition and Toxicity of Unsweetened Natural Cocoa Powder in Sprague-Dawley Rats.

    PubMed

    Asiedu-Gyekye, Isaac Julius; Frimpong-Manso, Samuel; N'guessan, Benoit Banga; Abdulai Seidu, Mahmood; Osei-Prempeh, Paul; Kwaku Boamah, Daniel

    2016-01-01

    Unsweetened natural cocoa powder (UNCP) is a pulverized high-grade powder of compressed solid blocks which remains after extraction. Little scientific data is available concerning its safety despite the presence of potential toxic elements. Elemental composition in UNCP was analyzed with ED-XRF spectroscopy. Single oral high dose toxicity study was conducted on adult male Sprague-Dawley rats (150 g) by the limit test method. One group received water and the test group 2000 mg/kg UNCP. All animals were observed for 14 days and then euthanized for haematological, biochemical, and histopathological examinations. Thirty-eight (38) elements were found in UNCP. There was an increase in HDL cholesterol (p < 0.05), reduction in LDL cholesterol (p > 0.05), alkaline phosphatase (p < 0.05), and creatinine levels, and slight increase in urea levels (p > 0.05). Haematological changes were not significant. Histopathological analysis showed no toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Intestinal erosion was observed in the test group. UNCP appears to be relatively safe when taken as a single oral high dose of 2000 mg/kg b.w.t. in rats. Caution should however be exercised at high doses due to the high elemental content of copper and high possibility of intestinal lining erosion. PMID:27610134

  17. Variations in Lead Isotopic Abundances in Sprague-Dawley Rat Tissues: Possible Reason of Formation

    PubMed Central

    Liu, Duojian; Wu, Jing; Ouyang, Li; Wang, Jingyu

    2014-01-01

    It has been reported in previous research that the lead isotopic composition of blood, urine and feces samples statistically differed from the given lead sources in Sprague-Dawley (SD) rats. However, the reason for this phenomenon is still unclear. An animal experiment was performed to investigate the lead isotope fractionation in diverse biological samples (i.e., lungs, liver, kidneys, bone) and to explore the possible reasons. SD rats were intratracheally instilled with lead acetate at the concentrations of 0, 0.02, 0.2, and 2 mg/kg body weight. Biological samples were collected for lead isotope analysis using an inductively coupled plasma mass spectrometry (ICP-MS). Significant differences are observed in lead isotope abundances among the diverse biological samples. The lead isotope abundances (206Pb, 207Pb and 208Pb) in diverse biological samples show different degrees and directions of departure from the given lead source. The results suggest that differences in enrichment or depletion capacity for each lead isotope in the various tissues might lead to the variation in lead isotopic abundances in tissues. Moreover, a nonlinear relationship between the blood lead level and the lead isotope abundances in liver and bone is observed. When the whole-blood level is higher than 50 ng/mL, the lead isotopic compositions of biological samples tend to be the same. Thus, the data support the speculation of a fractionation functional threshold. PMID:24587048

  18. Tobramycin-induced changes in renal histology of fetal and newborn Sprague-Dawley rats.

    PubMed

    Mantovani, A; Macrì, C; Stazi, A V; Ricciardi, C; Guastadisegni, C; Maranghi, F

    1992-01-01

    Effects on renal development were studied using tobramycin (TBM) as a model compound. Pregnant Sprague-Dawley rats were injected i.p. with TBM at 30 or 60 mg/kg body weight/day on gestational days (GD) 10-19. Kidneys from dams and conceptuses were examined on GD 20 and on postnatal day (PD) 9. The dosing regimen caused in dams moderate proximal tubular alterations and increased concentrations in serum creatinine. Fetal kidneys showed granularity and swelling of proximal tubule cells at the 30 mg/kg dose, poor glomerular differentiation at the 60 mg/kg dose, increased glomerular density at both doses, and no changes on macroscopic examination at either dose. In newborns were observed a moderate developmental delay and tubular lesions at the higher dose, and dose-related increases of glomerular density and relative medullary area at both doses. All findings were more pronounced in males. A maturational disruption of the tubular structures possibly leading to increased glomerular density was attributed to TBM exposure during renal organogenesis in the rat.

  19. Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats

    PubMed Central

    Patlolla, Anita K.; Randolph, Jonathan; Kumari, S. Anitha; Tchounwou, Paul B.

    2016-01-01

    Recently, graphene and graphene-related materials have attracted a great deal of attention due their unique physical, chemical, and biocompatibility properties and to their applications in biotechnology and medicine. However, the reports on the potential toxicity of graphene oxide (GO) in biological systems are very few. The present study investigated the response of kidneys in male Sprague-Dawley rats following exposure to 0, 10, 20 and 40 mg/Kg GO for five days. The results showed that administration of GOs significantly increased the activities of superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner in the kidneys compared with control group. Serum creatinine and blood urea nitrogen levels were also significantly increased in rats intoxicated with GO compared with the control group. There was a significant elevation in the levels of hydrogen peroxide and lipid hydro peroxide in GOs-treated rats compared to control animals. Histopathological evaluation showed significant morphological alterations of kidneys in GO-treated rats compared to controls. Taken together, the results of this study demonstrate that GO is nephrotoxic and its toxicity may be mediated through oxidative stress. In the present work, however, we only provided preliminary information on toxicity of GO in rats; further experimental verification and mechanistic elucidation are required before GO widely used for biomedical applications. PMID:27043588

  20. Subchronic toxicity study of standardized methanolic extract of Mitragyna speciosa Korth in Sprague-Dawley Rats.

    PubMed

    Ilmie, Mohd U; Jaafar, Hasnan; Mansor, Sharif M; Abdullah, Jafri M

    2015-01-01

    Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days). Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardized methanolic extract of ketum (SMEMS) in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for hematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals. PMID:26136645

  1. Macro- and Microelemental Composition and Toxicity of Unsweetened Natural Cocoa Powder in Sprague-Dawley Rats

    PubMed Central

    Frimpong-Manso, Samuel; Abdulai Seidu, Mahmood; Osei-Prempeh, Paul; Kwaku Boamah, Daniel

    2016-01-01

    Unsweetened natural cocoa powder (UNCP) is a pulverized high-grade powder of compressed solid blocks which remains after extraction. Little scientific data is available concerning its safety despite the presence of potential toxic elements. Elemental composition in UNCP was analyzed with ED-XRF spectroscopy. Single oral high dose toxicity study was conducted on adult male Sprague-Dawley rats (150 g) by the limit test method. One group received water and the test group 2000 mg/kg UNCP. All animals were observed for 14 days and then euthanized for haematological, biochemical, and histopathological examinations. Thirty-eight (38) elements were found in UNCP. There was an increase in HDL cholesterol (p < 0.05), reduction in LDL cholesterol (p > 0.05), alkaline phosphatase (p < 0.05), and creatinine levels, and slight increase in urea levels (p > 0.05). Haematological changes were not significant. Histopathological analysis showed no toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Intestinal erosion was observed in the test group. UNCP appears to be relatively safe when taken as a single oral high dose of 2000 mg/kg b.w.t. in rats. Caution should however be exercised at high doses due to the high elemental content of copper and high possibility of intestinal lining erosion. PMID:27610134

  2. Advantame sweetener preference in C57BL/6J mice and Sprague-Dawley rats.

    PubMed

    Sclafani, Anthony; Ackroff, Karen

    2015-03-01

    Advantame is a new ultrahigh-intensity noncaloric sweetener derived from aspartame and approved for human use. Rats and mice are not attracted to the taste of aspartame and this study determined their preference for advantame. In 24-h choice tests with water, C57BL/6J mice and Sprague-Dawley rats were indifferent to advantame at concentrations of 0.01, 0.03, and 0.1mM but significantly preferred 0.3 and 1mM advantame to water. Both species also preferred 1mM advantame to 1mM saccharin in direct choice tests, but preferred 10mM saccharin to 1mM advantame, which is near the solubility limit for this sweetener. Mice also preferred 1mM advantame to 1mM sucralose or acesulfame K, but preferred both sweeteners at 10mM to 1mM advantame. In addition, mice preferred 1mM advantame to 1 and 10mM aspartame. Thus, advantame is a potent sweetener for rodents but, because of limited solubility, is not an effective alternative to saccharin, sucralose, or acesulfame K at higher concentrations.

  3. Indomethacin attenuates post-suspension hypotension in Sprague-Dawley rats

    NASA Technical Reports Server (NTRS)

    Bayorh, M. A.; Eatman, D.; Wang, M.; Socci, R. R.; Emmett, N.; Thierry-Palmer, M.

    2001-01-01

    Orthostatic hypotension is a serious condition that is sometimes manifested in astronauts during standing postflight. These observations may be related to impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. To evaluate the role of the cyclooxygenase inhibitor indomethacin as a countermeasure against the post-suspension reduction in mean arterial pressure (MAP), we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-hr post-suspension period in conscious male Sprague-Dawley rats. Indomethacin (2 mg/kg) or saline were administered intravenously prior to release from suspension and at 2 and 4 hrs post-suspension. Direct MAP and heart rate were determined prior to suspension, daily and every 2 hrs post-suspension. During suspension, MAP did not change, in contrast, during post-suspension; it decreased compared to parallel non-suspended, untreated animals. There were no significant changes in heart rate. The reduction in MAP post-suspension was associated with significant increases in plasma prostacyclin. Indomethacin attenuated the observed post-suspension reduction in MAP and reduced plasma prostacyclin levels. Also, the baroreflex sensitivity for heart rate was modified by indomethacin--the MAP threshold for baroreflex activation was raised and the effective MAP range expanded. Thus, the post suspension reduction in mean arterial pressure may be due to overproduction of vasodilatory prostaglandins and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.

  4. Post-suspension hypotension is attenuated in Sprague-Dawley rats by prostacyclin synthase inhibition

    NASA Technical Reports Server (NTRS)

    Bayorh, M. A.; Eatman, D.; Walton, M.; Socci, R. R.; Emmett, N.

    2002-01-01

    Cardiovascular deconditioning, sometimes manifested in astronauts during standing postflight, may be related to the impairment of autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, we examined the cardiovascular responses to 7-day 30 degrees tail-suspension and a subsequent 6-h post-suspension period in conscious male Sprague-Dawley rats to determine the role of prostacyclin in the observed post-suspension reduction in mean arterial pressure (MAP). The specific prostacyclin synthase inhibitor U-51605 (0.3 mg/kg), or saline, was administered intravenously prior to release from suspension and at 2 and 4 h post-suspension. During 7 days of suspension, MAP did not change, however, there was a post-suspension reduction in MAP which was associated with significant increases in plasma prostacyclin and nitric oxide. U-51605 attenuated the observed post-suspension hypotension and reduced plasma prostacyclin levels, but not nitric oxide levels. The baroreflex sensitivity for heart rate was modified by U-51605: increased MAP threshold and effective MAP range. Thus, the post-suspension reduction in mean arterial pressure may be due to overproduction of prostacyclin and/or other endothelium-dependent relaxing factors and alteration in baroreflex activity.

  5. NOS II inhibition attenuates post-suspension hypotension in Sprague-Dawley rats

    NASA Technical Reports Server (NTRS)

    Eatman, D.; Walton, M.; Socci, R. R.; Emmett, N.; Bayorh, M. A.

    2003-01-01

    The reduction in mean arterial pressure observed in astronauts may be related to the impairment of autonomic function and/or excessive production of endothelium-derived relaxing factors. Here, we examined the role of a nitric oxide synthase II (NOS II) inhibitor AMT (2-amino-dihydro-6-methyl-4H-1,3-thiazine) against the post-suspension reduction in mean arterial pressure (MAP) in conscious male Sprague-Dawley rats. Direct MAP and heart rate were determined prior to tail-suspension, daily during the 7-day suspension and every 2 hrs post-suspension. Prior to release from suspension and at 2 and 4 hrs post-suspension, AMT (0.1 mg/kg), or saline, were administered intravenously. During the 7-day suspension, MAP was not altered, nor were there significant changes in heart rate. The reduction in MAP post-suspension in saline-treated rats was associated with significant increases in plasma nitric oxide and prostacyclin. 2-Amino-dihydro-6-methyl4H-1,3-thiazine reduced plasma nitric oxide levels, but not those of prostacyclin, attenuated the observed post-suspension reduction in MAP and modified the baroreflex sensitivity for heart rate. Thus, the post suspension reduction in mean arterial pressure is due, in part, to overproduction of nitric oxide, via the NOS II pathway, and alteration in baroreflex activity.

  6. Six months chronic toxicological evaluation of naringin in Sprague-Dawley rats.

    PubMed

    Li, Peibo; Wang, Sheng; Guan, Xiaolin; Cen, Xiaobo; Hu, Chunyan; Peng, Wei; Wang, Yonggang; Su, Weiwei

    2014-04-01

    Naringin is a flavonoid showing variable pharmacological properties and is distributed ubiquitously in plant foods. There is a paucity of reported data regarding its safety profile. In the present study, chronic toxicity studies of naringin was designed and conducted by oral gavage at doses of 0, 50, 250 and 1250 mg/kg in Sprague-Dawley (SD) rats for six months followed by 1-month recovery period. During the 6-month treatment period and one month recovery period, no mortality and toxicologically significant changes in clinical signs, opthalmoscopic examination, hematology, clinical biochemistry, serumsexhormone, macroscopic findings, organ weights and histopathological examination were noted and attributed to naringin administration. Although consecutive and/or isolated periods of significant body weights and food consumption decreases were relevant to naringin administration, they were not considered toxicologically significant. In addition, slight, non-pathological and reversible hair loss was noted during the 6-month treatment period and considered as a kind of change possibly relevant to naringin administration; however, it was not considered adverse change and to be of toxicological significance. Based on the results of this study, the no-observed-adverse-effect-level (NOAEL) of naringin in rats is greater than 1250 mg/kg/day when administered orally for 6 consecutive months. PMID:24462649

  7. Decreased reproductive effects from snakeweed (Gutierrezia microcephala) in Sprague-Dawley rats with increased dietary snakeweed consumption.

    PubMed

    Staley, E C; Smith, G S; Greenberg, J A

    1996-08-01

    Sprague-Dawley rats have been used to study the pathogenesis and toxicokinetics of snakeweed (Gutierrezia microcephala and G sarothrae) toxicosis. Diets containing as little as 10% snakeweed (SW) will induce early embryonic toxicosis and abortion in Sprague-Dawley rats. The sc administration of safflower oil to inseminated female rats will provide protection/tolerance against SW embryotoxins. Two studies evaluated this embryotoxin protection. In the first study, an increase in daily consumption of SW resulted in increased embryo-fetal survival in the SW-containing diet+saline group from 0% in previous studies to 35%. In the second study, once again an increase in diet consumption was associated with 40% of the females in the SW-containing diet+saline group carrying litters to term. PMID:8829342

  8. Cardiovascular changes in unanesthetized and ketamine-anesthetized Sprague-Dawley rats exposed to 2. 8-GHz radiofrequency radiation

    SciTech Connect

    Jauchem, J.R.; Frei, M.R. )

    1991-01-01

    Sprague-Dawley rats were exposed to 2.8-GHz radiofrequency radiation, first while unanesthetized and then while anesthetized with ketamine (150 mg/kg.I.M.). Irradiation at a power density of 60 mW/cm2 (whole-body average specific absorption rate of approximately 14 W/kg) was conducted for sufficient duration to increase colonic temperature from 38.5 to 39.5 degrees C. The time required for the temperature increase was significantly longer in the anesthetized state. During irradiation, heart rate increased significantly both with and without anesthesia, while mean arterial blood pressure increased only when the rats were unanesthetized. The heart rate increase in the anesthetized state contrasts with a lack of change in a previous study of Fischer rats. This difference between anesthetized Sprague-Dawley and Fischer rats should be considered when comparing cardiovascular data obtained from these two strains of rats.

  9. Comparison of the carcinogenicity of methylazoxymethanol-beta-D-glucosiduronic acid in conventional and germfree Sprague-Dawley rats.

    PubMed

    Laqueur, G L; Matsumoto, H; Yamamoto, R S

    1981-11-01

    Methylazoxymethanol-beta-D-glucosiduronic acid (MAM-GlcUA) was administered to young adult male Sprague-Dawley rats by oral and ip routes. Most neoplasms developed in rats that had received the compound orally. The most prevalent site for the neoplasms was the intestinal tract, predominantly the colon. Comparatively fewer tumors occurred in the liver and kidneys. Germfree rats did not develop tumors when MAM-GlcUA was administered either orally or ip.

  10. Differential organization of male copulatory patterns in high- and low-yawning-frequency sublines versus outbred Sprague-Dawley rats.

    PubMed

    Eguibar, Jose R; Cortes, Carmen; Toriz, Cesar G; Romero-Carbente, Jose C; González-Flores, Oscar; Fernández-Guasti, Alonso

    2016-01-01

    The temporal organization of masculine sexual behavior in rats is highly stereotyped; involving a sequence of mounts, intromissions and ejaculations. Sexual behavior has been described in exogamic and genetically manipulated rodent species. In this work, we compare the male sexual behavior of outbred Sprague-Dawley (SD) to those of rats inbred for high (HY)- and low (LY)- spontaneous yawning frequency. In the first experiment, the percentage of inexperienced rats' ejaculatory behavior is significantly lower in the HY and LY respect to Sprague-Dawley rats. The latency to ejaculate for inexperienced HY was shorter than the LY and SD rats. In the second experiment, we examined the differences between inbred sublines and Sprague-Dawley rats once the subjects had become sexually experienced after four copulatory sessions. HY rats still have slower proportion of ejaculators respect to LY and SD rats. Additionally, postejaculatory latencies were longer for HY rats, with longer intercopulatory intervals and higher number of copulatory bouts that delayed ejaculation. Both sublines show lower copulatory efficiency respect to SD rats. In conclusion, both sublines show alterations in the temporal organization of sexual motor pattern that are due at least partially to strong inbreeding process to select them.

  11. Single-dose Intramuscular Injection Toxicology of Danggui Pharmacopuncture (DGP) in Sprague-Dawley Rats

    PubMed Central

    Sun, SeungHo; Jeong, JongJin; Park, Sunju; Lee, KwangHo; Yu, JunSang; Seo, Hyung-Sik; Kwon, KiRok

    2015-01-01

    Objectives: The purpose of the study is to assess both the approximate lethal dose and the single dose intramuscular injection toxicity of Danggui (Angelica gigantis radix) pharmacopuncture (DGP) in Sprague-Dawley (SD) rats. Methods: The experiments were conducted at the good laboratory practice (GLP) laboratory, Biotoxtech Co., which is a laboratory approved by the ministry of food and drug safety (MFDS). The study was performed according to the GLP regulation and the toxicity test guidelines of the MFDS (2009) after approval of the institutional animal care and use committee of Biotoxtech. Single doses of DGP were injected intramuscularly into the rats in three test groups of 6 week old SD rats (5 male and 5 female rats per groups) in the amounts of 0.1, 0.5, and 1.0 mL/animal for groups 2, 3, and 4, respectively, and normal saline solution in the amount of 1.0 mL/animal was injected intramuscularly into the rats (5 male and 5 female rats) in the control group. Observations of the general symptoms and weight measurements were performed during the 14 day observation period after the injection. Hematologic and serum biochemical examination, necropsy, and a local tolerance test at the injection site were done after the observation period. Results: No death was observed in three test groups (0.1, 0.5 and 1.0 mL/animal group). In addition, the injection of DGP had no effect on general symptoms, weights, hematologic and serum biochemical examination, and necropsy. The results from the local tolerance tests at injection site showed no treatment related effects in the SD rats. Conclusion: The results of single dose intramuscular injection of DGP suggest that the approximate lethal dose is above 1.0 mL/animal for both male and female SD rats and that intramuscular injection of DGP may be safe. PMID:25830059

  12. Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmcopuncture in Sprague-Dawley Rats

    PubMed Central

    Sun, Seung-Ho; Park, Sunju; Jeong, Jong-Jin; Lee, Kwang-Ho; Yu, Jun-Sang; Seo, Hyung-Sik; Kwon, Ki-Rok

    2015-01-01

    Objectives: The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg. PMID:26120487

  13. Recovery from carotid artery catheterization performed under various anesthetics in male, Sprague-Dawley rats.

    PubMed

    Lawson, D M; Duke, J L; Zammit, T G; Collins, H L; DiCarlo, S E

    2001-07-01

    This study was designed to determine the time to recovery from carotid artery catheterization using multiple criteria and to compare recovery times between three common anesthetics. Male Sprague-Dawley rats, chronically instrumented with radio-telemetry transmitters, were anesthetized with sodium pentobarbital, halothane or a mixture of ketamine, xylazine and acepromazine before an indwelling catheter was placed in the carotid artery. The procedure was completed in less than 15 min. Changes in body weight, food and water consumption, blood pressure, heart rate and activity were used to determine recovery. As judged by recovery of body weight, animals anesthetized with each of the anesthetics recovered by the 4th day after catheterization. Food and water consumption normalized by 1-2 days after surgery. Heart rates and blood pressures during the light phase of the photoperiod were significantly increased for 2 days by all anesthetics. During the dark phase of the photoperiod, heart rates and blood pressures were not significantly affected by pentobarbital or halothane anesthesia, but were significantly decreased and increased respectively on the night immediately following surgery in the ketamine / xylazine / acepromazine-anesthetized rats. Delayed elevations of heart rate were observed in pentobarbital and halothane anesthetized rats on days and/or nights 5 and 6 post surgery. Animal activity patterns during the light phase of the photoperiod were not affected by pentobarbital or halothane, but were increased by ketamine 2 days after surgery. During the dark phase, halothane transiently reduced activity whereas ketamine-anesthetized rats showed reduced activity for 4 nights post surgery. These studies show that recovery depends on the criteria selected and the anesthetic used, but, in general, 2-4 days were required for recovery from this relatively simple procedure.

  14. Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

    PubMed

    Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-02-01

    Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only. PMID:25560395

  15. Anti-inflammatory effect of longan seed extract in carrageenan stimulated Sprague-Dawley rats

    PubMed Central

    Lee, Ching-Hsiao; Chen, Yuh-Shuen; Hou, Chien-Wei; Jeng, Kee-Ching; Chen, Kuo-Shu

    2016-01-01

    Objective(s): Longan seeds have been used as a folk medicine in China. Longan seed extract (LSE) is known for antioxidative, antiproliferative, hypoglycemic, and hypouremic effects. However, its anti-inflammatory effect has not been shown. Materials and Methods: In this study, Sprague-Dawley (SD) rats were given LSE orally (vehicle, 10, and 30 mg/kg) for 3 days to its test anti-inflammatory effect by injecting λ-carrageenan (CARR) in the right hind paw or lipopolysaccharide (LPS), IP. For the positive control, animals were given aspirin (20 mg/kg) orally and treated likewise. Serum or tissue samples from treated rats were collected after 3 hr of stimulation. Regarding the in vitro study, BV2 microglial cells were stimulated with LPS in the presence of LSE or normal saline for 10 min or 24 hr for Western blot and ELISA assay, respectively. Results: LSE reduced CARR-induced edema in the experimental animals. LSE also reduced LPS/CARR-induced nitric oxide (NO), interleukin-1β (IL1β), IL6, and COX2 productions. These inflammatory factors were also reduced dose dependently by LSE in LPS-stimulated BV2 cells. Furthermore, Western blot analysis revealed that LSE inhibited LPS activated c-Jun NH2-terminal protein kinase (JNK), extracellular signal-regulated kinases (ERKs), and p38 MAP kinases signaling pathways, caspase-3, inducible NO synthase, and COX2 expressions. Conclusion: LSE pretreatment suppressed CARR- and LPS-induced inflammations and these effects might be through the inhibition of MAP kinases signaling pathways and inflammatory factors. PMID:27746869

  16. Effects of perinatal methylphenidate (MPH) treatment in male and female Sprague-Dawley offspring.

    PubMed

    Panos, John J; Law, C Delbert; Ferguson, Sherry A

    2014-01-01

    MPH is a common treatment for adult Attention Deficit Hyperactivity Disorder (ADHD). However, little information exists regarding its safety during pregnancy and thus, women with ADHD face difficult decisions regarding continued use during pregnancy. Here, Sprague-Dawley rats were orally treated 3 ×/day with 0 (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14 mg/kg at each treatment time) on gestational days 6-21. On postnatal days (PNDs) 1-21, all offspring/litter were orally treated 2 ×/day with the same dose. Righting reflex (PNDs 3-6) and slant board performance (PNDs 8-11) were assessed. T3, T4, E2, testosterone, LH and corticosterone were measured at PND 22. Separate pregnant dams and resulting litters were used for serum MPH measurements. MPH treatment had mild, but significant, effects on gestational body weight and food intake. Birth weight of high MPH offspring was 5% more than controls (p<0.0500). Relative to same-sex controls on PNDs 1-22, low and mid MPH males weighed more (p<0.0094), low MPH females weighed more (p<0.0001), while high MPH females weighed less (p<0.0397). PND 22 serum E2 levels were significantly decreased (20-25%) in high MPH males and females (p<0.0500). Behavioral performance was unaffected by treatment. Serum MPH levels of the low MPH pregnant dams were within the range produced by therapeutic MPH doses in adults; however, offspring levels in all groups were substantially higher. These results indicate that developmental MPH treatment has mild effects on gestational body weight and food intake and offspring preweaning body weight. Potential functional consequences of decreased serum E2 levels are not clear, but may impact later behavior or physiology.

  17. Dysregulation of Glucose Homeostasis Following Chronic Exogenous Administration of Leptin in Healthy Sprague-Dawley Rats

    PubMed Central

    Wjidan, Khalil; Ibrahim, Effendi; Caszo, Brinnell; Gnanou, Justin

    2015-01-01

    Introduction Impaired glucose utilization is seen in chronic hyperleptinaemia associated conditions such as obesity and type 2 diabetes mellitus. It is unclear if this impaired glucose utilization is due to the effect of persistent hyperleptinaemia on insulin secretion from the beta cells of pancreas. Aim To examine the effects of chronic leptin administration on plasma glucose regulation in rats. Materials and Methods Glucose challenge curves were plotted for male Sprague-Dawley rats treated with either normal saline (Control; n=8) or subcutaneous leptin injection for 42 days (60 μg/kg body weight/day; n=8). Plasma glucose and plasma insulin levels were measured at 0, 5, 10, 15, 20 and 25 minutes after glucose challenege. Skeletal muscle tissue was collected at the end of a glucose challenge for glucose transporter-4 protein content, insulin receptor and glucose transporter-4 mRNA expression. Data were analysed using repeated measures and one-way ANOVA with post-hoc analysis. Results Chronic leptin treatment caused significantly higher fasting insulin level. Post glucose challenge, there was a significant increase in blood glucose levels and insulin level in the leptin treated rats. There was no significant difference in the skeletal muscle glucose transporter-4 content. However, leptin treated rats showed decreased mRNA expression of Insulin Receptor and glucose transporter-4 in the skeletal muscle. Conclusion Leptin administration for 42 days caused hyperinsulinaemia and decreased the expression of insulin receptors in insulin sensitive tissues leading to the development of an insulin resistance-like state in the rats. PMID:26816939

  18. Responses in gut microbiota and fat metabolism to a halogenated methane analogue in Sprague Dawley rats

    PubMed Central

    Su, Yong; Luo, Yu-Heng; Zhang, Ling-Li; Smidt, Hauke; Zhu, Wei-Yun

    2015-01-01

    Recent studies on germ-free mice show that intestinal methanogens may be closely associated with host's adipose metabolism. The present study aimed to investigate effects of inhibition of intestinal methanogen populations on host fat metabolism by establishing a healthy Sprague Dawley (SD) rat model through the intragastric administration of bromochlordomethane (BCM). Forty-five 8-week old healthy male SD rats were randomly divided into five groups including one control and four BCM treatments. The experiment lasted 60 days with two separate 30-day experimental periods. At the end of first period, three BCM treatment groups were further used: one group continued with BCM treatment, one group stopped with BCM treatment, and the other one inoculated with faecal mixture of methanogens from rats. Results showed that the methanogen population in feces was reduced sixfold with no effect on the bacterial community by daily dosing with BCM. Daily gain, epididymal fat pad weight, levels of plasma low-density lipoprotein and cholesterol were significantly higher in the BCM-treated animals, while the high-density lipoprotein was lower than that of the control. The expression of PPARγ, LPL, PP2A, SREBP-1c, ChREBP, FASN and adiponectin genes in BCM treatment group was universally upregulated, while the expression of Fiaf gene was downregulated. After termination of BCM treatment and followed either with or without re-inocubation with faecal methanogen mixture, the rats had their faecal methanogen populations, blood parameters and gene expression returned to the original level. Results suggest that regulation of gut methanogens might be a possible approach to control host body weight. PMID:25752448

  19. Organ growth functions in maturing male Sprague-Dawley rats based on a collective database.

    PubMed

    Mirfazaelian, Ahmad; Fisher, Jeffrey W

    2007-06-01

    Ten different organ weights (liver, spleen, kidneys, heart, lungs, brain, adrenals, testes, epididymes, and seminal vesicles) of male Sprague-Dawley (S-D) rats of different ages (1-280 d) were extracted based on a thorough literature survey database. A generalized Michaelis-Menten (GMM) model, used to fit organ weights versus age in a previous study (Schoeffner et al., 1999) based on a limited data, was used to find the best fit model for the present expanded data compilation. The GMM model has the functional form: Wt = (Wt(o).K(gamma) + Wt(max).Age(gamma))/(K(gamma) + Age(gamma)) where Wt is organ/tissue weight at a specified age, Wt(o) and Wt(max) are weight at birth and maximal growth, respectively, and K and gamma are constants. Organ weights were significantly correlated with their respective ages for all organs and tissues. GMM-derived organ growth and percent body weight (%BW) fractions of different tissues were plotted against animal age and compared with experimental values as well as previously published models. The GMM-based organ growth and %BW fraction profiles were in general agreement with our empirical data as well as with previous studies. The present model was compared with the GMM model developed previously for six organs--liver, spleen, kidneys, heart, lungs, and brain--based on a limited data, and no significant difference was noticed between the two sets of predictions. It was concluded that the GMM models presented herein for different male S-D rats organs (liver, spleen, kidneys, heart, lungs, brain, adrenals, testes, epididymes, and seminal vesicles) are capable of predicting organ weights and %BW ratios accurately at different ages. PMID:17497417

  20. Effects of the phytoestrogen genistein on the development of the reproductive system of Sprague Dawley rats

    PubMed Central

    Zin, Siti Rosmani Md; Omar, Siti Zawiah; Khan, Norhayati Liaqat Ali; Musameh, Nurul Iftitah; Das, Srijit; Kassim, Normadiah M

    2013-01-01

    OBJECTIVES: Genistein is known to influence reproductive system development through its binding affinity for estrogen receptors. The present study aimed to further explore the effect of Genistein on the development of the reproductive system of experimental rats. METHODS: Eighteen post-weaning female Sprague Dawley rats were divided into the following groups: (i) a control group that received vehicle (distilled water and Tween 80); (ii) a group treated with 10 mg/kg body weight (BW) of Genistein (Gen 10); and (iii) a group treated with a higher dose of Genistein (Gen 100). The rats were treated daily for three weeks from postnatal day 22 (P22) to P42. After the animals were sacrificed, blood samples were collected, and the uteri and ovaries were harvested and subjected to light microscopy and immunohistochemical study. RESULTS: A reduction of the mean weekly BW gain and organ weights (uteri and ovaries) were observed in the Gen 10 group compared to the control group; these findings were reversed in the Gen 100 group. Follicle stimulating hormone and estrogen levels were increased in the Gen 10 group and reduced in the Gen 100 group. Luteinizing hormone was reduced in both groups of Genistein-treated animals, and there was a significant difference between the Gen 10 and control groups (p<0.05). These findings were consistent with increased atretic follicular count, a decreased number of corpus luteum and down-regulation of estrogen receptors-α in the uterine tissues of the Genistein-treated animals compared to the control animals. CONCLUSION: Post-weaning exposure to Genistein could affect the development of the reproductive system of ovarian-intact experimental rats because of its action on the hypothalamic-pituitary-gonadal axis by regulating hormones and estrogen receptors. PMID:23525324

  1. Isomer-specific biotransformation of perfluorooctane sulfonamide in Sprague-Dawley rats.

    PubMed

    Ross, Matthew S; Wong, Charles S; Martin, Jonathan W

    2012-03-20

    Great variability exists in perfluorooctane sulfonate (PFOS) isomer patterns in human and wildlife samples, including unexpectedly high percentages (e.g., >40%) of branched isomers in human sera. Previous in vitro tests showed that branched PFOS-precursors were biotransformed faster than the corresponding linear isomer. Thus, high percentages of branched PFOS may be a biomarker of PFOS-precursor exposure in humans. We evaluated this hypothesis by examining the isomer-specific fate of perfluorooctane sulfonamide (PFOSA), a known PFOS-precursor, in male Sprague-Dawley rats exposed to commercial PFOSA via food for 77 days (83.0 ± 20.4 ng kg(-1) day(-1)), followed by 27 days of depuration. Elimination half-lives of the two major branched PFOSA isomers (2.5 ± 1.0 days and 3.7 ± 1.2 days) were quicker than for linear PFOSA (5.9 ± 4.6 days), resulting in a depletion of branched PFOSA isomers in blood and tissues relative to the dose. A corresponding increase in the total branched isomer content of PFOS, the ultimate metabolite, in rat serum was not observed. However, a significant enrichment of 5m-PFOS and a significant depletion of 1m-PFOS were observed, relative to authentic electrochemical PFOS. The data cannot be directly extrapolated to humans, due to known differences in the toxicokinetics of PFOS in rodents and humans. However, the results confirm that in vivo exposure to commercially relevant PFOS-precursors can result in a distinct PFOS isomer profile that may be useful as a biomarker of exposure source.

  2. Dietary selenium as a modulator of PCB 126-induced hepatotoxicity in male Sprague-Dawley rats.

    PubMed

    Lai, Ian K; Chai, Yingtao; Simmons, Donald; Watson, Walter H; Tan, Rommel; Haschek, Wanda M; Wang, Kai; Wang, Bingxuan; Ludewig, Gabriele; Robertson, Larry W

    2011-11-01

    Homeostasis of selenium (Se), a critical antioxidant incorporated into amino acids and enzymes, is disrupted by exposure to aryl hydrocarbon receptor (AhR) agonists. Here we examined the importance of dietary Se in preventing the toxicity of the most toxic polychlorinated biphenyl congener, 3,3',4,4',5-pentachlorobiphenyl (PCB 126), a potent AhR agonist. Male Sprague-Dawley rats were fed a modified AIN-93 diet with differing dietary Se levels (0.02, 0.2, and 2 ppm). Following 3 weeks of acclimatization, rats from each dietary group were given a single ip injection of corn oil (vehicle), 0.2, 1, or 5 μmol/kg body weight PCB 126, followed 2 weeks later by euthanasia. PCB exposure caused dose-dependent increases in liver weight and at the highest PCB 126 dose decreases in whole body weight gains. Hepatic cytochrome P-450 (CYP1A1) activity was significantly increased even at the lowest dose of PCB 126, indicating potent AhR activation. PCB exposure diminished hepatic Se levels in a dose-dependent manner, and this was accompanied by diminished Se-dependent glutathione peroxidase activity. Both these effects were partially mitigated by Se supplementation. Conversely, thioredoxin (Trx) reductase activity and Trx oxidation state, although significantly diminished in the lowest dietary Se groups, were not affected by PCB exposure. In addition, PCB 126-induced changes in hepatic copper, iron, manganese, and zinc were observed. These results demonstrate that supplemental dietary Se was not able to completely prevent the toxicity caused by PCB 126 but was able to increase moderately the levels of several key antioxidants, thereby maintaining them roughly at normal levels. PMID:21865291

  3. Tissue specificity of N-nitrosomorpholine metabolism in Sprague-Dawley rats.

    PubMed

    Löfberg, B; Tjälve, H

    1985-07-01

    The distribution and metabolism of N-nitroso[14C]morpholine ([14C]NMOR) in Sprague-Dawley rats were studied by autoradiographic and in vitro techniques. Low-temperature whole-body autoradiography indicated that the non-metabolized compound is able to pass freely through the cellular membranes and distribute evenly in most tissues of the body. Experiments in vitro showed that, in addition to the liver, the nasal mucosa had a high capacity to degrade the [14C]NMOR and a localization of metabolites was also observed in this tissue in vivo. Microautoradiography of the nasal olfactory mucosa showed the highest labelling over the subepithelial glands in the lamina propria mucosae. The nasal mucosa is, apart from the liver, the most prevalent site of NMOR carcinogenesis in the rat and the results indicate that a local bioactivation occurs in this tissue. Further experiments showed that NMOR metabolism in the nasal mucosa and the liver was inhibited by metyrapone and by a carbon monoxide atmosphere, indicating that the metabolism is cytochrome P-450 dependent. In addition to the nasal mucosa and the liver, a localization of metabolites was demonstrated in the oesophageal mucosa in vivo, while in vitro this tissue showed a capacity to degrade the [14C]NMOR. A low incidence of tumours of the oesophagus has been reported in rats treated with NMOR. It is concluded that NMOR is metabolized in the nasal and oesophageal mucosa as well as in the liver, and that local bioactivation at these sites may give rise to tumours.

  4. Acute oral toxicity studies of Swietenia macrophylla seeds in Sprague Dawley rats

    PubMed Central

    Balijepalli, Madhu Katyayani; Suppaiah, Velan; Chin, An-me; Buru, Ayuba Sunday; Sagineedu, Sreenivasa Rao; Pichika, Mallikarjuna Rao

    2015-01-01

    Background: Swietenia macrophylla King. (Meliaceae) seeds (SMS); commonly known as sky fruit and locally known in Malaysia as Tunjuk Langit; have been used in traditional Malay medicine for the treatment of diabetes and hypertension. The people eat only a tiny amount of raw seed, weighing not more than 5 mg. Aim: To evaluate the safety of Swietenia macrophylla seeds (SMS) at a single-dose oral administration of 2 g/kg body weight (bw) in sprague dawley (SD) rats. Materials and Methods: Eight-week old male and female SD rats were administered a single-oral dose of 2g/kg bw. The rats’ general behavior, and toxic signs were observed throughout the 14-day study period. The food and water intake by rats and their body weight were monitored during the study period. At the end of the study period, the relative weights of the organs (lung, liver, spleen, heart, kidney, testis, stomach); the hematological and biochemical parameters were measured; the architecture and histology of the organs (liver, kidney and lungs) were observed. Results: Oral administration of SMS to rats did not affect, either food or water intake; relative organ weight of vital organs; the hematological and biochemical parameters; did not show significant changes in the architecture and histology of vital organs. Overall, there were neither signs of toxicity nor deaths recorded during the study period. Conclusion: The rat dose of 2 g/kg bw is equivalent to the human dose of 325 mg/kg bw, which is well below the usual amount consumed by people, did not show any signs of toxicity in rats. PMID:25598633

  5. Cross-fostering inhalation toxicity study with HCFC-123 in lactating Sprague-Dawley rats.

    PubMed

    Buschmann, J; Bartsch, W; Dasenbrock, C; Fuhst, R; Pohlmann, G; Preiss, A; Berger-Preiss, E

    2001-08-01

    A study was performed in Sprague-Dawley rats (Crl:CD BR) to differentiate between effects of hydrofluorocarbon 123 (HCFC-123) on the lactating dam or on the fetus using fostering and cross-fostering of the offspring. Pregnant and/or lactating dams without the pups present were exposed to the test substance (1000 ppm) or clean air by whole-body inhalation for 6 h/day from day 6 to 19 post conceptionem (p.c.) and from day 5 to 21 post partum (p.p.). Pups were cross-fostered to new dams within the first 2 days after birth. Treatment of the mothers with HCFC-123 led to decreases in serum glucose, cholesterol, and triglycerides and increases in absolute and relative maternal liver weights. Decreased litter and individual pup weight and decreased serum triglycerides were observed in the pups of treated foster mothers. Treatment of the mothers with HCFC-123 did not influence milk production based on the body weight difference of the dam before suckling and 60 min after beginning of suckling using 12-pup "standard litters" of untreated dams. Total fat, glucose, and protein contents in the milk were also not influenced by the treatment. Trifluoroacetic acid (TFA), a main metabolite of HCFC-123, was observed in urine samples of standard litters that had been nursed by treated dams. In conclusion, the effects on offspring due to HCFC-123 treatment consisted of decreased pup weight and decreased serum triglycerides at weaning. All effects were due to treatment of the lactating dams, as no prenatally induced effects were found. Since milk production and nutritional constituents of the milk were not influenced, but significant amounts of the main metabolite were found in pup urine, an effect of HCFC-123 or its metabolite on the pups via maternal milk is considered to be a possible cause for their decreased weight gain. PMID:11498800

  6. Therapeutic effects of quercetin against bisphenol A induced testicular damage in male Sprague Dawley rats.

    PubMed

    Jahan, Sarwat; Ain, Qurat Ul; Ullah, Hizb

    2016-01-01

    The present study was designed to investigate protective effects of quercetin against bisphenol A (BPA) induced testicular toxicity in male Sprague Dawley rats. Twenty adult male rats were divided into four groups. The first group served as the control and was provided with normal saline. The second group of rats was treated with 50 mg/kg of BPA dissolved in alcoholic saline. The third group received oral gavage of 50 mg/kg quercetin while the fourth group was treated with quercetin (50 mg/kg) along with BPA (50 mg/kg). All of the treatments were carried out for 52 days. Testicular tissues and epididymis were used for histology while blood plasma was used for hormonal and biochemical analysis. BPA administration resulted in a significant reduction in seminiferous tubule diameter and epithelial height with impaired spermatogenesis. Quercetin treatment resulted in restoration of spermatogenesis and reversal of histological damage. In addition, BPA treatment significantly reduced (p < 0.05) plasma testosterone level (ng/ml) while estrogen was not affected. Similarly, BPA caused a significant alteration in the lipid profile. Interestingly, quercetin treatment led to a marked increase in plasma testosterone, decrease in estrogen concentration, as well as a normalized lipid profile. In conclusion, results indicated that BPA administration induces toxic effects on testis and epididymis, impairs spermatogenesis, with an imbalance in hormonal levels and lipid profile while quercetin amended these toxic effects by restoring normal spermatogenesis, testicular tissue damage, and hormonal levels. This suggests that quercetin may be a potential therapeutic against BPA induced testicular toxicity. PMID:26787223

  7. Effects of Nicotine Exposure on In Vitro Metabolism of Chlorpyrifos in Male Sprague-Dawley Rats

    SciTech Connect

    Lee, Sookwang; Busby, Andrea L.; Timchalk, Charles; Poet, Torka S.

    2009-01-30

    Chlorpyrifos (CPF) is a common organophosphate (OP) insecticide which is metabolized by CYP450s to the neurotoxic metabolite, chlorpyrifos-oxon (CPF-oxon) and a non-toxic metabolite, 3,5,6-trichloro-2-pyridinol (TCP). The objective of this study was to quantify the effect of repeated in vivo nicotine exposures on CPF in vitro metabolism and marker substrate activities in rats. Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg/, for up to 10 days. Animals showed signs of cholinergic crisis after the initial nicotine doses, but exhibited adaptation after a couple days of treatment. Rats were sacrificed on selected days 4 or 24 hr after the last nicotine-treatment. While CYP450 reduced CO spectra were not different across the treatments, the single nicotine dose group showed a 2-fold increase in CYP2E1 marker substrate (p-nitrophenol) activity 24 hr after a single nicotine treatment compared to saline controls. Conversely, repeated nicotine treatments resulted in decreased EROD marker substrate activity 4 hr after the 7th day of treatment. CPF-oxon Vmax and Km did not show significant changes across the different nicotine treatment groups. The Vmax describing the metabolism of CPF to TCP was increased on all groups (days 1, 7, and 10) 24 hr after nicotine treatment but were unchanged 4 hr after nicotine treatment. Results of this in vitro study suggest that repeated nicotine exposure (i.e., from smoking) may result in altered metabolism of CPF. Future in vivo experiments based on these results will be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.

  8. Central Angiotensin II Stimulation Promotes β Amyloid Production in Sprague Dawley Rats

    PubMed Central

    Zhu, Donglin; Shi, Jingping; Zhang, Yingdong; Wang, Bianrong; Liu, Wei; Chen, Zhicong; Tong, Qiang

    2011-01-01

    Background Stress and various stress hormones, including catecholamines and glucocorticoids, have recently been implicated in the pathogenesis of Alzheimer's disease (AD), which represents the greatest unresolved medical challenge in neurology. Angiotensin receptor blockers have shown benefits in AD and prone-to-AD animals. However, the mechanisms responsible for their efficacy remain unknown, and no studies have directly addressed the role of central angiotensin II (Ang II), a fundamental stress hormone, in the pathogenesis of AD. The present study focused on the role of central Ang II in amyloidogenesis, the critical process in AD neuropathology, and aimed to provide direct evidence for the role of this stress hormone in the pathogenesis of AD. Methodology/Principal Findings Increased central Ang II levels during stress response were modeled by intracerebroventricular (ICV) administration of graded doses of Ang II (6 ng/hr low dose, 60 ng/hr medium dose, and 600 ng/hr high dose, all delivered at a rate of 0.25 µl/hr) to male Sprague Dawley rats (280–310 g) via osmotic pumps. After 1 week of continuous Ang II infusion, the stimulation of Ang II type 1 receptors was accompanied by the modulation of amyloid precursor protein, α-, β-and γ-secretase, and increased β amyloid production. These effects could be completely abolished by concomitant ICV infusion of losartan, indicating that central Ang II played a causative role in these alterations. Conclusions/Significance Central Ang II is essential to the stress response, and the results of this study suggest that increased central Ang II levels play an important role in amyloidogenesis during stress, and that central Ang II-directed stress prevention and treatment might represent a novel anti-AD strategy. PMID:21297982

  9. Alagebrium attenuates acute methylglyoxal-induced glucose intolerance in Sprague-Dawley rats

    PubMed Central

    Dhar, Arti; Desai, Kaushik M; Wu, Lingyun

    2010-01-01

    Background and purpose: Alagebrium is a breaker of cross-links in advanced glycation endproducts. However, the acute effects of alagebrium on methylglyoxal (MG), a major precursor of advanced glycation endproducts have not been reported. MG is a highly reactive endogenous metabolite, and its levels are elevated in diabetic patients. We investigated whether alagebrium attenuated the acute effects of exogenous MG on plasma MG levels, glucose tolerance and distribution of administered MG in different organs in Sprague-Dawley rats. Experimental approach: We measured MG levels (by HPLC), glucose tolerance, adipose tissue glucose uptake, GLUT4, insulin receptor and insulin receptor substrate 1 (IRS-1) protein expression, and phosporylated IRS-1 in rats treated with MG at doses of either 17.25 mg·kg−1 i.p. (MG-17 i.p.) or 50 mg·kg−1 i.v. (MG-50 i.v.) with or without alagebrium, 100 mg·kg−1 i.p. Key results: Alagebrium attenuated the increased MG levels in the plasma, aorta, heart, kidney, liver, lung and urine after MG administration. In MG-treated rats, glucose tolerance was impaired, plasma insulin levels were higher and insulin-stimulated glucose uptake by adipose tissue was reduced, relative to the corresponding control groups. In rats treated with MG-50 i.v., GLUT4 protein expression and IRS-1 tyrosine phosphorylation were decreased. Alagebrium pretreatment attenuated these effects of MG. In an in vitro assay, alagebrium reduced the amount of detectable MG. Conclusions and implications: Alagebrium acutely attenuated MG-induced glucose intolerance, suggesting a possible preventive role for alagebrium against the harmful effects of MG. PMID:20002105

  10. Pharmacokinetics of bisphenol A in neonatal and adult Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.

    2010-09-01

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal Sprague-Dawley rats by oral and injection routes. Deuterated BPA was used to avoid issues of background contamination. Linear pharmacokinetics were observed in adult rats treated orally in the range of 0-200 {mu}g/kg bw. Evidence for enterohepatic recirculation of conjugated, but not aglycone, BPA was observed in adult rats. Significant inverse relationships were observed between postnatal age and measures of internal exposures to aglycone BPA and its elimination. In neonatal rats treated orally, internal exposures to aglycone BPA were substantially lower than from subcutaneous injection. The results reinforce the critical role for first-pass Phase II metabolism of BPA in gut and liver after oral exposure that attenuates internal exposure to the aglycone form in rats of all ages. The internal exposures to aglycone BPA observed in adult and neonatal rats following a single oral dose of 100 {mu}g/kg bw are inconsistent with effects mediated by classical estrogen receptors based on binding affinities. However, an impact on alternative estrogen signaling pathways that have higher receptor affinity cannot be excluded in neonatal rats. These findings emphasize the importance of matching aglycone BPA internal dosimetry with receptor affinities in experimental animal studies reporting toxicity.

  11. Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats

    NASA Technical Reports Server (NTRS)

    Tou, Janet C L.; Grindeland, Richard E.; Wade, Charles E.

    2004-01-01

    Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

  12. Probiotic amelioration of azotemia in 5/6th nephrectomized Sprague-Dawley rats.

    PubMed

    Ranganathan, Natarajan; Patel, Beena; Ranganathan, Pari; Marczely, Joseph; Dheer, Rahul; Chordia, Tushar; Dunn, Stephen R; Friedman, Eli A

    2005-08-24

    The present study was to test the hypothesis that, selected bacteria instilled into the gastrointestinal tract could help in converting nitrogenous wastes accumulated due to renal insufficiency into non-toxic compounds; thereby, ameliorating the biochemical imbalance. Herein we describe a prospective, blinded, placebo controlled pilot-study, using 5/6th nephrectomized Sprague Dawley rat, as a chronic renal failure model. The study group consisted of 36 nephrectomized and 7 non-nephrectomized (control) rats. After two-week nephrectomy stabilization, cohorts of six nephrectomized rats were fed casein-based diet plus one of the following regimens: (A) Control, (B) Placebo (casein-based diet without probiotics), (C) Bacillus pasteurii, (D) Sporolac(R), (E) Kibow cocktail, (F) CHR Hansen Cocktail, and (G) ECONORM. Subsequently, blood (retro-orbital) and urine (collected for measurements of blood urea-nitrogen and creatinine respectively), body weight and bacterial counts (feces) were obtained at regular intervals. The study end-points were to determine if any of the probiotic dietary supplements facilitated, (1) decreased blood concentrations of uremic toxins, (2) altered renal function, and (3) prolonged survival. After 16 weeks of treatment, regimens C and D significantly prolonged the life span of uremic rats, in addition to showing a reduction in blood urea-nitrogen levels, concluding that supplementation of probiotic formulation to uremic rats slows the progression of azotemia, which may correlate with prolonged life span of uremic rats. Derivative trials of probiotic treatment of larger animals and humans will further assess the potential role of probiotic formulations in delaying the onset and clinical severity of clinical illness at different stages of renal failure. PMID:16127597

  13. Increased methylglyoxal formation with upregulation of renin angiotensin system in fructose fed Sprague Dawley rats.

    PubMed

    Dhar, Indu; Dhar, Arti; Wu, Lingyun; Desai, Kaushik M

    2013-01-01

    The current epidemic of obesity and type 2 diabetes is attributed to a high carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly reactive dicarbonyl generated during glucose and fructose metabolism, and a major precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels are increased in hypertensive rats and diabetic patients. Our aim was to examine the levels of methylglyoxal, mediators of the renin angiotensin system and blood pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of total calories) for 4 months. The thoracic aorta and kidney were used for molecular studies, along with cultured vascular smooth muscle cells (VSMCs). HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats developed a significant increase in blood pressure. Methylglyoxal level and protein and mRNA for angiotensin II, AT1 receptor, adrenergic α1D receptor and renin were significantly increased, whereas GSH levels were decreased, in the aorta and/or kidney of fructose fed rats. The protein expression of the receptor for AGEs (RAGE) and NF-κB were also significantly increased in the aorta of fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II, AT1 receptor, and α1D receptor. The effects of methylglyoxal were attenuated by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we report a strong association between elevated levels of methylglyoxal, RAGE, NF-κB, mediators of the renin angiotensin system and blood pressure in high fructose diet fed rats. PMID:24040205

  14. Wheel running decreases palatable diet preference in Sprague-Dawley rats.

    PubMed

    Moody, Laura; Liang, Joy; Choi, Pique P; Moran, Timothy H; Liang, Nu-Chu

    2015-10-15

    Physical activity has beneficial effects on not only improving some disease conditions but also by preventing the development of multiple disorders. Experiments in this study examined the effects of wheel running on intakes of chow and palatable diet e.g. high fat (HF) or high sucrose (HS) diet in male and female Sprague-Dawley rats. Experiment 1 demonstrated that acute wheel running results in robust HF or HS diet avoidance in male rats. Although female rats with running wheel access initially showed complete avoidance of the two palatable diets, the avoidance of the HS diet was transient. Experiment 2 demonstrated that male rats developed decreased HF diet preferences regardless of the order of diet and wheel running access presentation. Running associated changes in HF diet preference in females, on the other hand, depended on the testing schedule. In female rats, simultaneous presentation of the HF diet and running access resulted in transient complete HF diet avoidance whereas running experience prior to HF diet access did not affect the high preference for the HF diet. Ovariectomy in females resulted in HF diet preference patterns that were similar to those in male rats during simultaneous exposure of HF and wheel running access but similar to intact females when running occurred before HF exposure. Overall, the results demonstrated wheel running associated changes in palatable diet preferences that were in part sex dependent. Furthermore, ovarian hormones play a role in some of the sex differences. These data reveal complexity in the mechanisms underlying exercise associated changes in palatable diet preference.

  15. Protective Effects of Quercetin Against HgCl₂-Induced Nephrotoxicity in Sprague-Dawley Rats.

    PubMed

    Shin, Yu Jin; Kim, Jeong Jun; Kim, Ye Ji; Kim, Won Hee; Park, Eun Young; Kim, In Young; Shin, Han-Seung; Kim, Kyeong Seok; Lee, Eui-Kyung; Chung, Kyu Hyuck; Lee, Byung Mu; Kim, Hyung Sik

    2015-05-01

    Mercury is a well-known environmental pollutant that can cause nephropathic diseases, including acute kidney injury (AKI). Although quercetin (QC), a natural flavonoid, has been reported to have medicinal properties, its potential protective effects against mercury-induced AKI have not been evaluated. In this study, the protective effect of QC against mercury-induced AKI was investigated using biochemical parameters, new protein-based urinary biomarkers, and a histopathological approach. A 250 mg/kg dose of QC was administered orally to Sprague-Dawley male rats for 3 days before administration of mercury chloride (HgCl2). All animals were sacrificed at 24 h after HgCl2 treatment, and biomarkers associated with nephrotoxicity were measured. Our data showed that QC absolutely prevented HgCl2-induced AKI, as indicated by biochemical parameters such as blood urea nitrogen (BUN) and serum creatinine (sCr). In particular, QC markedly decreased the accumulation of Hg in the kidney. Urinary excretion of protein-based biomarkers, including clusterin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular endothelial growth factor (VEGF) in response to HgCl2 administration were significantly decreased by QC pretreatment relative to that in the HgCl2-treated group. Furthermore, urinary excretion of metallothionein and Hg were significantly elevated by QC pretreatment. Histopathological examination indicated that QC protected against HgCl2-induced proximal tubular damage in the kidney. A TUNEL assay indicated that QC pretreatment significantly reduced apoptotic cell death in the kidney. The administration of QC provided significant protective effects against mercury-induced AKI.

  16. Effects of Cage Type and NASA Rodent Food Bar in Male Sprague-Dawley Rats

    NASA Technical Reports Server (NTRS)

    Lau, Angela; Ramirez, J.; Pruitt, S.; Melson, E.; Zirkle-Yoshida, M.; Girten, B.; Apseloff, G.

    2001-01-01

    Early prototype caging for the rodent Advanced Animal Habitat (P-AAH) for the International Space Station (ISS) is currently being tested. In this five week study, effects of the wire-bottom P-AAH cages and specialized NASA rodent food bars (FB) were compared to standard vivarium cages (VIV) with corn-cob, litter-filled bottoms, and standard Purina rat chow (CH). Ninety-six male Sprague-Dawley rats were divided into four treatment groups (24 rats/treatment): Group 1) VIV+CH, Group 2) P-AAH+CH, Group 3) VIV+FB, and Group 4) P-AAH+FB. Each VIV and P-AAH cage housed three and six rats, respectively. After five weeks of treatment rats were weighed, euthanized, and blood samples were collected. Weights of liver (LIV), kidney (KID), brain (BRN), epididymal fat (EPI), and perirenal fat (PERI) were also measured. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures (ANOVA) with a significance level of pLO.05. Results indicated P-AAH housed rats had significantly lower body weights (BW), LIV weights, and LIV/BW than VIV housed rats. FB fed rats had significantly lower blood urea nitrogen (BUN) levels and LIV/BW than CH fed rats. In addition, FB fed rats had significantly higher cholesterol (CHOL) levels, EPI/BW, PERI/BW, and total fat (EPI+PERI)/BW than CH fed rats. The P-AAH+FB group had significantly lower EPI, BRN, and total fat than VIV+FB rats. VIV+FB rats had significantly higher BRN, EPI, PERI, and total fat than VIV+CH rats. Triglycerides (TG), KID, KID/BW, and BRN/BW were not significantly different among treatment groups. These findings provide valuable information regarding cage design and food bar suitability for long-term use on the ISS.

  17. NSBRI Radiation Effects: Carcinogenesis in Sprague-Dawley Rats Irradiated with Iron Ions, Protons, or Photons

    NASA Technical Reports Server (NTRS)

    Dicello, J. F.; Cucinotta, F. A.; Gridley, D. S.; Howard, S. P.; Novak, G. R.; Ricart-Arbona, R.; Strandberg, J. D.; Vazquez, M. E.; Williams, J. R.; Zhang, Y.; Zhou, H.; Huso, D. L.

    1999-01-01

    Our ability to confidently develop appropriate countermeasures for radiations in space in terms of shielding and design of a spacecraft, the mission scenario, or chemoprevention is severely limited by the uncertainties in both the risk itself and the change in that risk with intervention. Despite the fact that the risk of carcinogenesis from exposures of personnel to radiations on long-term missions is considered one of the worst hazards in space, only a limited amount of in-vivo data exist for tumor induction from exposures to protons or energetic heavy ions (HZEs) at lower doses. The most extensive work remains the landmark study. for tumor development in the harderian gland of the mouse. The objective of this study is to characterize the level of risk for tumor induction in another relevant animal model. Subsequent experiments are designed to test the hypothesis that the level of risk can be reduced by pharmaceutical intervention in the promoting and progressing stages of the disease rather than in the initiating stage. The work presented here results from a cooperative effort on the part of investigators from two projects of the Radiation-Effects Team of the National Space Biomedical Research Institute (NSBRI). The collaborating projects are the Core Project which is investigating the risk of carcinogenesis in Sprague-Dawley rats and the Chemoprevention Project which is investigating the ability of Tamoxifen to reduce the number of malignant tumors in the irradiated animals. Research at the cellular and subcellular levels is being conducted in two other projects of the Radiation-Effects Team, Cytogenetics with J. R. Williams as Principal Investigator and Mutations from Repeated DNA Sequences. Results for these other projects also are being presented at this Workshop.

  18. Negligible Pharmacokinetic Interaction of Red Ginseng and Losartan, an Antihypertensive Agent, in Sprague-Dawley Rats.

    PubMed

    Ryu, Sung Ha; Kim, Yong Soon; Jang, Hyun-Jun; Kim, Kyu-Bong

    2015-01-01

    Red ginseng (RG) is one of the top selling herbal medicines in Korea, but is not recommended in hypertensive patients. In this study, the pharmacokinetic (PK) interaction between RG and losartan, an antihypertensive drug, was examined. RG was orally administered for 2 wk to male Sprague-Dawley (S-D) rats at either control (0), 0.5, 1, or 2 g/kg/d for 2 wk. After the last administration of RG and 30 min later, all animals were treated with 10 mg/kg losartan by oral route. In addition, some S-D rats were administered RG orally for 21 d at 2 g/kg followed by losartan intravenously (iv) at 10 mg/kg/d. Post losartan administration, plasma samples were collected at 5, 15, and 30 min and 1, 1.5, 2, 3, 6, 12, and 24 h. Plasma concentrations of losartan and E-3174, the active metabolite of losartan, were analyzed by a high-pressure liquid chromatography-tandem mass spectrometer system (LC-MS/MS). Oral losartan administration showed dose-dependent pharmacokinetics (PK) increase with time to maximum plasma, but this was not significant between different groups. There was no significant change in tmax with E-3174 PK. With iv losartan, pharmacokinetics showed elevation of area under the plasma concentration-time curve from time zero extrapolated to infinitity. There was not a significant change in AUCinf with E-3174 PK. Therefore, RG appeared to interfere with biotransformation of losartan, as RG exerted no marked effect on E-3174 PK in S-D rats. Data demonstrated that oral or iv treatment with losartan in rats pretreated with RG for 2 wk showed that losartan PK was affected but E-3174 PK remained unchanged among different dose groups. These results suggested that RG induces negligible influence on losartan and E-3174 PK in rats.

  19. A Safety Evaluation of a Nature-Identical l-Ergothioneine in Sprague Dawley Rats.

    PubMed

    Marone, Palma Ann; Trampota, Jan; Weisman, Steven

    2016-09-01

    l-(+) Ergothioneine is a naturally occurring thiol amino acid with antioxidant properties and potential benefits as a dietary supplement. Despite its century-old identification and wide distribution in human food, little is known of its mechanism of action and safety. The nature-identical biomimetic of l-(+) ergothioneine, produced by Mironova Labs and supplied as Mironova (EGT+), has been investigated in the present studies for its mutagenic and toxicologic potential. In a plate incorporation and preincubation assay with Salmonella typhimurium strains TA98, 100, 1,535, and 1,537 and Escherichia coli WP2uvrA strain, at dose concentrations of 1.58, 5, 15.8, 50, 158, 500, 1,580, and 5,000 μg/plate with and without metabolic activation, no cytotoxicity or mutagenicity was observed. Following a preliminary 28-day study, a repeated dose 90-day gavage study at dose levels of 0, 400, 800, and 1,600 mg/kg body weight (bw)/d in Sprague Dawley rats, in which dose-proportional systemic absorption was confirmed by plasma analysis, no adverse clinical, body weight/gain, food consumption and efficiency, clinical pathology, or histopathological changes associated with the administration of the nature-identical ergothioneine were observed. In conclusion, EGT+ administered over 90 days was well tolerated with a no adverse effect level at 1,600 mg/kg bw/d, the highest dose tested for male and female rats. In addition, the nature-identical test substance, EGT+ was not mutagenic in a bacterial reverse mutation assay at plate concentrations of up to 5,000 μg/mL in the presence or absence of metabolic activation. PMID:27306320

  20. Exercise prevents leptin-induced increase in blood pressure in Sprague-Dawley rats.

    PubMed

    Farhana, K; Effendi, I; Caszo, Brinnell; Satar, Nuraliza Abdul; Singh, H J

    2014-06-01

    Although leptin has been shown to increase blood pressure (BP), it is however unclear if this increase can be prevented by exercise. This study therefore investigated the effect of leptin treatment with concurrent exercise on blood pressure (BP), sodium output, and endothelin-1 (ET-1) levels in normotensive rats. Male Sprague-Dawley rats weighing 250-270 g were divided into four groups consisting of a control group (n = 6), leptin-treated (n = 8), non-leptin-treated exercise group (n = 8), and a leptin-treated exercise group (n = 8). Leptin was given subcutaneously daily for 14 days (60 μg/kg/day). Animals were exercised on a treadmill for 30 min at a speed of 0.5 m/s and at 5° incline four times per week. Measurement of systolic blood pressure (SBP) and collection of urine samples for estimation of sodium and creatinine was done once a week. Serum samples were collected at the end of the experiment for determination of sodium, creatinine and ET-1. At day 14, mean SBP and serum ET-1 level in the leptin-treated group was significantly higher than that in the control group whereas mean SBP and serum ET-1 level was significantly lower in the leptin-treated exercise group than those in leptin-treated and control groups. Creatinine clearance, urinary sodium excretion, and urine output were not different between the four groups. Regular treadmill exercise prevents leptin-induced increases in SBP in rats, which might in part result from increased urinary sodium excretion and preventing the leptin-induced increases in serum ET-1 concentration.

  1. Effects of coconut oil on testosterone-induced prostatic hyperplasia in Sprague-Dawley rats.

    PubMed

    de Lourdes Arruzazabala, María; Molina, Vivian; Más, Rosa; Carbajal, Daisy; Marrero, David; González, Víctor; Rodríguez, Eduardo

    2007-07-01

    Benign prostatic hyperplasia (BPH) is the benign uncontrolled growth of the prostate gland, leading to difficulty with urination. Saw palmetto lipid extracts (SPLE), used to treat BPH, have been shown to inhibit prostate 5a-reductase, and some major components, such as lauric, myristic and oleic acids also inhibit this enzyme. Coconut oil (CO) is also rich in fatty acids, mainly lauric and myristic acids. We investigated whether CO prevents testosterone-induced prostate hyperplasia (PH) in Sprague-Dawley rats. Animals were distributed into seven groups (10 rats each). A negative control group were injected with soya oil; six groups were injected with testosterone (3 mg kg(-1)) to induce PH: a positive control group, and five groups treated orally with SPLE (400 mg kg(-1)), CO or sunflower oil (SO) (400 and 800 mg kg(-1)). Treatments were given for 14 days. Rats were weighed before treatment and weekly thereafter. Rats were then killed and the prostates were removed and weighed. CO (400 and 800 mg kg(-1)), SPLE (400 mg kg(-1)) and SO at 800 mg kg(-1), but not at 400 mg kg(-1), significantly reduced the increase in prostate weight (PW) and PW:body weight (BW) ratio induced by testosterone (% inhibition 61.5%, 82.0%, 43.8% and 28.2%, respectively). Since CO and SPLE, but not SO, contain appreciable concentrations of lauric and myristic acids, these results could be attributed to this fact. In conclusion, this study shows that CO reduced the increase of both PW and PW:BW ratio, markers of testosterone-induced PH in rats.

  2. PROCHLORAZ INHIBITS TESTOSTERONE PRODUCTION AT DOSAGE BELOW THOSE THAT AFFECT ANDROGEN-DEPENDENT ORGAN WEIGHTS OR THE ONSET OF PUBERTY IN THE MALE SPRAGUE DAWLEY RAT

    EPA Science Inventory

    ABSTRACT: Since prochloraz (PCZ) is an imidazole fungicide that inhibits gonadal steroidogenesis and antagonizes the androgen receptor (AR), we hypothesized that pubertal exposure to PCZ would delay male rat reproductive development. Sprague Dawley rats were dosed by gavage with...

  3. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Brown, Ronald P.; Fisher, Jeffrey W.

    2011-09-15

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral

  4. Effects of Gelam and Acacia honey acute administration on some biochemical parameters of Sprague Dawley rats

    PubMed Central

    2014-01-01

    Background Since ancient times, honey has been used for medicinal purposes in many cultures; it is one of the oldest and most enduring substances used in wound management. Scientific evidence for its efficacy is widely studied, but systemic safety studies are still lacking. It is essential to study the impact of consumption of honey on the health and proper development of the consumer. Therefore, the present study was designed to observe the effects of acute administration (14 days) of Gelam honey (GH), a wild harvesting honey and Acacia honey (AH), a beekeeping honey, on male and female Sprague Dawley (SD) rats. Methods An acute oral study was performed following OECD test guideline 423, with minor modifications. In the study, GH, AH and sucrose (S) were administered at 2000 mg/kg body weight. Animals were observed for the next 14 days. Gross pathology was performed at the end of the study. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Clinical biochemistry, gross pathology, relative organ weight and histopathological examination were performed. Results Rats fed with honey did not exhibit any abnormal signs or deaths. Results showed a decrease in weight gain and energy efficiency, but significantly increased in total food intake and total calories in female rats fed with GH, compared to control (p < 0.05). Nevertheless, a significant increase in body weight was observed in male rats in all honey-treated groups. Male rats fed with AH significantly decreased in total food intake, total calories and energy efficiency. Both male and female rats fed with GH displayed a significant decrease in triglycerides compared to control group. Hepatic and renal function levels were within acceptable range. The gross necropsy analysis did not reveal changes in any of the organs examined. Conclusions Our results suggest that acute consumption of GH and AH at 2000 mg/kg body weight of male and female SD rats has some discrepancy

  5. Comparative 90-day dietary study of paraffin wax in Fischer-344 and Sprague-Dawley rats.

    PubMed

    Griffis, L C; Twerdok, L E; Francke-Carroll, S; Biles, R W; Schroeder, R E; Bolte, H; Faust, H; Hall, W C; Rojko, J

    2010-01-01

    Highly refined mineral hydrocarbons (MHCs) such as low melting point paraffin wax (LMPW) and low viscosity white oils can cause inflammatory changes in the liver and mesenteric lymph nodes (MLNs) of the Fischer-344 (F-344) rat. In contrast, only minimal MLN changes are seen in the Sprague-Dawley (S-D) rat with no changes in the liver. In this study, the response of female F-344 and S-D rats was compared after 90days dietary treatment with 0%, 0.2% or 2% LMPW. Effects in the F-344 rats were significantly greater than in the S-D rats: increased liver and splenic weights and inflammatory changes (hepatic microgranulomas) in these tissues were observed only in the F-344 rats. Microgranulomas in the MLNs were observed in both strains but the effects were substantially greater in the F-344 rats. Cellular markers of inflammation were examined in a subset of rats from each group using immunohistochemical staining. An increase in staining for CD3 (T-cells), CD8a (suppresser/cytotoxic T-cells) and CD4 (helper T-cells) correlated with an increase in lymphoid cells in the livers of treated F-344 rats. The majority of macrophages in the hepatic microgranulomas of treated F-344 rats were negative for the ED2 marker, indicating a likely origin from non-resident macrophages. Electron microscopy showed Kupffer cell hypertrophy and hyperplasia in treated F-344 rats. However, lysozyme staining (indicating activation of epithelioid macrophages) decreased with increasing granuloma size. Non-ED2 expressing cells may have been recruited but not sufficiently activated to be lysozyme positive. Inflammatory changes in the cardiac mitral valve noted in previous studies of LMPW were also seen in the F-344 rats in this study but not in the S-D rats. Chemical analysis showed that MHC accumulated in livers from treated F-344 but not S-D rats and the concentration was more than 2-fold greater in MLNs from the F-344 than from the S-D rats. The F-344 appears to be more immunologically sensitive to

  6. 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

    PubMed

    Kim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il Je

    2016-09-01

    Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung

  7. Chronic dietary toxicity and carcinogenicity study with potassium perfluorooctanesulfonate in Sprague Dawley rats.

    PubMed

    Butenhoff, John L; Chang, Shu-Ching; Olsen, Geary W; Thomford, Peter J

    2012-03-11

    To investigate toxicity and neoplastic potential from chronic exposure to perfluorooctanesulfonate (PFOS), a two-year toxicity and cancer bioassay was conducted with potassium PFOS (K⁺ PFOS) in male and female Sprague Dawley rats via dietary exposure at nominal K⁺ PFOS concentrations of 0, 0.5, 2, 5, and 20 μg/g (ppm) diet for up to 104 weeks. Additional groups were fed 20 ppm for the first 52 weeks, after which they were fed control diet through study termination (20 ppm Recovery groups). Scheduled interim sacrifices occurred on Weeks 4, 14, and 53, with terminal sacrifice between Weeks 103 and 106. K⁺ PFOS appeared to be well-tolerated, with some reductions in body weight occurring in treated rats relative to controls over certain study periods. Male rats experienced a statistically significant decreased trend in mortality with significantly increased survival to term at the two highest treatment levels. Decreased serum total cholesterol, especially in males, and increased serum urea nitrogen were consistent clinical chemistry observations that were clearly related to treatment. The principal non-neoplastic effect associated with K⁺ PFOS exposure was in livers of males and females and included hepatocellular hypertrophy, with proliferation of endoplasmic reticulum, vacuolation, and increased eosinophilic granulation of the cytoplasm. Statistically significant increases in hepatocellular adenoma were observed in males (p=0.046) and females (p=0.039) of the 20 ppm treatment group, and all of these tumors were observed in rats surviving to terminal sacrifice. The only hepatocellular carcinoma observed was in a 20 ppm dose group female. There were no treatment-related findings for thyroid tissue in rats fed K⁺ PFOS through study termination; however, male rats in the 20 ppm Recovery group had statistically significantly increased thyroid follicular cell adenoma, which was considered spurious. There was no evidence of kidney or bladder effects. In rats, the

  8. Effects of Didecyldimethylammonium Chloride on Sprague-Dawley Rats after Two Weeks of Inhalation Exposure

    PubMed Central

    Chung, Yong-Hyun

    2014-01-01

    Didecyldimethylammonium chloride (DDAC) is used for various purposes, such as a fungicide for coolants, an antiseptic for wood, and disinfectant for cleaning. Despite the increasing likelihood of DDAC inhalation, available data on its toxicity from inhalation are scarce. Therefore, this study was aimed at confirming the toxicity of DDAC after inhalation exposure for 2 wk. Male Sprague-Dawley rats were exposed to approximately 0.15 mg/m3, 0.6 mg/m3, and 3.6 mg/m3 DDAC aerosols in whole-body exposure chambers. After DDAC exposure for 2 wk, effects of DDAC on body weight, blood, bronchoalveolar lavage (BAL), and the lungs were verified. The mass median aerodynamic diameter of DDAC aerosols was 1.86 μm and the geometric standard deviation was 2.75. The concentrations of DDAC aerosols for the low, medium, and high groups were 0.15 ± 0.15 mg/m3, 0.58 ± 0.40 mg/m3, and 3.63 ± 1.56 mg/m3, respectively. Body weight gain was significantly influenced by DDAC exposure. In the high group, a body weight decrease of 2.6 g was observed, whereas a 25.8 g increase was observed in the normal control group after the first 3 days. The low and medium groups showed 23.3 g and 20.4 g increases, respectively, after the first 3 days. Decreases in body weight were recovered during the next 4 days. In contrast, no changes were noted in hematological and blood biochemistry parameters after DDAC exposure. Furthermore, only mild effects were observed on bronchoalveolar cell differentiation counts and cell damage parameters in the BAL fluids of the medium and high groups. Although inflammatory cell infiltration and interstitial pneumonia were partially observed, fibrosis was not found in the lungs of the medium and high groups. In conclusion, body weight gain and the lungs were mainly affected by DDAC exposure. The noobserved-adverse-effect level (NOAEL) for DDAC was determined as 0.15 mg/m3. PMID:25343015

  9. 28-Day inhalation toxicity of graphene nanoplatelets in Sprague-Dawley rats.

    PubMed

    Kim, Jin Kwon; Shin, Jae Hoon; Lee, Jong Seong; Hwang, Joo Hwan; Lee, Ji Hyun; Baek, Jin Ee; Kim, Tae Gyu; Kim, Boo Wook; Kim, Jin Sik; Lee, Gun Ho; Ahn, Kangho; Han, Sung Gu; Bello, Dhimiter; Yu, Il Je

    2016-09-01

    Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 μm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung

  10. Lead acetate does not impair secretion of Sertoli cell function marker proteins in the adult Sprague Dawley rat.

    PubMed

    Nathan, E; Huang, H F; Pogach, L; Giglio, W; Bogden, J D; Seebode, J

    1992-01-01

    This study was conducted to determine the effects of lead on Sertoli cell function. Androgen binding protein and inhibin in testicular fluids and classical parameters of the hypothalamic-pituitary-gonadal axis were measured in adult male rats. For 10 wk, the rats were given water that contained 0.05%, 0.1%, 0.5%, and 1% lead acetate. Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels in all animals that ingested lead were normal at the middle and end of the experiment, as was the pituitary content of follicle-stimulating hormone and luteinizing hormone. Histologic examination revealed no disruption of spermatogenesis. Distribution of androgen binding protein in serum, seminiferous tubular fluid, and interstitial fluid was normal, as was the concentration of inhibin in interstitial fluid and seminiferous tubular fluid. However, a significant increase in epididymal androgen binding protein level and a decrease in seminal vesicle weight were observed in rats that ingested water containing 1% lead acetate. These results suggest that the effect of lead on spermatogenesis is not marked in adult Sprague Dawley rats, nor does Sertoli cell function appear to be affected adversely. Lead has been reported to alter in vitro metabolic function of Sertoli cells obtained from 16- to 21-d-old Sprague Dawley rats, and the Sertoli cells of juvenile animals may be more susceptible to lead than those of adult animals. The significant decrease in seminal vesicle weight and the abnormal epididymal androgen binding protein content indicate that lead could affect the male reproductive function in Sprague Dawley rats via its action on male accessory organs.

  11. Dopaminergic D2-like agonists produce yawning in the myelin mutant taiep and Sprague-Dawley rats.

    PubMed

    Eguibar, Jose R; Cortes, Ma del Carmen; Lara-Lozano, Manuel; Mendiola, Diana M

    2012-07-01

    Systemic administration of D2-like dopaminergic-receptor agonists increases yawning behavior. However, only a few studies have been done in animals with pathological conditions. The taiep rat is a myelin mutant with an initial hypomyelination followed by progressive demyelination, being the brainstem one of the most affected areas. In our experiments, we analyzed the effects of systemic administration of the D2-family agonists and antagonists on yawning behavior, and correlated them with the lipid myelin content in the brainstem and other areas in the central nervous system (CNS) in 8 month old male taiep and Sprague-Dawley rats. Subjects were maintained under standard conditions in Plexiglas cages with a 12:12 light-dark cycle, lights on at 0700 and free access to rodent pellets and tap water. Drugs were freshly prepared injected ip at 0800 and subjects were observed for 60 min. When antagonists were used it was administered 15 min before the agonist. Sprague-Dawley and taiep rats significantly increased their yawning frequency after systemic injection of (-)-quinpirole hydrochloride, R(+)-7-Hydroxy-2-(dipropylamino)tetralin hydrobromide (7-OH-DPAT) or trans-(±)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano [4,3-b]-1,4-oxazin-9-ol hydrochloride ((±)-PD 128,907). Among D2-like agonists used higher effects are obtained with (-)-quinpirole. The effects caused by (-)-quinpirole can be reduced by (-)-sulpiride; and yawning caused by 7-OH-DPAT was decreased by tiapride only in taiep rats. In Sprague-Dawley only (-)-sulpiride is able to decrease (-)-quinpirole-caused yawning. In conclusion, dopaminergic D2-like agonists are still able to cause yawning despite the severe myelin loss in taiep rats. Similarly, patients with various CNS illnesses that affect myelin, such as stroke or multiple sclerosis, are able to yawn suggesting that trigger neurons are still able to command this innate behavior.

  12. New findings regarding light intensity and its effects as a zeitgeber in the Sprague-Dawley rat

    NASA Technical Reports Server (NTRS)

    Tischler, A. C.; Winget, C. M.; Holley, D. C.; Deroshia, C. W.; Gott, J.; Mele, G.; Callahan, P. X.

    1993-01-01

    In most mammals, the suprachiasmatic nucleus of the anterior hypothalamus has been implicated as the central driving mechanism of circadian rhythmicity. The photic input from the retina, via the retino-hypothalamic tract, and modulation from the pineal gland help regulate the clock. In this study, we investigated the effects of low light intensity on the circadian system of the Sprague-Dawley rat. A series of light intensity experiments were conducted to determine if a light level of 0.1 Lux will maintain entrained circadian rhythms of feeding, drinking, and locomotor activity.

  13. Steroidogenic enzyme histochemistry in the testis of Sprague Dawley rats following the administration the water extracts from Carica papaya seed.

    PubMed

    Uche-Nwachi, E O; Mitchell, C V; McEwen, C

    2011-01-01

    Water extracts from pawpaw seed have been reported to reversibly decrease the testicular weight and to suppress spermatogenesis, and fertility of Wistar rats. The reversible changes become evident, 30 - 45 days after the withdrawal of the extract. The possible effect of this extract on the activities of steroidogenic enzymes of the testis has not been investigated. Water extract of papaya seeds was administered to male Sprague Dawley rats ad libitum for 84 days. Following the discontinuation of the extracts, ten rats each were sacrificed on days 0, 10, 20 and 30 after the withdrawal. Their testes were quickly dissected out and frozen. Cryostat sections, 10µm thick were cut. These sections were used for immunohistochemical stains for side chain cleavage enzyme and aromatase, and for histochemical stains for 17-β Hydroxysteroid dehydrogenase, 3-β Hydroxysteroid dehydrogenase. We conclude that the water extract of papaya seed suppresses the activities of steroidogenic enzymes in the testis of Sprague Dawley rats, and that this may contribute to reversible suppression of spermatogenesis, a property that gives a possible male contraceptive potential.

  14. Effect of dietary carbohydrates on plasma lipoproteins in Sprague-Dawley and LA/N-corpulent rats

    SciTech Connect

    Ellwood, K.C.

    1989-01-01

    Male Sprague-Dawley rats were fed diets containing 54% carbohydrate as either sucrose (S), fructose (F) or cooked cornstarch (CS) for 5 weeks. Plasma lipoproteins (LP) were isolated by density gradient ultracentrifugation and separated into very low density P (VLDL), low density LP (LDL) and high density LP (HDL) by gel filtration and affinity chromatography. ApoLP E-rich (R{sub 1} and R{sub 2}) and apoLP E-poor subfractions (NR) of HDL were prepared by heparin-sepharose affinity chromatography. Rats were injected intraperitoneally with {sup 3}H-leucine and sacrificed 2 hours later. Plasma lipoproteins were isolated as described above. The level of {sup 3}H-protein in plasma was greater in Sprague-Dawley rats fed F than those fed S or CS. The amount of {sup 3}H-protein in the chylomicron + VLDL fraction was affected by type of dietary carbohydrate: S > F > CS. Similar studies were conducted with the carbohydrate-sensitive obese and lean LA/N-corpulent rats. Levels of HDL-protein were lower in LA/N-corpulent rats fed S or F than in those fed CS. {sup 3}H-chylomicron + VLDL was higher in rats fed S or F than those fed CS. The concentration of {sup 3}H-protein in plasma and chylomicron + VLDL was greater in obese rats than in lean.

  15. A 90-day study of three bruchid-resistant mung bean cultivars in Sprague-Dawley rats.

    PubMed

    Yao, Yang; Cheng, Xuzhen; Ren, Guixing

    2015-02-01

    Mung bean has been traditionally and widely used as an edible and medicinal plant in the South and Southeast Asia. Bruchid resistance mung bean has more potential in commercial use, but scarcely been evaluated for safety through standard in vivo toxicological studies. In the present study, subchronic oral toxicity studies of bruchid-resistant mung bean were designed and conducted in Sprague-Dawley (SD) rats for 90 days. During the subchronic oral toxicity study, no mortality and toxicologically significant changes in clinical signs, food consumption, opthalmoscopic examination, hematology, clinical biochemistry, macroscopic findings, organ weights and histopathological examination were noted in animal administered diet containing bruchid-resistant mung bean. These results demonstrated that bruchid resistant mung bean is as safe as conventional mung bean.

  16. Using Histopathologic Evidence to Differentiate Reproductive Senescence from Xenobiotic Effects in Middle-aged Female Sprague-Dawley Rats.

    PubMed

    Shirai, Norimitsu; Houle, Christopher; Mirsky, Michael L

    2015-12-01

    The female reproductive cycle is orchestrated by cyclical and coordinated hormonal changes under the direction of the hypothalamic-pituitary-gonadal (HPG) axis. Any disruption of the HPG axis may lead to functional and structural alterations in the female reproductive system. Test article-related disturbances in the estrous cycle can be recognized in nonclinical toxicity studies by staging the cycle based on microscopic evaluation of female reproductive organs. In chronic rat toxicity studies, an additional complication is the development of reproductive senescence, which is associated with natural alterations in the reproductive cycle leading to changes in the female reproductive system that can potentially be confused with test article effects. The current article describes the features of persistent estrus, one stage of reproductive senescence, in middle-aged Sprague-Dawley rats and discusses elements to help differentiate senescence from induced effects.

  17. A high-fructose diet induces hippocampal insulin resistance and exacerbates memory deficits in male Sprague-Dawley rats.

    PubMed

    Wu, Hui-Wen; Ren, Lai-Feng; Zhou, Xing; Han, De-Wu

    2015-10-01

    The purpose of this study was to investigate the effects of a long-term high-fructose diet on the insulin-signaling pathway of the hippocampus. Sprague-Dawley rats were fed either on a control (0% fructose solution) or high-fructose diet (10% fructose solution). Food intake and body mass were measured regularly. Eight months later, peripheral insulin sensitivity, the activity of the hippocampal insulin pathway, and memory tasks were assessed. Compared to the control group, the high fructose group exhibited more weight gain, peripheral insulin resistance, metabolic disorders, and memory impairments. In addition, insulin signaling in the hippocampus was attenuated in the high fructose group. These results suggested that a high-fructose diet induced peripheral insulin resistance and an abnormal insulin-signaling pathway in the hippocampus which exacerbated memory deficits in the rats.

  18. Investigation of the anxiolytic effects of luteolin, a lemon balm flavonoid in the male Sprague-Dawley rat.

    PubMed

    Raines, Terry; Jones, Paul; Moe, Naomie; Duncan, Robert; McCall, Suzanne; Ceremuga, Thomas E

    2009-02-01

    The purpose of this study was to investigate the anxiolytic effects of luteolin and its potential interaction with the gamma-aminobutyric acid (GABAA) receptor in male Sprague-Dawley rats. Lemon balm has traditionally been used as an herbal remedy in the treatment of many medical conditions, including anxiety. Luteolin is a major component of the essential oil lemon balm. We divided 55 rats into 5 groups: (1) control (negative control), (2) luteolin, (3) midazolam (positive control), (4) flumazenil and luteolin, and (5) midazolam and luteolin. The behavioral component of anxiety was examined by using the elevated plus-maze (open arm time/total time) and motor movements. Data analyses were performed using a 2-tailed multivariate analysis of variance and Sheffé post hoc test. Our data suggest that luteolin does not produce anxiolysis by modulation of the GABAA receptor; however, luteolin may modulate motor movements and locomotion. PMID:19263826

  19. Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats.

    PubMed

    Han, Shiwen; Zou, Shiying; He, Xiaoyun; Huang, Kunlun; Mei, Xiaohong

    2016-08-01

    The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals' clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II. PMID:26919987

  20. Investigation of the anxiolytic effects of luteolin, a lemon balm flavonoid in the male Sprague-Dawley rat.

    PubMed

    Raines, Terry; Jones, Paul; Moe, Naomie; Duncan, Robert; McCall, Suzanne; Ceremuga, Thomas E

    2009-02-01

    The purpose of this study was to investigate the anxiolytic effects of luteolin and its potential interaction with the gamma-aminobutyric acid (GABAA) receptor in male Sprague-Dawley rats. Lemon balm has traditionally been used as an herbal remedy in the treatment of many medical conditions, including anxiety. Luteolin is a major component of the essential oil lemon balm. We divided 55 rats into 5 groups: (1) control (negative control), (2) luteolin, (3) midazolam (positive control), (4) flumazenil and luteolin, and (5) midazolam and luteolin. The behavioral component of anxiety was examined by using the elevated plus-maze (open arm time/total time) and motor movements. Data analyses were performed using a 2-tailed multivariate analysis of variance and Sheffé post hoc test. Our data suggest that luteolin does not produce anxiolysis by modulation of the GABAA receptor; however, luteolin may modulate motor movements and locomotion.

  1. Potential subchronic food safety of the stacked trait transgenic maize GH5112E-117C in Sprague-Dawley rats.

    PubMed

    Han, Shiwen; Zou, Shiying; He, Xiaoyun; Huang, Kunlun; Mei, Xiaohong

    2016-08-01

    The food safety of stacked trait genetically modified (GM) maize GH5112E-117C containing insect-resistance gene Cry1Ah and glyphosate-resistant gene G2-aroA was evaluated in comparison to non-GM Hi-II maize fed to Sprague-Dawley rats during a 90-day subchronic feeding study. Three different dietary concentrations (12.5, 25 and 50 %, w/w) of the GM maize were used or its corresponding non-GM maize. No biologically significant differences in the animals' clinical signs, body weights, food consumption, hematology, clinical chemistry, organ weights and histopathology were found between the stacked trait GM maize groups, and the non-GM maize groups. The results of the 90-day subchronic feeding study demonstrated that the stacked trait GM maize GH5112E-117C is as safe as the conventional non-GM maize Hi-II.

  2. Histological changes in kidney structure following a long-term administration of paracetamol (acetaminophen) in pregnant Sprague Dawley rats.

    PubMed

    Ucheya, R E; Igweh, J C

    2006-01-01

    Histological changes in kidney structure following paracetamol administration in pregnant Sprague - Dawley rats were studied. Ten (10) Sprague-Dawley rats divided into five animals per group were used for the study. They were divided into two groups (A and B). Group A served as a control group, while group B received 7.3 mg x 3/kg/day of paracetamol from 10th day of gestation till the 13th day after parturition. The drug was administered by gavage. They were allowed free access to feed and water ad libitum. The maternal rats were then sacrificed for tissue processing. Three deaths were recorded amongst the maternal rats in the paracetamol treated group during parturition and a prolonged gestation period was also observed in the same animals while two maternal rats had a normal gestation period and a safe parturition. Histopathology results of the maternal control animals showed normal kidney architecture (very minimal capsular spaces and rounded glomeruli intimately surrounded by the Bowman's capsule). Two of the paracetamol treated maternal rats that had a safe parturition at the end of the normal gestation period and showed vascular congestion and glomeruli haemorrhage, while one of the maternal rats that had prolonged gestation period (44 days) with signs of abnormally high bleeding during parturition showed higher degree of kidney derangement which was evidenced by shrunken glomerulus's plus droplets in the tubules, vascular congestion, haemorrhage and tubular necrosis. These findings reflect derangement of kidney architecture. The results suggest that paracetamol though considered safe at a considerable low dose especially in pregnant state, could cause kidney derangement during pregnancy. PMID:17242723

  3. A 90-Day Toxicology Study of Meat from Genetically Modified Sheep Overexpressing TLR4 in Sprague-Dawley Rats

    PubMed Central

    Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals. PMID:25874566

  4. A 90-day toxicology study of meat from genetically modified sheep overexpressing TLR4 in Sprague-Dawley rats.

    PubMed

    Bai, Hai; Wang, Zhixian; Hu, Rui; Kan, Tongtong; Li, Yan; Zhang, Xiaosheng; Zhang, Jinlong; Lian, Ling; Han, Hongbing; Lian, Zhengxing

    2015-01-01

    Genetic modification offers alternative strategies to traditional animal breeding. However, the food safety of genetically modified (GM) animals has attracted increasing levels of concern. In this study, we produced GM sheep overexpressing TLR4, and the transgene-positive offsprings (F1) were confirmed using the polymerase chain reaction (PCR) and Southern blot. The expression of TLR4 was 2.5-fold compared with that of the wild-type (WT) sheep samples. During the 90-day safety study, Sprague-Dawley rats were fed with three different dietary concentrations (3.75%, 7.5%, and 15% wt/wt) of GM sheep meat, WT sheep meat or a commercial diet (CD). Blood samples from the rats were collected and analyzed for hematological and biochemical parameters, and then compared with hematological and biochemical reference ranges. Despite a few significant differences among the three groups in some parameters, all other values remained within the normal reference intervals and thus were not considered to be affected by the treatment. No adverse diet-related differences in body weights or relative organ weights were observed. Furthermore, no differences were observed in the gross necropsy findings or microscopic pathology of the rats whose diets contained the GM sheep meat compared with rats whose diets contained the WT sheep meat. Therefore, the present 90-day rat feeding study suggested that the meat of GM sheep overexpressing TLR4 had no adverse effect on Sprague-Dawley rats in comparison with WT sheep meat. These results provide valuable information regarding the safety assessment of meat derived from GM animals.

  5. Histological changes in kidney structure following a long-term administration of paracetamol (acetaminophen) in pregnant Sprague Dawley rats.

    PubMed

    Ucheya, R E; Igweh, J C

    2006-01-01

    Histological changes in kidney structure following paracetamol administration in pregnant Sprague - Dawley rats were studied. Ten (10) Sprague-Dawley rats divided into five animals per group were used for the study. They were divided into two groups (A and B). Group A served as a control group, while group B received 7.3 mg x 3/kg/day of paracetamol from 10th day of gestation till the 13th day after parturition. The drug was administered by gavage. They were allowed free access to feed and water ad libitum. The maternal rats were then sacrificed for tissue processing. Three deaths were recorded amongst the maternal rats in the paracetamol treated group during parturition and a prolonged gestation period was also observed in the same animals while two maternal rats had a normal gestation period and a safe parturition. Histopathology results of the maternal control animals showed normal kidney architecture (very minimal capsular spaces and rounded glomeruli intimately surrounded by the Bowman's capsule). Two of the paracetamol treated maternal rats that had a safe parturition at the end of the normal gestation period and showed vascular congestion and glomeruli haemorrhage, while one of the maternal rats that had prolonged gestation period (44 days) with signs of abnormally high bleeding during parturition showed higher degree of kidney derangement which was evidenced by shrunken glomerulus's plus droplets in the tubules, vascular congestion, haemorrhage and tubular necrosis. These findings reflect derangement of kidney architecture. The results suggest that paracetamol though considered safe at a considerable low dose especially in pregnant state, could cause kidney derangement during pregnancy.

  6. Delta-9-tetrahydrocannabinol disrupts hippocampal neuroplasticity and neurogenesis in trained, but not untrained adolescent Sprague-Dawley rats.

    PubMed

    Steel, Ryan W J; Miller, John H; Sim, Dalice A; Day, Darren J

    2014-02-22

    Cannabis is the most widely used illicit drug, and disruption of learning and memory are commonly reported consequences of cannabis use. We have previously demonstrated a spatial learning impairment by ∆(9)-tetrahydrocannabinol (THC) in adolescent Sprague-Dawley rats (Steel et al., 2011). The molecular mechanisms underlying behavioural impairment by cannabis remain poorly understood, although the importance of adaptive changes in neuroplasticity (synaptic number and strength) and neurogenesis during learning are accepted. Here we aimed to identify any effects of THC on the early induction of these adaptive processes supporting learning, so we conducted our analyses at the mid-training point of our previous study. Both untrained and trained (15 days of training) adolescent (P28-P42) Sprague-Dawley rats were treated daily with THC (6 mg/kg i.p.) or its vehicle, and changes in the levels of markers of hippocampal neuroplasticity (CB1R, PSD95, synapsin-I, synapsin-III) and neurogenesis (Ki67, DCX, PSA-NCAM, BrdU labelling) by training were measured. Training of control animals, but not THC-treated animals increased neuroplasticity marker levels. However training of THC-treated animals, but not control animals reduced immature neuronal marker levels. Levels of hippocampal proliferation, and survival of the BrdU-labelled progeny of these divisions were unaffected by THC in trained and untrained animals. These data show a smaller neuroplastic response, and a reduction of new-born neuronal levels not attributable to effects on proliferation or survival by THC-treatment during training. Importantly no effects of THC were seen in the absence of training, indicating that these effects represent specific impairments by THC on training-induced responses.

  7. [Effect of consumption of bread with amaranth (Amaranthus dubius Mart. ex Thell.) on glycemic response and biochemical parameters in Sprague dawley rats].

    PubMed

    Montero-Quintero, Keyla Carolina; Moreno-Rojas, Rafael; Molina, Edgar Alí; Colina-Barriga, Máximo Segundo; Sánchez-Urdaneta, Adriana Beatriz

    2014-11-01

    Introducción: La incorporación de ingredientes funcionales como el amaranto (Amaranthus dubius Mart. ex Thell.) en la elaboración de pan es una estrategia para aumentar el consumo de fibra, el cual está relacionado con efectos beneficiosos para la salud, mejorando la respuesta glicémica y el perfil lipídico. Materiales y métodos: Treinta ratas machos Sprague dawley se distribuyeron al azar en tres grupos: dieta de pan con 0% de amaranto (PA0, control), dieta de pan con 10% de amaranto (PA10) y dieta de pan con 20% de amaranto (PA20) para determinar el consumo de alimento, ganancia en peso, triglicéridos, colesterol total, VLDL-C, LDL-C, HDL-C, proteínas y la respuesta glicémica postpandrial. Los datos fueron analizados a través de un análisis completamente aleatorizado con 10 repeticiones, utilizando la prueba de comparación de medias de Tukey para los parámetros bioquímicos. La respuesta glicémica postprandial fue analizada por el método de medidas repetidas en el tiempo. Resultados y discusión: La ingesta diaria y la ganancia de peso no se afecto (p>0,05) en los grupos con PA10 y PA20. La concentración de glucosa, triglicéridos y proteína presentó diferencias estadísticamente significativas (p>0,05) por la diferencia de contenido de amaranto de las dietas. Los valores de colesterol total, LDL-C, factor de riesgo e índice aterogénico presentaron diferencias estadísticamente significativas (p>0,05) resultando el grupo de menor valor el formado por PA10 y PA20. En los grupos PA10 y PA20 el pico de hiperglucemia y la fase de hiperglucemia total fue más bajo, mostrando una mejor respuesta glicémica. Conclusión: el amaranto podría ser utilizado como ingrediente funcional en la elaboraciones de panes ya que permitió mejorar el perfil lipídico así como la respuesta glicémica postpandrial.

  8. A MIXTURE OF ORGANOTINS FOUND IN POLYVINYL CHLORIDE (PVC) PIPE IS NOT IMMUNOTOXIC TO SPRAGUE-DAWLEY RATS WHEN GIVEN IN DRINKING WATER

    EPA Science Inventory

    Organotin compounds used in PVC pipe production are of concern to the U.S. EPA because they leach from supply pipes into drinking water and are reported multisystem toxicants. We assessed immune functions in male Sprague-Dawley rats exposed to the mixture of organotins used in P...

  9. Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A maternal low-protein (LP) diet results in low birth weight, increased offspring rapid adipose tissue catch-up growth, adult obesity, and insulin resistance in Sprague-Dawley rats. The placenta functions to fulfill the fetus’ nutrient demands. Placental function is dependent on regulation of immune...

  10. Maternal low protein diet leads to placental angiogenic compensation via dysregulated M1/M2 macrophages and TNFa expression in Sprague-Dawley rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A maternal low-protein (LP) diet results in low birth weight, increased offspring rapid adipose tissue catch-up growth, adult obesity, and insulin resistance in Sprague-Dawley rats. The placenta plays key roles in nutrient transport and fetal growth. Placental function is dependent on regulation of ...

  11. In utero exposure to dietheylhexyl phthalate differentially affects fetal testosterone and insl3 levels in the testes of male Sprague Dawley and Wistar rats: A dose response study

    EPA Science Inventory

    We previously reported that 750 mg/kg/day of diethylhexyl phthalate (DEHP) administered in utero during the period of sex differentiation resulted in a higher prevalence of gubernacular lesions in male Wistar offspring than in the male Sprague Dawley (SD) rat offspring, whereas D...

  12. EFFECTS OF ACUTE EXPOSURE TO CONCENTRATED AMBIENT PARTICULATES ON CARDIOPULMONARY, THERMOREGULATORY, AND BIOCHEMICAL PARAMETERS HEALTHY AND MONOCROTALINE-TREATED SPRAGUE-DAWLEY RATS

    EPA Science Inventory


    EFFECTS OF ACUTE EXPOSURE TO CONCENTRATED AMBIENT PARTICULATES ON CARDIOPULMONARY, THERMOREGULATORY, AND BIOCHEMICAL PARAMETERS IN HEALTHY AND MONOCROTALINE-TREATED SPRAGUE-DAWLEY RATS. LB Wichers1, JP Nolan2, DW Winsett2, UP Kodavanti2, MCJ Schladweiler2, DL Costa2, and WP ...

  13. EFFECTS OF EXPOSURE TO CONCENTRATED AMBIENT PARTICULATES ON INDICES OF CARDIOPULMONARY AND THERMOREGULATORY FUNCTION IN HEALTHY AND MONOCROTALINE-TREATED SPRAGUE-DAWLEY RATS

    EPA Science Inventory


    EFFECTS OF EXPOSURE TO CONCENTRATED AMBIENT PARTICULATES ON INDICES OF CARDIOPULMONARY AND THERMOREGULATORY FUNCTION IN HEALTHY AND MONOCROTALINE-TREATED SPRAGUE-DAWLEY RATS. LB Wichers1, JP Nolan2, UP Kodavanti2, MCJ Schladweiler2, DW Winsett2, DL Costa2, and WP Watkinson2....

  14. EFFECTS OF 20 WEEK EXPOSURES IN FEMALE SPRAGUE-DAWLEY (S-D) RATS TO THE DRINKING WATER DISINFECTION BY-PRODUCT DIBROMOACETIC ACID

    EPA Science Inventory

    Effects of 20 week exposures in female Sprague-Dawley (S-D) rats to the drinking water disinfection by-product dibromoacetic acid. A S Murr and J M Goldman, Endocrinol. Br., RTD, NHEERL, ORD, US EPA, Res. Tri. Pk, NC. Sponsor: Audrey Cummings

    The drinking water disinfect...

  15. EFFECTS OF 20 WEEK EXPOSURES IN FEMALE SPRAGUE-DAWLEY (S-D) RATS TO DIBROMOACETIC ACID, A DRINKING WATER DISINFECTANT BY-PRODUCT

    EPA Science Inventory

    Effects of 20 week exposures in female Sprague-Dawley (S-D) rats to the drinking water disinfection by-product dibromoacetic acid. A S Murr and J M Goldman, Endocrinol. Br., RTD, NHEERL, ORD, US EPA, Res. Tri. Pk, NC. Sponsor: Audrey Cummings

    The drinking water disinfect...

  16. Safety assessment of Maillard reaction products of chicken bone hydrolysate using Sprague-Dawley rats

    PubMed Central

    Wang, Jin-Zhi; Sun, Hong-Mei; Zhang, Chun-Hui; Hu, Li; Li, Xia; Wu, Xiao-Wei

    2016-01-01

    Background The Maillard reaction products of chicken bone hydrolysate (MRPB) containing 38% protein, which is a derived product from chicken bone, is usually used as a flavor enhancer or food ingredient. In the face of a paucity of reported data regarding the safety profile of controversial Maillard reaction products, the potential health effects of MRPB were evaluated in a subchronic rodent feeding study. Methods Sprague–Dawley rats (SD, 5/sex/group) were administered diets containing 9, 3, 1, or 0% of MRPB derived from chicken bone for 13 weeks. Results During the 13-week treatment period, no mortality occurred, and no remarkable changes in general condition and behavior were observed. The consumption of MRPB did not have any effect on body weight or feed and water consumption. At the same time, there was no significant increase in the weights of the heart, liver, lung, kidney, spleen, small intestine, and thymus in groups for both sexes. Serological examination showed serum alanine aminotransferase in both sexes was decreased significantly, indicating liver cell protection. No treatment-related histopathological differences were observed between the control and test groups. Conclusion Based on the results of this study, the addition of 9% MRPB in the diet had no adverse effect on both male and female SD rats during the 90-day observation. Those results would provide useful information on the safety of a meaty flavor enhancer from bone residue as a byproduct of meat industry. PMID:27016175

  17. Trichloroethylene, trichloroacetic acid, and dichloroacetic acid: do they affect eye development in the Sprague-Dawley rat?

    PubMed

    Warren, D A; Graeter, L J; Channel, S R; Eggers, J S; Goodyear, C D; Macmahon, K L; Sudberry, G L; Latendresse, J R; Fisher, J W; Baker, W H

    2006-01-01

    Maternal exposure to high doses of trichloroethylene (TCE) and its oxidative metabolites, trichloroacetic acid (TCA) and dichloroacetic acid (DCA), has been implicated in eye malformations in fetal rats, primarily micro-/anophthalmia. Subsequent to a cardiac teratology study of these compounds (Fisher et al. 2001, Int. J. Toxicol. 20:257-267), their potential to induce ocular malformations was examined in a subset of the same experimental animals. Pregnant, Sprague-Dawley Crl:CDR BR rats were orally treated on gestation days (GDs) 6 to 15 with bolus doses of either TCE (500 mg/kg/day), TCA (300 mg/kg/day), DCA (300 mg/kg/day), or all-trans retinoic acid (RA; 15 mg/kg/day). The heads of GD 21 fetuses were not only examined grossly for external malformations, but were sectioned using a modified Wilson's technique and subjected to computerized morphometry that allowed for the quantification of lens area, globe area, medial canthus distance, and interocular distance. Gross ocular malformations were essentially absent in all treatment groups except for the RA group in which 26% of fetuses exhibited micro-/anophthalmia. Using the litter as the experimental unit of analysis, lens area, globe area, and interocular distance were statistically significantly reduced in the DCA treatment group. Statistically significant reductions in lens and globe areas also occurred in the RA treatment group, all four ocular measures were reduced in the TCA treatment group but none significantly so, and TCE was without effect. Because DCA, TCA, and RA treatments were associated with significant reductions in fetal body weight (bw), data were also statistically analyzed after bw adjustment. Doing so dramatically altered the results of treatment group comparisons, but the severity of bw reduction and the degree of change in ocular measures did not always correlate. This suggests that bw reduction may not be an adequate explanation for all the changes observed in ocular measures. Thus, it is

  18. Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

    PubMed

    Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

    2016-01-15

    Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. PMID:26608659

  19. Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

    PubMed

    Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

    2016-01-15

    Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension.

  20. Nanosuspension of Phyllanthus amarus extract for improving oral bioavailability and prevention of paracetamol induced hepatotoxicity in Sprague-Dawley rats

    NASA Astrophysics Data System (ADS)

    Bhushan Mishra, Shanti; Pandey, Himanshu; Pandey, Avinash C.

    2013-09-01

    Phyllanthus amarus (P. amarus) is commonly used for traditional Indian medicine and as dietary adjuncts for the treatment of numerous physiological disorders including hepatic disorders. Due to the poor water solubility of its major constituents such as lignans and flavonoids, its absorption upon oral administration could be limited. The present study was designed to evaluate and compare the hepatoprotective effects of the ethanolic extract of P. amarus (PAE) and its nanoparticles (PAN) on paracetamol induced acute liver toxicity in Sprague-Dawley rats. An oral dose of PAE at 125 and 250 mg kg-1 and PAN at 25 and 50 mg kg-1 showed a significant hepatoprotective effect relatively to the same extent (P < 0.001) by reducing levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bile salts. These biochemical assessments were supported by rat hepatic biopsy examinations. Moreover, the results also indicated that the hepatoprotective effect of 50 mg kg-1 PAN was effectively better than 125 mg kg-1 PAE (P < 0.001), and an oral dose of PAN that is five times less than PAE could exhibit similar levels of outcomes. In conclusion, we suggest that the nanoparticles system can be applied to overcome other poorly water soluble herbal medicines and furthermore to decrease the treatment dosage.

  1. Pharmacokinetic studies and LC-MS/MS method development of ganciclovir and dipeptide monoester prodrugs in sprague dawley rats

    PubMed Central

    Gunda, Sriram; Earla, Ravinder; Cholkar, Kishore; Mitra, Ashim K

    2014-01-01

    Ganciclovir (GCV) is utilized as an anti-herpetic agent. Reports from our laboratory have suggested that dipeptide ester prodrugs of GCV exhibit high affinity towards the oligopeptide transporter hPEPT1 and therefore seem to be promising candidates for the treatment of oral herpes virus infections. In this study, we have examined the bio-availability of a dipeptide prodrug of GCV after oral administration in jugular cannulated Sprague-Dawley rats. A new bio-analytical method was developed with Q-TRAP liquid chromatography tandem mass spectroscopy (LC-MS/MS) for simultaneous analysis of GCV, Valine-GCV (VGCV) and Tyrosine-Valine-GCV (YVGCV). Acyclovir (ACV) was used as an internal standard in the analysis. Area under plasma-concentration (AUC) time curves for total concentration of GCV after oral administration of YVGCV was found to be approximately 200% more than that of GCV following intestinal absorption. A complete conversion of the dipeptide prodrug (YVGCV) to parent compound, GCV, by hepatic first pass metabolism was evident due to the absence of intermediate metabolite VGCV and administered prodrug YVGCV. The dipeptide prodrugs of GCV exhibits higher systemic availability of regenerated GCV upon oral administration and thus seem to be promising drug candidate in the treatment of systemic herpes infections. PMID:24943988

  2. PVP formulated Fullerene (C60) increases Rho-kinase dependent Vascular Tissue Contractility in Pregnant Sprague Dawley Rats

    PubMed Central

    Vidanapathirana, Achini K.; Thompson, Leslie C.; Mann, Erin. E.; Odom, Jillian T.; Holland, Nathan A.; Sumner, Susan J.; Han, Li; Lewin, Anita H.; Fennell, Timothy R.; Brown, Jared M.; Wingard, Christopher J.

    2014-01-01

    Pregnancy is a unique physiological state, in which C60 fullerene is reported to be distributed in both maternal and fetal tissues. Tissue distribution of C60 differs between pregnant and non-pregnant states, presumably due to functional changes in vasculature during pregnancy. We hypothesized that, polyvinylpyrorrolidone (PVP) formulated C60 (C60/PVP) increases vascular tissue contractility during pregnancy by increasing Rho-kinase activity. C60/PVP was administered intravenously to pregnant and non-pregnant female Sprague Dawley rats. Vascular responses were assessed using wire myography 24 hours post-exposure. Increased stress generation was observed in uterine artery, thoracic aorta and umbilical vein. Rho-Rho-kinase mediated force maintenance was increased in arterial segments from C60/PVP exposed pregnant rats when compared to PVP exposed rats. Our findings suggest that intravenous exposure to C60/PVP during pregnancy increases vascular tissue contractility of the uterine artery through elements of Rho-Rho-kinase signaling during late stages of pregnancy. PMID:25088243

  3. 13-Week oral toxicity study of oil derived from squid (Todarodes pacificus) in Sprague-Dawley rats.

    PubMed

    Park, Joung-Hyun; Musa-Veloso, Kathy; Lynch, Barry; Leslie, Heather; Koo, Kyo-Hwan; Kim, Seon-Bong; Kang, Suk-Nam

    2012-11-01

    Recommendations to increase the consumption of the long-chain omega-3 fatty acids are challenged by the global problem of declining fish stocks. Non-traditional and more sustainable sources of the long-chain omega-3 fatty acids are needed. Squid (Todarodes pacificus) represents a uniquely sustainable source of these fatty acids. A 13-week oral toxicity study was conducted in male and female Sprague-Dawley rats administered either 0, 250, 500, or 1000μl/kg body weight (bw)/day of a refined squid oil. All of the rats survived through to the end of the study. All of the rats grew normally and had normal clinical and ophthalmic observations. No signs of toxicity were evident from clinical chemistry, hematology, and urinalysis data measured. No abnormal findings attributable to exposure to purified squid oil were observed following the necropsy of male and female rats and the histopathological examination of the organs. The no-observed-adverse-effect level for refined squid oil was determined to be 1000μl/kg bw/day, the highest dose tested.

  4. Evaluation of the anxiolytic properties of myristicin, a component of nutmeg, in the male Sprague-Dawley rat.

    PubMed

    Leiter, Emily; Hitchcock, Gavin; Godwin, Stuart; Johnson, Michelle; Sedgwick, William; Jones, Wendy; McCall, Suzanne; Ceremuga, Thomas E

    2011-04-01

    The purpose of this study was to investigate the anxiolytic effects of myristicin, a major compound found in nutmeg, and its potential interaction with the gamma-aminobutyric acid (GABA(A)) receptor in male Sprague-Dawley rats. Nutmeg has traditionally been used as a spice in food preparation and as an herbal remedy in the treatment of many medical conditions, including anxiety. Fifty-five rats were divided equally into 5 groups: control (vehicle); myristicin; midazolam (positive control); flumazenil and myristicin; and midazolam and myristicin. The behavioral component of anxiety was examined by using the elevated plus-maze (open-arm and closed-arm times) along with analysis of gross and fine motor movements. Data analysis was performed using a 2-tailed multivariate analysis of variance (MANOVA) and least significant difference post-hoc test. Our data suggest that myristicin does not decrease anxiety by modulation of the GABA(A) receptor but may promote anxiogenesis. When myristicin was combined with midazolam, an antagonist-like effect similar to the flumazenil and myristicin combination was exhibited by a decrease in anxiolysis compared with the midazolam-only group. Myristicin may antagonize the anxiolytic effects of midazolam, increase anxiety, and affect motor movements.

  5. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

    PubMed

    Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

    2012-04-10

    Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  6. The effects of acute tryptophan depletion on affective behaviour and cognition in Brown Norway and Sprague Dawley rats.

    PubMed

    Jans, L A W; Korte-Bouws, G A H; Korte, S M; Blokland, A

    2010-04-01

    Previous studies in rats and humans have shown that the essential amino acid tryptophan (TRP) is depleted after consumption of a gelatin-based protein-carbohydrate mixture, which is lacking L-tryptophan (TRP-). In rats, TRP depletion caused impaired object recognition but only had a modest effect on affective behaviour. Because these studies were preformed with Wistar rats, the aim of the present experiment was to evaluate strain differences in behavioural responses to acute TRP depletion between Brown Norway (BN) and Sprague Dawley (SD) rats. The rats were repeatedly treated with TRP- or a balanced control (TRP+) and were tested in tests of anxiety- and depression-related behaviour (open-field test, home cage emergence test, social interaction test, forced swim test) and memory. SD rats, but not BNs, showed more anxiety- and depression-related behaviour and impaired object recognition after TRP- treatment. There was a dissociation between plasma TRP levels, central 5-HT concentrations and 5-HIAA/5-HT turnover. Both strains showed about 60% decrease in plasma TRP/SigmaLNAA levels, whereas hippocampal 5-HT levels were lower after TRP- in BN but not SD rats. Conversely, 5-HIAA/5-HT turnover was lower after TRP- in SD but not BN rats, suggesting a dissociation between 5-HT storage and release in SDs. The present study suggests that acute tryptophan depletion effects are strain dependent on the behavioural and the neurochemical level. PMID:19074537

  7. Inhibition of secondary cartilage of the intermaxillary suture in Sprague-Dawley rats following the enucleation of maxillary molars

    SciTech Connect

    Forbes, D.P.; Al-Bareedi, S.

    1986-01-01

    A single craniofacial suture can undergo several morphologic transformations during its development. From 3 to 7 weeks of age, the intermaxillary suture of the rat is synchondrotic in character, featuring secondary cartilage; at later times, this suture is syndesmotic in character, featuring a fibrous tissue interface. Since intermittent mechanical stimulation has been reported to initiate secondary cartilage formation, a study was done to determine if the functioning dentition were responsible for secondary cartilage formation in the intermaxillary suture of the rat. Twenty-two female Sprague-Dawley rats were used. At 3 weeks of age, prior to eruption, the maxillary molars were enucleated from nine animals. Body weights were recorded weekly. Animals were sacrificed weekly from 4 to 7 weeks of age. One hour prior to sacrifice, each rat was injected with (/sup 35/S)sulfate at a dosage of 2 microCi/g body weight. The tissues were evaluated by light microscopy and autoradiography. In the experimental group, the midpalatal suture did not undergo the normal synchondrotic transformation. Instead, this suture remained fibrous with negligible metachromatic staining. In the control animals, the peak period of (/sup 35/S)sulfate incorporation was 4 weeks of age and was five times greater than in the experimental group. The primary stimulus for the initiation of secondary cartilage formation in the midpalatal suture of the rat was molar function. Also, functioning molars were found to be important in the maintenance of the palatal bone.

  8. The effect of genetically modified Lactobacillus plantarum 590 on the gut health of Sprague-Dawley rats.

    PubMed

    Liu, Hai-Yan; Xu, Wen-Tao; Yuan, Yan-Fang; Cao, Si-Shuo; He, Xiao-Yun; Li, Shuang-Ying; Huang, Kun-Lun; Luo, Yun-Bo

    2012-07-01

    Lp was a generally recognized as safe microorganism. Lactobacillus plantarum 590 was obtained by inserting nisI gene into Lp genome to help it tolerate higher concentration nisin. As the unintended effects of the genetically modified microorganism (GMM) are the most important barriers to the progress of GMM, we have performed a useful exploration to establish a new in vivo evaluation model for GMM from the point of view of intestinal health. In this study, Sprague-Dawley rats were orally administered with Lp 590 and Lp for 4 weeks. Fecal samples were collected to determine the number of beneficial bacteria Bifidobacterium and harmful bacteria Clostridium perfringens. Denaturing gradient gel electrophoresis was used to detect the bacterial profiles of every group. Fecal enzyme activities and short-chain fatty acids as main metabolites were also examined. Real time PCR (RT-PCR) and immunohistochemistry were used to analyze two proteins (ZO-1 and occludin) and secretory immunoglobulin A to detect intestinal permeability and mucosal immunity, gut permeability and gut mucosal immunity were analyzed to see whether GM Lp 590 can induce changes of the gut health when compared with non-GM Lp group, andeventually we concluded that there is no significant difference between GM Lp 590-fed group and non-GM Lp-fed group. The conclusion of gut health test was comparable withthat from traditional subchronic test. Evaluation of intestinal health will be a new approach of assessing the safety of GMM. PMID:22648689

  9. A subchronic feeding study of dicamba-tolerant soybean with the dmo gene in Sprague-Dawley rats.

    PubMed

    Wang, Xiaoyun; He, Xiaoyun; Zou, Shiyin; Xu, Wentao; Jia, Xin; Zhao, Bo; Zhao, Changhui; Huang, Kunlun; Liang, Zhihong

    2016-06-01

    The dicamba-tolerant soybean MON87708 expresses the dicamba mono-oxygenase (DMO) enzyme that is encoded by the dmo gene. In order to evaluate the safety of this soybean, a 90-day subchronic feeding toxicity study (13 weeks) was conducted on Sprague-Dawley rats. A total of 140 rats were divided into 7 groups (10/sex/group), including a standard commercial diet control group. The genetically modified (GM) soybean MON87708 and the near isogenic non-GM soybean A3525 were respectively processed to unhulled, full-fat, and heat-treated powder, then mixed into the diet at levels of 7.5%, 15%, and 30% (wt/wt) with the main nutrients of the various diets balanced and then fed to 6 groups. The remaining group of rats fed with a commercial rat diet served as blank control. Some isolated parameters indicated statistically significant differences in body weight, feed consumption/utilization, hematology, serum biochemistry, and relative organ weights. These differences were not consistent across gender or test-diet dose, which were attributed to incidental and biological variability. In conclusion, the results demonstrated that the transgenic soybean MON87708 containing DMO was as safe as non-transgenic isogenic counterpart with historical safe use. PMID:26850684

  10. Chemopreventive potential of fungal taxol against 7, 12-dimethylbenz[a]anthracene induced mammary gland carcinogenesis in Sprague Dawley rats.

    PubMed

    Gokul Raj, Kathamuthu; Chidambaram, Ranganathan; Varunkumar, Krishnamoorthy; Ravikumar, Vilwanathan; Pandi, Mohan

    2015-11-15

    Breast cancer is the second most prevalent cancer and foremost global public health problem. The present study was designed to appraise the chemopreventive potential of fungal taxol against 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary gland carcinogenesis in Sprague Dawley rats. After 90 days of tumor induction, fungal and authentic taxol were given intraperitoneally once in a week for four weeks. Infrared thermal imaging analysis, serum biochemical parameters such as lipid peroxidase (LPO), creatinine, enzymic and non enzymic antioxidants, liver markers tests such as alanine transaminase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG) and lipoproteins was analysed. In addition, histopathological observation (breast, kidney and liver), immunohistochemical analysis (p53 and Her2/neu) and western blotting experiments (bcl-2, bax and caspase-9) were performed both in control and experimental animals. In thermal imaging, decreased temperature was observed in rat treated with fungal and authentic taxol when compared to tumor induced rats. The significant decrease in LPO, creatinine, ALT, AST, TC, TG, lipoproteins and increase in enzymic, non-enzymic antioxidants were exemplified in serum of treated groups. Further histopathology, immunohistochemical and western blot analysis (bax, cas-9 and bcl-2) of apoptotic markers in breast tissues clearly showed the anti-carcinogenic property of fungal taxol. Our findings implement that fungal taxol is a potential chemo preventive agent against DMBA induced mammary gland carcinogenesis.

  11. Lifetime toxicity/carcinogenicity study of FD & C Red No. 40 (allura red) in Sprague-Dawley rats.

    PubMed

    Borzelleca, J F; Olson, J W; Reno, F E

    1989-11-01

    FD & C Red No. 40 was fed to Charles River CD (Sprague-Dawley) rats as a dietary admixture in a lifetime toxicity/carcinogenicity study. The study included a phase during which the colouring was administered to parental rats (30 of each sex per group) at concentrations of 0.0, 0.37, 1.39 and 5.19%, throughout the mating, gestation and lactation periods. The concurrent control group received the basal diet. After random selection of the first-generation rats, the lifetime phase was initiated using the same dietary concentrations with 50 rats of each sex per group. The maximum durations of exposure to the colouring were 118 and 121 for males and females, respectively. No compound-related adverse effects were observed, except for a reduction in body weight in high-dose females at the end of the study. The no-adverse-effect levels in this study were 5.19% (2829 mg/kg/day) for male rats, and 1.39% (901 mg/kg/day) for female rats.

  12. General toxicity and reproductive screen of liquid propellant XM46 administered in the drinking water of Sprague-Dawley rats.

    PubMed

    Kinkead, E R; Wolfe, R E; Salins, S A; Flemming, C D; Leahy, H F; Caldwell, D J; Miller, C R; Marit, G B

    1995-01-01

    Liquid propellant XM46 is being considered as a replacement for solid propellants, both as part of a regenerative injection gun system and as a working fluid in an electrothermal gun system. The XM46 formulation contains hydroxylammonium nitrate, triethanolammonium nitrate, and water. Male and female Sprague-Dawley rats received XM46 in drinking water containing 2.0, 1.0, 0.2, or 0.0 g XM46/liter throughout a 90-day study. Mating occurred following 14 days of treatment. One-half the male rats per group were necropsied after 28 days of treatment; the remaining males and all dams were necropsied following 90 days of treatment. No mortality occurred in any of the parental animals during the study. The study did not demonstrate any adverse effects on reproduction or litter parameters. Hemolytic anemia and methemoglobinemia were common in both sexes of rats. Splenomegaly was found in both sexes; in male rats as early as 28 days. Exposures via drinking water containing XM46 for 90 days did not result in any decrease in reproductive performance in male or female rats, but it did result in clinical signs of hemolytic anemia at doses as low as 17 mg/kg/day.

  13. The Remedial Efficacy of Spirulina platensis versus Chromium-Induced Nephrotoxicity in Male Sprague-Dawley Rats.

    PubMed

    Elshazly, M O; Abd El-Rahman, Sahar S; Morgan, Ashraf M; Ali, Merhan E

    2015-01-01

    This study was conducted to investigate the possible protective effect of Spirulina platensis against chromium-induced nephrotoxicity. A total of 36 adult male Sprague-Dawley rats were divided into 4 equal groups (Gps). Gp1 served as control, rats of Gps 2, 3, and 4 were exposed to Spirulina platensis (300 mg/kg b.wt per os) and sodium dichromate dihydrate (SDD) via drinking water at concentration of 520 mg /l respectively. Chromium administration caused alterations in the renal function markers as evidenced by significant increase of blood urea and creatinine levels accompanied with significant increase in kidney's chromium residues and MDA level as well as decreased catalase activity and glutathion content in kidney tissue. Histologically, Cr provoked deleterious changes including: vascular congestion, wide spread tubular epithelium necrobiotic changes, atrophy of glomerular tuft and proliferative hyperplasia. The latter was accompanied with positive PCNA expression in kidney tissues as well as DNA ploidy interpretation of major cellular population of degenerated cells, appearance of tetraploid cells, high proliferation index and high DNA index. Morphometrical measurements revealed marked glomerular and tubular lumen alterations. On contrary, spirulina co-treatment with Cr significantly restored the histopathological changes, antioxidants and renal function markers and all the previously mentioned changes as well. PMID:26029926

  14. Effect of exercise and protein intake during pregnancy on maternal and fetal zinc content in the Sprague-Dawley rat

    SciTech Connect

    Asente, R.A.; Cameron, S.R.; Taper, L.J.

    1986-03-05

    Pregnant Sprague-Dawley rats (179) were divided into four groups: sedentary-standard protein diet, sedentary-high protein diet, exercising-standard protein diet and exercising-high protein diet. The standard protein diet contained 24.77% protein; all other nutrients were supplied in amounts required for normal parturition. After aclimitization, the exercising dams, regardless of diet, were forced to swim continuously for one and one-half hours/day until sacrifice. The four major groups were further subdivided into 28 groups, designated by three-day intervals according to gestational day - days 3, 6, 9, 12, 15, 18 and 21. Uterine tissues were analyzed for zinc; fetal and placental tissues were separated from uterine tissue for days 15 through 21 only. Uterine zinc was affected solely by gestation; absolute placental zinc values were lowest in the sedentary-high and exercising-low protein groups, while the exercising-high protein group possessed the greatest. No significant difference was detected in fetal zinc concentrations. Fetal tissues from exercising dams weighed significantly less than fetal tissue from the sedentary dams; and sedentary-high protein dams produced significantly more fetuses than the exercising-high protein dams. Both protein intake and exercise significantly affect normal parturition and zinc metabolism in the rat.

  15. Distribution of iodine into blood components of the Sprague-Dawley rat differs with the chemical form administered

    NASA Technical Reports Server (NTRS)

    Thrall, K. D.; Bull, R. J.; Sauer, R. L.

    1992-01-01

    It has been reported previously that radioactivity derived from iodine distributes differently in the Sprague-Dawley rat depending on the chemical form administered (Thrall and Bull, 1990). In the present communication we report the differential distribution of radioactivity derived from iodine (I2) and iodide (I-) into blood components. Twice as much radioiodine is in the form of I- in the plasma of animals treated with 125I- compared to 125I2-treated rats. No I2 could be detected in the plasma. With an increase in dose, increasing amounts of radioactivity derived from 125I2-treated animals distribute to whole blood compared to equivalent doses of 125I-, reaching a maxima at a dose of 15.8 mumol I/kg body weight. Most of the radioactivity derived from I2 associates with serum proteins and lipids, in particular with albumin and cholesteryl iodide. These data indicate a differential distribution of radioactivity depending on whether it is administered as iodide or iodine. This is inconsistent with the commonly held view that iodine (I2) is reduced to iodide (I-) before it is absorbed systemically from the gastrointestinal tract.

  16. Effect of leptin combined with CoCl2 on healing in Sprague Dawley Rat fracture model

    PubMed Central

    Liu, Pengcheng; Liu, Junfeng; Xia, Kuo; Chen, Liyang; Wu, Xing

    2016-01-01

    To evaluate the effect of leptin combined with CoCl2 on rat femur fracture healing. 48 male Sprague Dawley rats were randomly divided into two main groups. Then standardized femur fractures were created to all rats. Control group rats were treated with 0.5 mL physiological saline, and experimental group rats were treated with 5 μg/Kg.d leptin and 15 mg/Kg.d CoCl2 along with 0.5 mL physiological saline for 42 days intraperitoneally. Each main group was divided into three subgroups for each evaluation at second, fourth and sixth weeks, each subgroup included eight rats. The radiological evaluation showed that the fracture healing progress of experimental group was superior to control group from second week. At fourth week, experimental group had better fracture healing progress than control group significantly. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of experimental group was significantly increased than that in control group from fourth week. The present result demonstrated that leptin combined with CoCl2 significantly increased the mRNA expression levels of HIF1A, Vegfa, Runx2, Bmp2, Bglap and Alpl. It suggested that leptin combined with CoCl2 have a positive effect on rat femur fracture healing by activating the HIF1A pathway. PMID:27468656

  17. Protective Effects of Tamarillo (Cyphomandra betacea) Extract against High Fat Diet Induced Obesity in Sprague-Dawley Rats

    PubMed Central

    Abdul Kadir, Noor Atiqah Aizan; Rahmat, Asmah; Jaafar, Hawa Z. E.

    2015-01-01

    This study aims to investigate the protective effect of Cyphomandra betacea in adult male Sprague-Dawley rats fed with high fat diet. Rats were fed on either normal chow or high fat diet for 10 weeks for obesity induction phase and subsequently received C. betacea extract at low dose (150 mg kg−1), medium dose (200 mg kg−1), or high dose (300 mg kg−1) or placebo via oral gavages for another 7 weeks for treatment phase. Treatment of obese rats with C. betacea extracts led to a significant decrease in total cholesterol and significant increase in HDL-C (p < 0.05). Also there was a trend of positive reduction in blood glucose, triglyceride, and LDL-C with positive reduction of body weight detected in medium and high dosage of C. betacea extract. Interestingly, C. betacea treated rats showed positive improvement of superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity along with a significant increase of total antioxidant status (TAS) (p < 0.05). Further, rats treated with C. betacea show significantly lower in TNF-α and IL-6 activities (p < 0.05). This study demonstrates the potential use of Cyphomandra betacea extract for weight maintenance and complimentary therapy to suppress some obesity complication signs. PMID:26171246

  18. Dose-rate effects of mammary tumor development in female Sprague-Dawley rats exposed to X and gamma radiation

    SciTech Connect

    Johnson, J.R.; Gragtmans, N.J.; Myers, D.K.; Jones, A.R.

    1989-06-01

    Mammary tumour development was followed in two experiments involving a total of 2229 female Sprague-Dawley rats exposed to various doses of X or gamma rays at different dose rates. The data for another 462 rats exposed to tritiated water in one of these experiments were also analyzed. The incidence of adenocarcinomas and fibroadenomas at a given time after exposure increased linearly in proportion to total radiation dose for most groups. However, no significant increase in adenocarcinomas was observed with chronic gamma exposures up to 1.1 Gy, and the increase in fibroadenomas observed with chronic gamma exposures at a dose rate of 0.0076 Gy h-1 up to an accumulated dose of 3.3 Gy was small compared to that observed after acute exposures. The incidence of all mammary tumors increased almost linearly with the log of dose rate in the range 0.0076 to 26.3 Gy h-1 for 3 Gy total dose of gamma rays. The effects of X rays appeared to be less influenced by dose rate than were the effects of gamma rays.

  19. Safety Evaluation of Oral Toxicity of Carica papaya Linn. Leaves: A Subchronic Toxicity Study in Sprague Dawley Rats.

    PubMed

    Ismail, Zakiah; Halim, Siti Zaleha; Abdullah, Noor Rain; Afzan, Adlin; Abdul Rashid, Badrul Amini; Jantan, Ibrahim

    2014-01-01

    The subchronic toxicity effect of the leaf extract of Carica papaya Linn. in Sprague Dawley (SD) rats was investigated in this study. The extract was prepared by dissolving the freeze dried extract of the leaves in distilled water and was administered orally to SD rats (consisted of 10 rats/sex/group) at 0 (control), 0.01, 0.14, and 2 g/kg body weight (BW) for 13 weeks. General observation, mortality, and food and water intake were monitored throughout the experimental period. Hematological and biochemical parameters, relative organ weights, and histopathological changes were evaluated. The study showed that leaf extract when administered for 13 weeks did not cause any mortality and abnormalities of behavior or changes in body weight as well as food and water intake. There were no significant differences observed in hematology parameters between treatment and control groups; however significant differences were seen in biochemistry values, for example, LDH, creatinine, total protein, and albumin. However, these changes were not associated with histopathological changes. In conclusion, the results suggested that daily oral administration of rats with C. papaya leaf extract for 13 weeks at a dose up to fourteen times the levels employed in traditional medicine practice did not cause any significant toxic effect. PMID:25530788

  20. Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague-Dawley Rat.

    PubMed

    Filgo, Adam J; Foley, Julie F; Puvanesarajah, Samantha; Borde, Aditi R; Midkiff, Bentley R; Reed, Casey E; Chappell, Vesna A; Alexander, Lydia B; Borde, Pretish R; Troester, Melissa A; Bouknight, Schantel A Hayes; Fenton, Suzanne E

    2016-10-01

    There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies. PMID:27613106

  1. Molecular basis for the effects of zinc deficiency on spermatogenesis: An experimental study in the Sprague-dawley rat model

    PubMed Central

    Omu, Alexander E.; Al-Azemi, Majedah K.; Al-Maghrebi, May; Mathew, Chacko T.; Omu, Florence E.; Kehinde, Elijah O.; Anim, Jehoram T.; Oriowo, Mabayoje A.; Memon, Anjum

    2015-01-01

    Introduction: The objective of this study is to investigate the molecular mechanisms underlying the effects of zinc deficiency on spermatogenesis in the Sprague-Dawley (SD) rat. Materials and Methods: Three groups of eight adult male SD rats were maintained for 4 weeks on a normal diet as control, zinc deficient diet and zinc deficient diet with zinc supplementation of 28 mg zinc/kg body weight respectively. Using standard techniques, the following parameters were compared between the three groups of experimental animals at the end of 4 weeks: (a) Serum zinc, magnesium (Mg), copper (Cu), selenium (Se) and cadmium (Cd), (b) serum sex hormones, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX), (c) interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), Bcl-2, Bax and caspase-3 expression in the testes, (d) assessment of apoptosis of testicular cells using electron microscopy and (e) testicular volume and histology using the orchidometer and Johnsen score, respectively. Results: The zinc deficient group showed a reduction of testicular volume, serum concentrations of Zn, Cu, Se, Mg, SOD, GPX, IL-4, Bcl-2 and testosterone (P < 0.05), as well as increased levels of serum Cd, MDA and tissue TNF-α, Bax, caspase-3 and apoptosis of the germ cells (P < 0.05) compared with control and zinc supplementation groups. Conclusion: Zinc deficiency is associated with impaired spermatogenesis because of reduced testosterone production, increased oxidative stress and apoptosis. These findings suggest that zinc has a role in male reproduction. PMID:25624578

  2. The estrogenicity of methylparaben and ethylparaben at doses close to the acceptable daily intake in immature Sprague-Dawley rats.

    PubMed

    Sun, Libei; Yu, Tong; Guo, Jilong; Zhang, Zhaobin; Hu, Ying; Xiao, Xuan; Sun, Yingli; Xiao, Han; Li, Junyu; Zhu, Desheng; Sai, Linlin; Li, Jun

    2016-01-01

    The estrogenicity of parabens at human exposure levels has become a focus of concern due to the debate over whether the estrogenicity of parabens is strong enough to play a role in the increased incidence of breast cancer. In this study, the uterotrophic activities of methylparaben (MP) and ethylparaben (EP) at doses close to the acceptable daily intake as allocated by JECFA were demonstrated in immature Sprague-Dawley rats by intragastric administration, and up-regulations of estrogen-responsive biomarker genes were found in uteri of the rats by quantitative real-time RT-PCR (Q-RT-PCR). At the same time, the urinary concentrations of MP and EP, as measured by gas chromatography-mass spectrometry (GC-MS) in rats that received the same doses of MP and EP, were found to be near the high urinary levels reported in human populations in recent years. These results show the in vivo estrogenicity of MP and EP at human exposure levels, and indicate that populations exposed to large amounts of MP and EP may have a high burden of estrogenicity-related diseases. In addition, a molecular docking simulation showed interaction between the parabens and the agonist-binding pocket of human estrogen receptor α (hERα). PMID:27121550

  3. Protective role of tannin-rich fraction of Camellia sinensis in tissue arsenic burden in Sprague Dawley rats.

    PubMed

    Chandronitha, C; Ananthi, S; Ramakrishnan, G; Lakshmisundaram, R; Gayathri, V; Vasanthi, Hannah R

    2010-09-01

    The protective effect of green tea (Camellia sinensis) was tested against arsenic-induced toxicity. However, the possible role of tannins in green tea in alleviating hepatic and renal oxidative injury has also been studied. Administration of sodium arsenite (100 mg/kg/day) for 28 days in Sprague Dawley female rats resulted in significant reduction of biochemical parameters such as delta-aminolevulinic acid dehydratase (ALAD), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and elevation of thiobarbituric acid reactive substances (TBARS) and the index of nitrite/nitrate (NOx) levels. The tissue arsenic burden was increased after arsenic exposure for a period of 28 days. Green tea crude fraction (GTC) co-treated with sodium arsenite for 28 days caused significant (p < .01) elevation of ALAD, GSH, GPx, SOD, and nitrate/nitrite levels and reduction of the TBARS level and tissue burden when compared to detannified green tea fraction (GTDT)-treated groups. The protective role of tannin-rich fraction of C. sinensis when compared to the detannified fraction was also confirmed by histological examinations. The greater activity of GTC than that of detannified green tea fraction correlates with the higher content of tannins in green tea. Overall, these results indicate that the tannin-rich green tea could have improved the defense mechanism against arsenic-induced oxidative stress and reduced the tissue arsenic burden. PMID:20144955

  4. A chronic toxicity study of the ground root bark of Capparis erythrocarpus (Cappareceae) in male Sprague-Dawley rats.

    PubMed

    Martey, O N K; Armah, G E; Sittie, A A; Okine, L K N

    2013-12-01

    The safety evaluation of Capparis erythrocarpus (CE) on chronic administration at 18 and 180 mg kg(-1) body weight for 6 months was investigated in male Sprague-Dawley rats. The effects of CE on certain serum biochemical, haematological, urine and histopathological determinations were used as indices of organ specific toxicity. Also the effects of CE on rat blood clotting time and pentobarbital-induced sleeping time were determined. Results indicate that CE had no effect on urine, haematological and serum biochemical indices at termination of treatment with the exception of serum ALT level which was significantly (p < 0.05) attenuated in a dose-dependent fashion (21-35%). There were also no differences in blood clotting time and pentobarbital-induced sleeping time between CE-treated and control animals. Histopathological studies showed that CE did not adversely affect the morphology of the liver, kidney and heart tissues. However, lungs of CE-treated animals showed slight but insignificant inflammatory response in alveolar areas and Clara cell hyperplasia without the thickening of alveolar septa and bronchiolar epithelial wall. Organ weights were not adversely affected by CE treatment. There were significant (p < 0.05) changes in weight of CE-treated animals with duration of treatment compared to control. These results suggest that there is no organ specific toxicity associated with chronic administration of CE in rats and its ability to reduce body weight may be useful for slimming in obese persons.

  5. Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats

    PubMed Central

    Burnett, A; McKoy, M-L; Singh, P

    2015-01-01

    ABSTRACT The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract. PMID:26624580

  6. Intravascular streaming and variable delivery to brain following carotid artery infusions in the Sprague-Dawley rat

    SciTech Connect

    Saris, S.C.; Wright, D.C.; Oldfield, E.H.; Blasberg, R.G.

    1988-02-01

    Intracarotid artery infusions in animals are commonly performed in studies of the blood-brain barrier and in chemotherapy trials. Implicit in the analysis of these experiments is that the infusate will be distributed to the territory of the internal carotid artery in a manner that is proportional to blood flow. Fifteen Sprague-Dawley rats were studied to determine if poor infusate mixing with blood due to intravascular streaming occurred during intracarotid artery drug infusions and if it could be eliminated with fast retrograde infusion. In three experimental groups, a radiolabeled flow tracer--/sup 14/C-iodoantipyrine (IAP)--was infused retrograde through the external carotid artery into the common carotid artery at slow, medium, and fast rates (0.45, 1.5, and 5.0 ml/min). In a control group, IAP was injected intravenously (i.v.). Local isotope concentrations in the brain were determined by quantitative autoradiography, and the variability of isotope delivery was assessed in the frontoparietal cortex, temporal cortex, and caudate putamen of all animals. Streaming phenomena were manifest in all selected anatomic areas after the slow and medium rates of intraarterial infusion. After fast intracarotid infusion or i.v. injection, there was uniform distribution of isotope in the same brain regions.

  7. Hormonal profile and reproductive performance in lactation deficient (OFA hr/hr) and normal (Sprague-Dawley) female rats.

    PubMed

    Valdez, Susana R; Penissi, Alicia B; Deis, Ricardo P; Jahn, Graciela A

    2007-04-01

    Lactation deficiency may have important consequences on infant health, particularly in populations of low socioeconomic status. The OFA hr/hr (OFA) strain of rats, derived from Sprague-Dawley (SD) rats, has deficient lactation and is a good model of lactation failure. We examined the reproductive performance and hormonal profiles in OFA and SD strains to determine the cause(s) of the lactation failure of the OFA strain. We measured hormonal (PRL, GH, gonadotropins, oxytocin, and progesterone) levels by RIA in cycling, pregnant, and lactating rats and in response to suckling. Dopaminergic metabolism was assessed by determination of mediobasal hypothalamic dopamine and dihydroxyphenylacetic acid (DOPAC) concentrations by HPLC and tyrosine hydroxylase expression by immunocytochemistry and western blot. OFA rats have normal fertility but 50% of the litters die of malnutrition on early lactation; only 6% of the mothers show normal lactation. The OFA rats showed lower circulating PRL during lactation, increased hypothalamic dopamine and DOPAC, and impaired milk ejection with decreased PRL and oxytocin response to suckling. Before parturition, PRL release and lactogenesis were normal, but dopaminergic metabolism was altered, suggesting activation of the dopaminergic system in OFA but not in SD rats. The number of arcuate and periventricular neurons expressing tyrosine hydroxylase was higher in SD rats, but hypothalamic expression of TH was higher in OFA rats at the end of pregnancy and early lactation. These results suggest that the OFA rats have impaired PRL release linked with an augmented dopaminergic tone which could be partially responsible for the lactational failure.

  8. Effect of TCDD on ACARAT activity and vitamin A accumulation in the kidney of male Sprague-Dawley rats

    SciTech Connect

    Jurek, M.A.; Powers, R.H.; Gilbert, L.C.; Aust, S.D.

    1987-05-01

    Previous studies have shown that rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit symptoms of vitamin A deficiency, including hypophagia, failure of normal growth, loss of hepatic vitamin A and accumulation of vitamin A in the kidney. They observed that male Sprague-Dawley rats treated with a single dose of TCDD gained less weight than control rats over a 12 day period. Treated rats showed a progressive loss of hepatic retinyl esters to levels 55% that of control rats. Treated rats accumulated renal vitamin A, with retinyl palmitate levels reaching 5.2x that of control animals, while retinol levels were elevated to 1.5x that of control rats. The ratio of retinyl palmitate to retinol was significantly greater in treated rats than in the control rats. Acyl CoA:Retinol Acyl Transferase (ACARART) activity was 2x greater in kidneys from treated rats, and positively correlated with retinyl palmitate concentrations. They suggest that accumulation of retinyl esters in the kidney occurs as a result of retinol esterification, in response to the TCDD-induced vitamin A deficiency.

  9. The effects of acute tryptophan depletion on affective behaviour and cognition in Brown Norway and Sprague Dawley rats.

    PubMed

    Jans, L A W; Korte-Bouws, G A H; Korte, S M; Blokland, A

    2010-04-01

    Previous studies in rats and humans have shown that the essential amino acid tryptophan (TRP) is depleted after consumption of a gelatin-based protein-carbohydrate mixture, which is lacking L-tryptophan (TRP-). In rats, TRP depletion caused impaired object recognition but only had a modest effect on affective behaviour. Because these studies were preformed with Wistar rats, the aim of the present experiment was to evaluate strain differences in behavioural responses to acute TRP depletion between Brown Norway (BN) and Sprague Dawley (SD) rats. The rats were repeatedly treated with TRP- or a balanced control (TRP+) and were tested in tests of anxiety- and depression-related behaviour (open-field test, home cage emergence test, social interaction test, forced swim test) and memory. SD rats, but not BNs, showed more anxiety- and depression-related behaviour and impaired object recognition after TRP- treatment. There was a dissociation between plasma TRP levels, central 5-HT concentrations and 5-HIAA/5-HT turnover. Both strains showed about 60% decrease in plasma TRP/SigmaLNAA levels, whereas hippocampal 5-HT levels were lower after TRP- in BN but not SD rats. Conversely, 5-HIAA/5-HT turnover was lower after TRP- in SD but not BN rats, suggesting a dissociation between 5-HT storage and release in SDs. The present study suggests that acute tryptophan depletion effects are strain dependent on the behavioural and the neurochemical level.

  10. In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

    PubMed Central

    Mopuri, Ramgopal; Meriga, Balaji

    2014-01-01

    Objective To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata (T. paniculata) ethanolic extract in Sprague Dawley rats. Methods The solvent extracts (hexane, ethyl acetate and ethanol) of T. paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed. The oral acute toxicity was evaluated using ethanolic extract of T. paniculata. Results Ethyl acetate and ethanolic extracts showed more phytochemicals, whereas highest DPPH scavenging activity was found in ethanolic extract. In an acute toxicity study, T. paniculata ethanolic extract was orally administered (1 000 mg/kg body weight) to rats and observed for 72 h for any toxic symptoms and the dose was continued up to 14 d. On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters. We did not observe any behavioral changes in test groups in comparison with their controls. Also, there were no significant alterations in biochemical, hematological (hemoglobin content and blood cells count) and liver function parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total proteins, albumin and bilirubin levels between T. paniculata ethanolic extract treated and normal control groups. Conclusions Together our results demonstrated that T. paniculata ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy. PMID:25182554

  11. Protective role of tannin-rich fraction of Camellia sinensis in tissue arsenic burden in Sprague Dawley rats.

    PubMed

    Chandronitha, C; Ananthi, S; Ramakrishnan, G; Lakshmisundaram, R; Gayathri, V; Vasanthi, Hannah R

    2010-09-01

    The protective effect of green tea (Camellia sinensis) was tested against arsenic-induced toxicity. However, the possible role of tannins in green tea in alleviating hepatic and renal oxidative injury has also been studied. Administration of sodium arsenite (100 mg/kg/day) for 28 days in Sprague Dawley female rats resulted in significant reduction of biochemical parameters such as delta-aminolevulinic acid dehydratase (ALAD), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and elevation of thiobarbituric acid reactive substances (TBARS) and the index of nitrite/nitrate (NOx) levels. The tissue arsenic burden was increased after arsenic exposure for a period of 28 days. Green tea crude fraction (GTC) co-treated with sodium arsenite for 28 days caused significant (p < .01) elevation of ALAD, GSH, GPx, SOD, and nitrate/nitrite levels and reduction of the TBARS level and tissue burden when compared to detannified green tea fraction (GTDT)-treated groups. The protective role of tannin-rich fraction of C. sinensis when compared to the detannified fraction was also confirmed by histological examinations. The greater activity of GTC than that of detannified green tea fraction correlates with the higher content of tannins in green tea. Overall, these results indicate that the tannin-rich green tea could have improved the defense mechanism against arsenic-induced oxidative stress and reduced the tissue arsenic burden.

  12. The estrogenicity of methylparaben and ethylparaben at doses close to the acceptable daily intake in immature Sprague-Dawley rats

    PubMed Central

    Sun, Libei; Yu, Tong; Guo, Jilong; Zhang, Zhaobin; Hu, Ying; Xiao, Xuan; Sun, Yingli; Xiao, Han; Li, Junyu; Zhu, Desheng; Sai, Linlin; Li, Jun

    2016-01-01

    The estrogenicity of parabens at human exposure levels has become a focus of concern due to the debate over whether the estrogenicity of parabens is strong enough to play a role in the increased incidence of breast cancer. In this study, the uterotrophic activities of methylparaben (MP) and ethylparaben (EP) at doses close to the acceptable daily intake as allocated by JECFA were demonstrated in immature Sprague-Dawley rats by intragastric administration, and up-regulations of estrogen-responsive biomarker genes were found in uteri of the rats by quantitative real-time RT–PCR (Q-RT-PCR). At the same time, the urinary concentrations of MP and EP, as measured by gas chromatography–mass spectrometry (GC-MS) in rats that received the same doses of MP and EP, were found to be near the high urinary levels reported in human populations in recent years. These results show the in vivo estrogenicity of MP and EP at human exposure levels, and indicate that populations exposed to large amounts of MP and EP may have a high burden of estrogenicity-related diseases. In addition, a molecular docking simulation showed interaction between the parabens and the agonist-binding pocket of human estrogen receptor α (hERα). PMID:27121550

  13. Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague-Dawley Rat.

    PubMed

    Filgo, Adam J; Foley, Julie F; Puvanesarajah, Samantha; Borde, Aditi R; Midkiff, Bentley R; Reed, Casey E; Chappell, Vesna A; Alexander, Lydia B; Borde, Pretish R; Troester, Melissa A; Bouknight, Schantel A Hayes; Fenton, Suzanne E

    2016-10-01

    There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies.

  14. The Remedial Efficacy of Spirulina platensis versus Chromium-Induced Nephrotoxicity in Male Sprague-Dawley Rats

    PubMed Central

    Elshazly, M. O.; Abd El-Rahman, Sahar S.; Morgan, Ashraf M.; Ali, Merhan E.

    2015-01-01

    This study was conducted to investigate the possible protective effect of Spirulina platensis against chromium-induced nephrotoxicity. A total of 36 adult male Sprague-Dawley rats were divided into 4 equal groups (Gps). Gp1 served as control, rats of Gps 2, 3, and 4 were exposed to Spirulina platensis (300 mg/kg b.wt per os) and sodium dichromate dihydrate (SDD) via drinking water at concentration of 520 mg /l respectively. Chromium administration caused alterations in the renal function markers as evidenced by significant increase of blood urea and creatinine levels accompanied with significant increase in kidney’s chromium residues and MDA level as well as decreased catalase activity and glutathion content in kidney tissue. Histologically, Cr provoked deleterious changes including: vascular congestion, wide spread tubular epithelium necrobiotic changes, atrophy of glomerular tuft and proliferative hyperplasia. The latter was accompanied with positive PCNA expression in kidney tissues as well as DNA ploidy interpretation of major cellular population of degenerated cells, appearance of tetraploid cells, high proliferation index and high DNA index. Morphometrical measurements revealed marked glomerular and tubular lumen alterations. On contrary, spirulina co-treatment with Cr significantly restored the histopathological changes, antioxidants and renal function markers and all the previously mentioned changes as well. PMID:26029926

  15. Influences of prostanoids and nitric oxide on post-suspension hypotension in female Sprague-Dawley rats

    NASA Technical Reports Server (NTRS)

    Eatman, D.; Listhrop, R. A.; Beasley, A. S.; Socci, R. R.; Abukhalaf, I.; Bayorh, M. A.

    2003-01-01

    Impairment in cardiovascular functions sometimes manifested in astronauts during standing postflight, may be related to the diminished autonomic function and/or excessive production of endothelium-dependent relaxing factors. In the present study, using the 30 degrees head-down tilt (HDT) model, we compared the cardiovascular and biochemical effects of 7 days of suspension and a subsequent 6-h post-suspension period between suspended and non-suspended conscious female Sprague-Dawley rats. Mean arterial pressure (MAP) and heart rate were measured prior to suspension (basal), daily thereafter, and every 2h post-suspension. Following 7 days of suspension, MAP was not different from their basal values, however, upon release from suspension, MAP was significantly reduced compared to the non-suspended rats. Nitric oxide levels were elevated while thromboxane A(2) levels declined significantly in both plasma and tissue samples following post-suspension. The levels of prostacyclin following post-suspension remained unaltered in plasma and aortic rings but was significantly elevated in carotid arterial rings. Therefore, the post-suspension reduction in mean arterial pressure is due mostly to overproduction of nitric oxide and to a lesser extent prostacyclin.

  16. Reproductive toxicity screen of 1,3,5-trinitrobenzene administered in the diet of Sprague-Dawley rats.

    PubMed

    Kinkead, E R; Wolfe, R E; Flemming, C D; Caldwell, D J; Miller, C R; Marit, G B

    1995-01-01

    Several Army installations targeted for restoration have measurable quantities of 1,3,5-trinitrobenzene (TNB) in the soil and groundwater. As part of the process of developing environmental and health effects criteria for restoration, a modified Screening Information Data Set (SIDS) reproductive study was performed. Male and female Sprague-Dawley rats received a diet containing approximately 30, 150, or 300 mg TNB/kg diet. Mating occurred following 14 days of treatment. All dams, one-half the males, and representative pups were maintained for a total of 90 days of treatment. No mortality occurred during the study; however, a decrease in mean body weights was noted in both sexes of high-dose rats. A dose-related effect was noted in measurements of sperm function/activity. Sperm depletion and degeneration of the seminiferous tubules were noted histopathologically. Methemoglobinemia and splenic hemosiderosis were common findings in the high- and mid-dose levels of both sexes at necropsy. No adverse effects were noted in mating or fertility indices. No significant treatment-related differences were found in length of gestation, sex ratio, gestation index, or mean number of pups per litter.

  17. A 90-day toxicology study of high-amylose transgenic rice grain in Sprague-Dawley rats.

    PubMed

    Zhou, Xing Hua; Dong, Ying; Xiao, Xiang; Wang, Yun; Xu, Yong; Xu, Bin; Shi, Wei Dong; Zhang, Yi; Zhu, Li Jia; Liu, Qiao Quan

    2011-12-01

    A transgenic rice line (TRS) with high amylose level has been developed by antisense RNA inhibition of starch branching enzymes. Compositional analysis of TRS demonstrated that the content of resistant starch (RS) was significantly higher compared to conventional non-transgenic rice. High level of RS is an important raw material in food industry and has various physiological effects for human health. In order to provide the reliable theory basis for field release of TRS rice, we evaluated the potential health effects of long-term consumption of the TRS. The 90-day toxicology feeding experiment was conducted in Sprague-Dawley rats fed with diets containing 70% of either TRS rice flour, its near-isogenic rice flour or the control diet. The clinical performance variables (body weight, body weight gain and food consumption) were measured and pathological responses (hematological parameters and serum chemistry at the midterm and the completion of the experiment, urinalysis profile and serum sex hormone response at the completion of the experiment) were performed. Besides, clinical signs, relative organ weights and microscopic observations were also compared between TRS group and its near-isogenic rice group. The combined data indicates that high-amylose TRS grain is as safe as the conventional non-transgenic rice for rat consumption.

  18. A subchronic feeding study of dicamba-tolerant soybean with the dmo gene in Sprague-Dawley rats.

    PubMed

    Wang, Xiaoyun; He, Xiaoyun; Zou, Shiyin; Xu, Wentao; Jia, Xin; Zhao, Bo; Zhao, Changhui; Huang, Kunlun; Liang, Zhihong

    2016-06-01

    The dicamba-tolerant soybean MON87708 expresses the dicamba mono-oxygenase (DMO) enzyme that is encoded by the dmo gene. In order to evaluate the safety of this soybean, a 90-day subchronic feeding toxicity study (13 weeks) was conducted on Sprague-Dawley rats. A total of 140 rats were divided into 7 groups (10/sex/group), including a standard commercial diet control group. The genetically modified (GM) soybean MON87708 and the near isogenic non-GM soybean A3525 were respectively processed to unhulled, full-fat, and heat-treated powder, then mixed into the diet at levels of 7.5%, 15%, and 30% (wt/wt) with the main nutrients of the various diets balanced and then fed to 6 groups. The remaining group of rats fed with a commercial rat diet served as blank control. Some isolated parameters indicated statistically significant differences in body weight, feed consumption/utilization, hematology, serum biochemistry, and relative organ weights. These differences were not consistent across gender or test-diet dose, which were attributed to incidental and biological variability. In conclusion, the results demonstrated that the transgenic soybean MON87708 containing DMO was as safe as non-transgenic isogenic counterpart with historical safe use.

  19. A 90-day toxicology study of transgenic lysine-rich maize grain (Y642) in Sprague-Dawley rats.

    PubMed

    He, Xiao Yun; Tang, Mao Zhi; Luo, Yun Bo; Li, Xin; Cao, Si Shuo; Yu, Jing Juan; Delaney, Bryan; Huang, Kun Lun

    2009-02-01

    The gene for a lysine-rich protein (sb401) obtained from potatoes (Solanum berthaultii) was inserted into maize seed to produce Y642 transgenic maize. Compositional analysis of Y642 grain demonstrated that the concentrations of lysine and total protein were higher than those observed in maize grain from a near-isogenic non-genetically modified (non-GM) commercially available control quality protein maize (Nongda 108). The safety of Y642 maize grain was assessed by comparison of toxicology response variables in Sprague-Dawley (SD) rats consuming diets containing Y642 maize grain with those containing Nongda 108 maize grain. Maize grains from Y642 or Nongda 108 were incorporated into rodent diets at low (30%) or high concentrations (76%) and administered to SD rats (n=10/sex/group) for 90 days. An additional group of negative control group of rats (n=10/sex/group) were fed AIN93G diets. No adverse diet-related differences in body weights, feed consumption/utilization, clinical chemistry, hematology, absolute and relative organ weights were observed. Further, no differences in gross or microscopic pathology were observed between rats consuming diets with Y642 maize grain compared with rats consuming diets containing Nongda 108 maize grain. These results demonstrated that Y642 lysine-rich maize is as safe and nutritious as conventional quality protein maize.

  20. Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not in males.

    PubMed

    Kanekar, Shami; Bogdanova, Olena V; Olson, Paul R; Sung, Young-Hoon; D'Anci, Kristen E; Renshaw, Perry F

    2015-03-01

    Rates of depression and suicide are higher in people living at altitude, and in those with chronic hypoxic disorders like asthma, chronic obstructive pulmonary disorder (COPD), and smoking. Living at altitude exposes people to hypobaric hypoxia, which can lower rat brain serotonin levels, and impair brain bioenergetics in both humans and rats. We therefore examined the effect of hypobaric hypoxia on depression-like behavior in rats. After a week of housing at simulated altitudes of 20,000 ft, 10,000 ft, or sea level, or at local conditions of 4500 ft (Salt Lake City, UT), Sprague Dawley rats were tested for depression-like behavior in the forced swim test (FST). Time spent swimming, climbing, or immobile, and latency to immobility were measured. Female rats housed at altitude display more depression-like behavior in the FST, with significantly more immobility, less swimming, and lower latency to immobility than those at sea level. In contrast, males in all four altitude groups were similar in their FST behavior. Locomotor behavior in the open field test did not change with altitude, thus validating immobility in the FST as depression-like behavior. Hypobaric hypoxia exposure therefore induces depression-like behavior in female rats, but not in males.

  1. Assay of 1-nitropropane, 2-nitropropane, 1-azoxypropane and 2-azoxypropane for carcinogenicity by gavage in Sprague-Dawley rats.

    PubMed

    Fiala, E S; Czerniak, R; Castonguay, A; Conaway, C C; Rivenson, A

    1987-12-01

    1-Nitropropane (1-NP), 2-nitropropane (2-NP), 1-azoxypropane (1-AP) and 2-azoxypropane (2-AP), were assayed for carcinogenicity by gavage in male Sprague-Dawley rats. 2-NP was given at 1 mmol/kg three times per week for 16 weeks. 1-NP (1 mmol/kg), 1-AP (0.1 mmol/kg), 2-AP (0.1 mmol/kg) or Emulphor EL-620 vehicle was given three times per week for 16 weeks, and then once per week for 10 weeks. In the 2-NP treated group both benign and malignant liver tumors occurred in 100% of the animals. No treatment related tumors occurred in rats receiving 1-NP. In rats treated with 1-AP, a high incidence of skin tumors (100%), mostly keratoacanthomas, and of tumors of the nasal cavity (59%) was observed. Rats which were given 2-AP also showed an increased incidence of skin keratoacanthomas (21%), but not of other tumors. These findings (i) confirm, using the oral route of administration, the results of inhalation studies by others indicating the potent hepatocarcinogenicity of 2-NP, (ii) establish a practical model in which the mechanism of 2-NP carcinogenicity can now be more readily studied, and (iii) demonstrate that 1-AP, and probably 2-AP, like other aliphatic azoxy compounds thus far examined, are carcinogenic in rats.

  2. Absorption, Distribution, Excretion, and Pharmacokinetics of 14C-Pyronaridine Tetraphosphate in Male and Female Sprague-Dawley Rats

    PubMed Central

    Park, Sang Hyun; Pradeep, Kannampalli

    2010-01-01

    The main objective of this investigation was to determine the absorption, distribution, excretion, and pharmacokinetics of the antimalarial drug pyronaridine tetraphosphate (PNDP) in Sprague-Dawley rats. Following oral administration of a single dose (10 mg/Kg) of 14C-PNDP, it was observed that the drug was readily absorbed from the small intestine within 1 hour following oral administration and was widely distributed in most of the tissues investigated as determined from the observed radioactivity in the tissues. The peak value of the drug in the blood was reached at around 8 hours postadministration, and radioactivity was detected in most of the tissues from 4 hours onwards. 14C-PNDP showed a poor permeability across the blood-brain barrier, and the absorption, distribution, and excretion of 14C-PNDP were found to be gender-independent as both male and female rats showed a similar pattern of radioactivity. Excretion of the drug was predominantly through the urine with a peak excretion post 24 hours of administration. A small amount of the drug was also excreted in the feces and also in the breath. It was found that the Cmax, AUC (0-inf), and Tmax values were similar to those observed in the Phase II clinical trials of pyronaridine/artesunate (Pyramax) conducted in Uganda. PMID:20379367

  3. Acute effects of aspartame on concentrations of brain amines and their metabolites in selected brain regions of Fischer 344 and Sprague-Dawley rats.

    PubMed

    Freeman, G; Sobotka, T; Hattan, D

    1990-01-01

    This study is the first in a series to define a rodent model to document the effects of amino acid-modulating compounds on central neurotransmitter function. A time-response curve for a single dose of orally intubated aspartame was determined in male Fischer 344 and Sprague-Dawley rats. Regional brain concentrations of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and their metabolites were analyzed in the hypothalamus, cerebellum, pons/medulla, hippocampus, striatum, cortex, and midbrain/thalamus at 30, 60, 120, or 240 min after oral aspartame (1000 mg/kg) administration. Without consideration for time and group variables, levels of most compounds were higher in the brain regions of Fischer than Sprague-Dawley rats. Aspartame in Fischer 344 or Sprague-Dawley rats had no significant effect on levels of the catecholamines or indoleamines at any of the time points monitored following its acute administration. From the results of this study, large oral loads of aspartame do not appear to lead to regional alterations in brain biogenic amine levels.

  4. Age differences in fear retention and extinction in male Sprague-Dawley rats: effects of ethanol challenge during conditioning.

    PubMed

    Broadwater, Margaret; Spear, Linda P

    2013-09-01

    Pavlovian fear conditioning is an ideal model to investigate how learning and memory are influenced by alcohol use during adolescence because the neural mechanisms involved have been studied extensively. In Exp 1, adolescent and adult male Sprague-Dawley rats were non-injected or injected with saline, 1 or 1.5 g/kg ethanol intraperitoneally 10 min prior to tone or context conditioning. Twenty-four hours later, animals were tested for tone or context retention and extinction, with examination of extinction retention conducted 24h thereafter. In Exp 2, a context extinction session was inserted between the tone conditioning and the tone fear retention/extinction days to reduce pre-CS baseline freezing levels at test. Basal levels of acquisition, fear retention, extinction, and extinction retention after tone conditioning were similar between adolescent and adult rats. In contrast adolescents showed faster context extinction than adults, while again not differing from adults during context acquisition, retention or extinction retention. In terms of ethanol effects, adolescents were less sensitive to ethanol-induced context retention deficits than adults. No age differences emerged in terms of tone fear retention, with ethanol disrupting tone fear retention at both ages in Exp 1, but at neither age in Exp 2, a difference seemingly due to group differences in pre-CS freezing during tone testing in Exp 1, but not Exp 2. These results suggest that age differences in the acute effects of ethanol on cognitive function are task-specific, and provide further evidence for age differences cognitive functioning in a task thought to be hippocampally related.

  5. Exposure to an environmentally relevant mixture of brominated flame retardants affects fetal development in Sprague-Dawley rats.

    PubMed

    Berger, Robert G; Lefèvre, Pavine L C; Ernest, Sheila R; Wade, Michael G; Ma, Yi-Qian; Rawn, Dorothea F K; Gaertner, Dean W; Robaire, Bernard; Hales, Barbara F

    2014-06-01

    Brominated flame retardants are incorporated into a wide variety of consumer products and are known to enter into the surrounding environment, leading to human exposure. There is accumulating evidence that these compounds have adverse effects on reproduction and development in humans and animal models. Animal studies have generally characterized the outcome of exposure to a single technical mixture or congener. Here, we determined the impact of exposure of rats prior to mating and during gestation to a mixture representative of congener levels found in North American household dust. Adult female Sprague-Dawley rats were fed a diet containing 0, 0.75, 250 or 750mg/kg of a mixture of flame retardants (polybrominated diphenyl ethers, hexabromocyclododecane) from two weeks prior to mating to gestation day 20. This formulation delivered nominal doses of 0, 0.06, 20 and 60mg/kg body weight/day. The lowest dose approximates high human exposures based on house dust levels and the dust ingestion rates of toddlers. Litter size and resorption sites were counted and fetal development evaluated. No effects on maternal health, litter size, fetal viability, weights, crown rump lengths or sex ratios were detected. The proportion of litters with fetuses with anomalies of the digits (soft tissue syndactyly or malposition of the distal phalanges) was increased significantly in the low (0.06mg/kg/day) dose group. Skeletal analysis revealed a decreased ossification of the sixth sternebra at all exposure levels. Thus, exposure to an environmentally relevant mixture of brominated flame retardants results in developmental abnormalities in the absence of apparent maternal toxicity. The relevance of these findings for predicting human risk is yet to be determined.

  6. Results of long-term carcinogenicity bioassays on Coca-Cola administered to Sprague-Dawley rats.

    PubMed

    Belpoggi, Fiorella; Soffritti, Morando; Tibaldi, Eva; Falcioni, Laura; Bua, Luciano; Trabucco, Francesca

    2006-09-01

    Coca-Cola was invented in May 1886 in Atlanta, Georgia by a pharmacist who, by accident or design, mixed carbonated water with the syrup of sugar, phosphoric acid, caffeine, and other natural flavors to create what is known as "the world's favorite soft drink." Coca-Cola is currently sold in more than 200 countries and in early 2000, the company sold its 10 billionth unit case of Coca-Cola branded products. Given the worldwide consumption of Coca-Cola, a project of experimental bioassays to study its long-term effects when administered as substitute for drinking water on male and female Sprague-Dawley rats was planned and executed. The objective of the project was to study whether and how long-term consumption of Coca-Cola affects the basic tumorigram of test animals. The bioassays were performed on rats beginning at different ages, namely: (a) on males and females exposed since embryonic life or from 7 weeks of age; and (b) on males and females exposed from 30, 39, or 55 weeks of age. Overall, the project included 1999 rats. During the biophase, data were collected on fluid and feed consumption, body weight, and survival. Animals were kept under observation until spontaneous death and underwent complete necropsy. The results indicate: (a) an increase in body weight in all treated animals; (b) a statistically significant increase of the incidence in females, both breeders and offspring, bearing malignant mammary tumors; (c) a statistically significant increase in the incidence of exocrine ademonas of the pancreas in both male and female breeders and offspring; and (d) an increased incidence, albeit not statistically significant, of pancreatic islet cell carcinomas in females, a malignant tumor which occurs very rarely in our historical controls. On the basis of the results of this study, excessive consumption of regular soft-drinks should be generally discouraged, in particular for children and adolescents.

  7. Evaluation of the developmental toxicity of 60 Hz magnetic fields and harmonic frequencies in Sprague-Dawley rats.

    PubMed

    Ryan, B M; Polen, M; Gauger, J R; Mallett, E; Kearns, M B; Bryan, T L; McCormick, D L

    2000-05-01

    Experimental data suggest that exposure to the 50 and 60 Hz sinusoidal components of power-frequency magnetic fields (MFs) does not have an adverse impact on fetal development. However, the possible developmental toxicity of MF harmonics has not been investigated. This study was designed to determine whether exposure to 180 Hz MFs (third harmonic), alone or in combination with 60 Hz MFs, induces birth defects in Sprague-Dawley rats. Groups of sperm-positive dams (> or =20/group) were exposed for 18.5 h per day from gestation days 6 through 19 to (1) ambient MFs only (<0.0001 mT; sham controls); (2) 60 Hz MFs at 0.2 mT; (3) 180 Hz MFs at 0.2 mT; or (4) 60 Hz + 180 Hz MFs (10% third harmonic; total field strength = 0.2 mT). Litter size, litter weight, percentage live births, sex ratio, and number of resorption sites were determined for each dam, and gross external, visceral, cephalic and skeletal examinations were performed on all fetuses. MF exposure had no significant effects on litter size, litter weight, or fetal development. With the exception of common rib variants, the incidence of fetal anomalies was comparable in all groups. A small increase in the incidence of rib variants was seen in the group exposed to 60 Hz + 180 Hz MFs; however, the incidence of rib variants in this group was similar to that in historical controls from our laboratory. These data extend the existing database on developmental toxicity of MFs by demonstrating that exposure to 180 Hz MFs, either alone or superimposed on an underlying 60 Hz signal, does not induce biologically significant developmental toxicity. These data do not support the hypothesis that exposure to power-frequency MFs is an important risk factor for fetal development. PMID:10790286

  8. C60 Exposure Augments Cardiac Ischemia/Reperfusion Injury and Coronary Artery Contraction in Sprague Dawley Rats

    PubMed Central

    Holland, Nathan A.; Vidanapathirana, Achini K.; Pitzer, Joshua E.; Han, Li; Sumner, Susan J.; Lewin, Anita H.; Fennell, Timothy R.; Lust, Robert M.; Brown, Jared M.; Wingard, Christopher J.

    2014-01-01

    The potential uses of engineered C60 fullerene (C60) have expanded in recent decades to include industrial and biomedical applications. Based on clinical findings associated with particulate matter exposure and our data with multi-walled carbon nanotubes, we hypothesized that ischemia/reperfusion (I/R) injury and pharmacological responses in isolated coronary arteries would depend upon the route of exposure and gender in rats instilled with C60. Male and female Sprague Dawley rats were used to test this hypothesis by surgical induction of cardiac I/R injury in situ 24 h after intratracheal (IT) or intravenous (IV) instillation of 28 μg of C60 formulated in polyvinylpyrrolidone (PVP) or PVP vehicle. Serum was collected for quantification of various cytokines. Coronary artery segments were isolated for assessment of vasoactive pharmacology via wire myography. Both IV and IT exposure to C60 resulted in expansion of myocardial infarction in male and female rats following I/R injury. Serum-collected post-I/R showed elevated concentrations of interleukin-6 and monocyte chemotactic protein-1 in male rats exposed to IV C60. Coronary arteries isolated from male rats exposed to IT C60 demonstrated augmented vasocontraction in response to endothelin-1 that was attenuated with Indomethacin. IV C60 exposure resulted in impaired acetylcholine relaxation in male rats and IT C60 exposure resulted in depressed vasorelaxation in response to sodium nitroprusside in female rats. Based on these data, we conclude that IT and IV exposure to C60 results in unique cardiovascular consequences that may favor heightened coronary resistance and myocardial susceptibility to I/R injury. PMID:24431213

  9. Cannabidiol fails to reverse hypothermia or locomotor suppression induced by Ù9-tetrahydrocannabinol in Sprague-Dawley rats

    PubMed Central

    Taffe, Michael A; Creehan, Kevin M; Vandewater, Sophia A

    2015-01-01

    Background and Purpose Growing evidence shows cannabidiol (CBD) modulates some of the effects of Δ9-tetrahydrocannabinol (THC). CBD is a constituent of some strains of recreational cannabis but its content is highly variable. High CBD strains may have less memory-impairing effects than low-CBD strains and CBD can reverse behavioural effects of THC in monkeys. CBD/THC interactions in rodents are more complicated as CBD can attenuate or exacerbate the effects of THC. This study was undertaken to determine if CBD could reverse hypothermia or hypolocomotor effects caused by THC in rats. Experimental Approaches Male Sprague-Dawley rats were prepared with radiotelemetry devices and then given doses of THC (10–30 mg·kg−1, i.p.) with or without CBD. Experiments determined the effect of simultaneous or 30 min pretreatment with CBD in a 1:1 ratio with THC, as well as the effect of CBD in a 3:1 ratio. Additional experiments determined the effects of pretreatment with the cannabinoid CB1 receptor antagonist SR141716 (rimonabant). Key Results CBD did not attentuate THC-induced hypothermia or hypolocomotion but instead exaggerated these effects in some conditions. The antagonist SR141716 blocked hypolocomotor effects of THC for the first hour after injection and the hypothermia for 6 h; thus validating the pharmacological model. Conclusions and Implications There is no evidence from this study that elevated CBD content in cannabis could provide protection from the physiological effects of THC, in rats. PMID:25425111

  10. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

    PubMed Central

    Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

    2014-01-01

    Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnOAE100[−]) or positively (ZnOAE100[+]) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnOAE100(−) and ZnOAE100(+) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

  11. Characterization of cardiovascular reflexes evoked by airway stimulation with allylisothiocyanate, capsaicin, and ATP in Sprague-Dawley rats.

    PubMed

    Hooper, J S; Hadley, S H; Morris, K F; Breslin, J W; Dean, J B; Taylor-Clark, T E

    2016-03-15

    Acute inhalation of airborne pollutants alters cardiovascular function and evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the effect of capsaicin [transient receptor potential (TRP) vanilloid 1 (TRPV1) agonist], AITC [TRP ankyrin 1 (TRPA1) agonist], and ATP (P2X2/3 agonist) on bronchopulmonary sensory activity and cardiovascular responses of conscious Sprague-Dawley (SD) rats. Single fiber recordings show that allyl isothiocyanate (AITC) and capsaicin selectively activate C fibers, whereas subpopulations of both A and C fibers are activated by stimulation of P2X2/3 receptors. Inhalation of the agonists by conscious rats caused significant bradycardia, atrioventricular (AV) block, and prolonged PR intervals, although ATP-induced responses were lesser than those evoked by AITC or capsaicin. Responses to AITC were inhibited by the TRP channel blocker ruthenium red and the muscarinic antagonist atropine. AITC inhalation also caused a biphasic blood pressure response: a brief hypertensive phase followed by a hypotensive phase. Atropine accentuated the hypertensive phase, while preventing the hypotension. AITC-evoked bradycardia was not abolished by terazosin, the α1-adrenoceptor inhibitor, which prevented the hypertensive response. Anesthetics had profound effects on AITC-evoked bradycardia and AV block, which was abolished by urethane, ketamine, and isoflurane. Nevertheless, AITC inhalation caused bradycardia and AV block in paralyzed and ventilated rats following precollicular decerebration. In conclusion, we provide evidence that activation of ion channels expressed on nociceptive airway sensory nerves causes significant cardiovascular effects in conscious SD rats via reflex modulation of the autonomic nervous system. PMID:26718787

  12. Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders

    PubMed Central

    Ku, Katherine M.; Weir, Ruth K.; Silverman, Jill L.; Berman, Robert F.; Bauman, Melissa D.

    2016-01-01

    The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26–56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions. PMID:27351457

  13. Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats From Gestation Day 6 Through Postnatal Day 90

    PubMed Central

    Delclos, K. Barry; Camacho, Luísa; Lewis, Sherry M.; Vanlandingham, Michelle M.; Latendresse, John R.; Olson, Greg R.; Davis, Kelly J.; Patton, Ralph E.; da Costa, Gonçalo Gamboa; Woodling, Kellie A.; Bryant, Matthew S.; Chidambaram, Mani; Trbojevich, Raul; Juliar, Beth E.; Felton, Robert P.; Thorn, Brett T.

    2014-01-01

    Bisphenol A (BPA) is a high production volume industrial chemical to which there is widespread human oral exposure. Guideline studies used to set regulatory limits detected adverse effects only at doses well above human exposures and established a no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day. However, many reported animal studies link BPA to potentially adverse effects on multiple organ systems at doses below the NOAEL. The primary goals of the subchronic study reported here were to identify adverse effects induced by orally (gavage) administered BPA below the NOAEL, to characterize the dose response for such effects and to determine doses for a subsequent chronic study. Sprague Dawley rat dams were dosed daily from gestation day 6 until the start of labor, and their pups were directly dosed from day 1 after birth to termination. The primary focus was on seven equally spaced BPA doses (2.5–2700 μg/kg bw/day). Also included were a naïve control, two doses of ethinyl estradiol (EE2) to demonstrate the estrogen responsiveness of the animal model, and two high BPA doses (100,000 and 300,000 μg/kg bw/day) expected from guideline studies to produce adverse effects. Clear adverse effects of BPA, including depressed gestational and postnatal body weight gain, effects on the ovary (increased cystic follicles, depleted corpora lutea, and antral follicles), and serum hormones (increased serum estradiol and prolactin and decreased progesterone), were observed only at the two high doses of BPA. BPA-induced effects partially overlapped those induced by EE2, consistent with the known weak estrogenic activity of BPA. PMID:24496637

  14. Lansoprazole increases testosterone metabolism and clearance in male Sprague-Dawley rats: implications for Leydig cell carcinogenesis.

    PubMed

    Coulson, Michelle; Gibson, G Gordon; Plant, Nick; Hammond, Tim; Graham, Mark

    2003-10-15

    Leydig cell tumours (LCTs) are frequently observed during rodent carcinogenicity studies, however, the significance of this effect to humans remains a matter of debate. Many chemicals that produce LCTs also induce hepatic cytochromes P450 (CYPs), but it is unknown whether these two phenomena are causally related. Our aim was to investigate the existence of a liver-testis axis wherein microsomal enzyme inducers enhance testosterone metabolic clearance, resulting in a drop in circulating hormone levels and a consequent hypertrophic response from the hypothalamic-pituitary-testis axis. Lansoprazole was selected as the model compound as it induces hepatic CYPs and produces LCTs in rats. Male Sprague-Dawley rats were dosed with lansoprazole (150 mg/kg/day) or vehicle for 14 days. Lansoprazole treatment produced effects on the liver consistent with an enhanced metabolic capacity, including significant increases in relative liver weights, total microsomal CYP content, individual CYP protein levels, and enhanced CYP-dependent testosterone metabolism in vitro. Following intravenous administration of [14C]testosterone, lansoprazole-treated rats exhibited a significantly smaller area under the curve and significantly higher plasma clearance. Significant reductions in plasma and testicular testosterone levels were observed, confirming the ability of this compound to perturb androgen homeostasis. No significant changes in plasma LH, FSH, or prolactin levels were detected under our experimental conditions. Lansoprazole treatment exerted no marked effects on testicular testosterone metabolism. In summary, lansoprazole treatment induced hepatic CYP-dependent testosterone metabolism in vitro and enhanced plasma clearance of radiolabelled testosterone in vivo. These effects may contribute to depletion of circulating testosterone levels and hence play a role in the mode of LCT induction in lansoprazole-treated rats.

  15. Strain differences in hepatic cytochrome P450 1A and 3A expression between Sprague-Dawley and Wistar rats.

    PubMed

    Kishida, Tomoyuki; Muto, Shin-ichi; Hayashi, Morimichi; Tsutsui, Masaru; Tanaka, Satoru; Murakami, Makoto; Kuroda, Junji

    2008-10-01

    Expression of hepatic cytochrome P450 (CYP) isoforms was compared in Sprague-Dawley (SD) and Wistar (WI) rats, which are commonly used strains in preclinical studies. Basal CYP1A1, CYP1A2, and CYP3A2 mRNA levels were higher in WI rats than in SD rats (by 8-, 3- and 2-fold, respectively). Treatment with phenobarbital, a potent CYP inducer, increased the predominance of expression of these three mRNAs in WI rats (by 26-, 4-, and 2-fold, respectively) along with the predominance of increased microsomal total P450 contents and smooth-surface endoplasmic reticulum in the centrilobular hepatocytes. CYP1A enzymatic activity was also higher in WI rats than in SD rats. No strain differences were observed in phenobarbital induction of CYP2B1/2, CYP2C6, or CYP3A1. CYP3A2 mRNA was more strongly induced by dexamethasone, a typical inducer of CYP3A, together with CYP3A1 mRNA, in WI rats than in SD rats (by 2-fold), whereas the CYP1A1 and CYP1A2 mRNA expression induced by beta-naphtoflavone, a typical inducer of CYP1A, did not differ between the two strains. Furthermore, WI rats exhibited predominantly arylhydrocarbon receptor, pregnane X receptor, and constitutive androstane receptor mRNAs, responsible for CYP1A or CYP3A induction, with phenobarbital or dexamethasone induction. In conclusion, significant, predominant expression of hepatic CYP1A and CYP3A mRNAs in WI rats was observed, possibly related to nuclear receptor-mediated induction. Considering the pharmacokinetic and toxicological importance of CYP1A and CYP3A, different outcomes might arise depending on the rat strains used in preclinical studies of drugs metabolized typically or mainly by both isoforms.

  16. High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats.

    PubMed

    Ha, Jung-Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen R; Collins, James F

    2016-01-01

    Iron-copper interactions were described decades ago; however, molecular mechanisms linking the two essential minerals remain largely undefined. Investigations in humans and other mammals noted that copper levels increase in the intestinal mucosa, liver and blood during iron deficiency, tissues all important for iron homeostasis. The current study was undertaken to test the hypothesis that dietary copper influences iron homeostasis during iron deficiency and iron overload. We thus fed weanling, male Sprague-Dawley rats (n = 6-11/group) AIN-93G-based diets containing high (~8800 ppm), adequate (~80) or low (~11) iron in combination with high (~183), adequate (~8) or low (~0.9) copper for 5 weeks. Subsequently, the iron- and copper-related phenotype of the rats was assessed. Rats fed the low-iron diets grew slower than controls, with changes in dietary copper not further influencing growth. Unexpectedly, however, high-iron (HFe) feeding also impaired growth. Furthermore, consumption of the HFe diet caused cardiac hypertrophy, anemia, low serum and tissue copper levels and decreased circulating ceruloplasmin activity. Intriguingly, these physiologic perturbations were prevented by adding extra copper to the HFe diet. Furthermore, higher copper levels in the HFe diet increased serum nonheme iron concentration and transferrin saturation, exacerbated hepatic nonheme iron loading and attenuated splenic nonheme iron accumulation. Moreover, serum erythropoietin levels, and splenic erythroferrone and hepatic hepcidin mRNA levels were altered by the dietary treatments in unanticipated ways, providing insight into how iron and copper influence expression of these hormones. We conclude that high-iron feeding of weanling rats causes systemic copper deficiency, and further, that copper influences the iron-overload phenotype. PMID:27537180

  17. Effects of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal injuries in Sprague-Dawley rats.

    PubMed

    Ibrahim, Ibrahim Abdel Aziz; Qader, Suhailah Wasmn; Abdulla, Mahmood Ameen; Nimir, Amal R; Abdelwahab, Siddig Ibrahim; Al-Bayaty, Fouad Hussain

    2012-01-01

    Current anti-gastric ulcer agents have side effects, despite the progression and expansion of advances in treatment. This study aimed to investigate the gastroprotective mechanisms of Pithecellobium jiringa ethanol extract against ethanol-induced gastric mucosal ulcers in rats. For this purpose, Sprague Dawley rats were randomly divided into five groups: Group 1 (normal control) rats were orally administered with vehicle (carboxymethyl cellulose), Group 2 (ulcer control) rats were also orally administered with vehicle. Group 3 (positive control) rats were orally administered with 20 mg/kg omeprazole, Groups 4 and 5 (experimental groups) received ethanol extract of Pithecellobium jiringa ethanol extract at a concentration of 250 and 500 mg/kg, respectively. Sixty minutes later, vehicle was given orally to the normal control group, and absolute ethanol was given orally to the ulcer control, positive control and experimental groups to generate gastric mucosal injury. The rats were sacrificed an hour later. The effect of oral administration of plant extract on ethanol-induced gastric mucosal injury was studied grossly and histology. The level of lipid peroxidation (malondialdehyde-MDA), superoxide dismutase (SOD) and gastric wall mucus were measured from gastric mucosal homogenate. The ulcer control group exhibited severe gastric mucosal injury, and this finding was also confirmed by histology of gastric mucosa which showed severe damage to the gastric mucosa with edema and leucocyte infiltration of the submucosal layer. Pre-treatment with plant extract significantly reduced the formation of ethanol-induced gastric lesions, and gastric wall mucus was significantly preserved. The study also indicated a significant increase in SOD activity in gastric mucosal homogenate, whereas a significant decrease in MDA was observed. Acute toxicity tests did not show any signs of toxicity and mortality up to 5 g/kg. The ulcer protective effect of this plant may possibly be due to its

  18. Developmental exposure to paraquat and maneb can impair cognition, learning and memory in Sprague-Dawley rats.

    PubMed

    Li, Bai; He, Xi; Sun, Yan; Li, Baixiang

    2016-10-20

    Paraquat and maneb are identified environmental pollutants. Combined exposure to paraquat and maneb is a latent risk factor for many diseases, particularly those of the central nervous system, including Parkinson's disease and Alzheimer's disease. Hippocampus is the key structure in memory formation and babies are more sensitive to environmental stimuli than adults, so we investigated the neurotoxicity of paraquat and maneb on the hippocampi of rat pups. Female and male Sprague-Dawley rats were mated (female : male = 2 : 1) every night for a week. The gravid rats were randomly divided into three groups (one control and two experimental groups). A mixed solution of paraquat-maneb was administered twice a week by lavage at a dose of 10 or 15 mg kg(-1) bodyweight (containing 30 or 45 mg kg(-1) bodyweight maneb, respectively) from day 6 after pregnancy till ablactation. Maternal weight gain and offspring bodyweights were not affected by the drugs. However, behavioral tests showed that reaction latency and mistake frequency increased after treatment. Intuitively, we found significant changes in the hippocampal neurons in the morphological observation. Taking into account the interaction of the related genes in the cAMP-PKA-CREB pathway, we used a variety of methods to detect the gene and protein levels. Reduced expression of cAMP and related genes and proteins in the hippocampus and serum was also observed. These results indicate that PQ-MB stimulates cAMP to reduce the production of PKA, thus reducing the phosphorylation of CREB and inhibiting the activation of other elements (BDNF, C-JUN, and C-FOS). These changes lead to hippocampal damage and impaired abilities (learning, cognition, and memory). Our results demonstrate that PQ-MB induces hippocampal toxicity in the early life of rats, and they thus provide a theoretical foundation for further investigation of the bathypelagic mechanism involved and measures that can be taken to avoid PQ-MB neurotoxicity

  19. Hippocampal proteoglycans brevican and versican are linked to spatial memory of Sprague-Dawley rats in the morris water maze.

    PubMed

    Saroja, Sivaprakasam R; Sase, Ajinkya; Kircher, Susanne G; Wan, Jia; Berger, Johannes; Höger, Harald; Pollak, Arnold; Lubec, Gert

    2014-09-01

    Proteoglycans (PGs) are major constituents of the extracellular matrix and have recently been proposed to contribute to synaptic plasticity. Hippocampal PGs have not yet been studied or linked to memory. The aim of the study, therefore, was to isolate and characterize rat hippocampal PGs and determine their possible role in spatial memory. PGs were extracted from rat hippocampi by anion-exchange chromatography and analyzed by nano LC-MS/MS. Twenty male Sprague-Dawley rats were tested in the morris water maze. PGs agrin, amyloid beta A4 protein, brevican, glypican-1, neurocan, phosphacan, syndecan-4, and versican were identified in the hippocampi. Brevican and versican levels in the membrane fraction were higher in the trained group, correlating with the time spent in the target quadrant. α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor GluR1 was co-precipitated with brevican and versican. Levels for a receptor complex containing GluR1 was higher in trained while GluR2 and GluR3-containing complex levels were higher in yoked rats. The findings provide information about the PGs present in the rat hippocampus, demonstrating that versican and brevican are linked to memory retrieval in the morris water maze and that PGs interact with α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor GluR1, which is linked to memory retrieval. Proteoglycans (PGs) are major constituents of the extracellular matrix of the brain and were proposed to contribute to synaptic plasticity. This report addressed PGs in rat hippocampus and suggests that PGs brevican and versican are linked to spatial memory, and form a complex with the GluR1 subunit of the AMPA receptor, a key signaling molecule in memory mechanisms.

  20. NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

    PubMed

    Liu, Haiyan; Tayyari, Fariba; Edison, Arthur S; Su, Zhihua; Gu, Liwei

    2016-08-01

    A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake. PMID:27309592

  1. Skeletal effect of casein and whey protein intake during catch-up growth in young male Sprague-Dawley rats.

    PubMed

    Masarwi, Majdi; Gabet, Yankel; Dolkart, Oleg; Brosh, Tamar; Shamir, Raanan; Phillip, Moshe; Gat-Yablonski, Galia

    2016-07-01

    The aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague-Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins - casein or whey. In terms of body weight, CU growth was incomplete in all study groups. Despite their similar food consumption, casein-re-fed rats had a significantly higher body weight and longer humerus than whey-re-fed rats in the long term. The height of the epiphyseal growth plate (EGP) in both casein and whey groups was greater than that of rats re-fed normal chow. Microcomputed tomography yielded significant differences in bone microstructure between the casein and whey groups, with the casein-re-fed animals having greater cortical thickness in both the short and long term in addition to a higher trabecular bone fraction in the short term, although this difference disappeared in the long term. Mechanical testing confirmed the greater bone strength in rats re-fed casein. Bone quality during CU growth significantly depends on the type of protein ingested. The higher EGP in the casein- and whey-re-fed rats suggests a better growth potential with milk-based diets. These results suggest that whey may lead to slower bone growth with reduced weight gain and, as such, may serve to circumvent long-term complications of CU growth.

  2. Developmental exposure to paraquat and maneb can impair cognition, learning and memory in Sprague-Dawley rats.

    PubMed

    Li, Bai; He, Xi; Sun, Yan; Li, Baixiang

    2016-10-20

    Paraquat and maneb are identified environmental pollutants. Combined exposure to paraquat and maneb is a latent risk factor for many diseases, particularly those of the central nervous system, including Parkinson's disease and Alzheimer's disease. Hippocampus is the key structure in memory formation and babies are more sensitive to environmental stimuli than adults, so we investigated the neurotoxicity of paraquat and maneb on the hippocampi of rat pups. Female and male Sprague-Dawley rats were mated (female : male = 2 : 1) every night for a week. The gravid rats were randomly divided into three groups (one control and two experimental groups). A mixed solution of paraquat-maneb was administered twice a week by lavage at a dose of 10 or 15 mg kg(-1) bodyweight (containing 30 or 45 mg kg(-1) bodyweight maneb, respectively) from day 6 after pregnancy till ablactation. Maternal weight gain and offspring bodyweights were not affected by the drugs. However, behavioral tests showed that reaction latency and mistake frequency increased after treatment. Intuitively, we found significant changes in the hippocampal neurons in the morphological observation. Taking into account the interaction of the related genes in the cAMP-PKA-CREB pathway, we used a variety of methods to detect the gene and protein levels. Reduced expression of cAMP and related genes and proteins in the hippocampus and serum was also observed. These results indicate that PQ-MB stimulates cAMP to reduce the production of PKA, thus reducing the phosphorylation of CREB and inhibiting the activation of other elements (BDNF, C-JUN, and C-FOS). These changes lead to hippocampal damage and impaired abilities (learning, cognition, and memory). Our results demonstrate that PQ-MB induces hippocampal toxicity in the early life of rats, and they thus provide a theoretical foundation for further investigation of the bathypelagic mechanism involved and measures that can be taken to avoid PQ-MB neurotoxicity.

  3. Assessment of Carbon Dioxide, Carbon Dioxide/Oxygen, Isoflurane and Pentobarbital Killing Methods in Adult Female Sprague-Dawley Rats

    PubMed Central

    Chisholm, Jessica M.

    2016-01-01

    Background Exposure to carbon dioxide (CO2) gas as a killing method is aversive and exposure to high concentrations is likely to be painful. Bradycardia during exposure to CO2 is associated with nociception and pain. However, it is unclear if bradycardia occurs before loss of consciousness as definitions of loss of consciousness vary in the literature. The objectives of this study were to explore the relationship between recumbency, loss of righting reflex (LORR) and a quiescent electromyograph as measures of loss of consciousness, and identify the onset of bradycardia in relation to these measures. Our primary hypothesis was that CO2 exposure would result in bradycardia, which would precede LORR. Methods Thirty-two adult, female Sprague-Dawley rats were instrumented with a telemetry device and randomly assigned to one of four killing methods (concentrations of 100% CO2, CO2 (70%)/O2 (30%), isoflurane (5%) and intraperitoneal pentobarbital (200 mg/kg). Time to achieve recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph, heart rate and apnea were recorded. Results The general order of progression was recumbency, LORR, quiescent electromyograph, isoelectric electrocorticograph and apnea. Recumbency preceded LORR in the majority of animals (CO2; 7/8, CO2/O2; 8/8, isoflurane; 5/8, pentobarbital; 4/8). Bradycardia occurred before recumbency in the CO2 (p = 0.0002) and CO2/O2 (p = 0.005) groups, with a 50% reduction in heart rate compared to baseline. The slowest (time to apnea) and least consistent killing methods were CO2/O2 (1180 ± 658.1s) and pentobarbital (875 [239 to 4680]s). Conclusion Bradycardia, and consequently nociception and pain, occurs before loss of consciousness during CO2 exposure. Pentobarbital displayed an unexpected lack of consistency, questioning its classification as an acceptable euthanasia method in rats. PMID:27648836

  4. A diet with 35% of energy from protein leads to kidney damage in female Sprague-Dawley rats.

    PubMed

    Wakefield, Andrew P; House, James D; Ogborn, Malcolm R; Weiler, Hope A; Aukema, Harold M

    2011-09-01

    High-protein (HP) diets for weight loss remain popular despite questions surrounding overall safety. In a recent study using the pig model, we showed that long-term intakes from whole proteins at 35 % energy (en %) cause moderate renal histological damage. To examine whether this observation may be species specific or more generalisable, the effect of this diet in rats was examined. Using plant and animal whole proteins, 70-d-old female Sprague-Dawley rats were randomised to either a normal-protein (NP; 15 en %) or a HP (35 en %) diet for 4, 8, 12 and 17 months. Renal function was assessed by creatinine clearance and urinary protein levels, and pathology was assessed by examination of glomerular hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis. Rats consuming the HP diet had 17 % higher kidney weights (P < 0·0001), three times higher proteinuria (P < 0·0001) and 27 % higher creatinine clearance (P = 0·0012) compared with those consuming the NP diet. Consistent with this, HP-fed rats had larger glomeruli (P < 0·0001) and more glomerulosclerosis (P = 0·0003) compared with NP-fed rats. The HP diet also resulted in altered levels of free monocyte chemoattractant protein-1 (P < 0·0001). The histological changes are consistent with those observed in the pig model. In contrast to the pig model, the elevated proteinuria and creatinine clearance observed in the rat model are also usually observed with HP consumption in human subjects. These results indicate that the rat is a useful model for HP effects on the kidney and, along with previous results using the pig model, suggest that long-term intake of high levels of protein may be detrimental to renal health.

  5. Skeletal effect of casein and whey protein intake during catch-up growth in young male Sprague-Dawley rats.

    PubMed

    Masarwi, Majdi; Gabet, Yankel; Dolkart, Oleg; Brosh, Tamar; Shamir, Raanan; Phillip, Moshe; Gat-Yablonski, Galia

    2016-07-01

    The aim of the present study was to determine whether the type of protein ingested influences the efficiency of catch-up (CU) growth and bone quality in fast-growing male rats. Young male Sprague-Dawley rats were either fed ad libitum (controls) or subjected to 36 d of 40 % food restriction followed by 24 or 40 d of re-feeding with either standard rat chow or iso-energetic, iso-protein diets containing milk proteins - casein or whey. In terms of body weight, CU growth was incomplete in all study groups. Despite their similar food consumption, casein-re-fed rats had a significantly higher body weight and longer humerus than whey-re-fed rats in the long term. The height of the epiphyseal growth plate (EGP) in both casein and whey groups was greater than that of rats re-fed normal chow. Microcomputed tomography yielded significant differences in bone microstructure between the casein and whey groups, with the casein-re-fed animals having greater cortical thickness in both the short and long term in addition to a higher trabecular bone fraction in the short term, although this difference disappeared in the long term. Mechanical testing confirmed the greater bone strength in rats re-fed casein. Bone quality during CU growth significantly depends on the type of protein ingested. The higher EGP in the casein- and whey-re-fed rats suggests a better growth potential with milk-based diets. These results suggest that whey may lead to slower bone growth with reduced weight gain and, as such, may serve to circumvent long-term complications of CU growth. PMID:27189324

  6. Oleanolic acid prevents progression of streptozotocin induced diabetic nephropathy and protects renal microstructures in Sprague Dawley rats

    PubMed Central

    Dubey, Vishal K.; Patil, Chandragouda R.; Kamble, Sarika M.; Tidke, Priti S.; Patil, Kalpesh R.; Maniya, Pragnesh J.; Jadhav, Ramchandra B.; Patil, Sudha P.

    2013-01-01

    Objective: To study the effect of oleanolic acid (OA) on streptozotocin induced diabetic nephropathy in Sprague Dawley rats. Materials and Methods: Four weeks after intra-peritoneal injection of streptozotocin (STZ; 55 mg/kg), the rats with proteinuria were grouped as: Control (non-diabetic, treated orally with vehicle), diabetic control (treated orally with vehicle) and three diabetic groups receiving 20, 40 and 60 mg/kg/day oral doses of OA. At the end of 8 weeks, urine and serum samples from the rats were processed for determination of creatinine, BUN and GFR. The kidney samples were processed for determination of weight changes, oxidative stress related parameters like catalase, superoxide dismutase and reduced glutathione levels. A part of one kidney from each rat was used for transmission electron microscopy (TEM). Result: As evident in TEM, OA inhibited the nephropathy induced alterations in podocyte integrity, basement membrane thickness and spacing between the podocytes at 60 mg/kg dose. It increased GFR and reduced oxidative stress in the kidneys in a dose dependent manner. These findings conclusively demonstrate the efficacy of OA in diabetic nephropathy. Significant decrease in the oxidative stress in kidneys indicates the role of anti-oxidant mechanisms in the effects of OA. However, OA is known to act through multiple mechanisms like inhibition of the generation of advanced glycation end products and improving the insulin secretion. These mechanisms might have contributed to its efficacy. Conclusion: These results conclusively demonstrate the efficacy of OA in diabetic nephropathy through its possible antioxidant activity. PMID:23662024

  7. Hepatic metabolism of 7,12-dimethylbenz(a)anthracene in male, female, and ovariectomized Sprague-Dawley rats

    SciTech Connect

    Vater, S.T.; Baldwin, D.M.; Warshawsky, D. )

    1991-01-15

    Dimethylbenz(a)anthracene (DMBA) is a potent inducer of mammary tumors in intact female Sprague-Dawley rats, but not in males or ovariectomized females (OVX). Qualitative and quantitative aspects of hepatic metabolism of DMBA were examined in these three groups of rats, using the nonrecirculating perfused liver, to determine whether the production of proximate carcinogenic metabolites of DMBA by the liver differed among these groups in the same manner as does sensitivity to tumor induction. DMBA was infused into the liver at a constant rate for 60 min. Rates of appearance of DMBA and its metabolites were measured in perfusate and bile during the infusion period and the first 60 min thereafter. The maximum rate of appearance of total metabolites in the perfusate, seen at the end of the infusion period, was highest in the intact female (2.6 +/- 0.3 nmol/(g x min)), slightly lower in the OVX (2.3 +/- 0.2 nmol/(g x min)) and significantly lower in the male (1.0 +/- 0.1 nmol/(g x min)). The rates of appearance of metabolites in the bile showed the same order as those seen in the perfusate. The major metabolites extracted from the perfusate in all three groups were dihydrodiols, hydroxymethyl metabolites, and several unidentified metabolites. The 3,4-dihydrodiol, a proximate carcinogenic metabolite, appeared in the perfusate at higher rates in the intact female and OVX than in the male. Hydrolysis of bile samples showed that glucuronidation was a major pathway in the excretion of DMBA metabolites in bile. High performance liquid chromatographic analysis indicated that hydrolysis of DMBA glucuronides yielded the 7- and 12-hydroxymethyl metabolites and an unidentified metabolite designated X. The major hydrolysis product in the male was 12-hydroxymethyl while X was found to be the major product in the intact female and OVX.

  8. Effects of perinatal methylphenidate (MPH) treatment on postweaning behaviors of male and female Sprague-Dawley rats.

    PubMed

    Ferguson, Sherry A; Delbert Law, C; Sahin, Leyla; Montenegro, Susan V

    2015-01-01

    Methylphenidate (MPH) is a common treatment for adult Attention Deficit Hyperactivity Disorder (ADHD). However, little information exists regarding its safety during pregnancy and thus, women with ADHD face difficult decisions regarding continued use during pregnancy. Thus, Sprague-Dawley rats were orally treated 3×/day with 0 (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14mg/kg at each treatment time) on gestational days 6-21. All offspring/litter were orally treated with the same dose their dam had received on postnatal days (PNDs) 1-21. After weaning, offspring were assessed for adolescent play behavior, locomotor activity, motor coordination, Barnes maze performance, acoustic startle response, novel object recognition, residential running wheel activity, flavored solution intake, home cage behavior, water maze performance, elevated plus maze behavior, locomotor response to an MPH challenge, and passive avoidance. At euthanasia, whole brain and striatal weights as well as serum hormone levels were measured. Body weights of the high MPH group were reduced in both sexes. Males of the high MPH group were less active than control males in open field assessments on PNDs 40-42. Latency to maximum acoustic startle was significantly altered in females of the medium and high MPH groups and residential running wheel activity of females of the low and medium MPH groups was lower than control females. Open arm entries in the elevated plus maze were increased in subjects of the medium MPH group. Females of the low MPH group were less sensitive to the locomotor-increasing effects of an acute 5mg/kg MPH challenge. Serum hormone levels and whole brain and striatal weights were not altered by prior MPH treatment. These results indicate that MPH treatment during development has sporadic effects on postweaning behaviors and those effects were generally exhibited by females. PMID:25514582

  9. Toxic effects of Litsea elliptica Blume essential oil on red blood cells of Sprague-Dawley rats*

    PubMed Central

    Taib, Izatus Shima; Budin, Siti Balkis; Siti Nor Ain, Seri Maseran; Mohamed, Jamaludin; Louis, Santhana Raj; Das, Srijit; Sallehudin, Sulaiman; Rajab, Nor Fadilah; Hidayatulfathi, Othman

    2009-01-01

    Litsea elliptica Blume leaves have been traditionally used as medicinal herbs because of its antimutagenicity, chemopreventative and insecticidal properties. In this study, the toxic effects of L. elliptica essential oil against Sprague-Dawley rat’s red blood cells (RBCs) were evaluated. L. elliptica essential oil was given by oral gavage 5 times per week for 3 treated groups in the doses of 125, 250, and 500 mg/(kg body weight), respectively, and the control group received distilled water. Full blood count, RBC osmotic fragility, RBC morphological changes, and RBC membrane lipid were analyzed 28 d after the treatment. Although L. elliptica essential oil administration had significantly different effects on hemoglobin (Hb), mean cell hemoglobin concentration (MCHC), mean cell volume (MCV), and mean cell hemoglobin (MCH) in the experimental groups as compared to the control group (P<0.05), the values were still within the normal range. L. elliptica induced morphological changes of RBC into the form of echinocyte. The percentage of echinocyte increased significantly among the treated groups in a dose-response manner (P<0.001). The concentrations of RBC membrane phospholipids and cholesterol of all treated groups were significantly lower than those of control group (P<0.001). However, the RBC membrane osmotic fragility and total proteins of RBC membrane findings did not differ significantly between control and treated groups (P>0.05). It is concluded that structural changes in the RBC membrane due to L. elliptica essential oil administration did not cause severe membrane damage. PMID:19882755

  10. Renal ischemic injury affects renal hemodynamics and excretory functions in Sprague Dawley rats: involvement of renal sympathetic tone.

    PubMed

    Salman, Ibrahim M; Sattar, Munavvar A; Abdullah, Nor A; Ameer, Omar Z; Yam, Mun F; Kaur, Gurjeet; Hye Khan, Md Abdul; Johns, Edward J

    2010-01-01

    The role of renal sympathetic nerves in the pathogenesis of ischemic acute renal failure (ARF) and the immediate changes in the renal excretory functions following renal ischemia were investigated. Two groups of male Sprague Dawley (SD) rats were anesthetized (pentobarbitone sodium, 60 mg kg(-1) i.p.) and subjected to unilateral renal ischemia by clamping the left renal artery for 30 min followed by reperfusion. In group 1, the renal nerves were electrically stimulated and the responses in the renal blood flow (RBF) and renal vascular resistance (RVR) were recorded, while group 2 was used to study the early changes in the renal functions following renal ischemia. In post-ischemic animals, basal RBF and the renal vasoconstrictor reperfusion to renal nerve stimulation (RNS) were significantly lower (all p < 0.05 vs. control). Mean arterial pressure (MAP), basal RVR, urine flow rate (UFR), absolute and fractional excretions of sodium (U(Na)V and FE(Na)), and potassium (U(K)V and FE(K)) were higher in ARF rats (all p < 0.05 vs. control). Post-ischemic animals showed markedly lower glomerular filtration rate (GFR) (p < 0.05 vs. control). No appreciable differences were observed in urinary sodium to potassium ratio (U(Na)/U(K)) during the early reperfusion phase of renal ischemia (p > 0.05 vs. control). The data suggest an immediate involvement of renal sympathetic nerve action in the pathogenesis of ischemic ARF primarily through altered renal hemodynamics. Diuresis, natriuresis, and kaliuresis due to impaired renal tubular functions are typical responses to renal ischemia and of comparable magnitudes.

  11. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats.

    PubMed

    Kim, Yu-Ri; Park, Jong-Il; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Kim, Jun-Ho; Kim, Geon-Yong; Meang, Eun-Ho; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Yun, Hyo-In; Kim, Meyoung-Kon

    2014-01-01

    Nanoparticles (NPs) are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s) of 100 nm negatively (ZnO(AE100[-])) or positively (ZnO(AE100[+])) charged zinc oxide (ZnO) NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s). After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg/kg, respectively. Both ZnO NPs had significant changes in hematological and blood biochemical analysis, which could correlate with anemia-related parameters, in the 500 mg/kg groups of both sexes. Histopathological examination showed significant adverse effects (by both test articles) in the stomach, pancreas, eye, and prostate gland tissues, but the particle charge did not affect the tendency or the degree of the lesions. We speculate that this inflammatory damage might result from continuous irritation caused by both test articles. Therefore, the target organs for both ZnO(AE100(-)) and ZnO(AE100(+)) are considered to be the stomach, pancreas, eye, and prostate gland. Also, the no observed adverse effect level for both test articles was identified as 31.25 mg/kg for both sexes, because the adverse effects were observed at all doses greater than 125 mg/kg. PMID:25565830

  12. A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Shin, Sung-Sup; Meang, Eun Ho; Hong, Jeong-sup; Park, Jong-Il; Kim, Su-Hyon; Koh, Sang-Bum; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Jong-Yun; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(−)) NPs in Sprague Dawley rats for 90 days. Methods The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results No rats died during the test period. However, ZnOSM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion A ZnOSM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution. PMID:25565828

  13. Male Roman high and low avoidance rats show different patterns of copulatory behaviour: comparison with Sprague Dawley rats.

    PubMed

    Sanna, Fabrizio; Corda, Maria Giuseppa; Melis, Maria Rosaria; Piludu, Maria Antonietta; Giorgi, Osvaldo; Argiolas, Antonio

    2014-03-29

    Roman high- (RHA) and low-avoidance (RLA) rats, selectively bred for, respectively, rapid vs. extremely poor acquisition of avoidant behaviour in the shuttle-box, display different coping strategies when exposed to aversive environmental conditions: RLA rats are reactive copers and show hyperemotional behaviour characterized by hypomotility and freezing, while RHA rats show a proactive coping behaviour aimed at gaining control over the stressor. RHA rats also display a robust sensation/novelty seeking profile, high baseline levels of impulsivity, and marked preference for, and intake of, natural and drug rewards. This study shows that the Roman lines also differ in sexual behaviour, a main source of natural reward. Thus, male RHA rats engaged in copulatory activity with a receptive female showing more mounts, intromissions and ejaculations in the first copulation test as compared with their RLA counterparts and Sprague Dawley rats used as an external reference strain. Such differences decreased only partially in subsequent copulation tests, with RHA rats always showing higher levels of sexual motivation and performance than RLA rats. Accordingly, analysis of copulatory parameters of five copulation tests performed at 3-day intervals confirmed that the Roman lines display different patterns of copulatory activity that persist after stabilization of copulatory behaviour by sexual experience. Finally, the weight of the testes, epididymides and seminal vesicles increased to a similar extent in both Roman lines after sexual activity. These results are discussed in terms of the relative contribution of differences in brain neurotransmission (mainly dopamine) and neuroendocrine function to the different patterns of copulatory behaviour of the Roman lines.

  14. Dietary effects of Moringa oleifera leaf powder on growth, gastrointestinal morphometry and blood and liver metabolites in Sprague Dawley rats.

    PubMed

    Zvinorova, P I; Lekhanya, L; Erlwanger, K; Chivandi, E

    2015-02-01

    We investigated the effects of Moringa oleifera leaf powder (MOLP) as a dietary supplement on growth performance, gastrointestinal (GIT) morphometry and liver function using weanling Sprague Dawley rats to model humans under ad libitum and restricted feeding. An MOLP-based diet was generated by supplementing normal rat feed with the leaf powder at 20%. Four dietary regimens included normal rat feed fed at 20% of body mass (NRF: ad libitum), NRF fed at 14% of body mass (NRFR, restricted), Moringa-supplemented feeds fed at 20% and 14% of body mass (MOF: ad libitum and MOFR: restrictedly) respectively. Thirty-two pups were randomly assigned to the diets and fed for 5 weeks, after which they were fasted, euthanased and GIT viscera masses, lengths and histology were assessed. Blood was collected for metabolite and markers of liver function assays. Tibiae and femora lengths were used to determine linear growth. Rats fed the restricted diets had lower weekly body mass gains (p = 0.0001) than those on ad libitum feeding; however, they showed compensatory growth by 5 weeks. Terminally, the rats fed MOFR had shorter (p < 0.05) femora and tibiae than their counterparts on the other diets. Except on the caeca, diet had no effect on the absolute masses and lengths of GIT viscera. Relative to tibia length, rats on the MOF had significantly heavier stomachs and caeca and longer small and large intestines than their counterparts on NRF, but this was not supported histologically. Level of feeding and supplementation did not affect blood metabolite concentration, liver glycogen and lipid storage nor the plasma activities AST and ALP in the rats. Supplementing diets with MOLP under restricted access to feed (low calorific supply) might compromise linear growth.

  15. The Effects of Exposure to Petrol Vapours on Growth, Haematological Parameters and Oxidative Markers in Sprague-Dawley Male Rats

    PubMed Central

    ABUBAKAR, Murtala Bello; ABDULLAH, Wan Zaidah; SULAIMAN, Siti Amrah; ANG, Boon Suen

    2015-01-01

    Background: Petrol is known to be hazardous to human health and is associated with various health effects, such as haematotoxicity and oxidative stress. Although Malaysia has adopted the European fuel quality standards in recent years in order to reduce petroleum pollutants and to improve air quality, gasoline with research octane number 95 (RON95), believed to contain benzene and other toxic substances, is still widely used all over the country. This study assessed the effect of RON95 gasoline on haemtological parameters of rats after 11 weeks of exposure. Methods: A total of 16 male Sprague-Dawley rats were randomly divided into two groups: control (exposed to ambient air daily) and gasoline exposed (exposed to petrol fumes at 11.13 ± 1.1cm3/h for 6h daily, 6 days/week) groups. Body weight was monitored daily. At the end of 11 weeks, the rats were sacrificed, bone marrow was extracted for cytological examination, and blood samples were collected for a full blood picture examination, full blood counts and oxidative markers. Results: The results show that gasoline inhalation was associated with a significant (P < 0.05) reduction in the rate of weight gain and a reduction in mean corpuscular haemoglobin concentration and red cell distribution width. It was also observed that the inhalation of gasoline was associated with changes in the nuclei of megakaryocytes, hence causing an increase in the percentage of abnormal megakaryocytes with detached nuclei, hypo-lobulation and/or disintegration. However, the inhalation of gasoline did not cause significant changes in oxidative markers in the erythrocytes. Conclusion: This study shows that 11 weeks of inhaling RON95 petrol vapours caused adverse effects on weight gain, blood cell indices and bone marrow megakaryocytes, but did not cause significant changes in oxidative markers in erythrocytes. The definitive effects of these changes on health require further confirmation. PMID:25892947

  16. High-Iron Consumption Impairs Growth and Causes Copper-Deficiency Anemia in Weanling Sprague-Dawley Rats

    PubMed Central

    Ha, Jung-Heun; Doguer, Caglar; Wang, Xiaoyu; Flores, Shireen R.; Collins, James F.

    2016-01-01

    Iron-copper interactions were described decades ago; however, molecular mechanisms linking the two essential minerals remain largely undefined. Investigations in humans and other mammals noted that copper levels increase in the intestinal mucosa, liver and blood during iron deficiency, tissues all important for iron homeostasis. The current study was undertaken to test the hypothesis that dietary copper influences iron homeostasis during iron deficiency and iron overload. We thus fed weanling, male Sprague-Dawley rats (n = 6-11/group) AIN-93G-based diets containing high (~8800 ppm), adequate (~80) or low (~11) iron in combination with high (~183), adequate (~8) or low (~0.9) copper for 5 weeks. Subsequently, the iron- and copper-related phenotype of the rats was assessed. Rats fed the low-iron diets grew slower than controls, with changes in dietary copper not further influencing growth. Unexpectedly, however, high-iron (HFe) feeding also impaired growth. Furthermore, consumption of the HFe diet caused cardiac hypertrophy, anemia, low serum and tissue copper levels and decreased circulating ceruloplasmin activity. Intriguingly, these physiologic perturbations were prevented by adding extra copper to the HFe diet. Furthermore, higher copper levels in the HFe diet increased serum nonheme iron concentration and transferrin saturation, exacerbated hepatic nonheme iron loading and attenuated splenic nonheme iron accumulation. Moreover, serum erythropoietin levels, and splenic erythroferrone and hepatic hepcidin mRNA levels were altered by the dietary treatments in unanticipated ways, providing insight into how iron and copper influence expression of these hormones. We conclude that high-iron feeding of weanling rats causes systemic copper deficiency, and further, that copper influences the iron-overload phenotype. PMID:27537180

  17. Oxidative stress increased hepatotoxicity induced by nano-titanium dioxide in BRL-3A cells and Sprague-Dawley rats.

    PubMed

    Sha, Baoyong; Gao, Wei; Wang, Shuqi; Gou, Xingchun; Li, Wei; Liang, Xuan; Qu, Zhiguo; Xu, Feng; Lu, Tian Jian

    2014-04-01

    Extensive studies have shown that titanium dioxide (TiO2 ) nanomaterials (NMs) can cause toxicity in vitro and in vivo under normal conditions. However, an adverse effect induced by nano-TiO2 in many diseased conditions, typically characterized by oxidative stress (OS), remains unknown. We investigated the toxicity of nano-TiO2 in rat liver cells (BRL-3A) and Sprague-Dawley (SD) rat livers under OS conditions, which were generated using hydrogen peroxide (H2 O2 ) in vitro and alloxan in vivo, respectively. In vitro results showed that cell death ratios after nano-TiO2 exposure were significantly enhanced (up to 2.62-fold) in BRL-3A cells under OS conditions, compared with normal controls. Significant interactions between OS conditions and nano-TiO2 resulted in the rapid G0/G1 to S phase transition and G2/M arrest, which were opposite to G0/G1 phase arrest in cells after NMs exposure only. In vivo results showed that obvious pathological changes in rat livers and the increased activities of four enzymes (i.e. aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase) owing to liver damage after nano-TiO2 exposure under OS conditions, compared with their healthy controls. In addition, compared with increased hepatotoxicity after nano-TiO2 exposure, micro-TiO2 showed no adverse effects to cells and rat livers under OS conditions. Our results suggested that OS conditions synergistically increase nano-TiO2 induced toxicity in vitro and in vivo, indicating that the evaluation of nanotoxicity under OS conditions is essentially needed prior to various applications of NMs in foods, cosmetics and potential treatment of diseases.

  18. Evaluation of N-Butylbenzenesulfonamide (NBBS) Neurotoxicity in Sprague-Dawley Male Rats Following 27-day Oral Exposure

    PubMed Central

    Rider, CV; Janardhan, KS; Rao, D; Morrison, JP; McPherson, CA; Harry, GJ

    2012-01-01

    N-Butylbenzenesulfonamide (NBBS) is widely used as a plasticizer in polyacetals, polyamides, and polycarbonates and has been found in ground water and effluent from wastewater treatment sites. The compound is lipophilic and distributes rapidly to the brain but also clears rapidly and shows little evidence of accumulation. Limited studies in the literature report neurotoxicity of NBBS in rabbits and rats. Adult Sprague-Dawley male rats (Harlan) received corn oil vehicle or NBBS (100, 200, or 400 mg/kg/d) via oral gavage (5 ml/kg bwt) daily/5 days/week for 27 days. Deaths were observed in the 400 mg/kg/d dose group in the first 5 days and dosing was decreased to 300 mg/kg/d. No alterations were observed in gait, locomotor activity, and rearing behavior. No histological lesions were observed in the testis, seminal vesicles, coagulating gland, epididymis, and prostate. In the liver, minimal centrilobular hypertrophy was evident in all rats of the high dose group. Contrary to previous reports, there was no evidence of peripheral nerve lesions or gliosis in the hippocampus or cerebellum. mRNA levels for glial fibrillary acidic acid protein, interferon gamma, CXCR-3, intracellular adhesion molecule-1, and CD11b were not altered in the hippocampus while Iba-1 levels were decreased. These data do not support previous reports of neurotoxicity for NBBS within a 4-week exposure regimen; however, neuropathological injury occurring over an extended period of exposure cannot be ruled out and given the potential for human exposure requires further examination. PMID:22824510

  19. Study of Intravenous Single-Dose Toxicity Test of Bufonis venonum Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

    Kwon, Ki-Rok; Yu, Jun-Sang; Sun, Seung-Ho; Lee, Kwang-Ho

    2016-01-01

    Objectives: Bufonis venonum (BV) is toad venom and is the dried, white secretions of the auricular and the skin glands of toads. This study was performed to evaluate the toxicity of intravenous injection of Bufonis venonum pharmacopuncture (BVP) through a single- dose test with sprague-dawley (SD) rats. Methods: Twenty male and 20 female 6-week-old SD rats were injected intravenously in the caudal vein with BVP or normal saline. The animals were divided into four groups with five female and five male rats per group: the control group injected with normal saline, the low-dosage group injected with 0.1 mL/animal of BVP, the medium-dosage group injected with 0.5 mL/ animal of BVP and the high-dosage group injected with 1.0 mL/animal of BVP. We performed clinical observations every day and body weight measurements on days 3, 7 and 14 after the injection. We also conducted hematology, serum biochemistry, and histological observations immediately after the observation period. Results: No mortalities were observed in any experimental group. Paleness occurred in the medium- and the high-dosage groups, and congestion on tails was observed in females in the medium- and the high-dosage groups. No significant changes in weight, hematology, serum biochemistry, and histological observations that could be attributed to the intravenous injection of BVP were observed in any experimental group. Conclusion: The lethal dose of intravenously-administered BVP in SD rats is over 1.0 mL/animal. PMID:27386149

  20. Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

    PubMed

    Ku, Katherine M; Weir, Ruth K; Silverman, Jill L; Berman, Robert F; Bauman, Melissa D

    2016-01-01

    The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions. PMID:27351457

  1. Effect of Agglomeration on the Toxicity of Nano-sized Carbon Black in Sprague-Dawley Rats

    PubMed Central

    Kang, Mingu; Han, Jeong-Hee; Yang, Jeong-Sun

    2012-01-01

    Objectives Recent studies have shown that nano-sized carbon black is more toxic than large respirable carbon black because of its higher surface area. However, it is not clear if carbon black made larger by agglomeration demonstrates decreased toxicity. The purpose of this study was to verify if agglomeration affects the toxicity of carbon black using three differently prepared nano-sized carbon black aerosols in nose-only inhalation chambers for 13 weeks. Methods Printex 90 was selected as a representative nano-sized carbon black. To generate aerosols of three different types of agglomerates, Printex 90 was dispersed in distilled water by three different methods: vortex, vortex+sonication, and vortex+sonication with dispersion in a stabilizer. Then, the three differently prepared solutions were aerosolized through venturi nozzles. Male Sprague-Dawley rats were exposed to Printex 90 aerosols in a nose-only exposure chamber for 6 h/d, 5 d/wk for 13 weeks at a concentration of approximately 9 mg/m3. Results Numbers of total cells in the bronchoalveolar lavage (BAL) fluid, macrophages, and polymorphonuclear leukocytes were increased and carbon black masses were clearly seen in BAL cells and lung tissues of rats exposed to Printex 90. However, few differences were found between the three differently agglomerated aerosols. In addition, there were no significant differences in other parameters, such as body weight, lung function or cytokine levels in BAL fluid following carbon black exposure. Conclusions Only mild to moderate respiratory effects were found in rats exposed to nano-sized carbon black at 9 mg/m3 for 13 weeks. Agglomeration did not affect the toxicity of nano-sized carbon particles. PMID:23106037

  2. Repeated Intramuscular-dose Toxicity Test of Watersoluble Carthami Flos (WCF) Pharmacopuncture in Sprague-Dawley Rats

    PubMed Central

    Choi, Yoo-min; Jung, Da-jung; Kim, Seok-hee; Kim, Jong-uk; Yook, Tae-han

    2015-01-01

    Objectives: Water-soluble carthami flos (WCF) is a new mixture of Carthami flos (CF) pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS). Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT) was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL) of WCF in male and female rats is expected for doses over 0.5 mL/animal/day. PMID

  3. Difference in the Pharmacokinetics and Hepatic Metabolism of Antidiabetic Drugs in Zucker Diabetic Fatty and Sprague-Dawley Rats.

    PubMed

    Zhou, Xin; Rougée, Luc R A; Bedwell, David W; Cramer, Jeff W; Mohutsky, Michael A; Calvert, Nathan A; Moulton, Richard D; Cassidy, Kenneth C; Yumibe, Nathan P; Adams, Lisa A; Ruterbories, Kenneth J

    2016-08-01

    The Zucker diabetic fatty (ZDF) rat, an inbred strain of obese Zucker fatty rat, develops early onset of insulin resistance and displays hyperglycemia and hyperlipidemia. The phenotypic changes resemble human type 2 diabetes associated with obesity and therefore the strain is used as a pharmacological model for type 2 diabetes. The aim of the current study was to compare the pharmacokinetics and hepatic metabolism in male ZDF and Sprague-Dawley (SD) rats of five antidiabetic drugs that are known to be cleared via various mechanisms. Among the drugs examined, metformin, cleared through renal excretion, and rosiglitazone, metabolized by hepatic cytochrome P450 2C, did not exhibit differences in the plasma clearance in ZDF and SD rats. In contrast, glibenclamide, metabolized by hepatic CYP3A, canagliflozin, metabolized mainly by UDP-glucuronosyltransferases (UGT), and troglitazone, metabolized by sulfotransferase and UGT, exhibited significantly lower plasma clearance in ZDF than in SD rats after a single intravenous administration. To elucidate the mechanisms for the difference in the drug clearance, studies were performed to characterize the activity of hepatic drug-metabolizing enzymes using liver S9 fractions from the two strains. The results revealed that the activity for CYP3A and UGT was decreased in ZDF rats using the probe substrates, and decreased unbound intrinsic clearance in vitro for glibenclamide, canagliflozin, and troglitazone was consistent with lower plasma clearance in vivo. The difference in pharmacokinetics of these two strains may complicate pharmacokinetic/pharmacodynamic correlations, given that ZDF is used as a pharmacological model, and SD rat as the pharmacokinetics and toxicology strain. PMID:27217490

  4. Behavioral Phenotyping of Juvenile Long-Evans and Sprague-Dawley Rats: Implications for Preclinical Models of Autism Spectrum Disorders.

    PubMed

    Ku, Katherine M; Weir, Ruth K; Silverman, Jill L; Berman, Robert F; Bauman, Melissa D

    2016-01-01

    The laboratory rat is emerging as an attractive preclinical animal model of autism spectrum disorder (ASD), allowing investigators to explore genetic, environmental and pharmacological manipulations in a species exhibiting complex, reciprocal social behavior. The present study was carried out to compare two commonly used strains of laboratory rats, Sprague-Dawley (SD) and Long-Evans (LE), between the ages of postnatal day (PND) 26-56 using high-throughput behavioral phenotyping tools commonly used in mouse models of ASD that we have adapted for use in rats. We detected few differences between young SD and LE strains on standard assays of exploration, sensorimotor gating, anxiety, repetitive behaviors, and learning. Both SD and LE strains also demonstrated sociability in the 3-chamber social approach test as indexed by spending more time in the social chamber with a constrained age/strain/sex matched novel partner than in an identical chamber without a partner. Pronounced differences between the two strains were, however, detected when the rats were allowed to freely interact with a novel partner in the social dyad paradigm. The SD rats in this particular testing paradigm engaged in play more frequently and for longer durations than the LE rats at both juvenile and young adult developmental time points. Results from this study that are particularly relevant for developing preclinical ASD models in rats are threefold: (i) commonly utilized strains exhibit unique patterns of social interactions, including strain-specific play behaviors, (ii) the testing environment may profoundly influence the expression of strain-specific social behavior and (iii) simple, automated measures of sociability may not capture the complexities of rat social interactions.

  5. Cognitive differences between Sprague-Dawley rats selectively bred for sensitivity or resistance to diet induced obesity.

    PubMed

    Gurung, Sunam; Agbaga, Martin-Paul; Myers, Dean A

    2016-09-15

    Epidemiological studies have shown strong correlations between high fat diets, diet-induced obesity and cognitive impairment, primarily focusing on cognitive defects after the onset of obesity. A remaining question is whether cognitive impairment precedes obesity in individuals metabolically prone to diet-induced obesity. The inbred diet-induced obesity sensitive (DIO) and resistant (DR) strains of Sprague-Dawley rats serve as models for human polygenic obesity. DIO rats become overweight on a standard rat chow and have metabolic symptoms similar to overweight humans. We hypothesized that cognitive impairment pre-exists in adult male DIO rats prior to exposure to high fat diet. Male DIO and DR rats were fed a standard rat chow diet from 4 through 20 weeks of age and subjected to the Morris water maze at 12 weeks of age. At 5 and 20 weeks of age, brains of DIO and DR males were examined for indices of inflammation, lipid peroxidation and neuroproliferation. DIO rats showed significant memory impairment on water maze and increased indices of hippocampal inflammation at 20 weeks of age compared to DR rats. At 5 weeks of age, DIO rats exhibited significantly less neural progenitor cell (NPCs) proliferation in the dentate gyrus and increased hippocampal lipid peroxidation compared to DR rats. Therefore, we conclude that DIO rats exhibit early post-weaning indices of hippocampal inflammation, lipid peroxidation and decreased NPC proliferation, as well as impaired hippocampal dependent memory by early adulthood suggesting that inherent metabolic differences predispose the DIO strain to cognitive deficit prior to exposure to high fat diet and/or obesity. PMID:27173431

  6. Bioaccumulation and locomotor effects of manganese sulfate in Sprague-Dawley rats following subchronic (90 days) inhalation exposure

    SciTech Connect

    Tapin, Danielle; Kennedy, Greg; Lambert, Jean; Zayed, Joseph . E-mail: joseph.zayed@umontreal.ca

    2006-03-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic compound that was introduced as an antiknock additive to replace lead in unleaded fuel. The combustion of MMT results in the emission of fine Mn particulates mainly in the form of manganese sulfate and manganese phosphate. The objective of this study is to determine the effects of subchronic exposure to Mn sulfate in different tissues, on locomotor activity, on neuropathology, and on blood serum biochemical parameters. A control group and three groups of 30 male Sprague-Dawley rats were exposed 6-h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 {mu}g/m{sup 3} Mn sulfate. Locomotor activity was measured during 36 h using an Auto-Track System. Blood and the following tissues were collected and analyzed for manganese content by neutron activation analysis: olfactory bulb, globus pallidus, caudate/putamen, cerebellum, frontal cortex, liver, lung, testis, and kidney. Neuronal cell counts were obtained for the caudate/putamen and the globus pallidus and clinical biochemistry was assessed. Manganese concentrations were increased in blood, kidney, lung, and testis and in all brain regions in the 3000 {mu}g/m{sup 3} exposure group. Significant differences were also noted in the 300 {mu}g/m{sup 3} exposure group. Neuronal cell counts for the globus pallidus were significantly different between the two highest exposed groups and the controls. Locomotor activity for all exposure concentrations and resting time for the middle and highest concentrations for the two night resting periods were significantly increased. Total ambulatory count was decreased significantly for all exposure concentrations. Biochemical profiles also presented significant differences. No body weight loss was observed between all groups. These results suggest that neurotoxicity could occur at low exposure levels of Mn sulfate, one of the main combustion products of MMT.

  7. NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

    PubMed

    Liu, Haiyan; Tayyari, Fariba; Edison, Arthur S; Su, Zhihua; Gu, Liwei

    2016-08-01

    A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake.

  8. Anti-inflammatory activity of lycopene isolated from Chlorella marina on type II collagen induced arthritis in Sprague Dawley rats.

    PubMed

    Renju, G L; Muraleedhara Kurup, G; Saritha Kumari, C H

    2013-04-01

    The role of commercially available lycopene (all-trans) from tomato in controlling arthritis has been reported. Even though many reports are available that the cis form of lycopene is more biologically active, no report seems to be available on lycopene (cis and trans) isolated from an easily available and culturable sources. In the present study, the anti-arthritic effect of lycopene (cis and trans) from the algae Chlorella marina (AL) has been compared with lycopene (all-trans) from tomato (TL) and indomethacin (Indo). Arthritis (CIA) was developed in male Sprague dawley rats by collagen and the following parameters were studied. The activities of inflammatory marker enzymes like cyclooxygenase (COX), lipoxygenase (LOX) and myeloperoxidase (MPO) were found to be decreased on treatment with AL when compared to TL and Indo. Changes in Erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, red blood cells (RBC) count, hemoglobin (Hb), C-reactive protein (CRP), rheumatoid factor (RF), and ceruloplasmin levels observed in the blood of arthritic animals were brought back to normal by AL when compared to TL and Indo. Histopathology of paw and joint tissues showed marked reduction in edema on supplementation of AL. Thus these results indicate the potential beneficiary effect of algal lycopene on collagen induced arthritis in rats when compared to TL and even to the commonly used anti-inflammatory drug indomethacin. Therefore lycopene from C. marina would be recommended as a better natural source with increased activity and without side effects in the treatment of anti-inflammatory diseases. PMID:23237458

  9. Trabecular bone response to mechanical loading in ovariectomized Sprague-Dawley rats depends on baseline bone quantity.

    PubMed

    Ko, Chang-Yong; Jung, Young Jin; Park, Ji Hyung; Seo, Donghyun; Han, Paul; Bae, Kiho; Schreiber, Jürgen; Kim, Han Sung

    2012-07-26

    Mechanical loading is one of the determining factors for bone modulation, and is therefore frequently used to treat or prevent bone loss; however, there appears to be no data on the effects of baseline bone quantity on this response. This study aimed to verify whether baseline bone quantity affects osteoporotic trabecular bone adaptive response to mechanical stimulation. Twenty-four female Sprague-Dawley (SD) rats were ovariectomized (OVX). After 3 weeks of OVX, rats were divided into a high bone quantity and a low bone quantity group, and rats in each group were then subdivided into 4 groups that were exposed to different loading strategies. In the loading groups, tibiae were stimulated through axial loading at 2000με of strain, for 1500 cycles each of 75s, 150s, or 250s. The sham treatment groups received no loading. Changes in BV/TV for trabecular bone in the tibia were measured at the baseline (before loading), and at 3 weeks and 6 weeks after loading. BV/TVs in loading groups of the low baseline bone quantity group were significantly increased at 6 weeks, compared with those in the no-loading groups (p<0.05), while those in the high quantity groups were not increased (p>0.05). A significant negative correlation was observed between baseline BV/TV and its relative variations at 3 weeks or 6 weeks (p<0.05). These results indicate that adaptive responses of osteoporotic trabecular bone to mechanical loading depend on baseline bone quantity. PMID:22663762

  10. The toxicity of p-aminophenol in the Sprague-Dawley rat: effects on growth, reproduction and foetal development.

    PubMed

    Burnett, C M; Re, T A; Rodriguez, S; Loehr, R F; Dressler, W E

    1989-10-01

    p-Aminophenol (p-AP) was fed in the diet to groups of 40 male and 45 female Sprague-Dawley rats at levels of 0.07, 0.2 or 0.7% for up to 6 months. Methaemoglobin levels were determined after 6 wk. During wk 12, urine was collected from ten rats/sex/group for evaluation of mutagenicity in the Ames test. Clinical chemistry, haematology and histopathology studies were performed in subgroups after 13 and 27 wk. In addition, after 13 wk, 25 females/group were mated to untreated males in a teratology study. After 20 wk, 20 males/group were removed from the test diets and mated to untreated virgin females in a dominant lethal mutagenicity study. These males remained untreated until they were killed at 27 wk. Rats that had been maintained on the test diets throughout the study were also killed at wk 27. The high dose level of 0.7% p-AP resulted in a significant (10-15%) reduction in body-weight gain in both sexes. There was no increase in the level of methaemoglobin and, other than slight reductions in total erythrocytes and haemoglobin in female rats at 13 wk, there were no toxicologically important differences between groups in haematology or clinical chemistry values at any time during the 27 wk of treatment. Dose-related nephrosis was seen in both sexes after 13 and 27 wk and in the high-dose males that were removed from the test diet for a 7-wk recovery period. The compound was not teratogenic, but an increase in developmental variations associated with maternal toxicity was noted at the mid- and high-dose levels. In the dominant lethal study, an increase in the total number of resorptions (but not litters with resorptions) was observed in the high-dose group in the first of two matings but this observation was not confirmed in a follow-up study. Mutagenic activity was not detected in the urine of rats fed p-AP. PMID:2606405

  11. Spinal NMDA receptor activation constrains inactivity-induced phrenic motor facilitation in Charles River Sprague-Dawley rats

    PubMed Central

    Streeter, K. A.

    2014-01-01

    Reduced spinal synaptic inputs to phrenic motor neurons elicit a unique form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). iPMF requires tumor necrosis factor-α (TNF-α) and atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize early, transient increases in phrenic burst amplitude into long-lasting iPMF. Here we tested the hypothesis that spinal N-methyl-d-aspartate receptor (NMDAR) activation constrains long-lasting iPMF in some rat substrains. Phrenic motor output was recorded in anesthetized, ventilated Harlan (HSD) and Charles River (CRSD) Sprague-Dawley rats exposed to a 30-min central neural apnea. HSD rats expressed a robust, long-lasting (>60 min) increase in phrenic burst amplitude (i.e., long-lasting iPMF) when respiratory neural activity was restored. By contrast, CRSD rats expressed an attenuated, transient (∼15 min) iPMF. Spinal NMDAR inhibition with DL-2-amino-5-phosphonopentanoic acid (APV) before neural apnea or shortly (4 min) prior to the resumption of respiratory neural activity revealed long-lasting iPMF in CRSD rats that was phenotypically similar to that in HSD rats. By contrast, APV did not alter iPMF expression in HSD rats. Spinal TNF-α or aPKC inhibition impaired long-lasting iPMF enabled by NMDAR inhibition in CRSD rats, suggesting that similar mechanisms give rise to long-lasting iPMF in CRSD rats with NMDAR inhibition as those giving rise to long-lasting iPMF in HSD rats. These results suggest that NMDAR activation can impose constraints on TNF-α-induced aPKC activation after neural apnea, impairing stabilization of transient iPMF into long-lasting iPMF. These data may have important implications for understanding differential responses to reduced respiratory neural activity in a heterogeneous human population. PMID:25103979

  12. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats

    PubMed Central

    Ibrahim, Ibrahim Abdel Aziz; Abdulla, Mahmood Ameen; Hajrezaie, Maryam; Bader, Ammar; Shahzad, Naiyer; Al-Ghamdi, Saeed S; Gushash, Ahmad S; Hasanpourghadi, Mohadeseh

    2016-01-01

    Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid–Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of

  13. Hesperidin a flavanoglycone protects against gamma-irradiation induced hepatocellular damage and oxidative stress in Sprague-Dawley rats.

    PubMed

    Pradeep, Kannampalli; Park, Sang Hyun; Ko, Kyong Cheol

    2008-06-10

    Oxidative stress plays a pivotal role in the pathogenesis and progression of gamma-irradiation induced cellular damage and the administration of dietary antioxidants has been suggested to protect against the subsequent tissue damage. Here, we present the data to explore the hepatoprotective and antioxidant effect of hesperidin, a naturally occurring citrus flavanoglycone, against gamma-irradiation induced oxidative damage in the liver of rats. Healthy male Sprague-Dawley rats were exposed to gamma-irradiation (1 Gy, 3 Gy and 5 Gy) and were administered hesperidin (50 mg/kg and 100 mg/kg, b.w, orally) for 7 days post irradiation. The changes in body weight, liver weight, spleen index, serum and liver aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and serum ceruloplasmin levels were determined along with differences in the liver histopathology. Liver thiobarbuturic acid reactive substance as an index for lipid peroxidation and the levels of enzymatic antioxidants like superoxide dismutase, catalase, glutathione peroxidase and the status of non-enzymatic antioxidants as an index for oxidative stress were also determined. Exposure to gamma-irradiation resulted in hepatocellular damage in a dose-dependent manner, featuring a significantly decreased body weight and liver weight and higher levels of serum AST, ALT, ALP, LDH and gamma-GT levels and a simultaneous decrease in their levels in the liver tissue. Oxidative stress was evidenced by elevated levels of lipid peroxidation and a decrease in the levels of key enzymatic and non-enzymatic antioxidants in the liver. However, the gamma-irradiation induced toxic effects were dramatically and dose-dependently inhibited by hesperidin treatment as observed by the restoration in the altered levels of the marker enzymes, lipid peroxidation, enzymatic and non-enzymatic antioxidants. The results of the biochemical

  14. Effect of feeding grape pomace on selected metabolic parameters associated with high fructose feeding in growing Sprague-Dawley rats.

    PubMed

    Khanal, Ramesh C; Howard, Luke R; Rogers, Theodore J; Wilkes, Samuel E; Dhakal, Ishwori B; Prior, Ronald L

    2011-12-01

    The effect of feeding grape pomace on certain metabolic parameters associated with high fructose (HF) feeding was studied. Forty male growing Sprague-Dawley rats were randomly assigned into groups: (1) control; (2) HF; (3) HF with low-level (1.5% of diet) grape pomace (HF+LP), and (4) HF with high-level (5.0% of diet) grape pomace (HF+HP). The HF+LP and HF+HP diets provided 115 and 218 mg of procyanidins/kg, respectively. Compared with the controls, HF-fed animals consumed less and were smaller, whereas animals in the HF+LP and HF+HP groups were in between. A similar trend was observed for abdominal fat and abdominal fat as a percentage of body weight. No change in heart or kidney weight occurred. Liver weight as a percentage of body weight was higher for animals when fructose was included in the diet compared with those on control diet, and inclusion of grape pomace had no effect. Fasting plasma glucose, insulin, and triglyceride levels tended to be higher in animals fed HF diet, and grape pomace reduced their levels to values similar to the control animals. Compared with control animals, HF-fed animals had higher weekly postprandial plasma triglycerides, which were reduced by feeding grape pomace, but no change in plasma cholesterol was observed. Glucose intolerance was observed in animals fed HF diet and was accompanied by a 25% increase in homeostatic model assessment (HOMA) of insulin resistance. Inclusion of grape pomace increased glucose tolerance and insulin sensitivity. No significant change (P>.1) in HOMA of β-cell function or Quantitative Insulin-Sensitivity Check Index was observed. Overall, HF diet did not produce as strong a response of metabolic syndrome as has been shown in the literature. The inclusion of grape pomace in the diet was effective in modulating some aspects of metabolic parameters associated with metabolic syndrome, and the higher level of grape pomace in the diet produced a slightly better response than the lower level.

  15. Identity and pathogenesis of stomach tumors in Sprague-Dawley rats associated with the dietary administration of butachlor.

    PubMed

    Hard, G C; Iatropoulos, M J; Thake, D C; Wheeler, D; Tatematsu, M; Hagiwara, A; Williams, G M; Wilson, A G

    1995-05-01

    Macroscopic stomach tumors induced in Sprague-Dawley rats during two chronic bioassays with the acetanilide herbicide butachlor at a dietary concentration of 3000 ppm, were evaluated histologically and immunohistochemically in order to determine their identity and pathogenesis. The tumors, which occurred primarily in female rats, were a heterogeneous series, including a few consisting wholly or partly of classic solid or anaplastic epithelium, but with the majority containing diffusely distributed primitive neoplastic cells. The latter had either the general appearance of undifferentiated epithelium or presented a more "mesenchyme-like" pattern where the cells were epithelioid, blastema-like, neuroendocrine-like or sarcoma-like with fascicular disposition. Gastric glandular profiles were also present, usually located near the periphery of the tumors, but in some cases extending into the diffuse tumor tissue. Most of the tumors displayed variable immunohistochemical reactivity for cytokeratin, vimentin and neuron-specific enolase but were negative for muscle-specific actin or desmin except in the stromal tracts. Detailed examination of all available gastric tissue revealed the presence of additional microscopic neoplasms and precursor hyperplastic lesions. All of these were typical gastric neuroendocrine cell lesions (gastric carcinoids) originating in the fundic mucosa but occasionally invading submucosally, and consisting of epithelial cells in organized clusters, rosettes or primitive tubules. The enterochromaffin-like (ECL) nature of these microscopic neoplasms and precursor lesions was substantiated by strong immunohistochemical reactivity for cytokeratin, neuron-specific enolase and chromogranin A, and a negative reaction for vimentin. One microscopic tumor showed a transition from differentiated neuroendocrine type in the fundic mucosa to a dispersed "mesenchyme-like" pattern in the submucosal extension. An additional finding in the butachlor-treated male and

  16. Consequences of adolescent ethanol exposure in male Sprague-Dawley rats on fear conditioning and extinction in adulthood

    NASA Astrophysics Data System (ADS)

    Broadwater, Margaret A.

    Some evidence suggests that adolescents are more vulnerable than adults to alcohol-induced cognitive deficits and that these deficits may persist into adulthood. Five experiments were conducted to assess long-term consequences of ethanol exposure on tone and context Pavlovian fear conditioning in male Sprague-Dawley rats. Experiment 1 examined age-related differences in sensitivity to ethanol-induced disruptions of fear conditioning to a pre-conditioning ethanol challenge. Experiments 2 examined fear conditioning 22 days after early-mid adolescent (P28-48) or adult (P70-90) exposure to 4 g/kg i.g. ethanol or water given every other day (total of 11 exposures). In Experiment 3, mid-late adolescents (P35-55) were exposed in the same manner to assess whether timing of ethanol exposure within the adolescent period would differentially affect later fear conditioning. Experiment 4 assessed the influence of prior adolescent or adult ethanol exposure on the disrupting effects of a pre-conditioning ethanol challenge. In Experiment 5, neurogenesis (doublecortin---DCX) and cholinergic (choline acetyltransferase---ChAT) markers were measured to assess potential long-term ethanol-induced changes in neural mechanisms important for learning and memory. Results indicated that the long-lasting behavioral effects of ethanol exposure varied depending on exposure age, with early-mid adolescent exposed animals showing attenuated context fear retention (a relatively hippocampal-dependent task), whereas mid-late adolescent and adult exposed animals showed slower context extinction (thought to be reliant on the mPFC). Early-mid adolescent ethanol-exposed animals also had significantly less DCX and ChAT expression than their water-exposed counterparts, possibly contributing to deficits in context fear. Tone fear was not influenced by prior ethanol exposure at any age. In terms of age differences in ethanol sensitivity, adolescents were less sensitive than adults to ethanol

  17. Potent carcinogenicity of 2,7-dinitrofluorene, an environmental pollutant, for the mammary gland of female Sprague-Dawley rats.

    PubMed

    Malejka-Giganti, D; Niehans, G A; Reichert, M A; Bennett, K K; Bliss, R L

    1999-10-01

    Nitrofluorene compounds are environmental pollutants chiefly from incomplete combustion. This study examined carcinogenicities after one intramammary injection of 2-nitrofluorene (2-NF), 2, 7-dinitrofluorene (2,7-diNF) or dimethyl sulfoxide (DMSO) (solvent control) to 30-day-old and of 2-NF, 9-OH-2-NF, 9-oxo-2-NF, 2,7-diNF, 9-oxo-2,7-diNF, 2,5-dinitrofluorene, 9-oxo-2,4,7-trinitrofluorene, N-OH-2-acetylaminofluorene (N-OH-2-AAF) (carcinogen control) or DMSO to 50-day-old female Sprague-Dawley rats. In 30- and 50-day-old rats 6 and 8 glands/rat, respectively, were injected with 2.04 micromol of compound in 50 microliter/gland of DMSO. Whereas all compounds including DMSO yielded combined malignant and benign mammary tumor incidences of 33-87% by week 82 after injection, 2,7-diNF produced 100 and 93% incidences significantly (P < 0.001) sooner than did DMSO, i.e. by weeks 23-49 and 18-48 after treatment of 30- and 50-day-old rats, respectively. Rats treated with 2,7-diNF and 9-oxo-2,7-diNF had significantly (P < 0.0001) and marginally (P = 0. 0536) more mammary tumors, respectively, than DMSO-treated rats. In 2,7-diNF-treated rats, the ratio of malignant to benign mammary tumors was 5.4, whereas in all other groups it was <0.5. N-OH-2-AAF, a potent tumorigen when applied to the mammary gland as a solid or in suspension, did not yield the expected tumorigenicity here. The contrasting tumorigenic potencies of 2,7-diNF and N-OH-2-AAF may have been prompted by differences in their solubilities in DMSO. Thus, the poorly soluble 2,7-diNF was slowly absorbed from the injection sites since residues (up to 0.9% of the dose injected) were recovered even after 45 weeks. The data indicate prolonged exposure of the mammary gland to 2,7-diNF and suggest that contamination of the environment with 2,7-diNF, even at low levels, poses substantial carcinogenic risk. PMID:10506119

  18. The gastroprotective effects of hydroalcoholic extract of Monolluma quadrangula against ethanol-induced gastric mucosal injuries in Sprague Dawley rats.

    PubMed

    Ibrahim, Ibrahim Abdel Aziz; Abdulla, Mahmood Ameen; Hajrezaie, Maryam; Bader, Ammar; Shahzad, Naiyer; Al-Ghamdi, Saeed S; Gushash, Ahmad S; Hasanpourghadi, Mohadeseh

    2016-01-01

    Monolluma quadrangula (Forssk.) Plowes is used in Saudi traditional medicines to treat gastric ulcers. The hydroalcoholic extract of M. quadrangula (MHAE) was used in an in vivo model to investigate its gastroprotective effects against ethanol-induced acute gastric lesions in rats. Five groups of Sprague Dawley rats were used. The first group was treated with 10% Tween 20 as a control. The other four groups included rats treated with absolute ethanol (5 mL/kg) to induce an ulcer, rats treated with 20 mg/kg omeprazole as a reference drug, and rats treated with 150 or 300 mg/kg MHAE. One hour later, the rats were administered absolute ethanol (5 mL/kg) orally. Animals fed with MHAE exhibited a significantly increased pH, gastric wall mucus, and flattening of the gastric mucosa, as well as a decreased area of gastric mucosal damage. Histology confirmed the results; extensive destruction of the gastric mucosa was observed in the ulcer control group, and the lesions penetrated deep into the gastric mucosa with leukocyte infiltration of the submucosal layer and edema. However, gastric protection was observed in the rats pre-fed with plant extracts. Periodic acid-Schiff staining of the gastric wall revealed a remarkably intensive uptake of magenta color in the experimental rats pretreated with MHAE compared to the ulcer control group. Immunohistochemistry staining revealed an upregulation of the Hsp70 protein and a downregulation of the Bax protein in rats pretreated with MHAE compared with the control rats. Gastric homogenate showed significantly increased catalase and superoxide dismutase, and the level of malondialdehyde (MDA) was reduced in the rats pretreated with MHAE compared to the control group. In conclusion, MHAE exhibited a gastroprotective effect against ethanol-induced gastric mucosal injury in rats. The mechanism of this gastroprotection included an increase in pH and gastric wall mucus, an increase in endogenous enzymes, and a decrease in the level of MDA

  19. First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats.

    PubMed

    Soffritti, Morando; Belpoggi, Fiorella; Degli Esposti, Davide; Lambertini, Luca; Tibaldi, Eva; Rigano, Anna

    2006-03-01

    The Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation has conducted a long-term bioassay on aspartame (APM), a widely used artificial sweetener. APM was administered with feed to 8-week-old Sprague-Dawley rats (100-150/sex/group), at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. The treatment lasted until natural death, at which time all deceased animals underwent complete necropsy. Histopathologic evaluation of all pathologic lesions and of all organs and tissues collected was routinely performed on each animal of all experimental groups. The results of the study show for the first time that APM, in our experimental conditions, causes a) an increased incidence of malignant-tumor-bearing animals with a positive significant trend in males (p < or = 0.05) and in females (p < or = 0.01), in particular those females treated at 50,000 ppm (p < or = 0.01); b) an increase in lymphomas and leukemias with a positive significant trend in both males (p < or = 0.05) and females (p < or = 0.01), in particular in females treated at doses of 100,000 (p < or = 0.01), 50,000 (p < or = 0.01), 10,000 (p < or = 0.05), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.01); c) a statistically significant increased incidence, with a positive significant trend (p < or = 0.01), of transitional cell carcinomas of the renal pelvis and ureter and their precursors (dysplasias) in females treated at 100,000 (p < or = 0.01), 50,000 (p < or = 0.01), 10,000 (p < or = 0.01), 2,000 (p < or = 0.05), or 400 ppm (p < or = 0.05); and d) an increased incidence of malignant schwannomas of peripheral nerves with a positive trend (p < or = 0.05) in males. The results of this mega-experiment indicate that APM is a multipotential carcinogenic agent, even at a daily dose of 20 mg/kg body weight, much less than the current acceptable daily intake. On the basis of these results, a reevaluation of the present guidelines on the use and consumption of APM is urgent and

  20. Results of long-term carcinogenicity bioassay on Sprague-Dawley rats exposed to aspartame administered in feed.

    PubMed

    Belpoggi, Fiorella; Soffritti, Morando; Padovani, Michela; Degli Esposti, Davide; Lauriola, Michelina; Minardi, Franco

    2006-09-01

    Aspartame (APM) is one of the most widely used artificial sweeteners in the world. Its ever-growing use in more than 6000 products, such as soft drinks, chewing gum, candy, desserts, etc., has been accompanied by rising consumer concerns regarding its safety, in particular its potential long-term carcinogenic effects. In light of the inadequacy of the carcinogenicity bioassays performed in the 1970s and 1980s, a long-term mega-experiment on APM was undertaken at the Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation on groups of male and female Sprague-Dawley rats (100-150/sex/group), 8 weeks old at the start of the experiment. APM was administered in feed at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. Treatment lasted until spontaneous death of the animals. The results of the study demonstrate that APM causes: (a) an increased incidence of malignant tumor-bearing animals, with a positive significant trend in both sexes, and in particular in females treated at 50,000 ppm (P < or = 0.01) when compared to controls; (b) an increase in lymphomas-leukemias, with a positive significant trend in both sexes, and in particular in females treated at doses of 100,000 (P < or = 0.01), 50,000 (P < or = 0.01), 10,000 (P < or = 0.05), 2000 (P < or = 0.05), and 400 ppm (P < or = 0.01); (c) a statistically significant increased incidence, with a positive significant trend, of transitional cell carcinomas of the renal pelvis and ureter in females and particularly in those treated at 100,000 ppm (P < or = 0.05); and (d) an increased incidence of malignant schwannomas of the peripheral nerves, with a positive trend in males (P < or = 0.05). The results of this mega-experiment indicate that APM, in the tested experimental conditions, is a multipotential carcinogenic agent.

  1. AC Electric Field Enhances Cryopreservation Efficiency of Sprague-Dawley Rat Liver During a Slow Freezing Procedure.

    PubMed

    Ma, Ya H; Qin, Guo F; Li, Jing; Ding, Gui R; Xu, Sheng L; Zhou, Yan; Guo, Guo Z

    2016-02-01

    Slow freezing coupled with an AC electric field (ACEF) has been demonstrated to miniaturize the ice crystals of a 0.9% (w/v) NaCl solution in a prior study. The aim of this study was to assess the effect of ACEF on Sprague-Dawley (SD) rat liver in vitro during the slow cooling procedure. SD rat liver exposed to an oscillating electric field was frozen in a programmed freezer initially down to -30°C at a cooling rate of -1°C/min and continuing down to -80°C at a cooling rate of -5°C/min. The cryovials were finally transferred into liquid nitrogen for 7 days. The frequency range was 0-20 MHz, and peak field strength was 1,000 V/m. For the sham and electric-exposed groups, the freezing solution consisted of 0%, 2.5%, 5.0%, 7.5%, or 10% (v/v) dimethyl sulfoxide (DMSO) Dulbecco's modified Eagles' medium culture solution, and fresh tissue was selected as the control group. The changes in cell survival rate, adenosine triphosphate (ATP) content, and morphology of fresh and frozen-thawed liver tissue were examined. Compared with the sham group with 5.0% DMSO, the result showed that slow freezing coupled with 2.45 MHz or 5 MHz ACEF significantly increased the relative survival rate by 43.27% and 26.31% (P < 0.001), respectively. However, ACEF exposure increased the ATP content compared with the sham group. Especially in 5% and 10% DMSO with 2.45 MHz ACEF exposure, the ATP content approximated the fresh group (7.3 ± 2.7 nmol/piece), corresponding to 94.52% and 80.82%. In addition, the cellular membrane and some organelles (e.g., mitochondria) in the electric-exposed group appeared to be more intact according to the transmission electron microscopy images. The underlying mechanism might be that the ACEF affects the formation and growth of the ice crystallization, and thus inhibits cryoinjury. These results show that ACEF would provide an efficient method for cryopreservation banking with a low concentration of CPA during the slow freezing process

  2. Effect of Ambient Temperature on the Thermoregulatory and Locomotor Stimulant Effects of 4-Methylmethcathinone in Wistar and Sprague-Dawley Rats

    PubMed Central

    Wright, M. Jerry; Angrish, Deepshikha; Aarde, Shawn M.; Barlow, Deborah J.; Buczynski, Matthew W.; Creehan, Kevin M.; Vandewater, Sophia A.; Parsons, Loren H.; Houseknecht, Karen L.; Dickerson, Tobin J.; Taffe, Michael A.

    2012-01-01

    The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, “plant food”, “bath salts”) is a recent addition to the list of popular recreational psychomotor-stimulant compounds. Relatively little information about this drug is available in the scientific literature, but popular media reports have driven recent drug control actions in the UK and several US States. Online user reports of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) prompted the current investigation of the thermoregulatory and locomotor effects of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1–10 mg/kg ) using an implantable radiotelemetry system under conditions of low (23°C) and high (27°C) ambient temperature. A reliable reduction of body temperature was produced by 4-MMC in Wistar rats at 23°C or 27°C with only minimal effect in Sprague-Dawley rats. Increased locomotor activity was observed after 4-MMC administration in both strains with significantly more activity produced in the Sprague-Dawley strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain. Furthermore, hypothermia produced by the serotonin 1A/7 receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) was similar in each strain. These results show that the cathinone analog 4-MMC exhibits thermoregulatory and locomotor properties that are distinct from those established for methamphetamine or MDMA in prior work, despite recent evidence of neuropharmacological similarity with MDMA. PMID:22952999

  3. Effect of ambient temperature on the thermoregulatory and locomotor stimulant effects of 4-methylmethcathinone in Wistar and Sprague-Dawley rats.

    PubMed

    Wright, M Jerry; Angrish, Deepshikha; Aarde, Shawn M; Barlow, Deborah J; Buczynski, Matthew W; Creehan, Kevin M; Vandewater, Sophia A; Parsons, Loren H; Houseknecht, Karen L; Dickerson, Tobin J; Taffe, Michael A

    2012-01-01

    The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, "plant food", "bath salts") is a recent addition to the list of popular recreational psychomotor-stimulant compounds. Relatively little information about this drug is available in the scientific literature, but popular media reports have driven recent drug control actions in the UK and several US States. Online user reports of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") prompted the current investigation of the thermoregulatory and locomotor effects of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1-10 mg/kg ) using an implantable radiotelemetry system under conditions of low (23°C) and high (27°C) ambient temperature. A reliable reduction of body temperature was produced by 4-MMC in Wistar rats at 23°C or 27°C with only minimal effect in Sprague-Dawley rats. Increased locomotor activity was observed after 4-MMC administration in both strains with significantly more activity produced in the Sprague-Dawley strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain. Furthermore, hypothermia produced by the serotonin 1(A/7) receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) was similar in each strain. These results show that the cathinone analog 4-MMC exhibits thermoregulatory and locomotor properties that are distinct from those established for methamphetamine or MDMA in prior work, despite recent evidence of neuropharmacological similarity with MDMA.

  4. Long-term metabolic effects of different doses of niacin-bound chromium on Sprague-Dawley rats.

    PubMed

    Perricone, N V; Bagchi, D; Echard, B; Preuss, Harry G

    2010-05-01

    We simultaneously assessed benefits and risks of niacin-bound chromium (NBC) intake at varying doses over a prolonged period of time (>1.2 years) in male and female Sprague-Dawley (SD) rats. We performed the study in two phases. First, we followed 60 male and 60 female SD rats, each gender divided into six groups. Through day 150 (phase 1A), all SD rats received a high sucrose diet (30% w/w) with or without different concentrations of NBC. The male/female groups were: 1] control without NBC n = 10, 2] low NBC (2.8 ppm, n = 10), 3] medium NBC (8.7 ppm, n = 20), 4] high NBC (28.0 ppm, n = 20). Based on dosing, we refer to the three treatment groups as 1X, 3X, and 10X. During days 151-312 (phase 1B), NBC was removed from diets of one half of the 3X and 10X groups. These are referred to as 3X satellite and 10X satellite. In phase 2 (days 313-460), males from groups 1X, 3X, 10X, 3X satellite, and 10X satellite received the same 3X dose of NBC (8.7 ppm). The last two groups also ingested different doses of a formulation of natural products in addition to NBC. We examined blood pressure, the renin-angiotensin system (RAS), nitric oxide (NO), and insulin systems and inflammatory parameters. Results in male and female SD rats were comparable. NBC lowered systolic blood pressure (SBP) in a dose-dependent fashion; however, after 200 days, the SBP of the low dose group (1X) began to rise and returned to baseline control. After raising the dose of NBC to 3X, the SBP in the 1X group decreased significantly once more. When half the test rats (3X and 10X) were deprived of NBC, SBP rose gradually to control levels after 2 to 3 months. However, the SBP decreased significantly once more when each satellite group returned to the 3X dose. Special testing suggests that NBC at adequate dosing increases insulin sensitivity, lowers HbA1C, decreases activity of the RAS, at least in part, through ACE inhibition, enhances NO activity, and is without signs of toxicity. The addition of a

  5. Long-term metabolic effects of different doses of niacin-bound chromium on Sprague-Dawley rats.

    PubMed

    Perricone, N V; Bagchi, D; Echard, B; Preuss, Harry G

    2010-05-01

    We simultaneously assessed benefits and risks of niacin-bound chromium (NBC) intake at varying doses over a prolonged period of time (>1.2 years) in male and female Sprague-Dawley (SD) rats. We performed the study in two phases. First, we followed 60 male and 60 female SD rats, each gender divided into six groups. Through day 150 (phase 1A), all SD rats received a high sucrose diet (30% w/w) with or without different concentrations of NBC. The male/female groups were: 1] control without NBC n = 10, 2] low NBC (2.8 ppm, n = 10), 3] medium NBC (8.7 ppm, n = 20), 4] high NBC (28.0 ppm, n = 20). Based on dosing, we refer to the three treatment groups as 1X, 3X, and 10X. During days 151-312 (phase 1B), NBC was removed from diets of one half of the 3X and 10X groups. These are referred to as 3X satellite and 10X satellite. In phase 2 (days 313-460), males from groups 1X, 3X, 10X, 3X satellite, and 10X satellite received the same 3X dose of NBC (8.7 ppm). The last two groups also ingested different doses of a formulation of natural products in addition to NBC. We examined blood pressure, the renin-angiotensin system (RAS), nitric oxide (NO), and insulin systems and inflammatory parameters. Results in male and female SD rats were comparable. NBC lowered systolic blood pressure (SBP) in a dose-dependent fashion; however, after 200 days, the SBP of the low dose group (1X) began to rise and returned to baseline control. After raising the dose of NBC to 3X, the SBP in the 1X group decreased significantly once more. When half the test rats (3X and 10X) were deprived of NBC, SBP rose gradually to control levels after 2 to 3 months. However, the SBP decreased significantly once more when each satellite group returned to the 3X dose. Special testing suggests that NBC at adequate dosing increases insulin sensitivity, lowers HbA1C, decreases activity of the RAS, at least in part, through ACE inhibition, enhances NO activity, and is without signs of toxicity. The addition of a

  6. Suppression of Kupffer cell function prevents cadmium induced hepatocellular necrosis in the male Sprague-Dawley rat.

    PubMed

    Sauer, J M; Waalkes, M P; Hooser, S B; Kuester, R K; McQueen, C A; Sipes, I G

    1997-08-15

    Exposure of humans to toxic metals and metalloids is a major environmental problem. Many metals, such as cadmium, can be hepatotoxic. However, the mechanisms by which metals cause acute hepatic injury are in many cases unknown. Previous reports suggest a major role for inflammation in acute cadmium induced hepatotoxicity. In initial experiments we found that a non-hepatotoxic dose of cadmium chloride (CdCl2; 2.0 mg/kg, i.v.) markedly increased the clearance rate of colloidal carbon from the blood, which is indicative of enhanced phagocytic activity by Kupffer cells (resident hepatic macrophages). Thus. the objective these studies was to determine the involvement of Kupffer cells in cadmium induced liver injury by inhibiting their function with gadolinium chloride (GdCl3). Male Sprague-Dawley rats were administered GdCl3 (10 mg/kg, i.v.) followed 24 h later by a single dose of CdCl2 (3.0 and 4.0 mg/kg, i.v.). Twenty four hours after CdCl2 administration animals were killed and the degree of liver toxicity was assessed using plasma alanine aminotransferase (ALT), as well as light microscopy. Cadmium chloride administration produced multifocal hepatocellular necrosis and increased plasma ALT activity. Pretreatment with GdCl3 significantly reduced both the morphological changes and hepatic ALT release caused by CdCl2. However, the protection was specific to the liver, and did not alter CdCl2 induced testicular injury, as determined by histopathological damage. In many cases, the inducible cadmium-binding protein, metallothionein (MT) is often an essential aspect of the acquisition of cadmium tolerance in the liver. Although cadmium caused a dramatic induction of hepatic MT (32-fold), GdCl3 caused only a minor increase (2-fold). Combined CdCl2 and GdCl3 treatment did not induce levels to an extent greater than CdCl2 alone. As expected, GdCl3 also caused a slight increase in the amount of cadmium associated with the liver. In cultured hepatocytes isolated from GdCl3

  7. Effects of leptin on sperm count and morphology in Sprague-Dawley rats and their reversibility following a 6-week recovery period.

    PubMed

    Almabhouh, F A; Osman, K; Siti Fatimah, I; Sergey, G; Gnanou, J; Singh, H J

    2015-09-01

    Altered epididymal sperm count and morphology following leptin treatment has been reported recently. This study examined the effects of 42 days of leptin treatment on sperm count and morphology and their reversibility during a subsequent 56-day recovery period. Twelve-week-old male Sprague-Dawley rats were randomised into four leptin and four saline-treated control groups (n = 6). Intraperitoneal injections of leptin were given daily (60 μg Kg(-1) body weight) for 42 days. Controls received 0.1 ml of 0.9% saline. Leptin-treated animals and their respective age-matched controls were euthanised on either day 1, 21, 42 or 56 of recovery for collection of epididymal spermatozoa. Sperm concentration was determined using a Makler counting chamber. Spermatozoa were analysed for 8-hydroxy-2-deoxyguanosine and DNA fragmentation (Comet assay). Data were analysed using anova. Sperm concentration was significantly lower but fraction of abnormal spermatozoa, and levels of 8-hydroxy-2-deoxyguanosine were significantly higher in leptin-treated rats on day 1 of recovery. Comet assays revealed significant DNA fragmentation in leptin-treated rats. These differences were reduced by day 56 of recovery. It appears that 42 days of leptin treatment to Sprague-Dawley rats has significant adverse effects on sperm count and morphology that reverse following discontinuation of leptin treatment.

  8. Effects on reproduction in female offspring from Sprague-Dawley rats fed 10% snakeweed (Gutierrezia microcephala) throughout pregnancy and concurrent treatment with safflower oil.

    PubMed

    Staley, E C; Smith, G S; Greenberg, J A

    1995-10-01

    Previous studies determined that safflower oil administration provided protection against the embryotoxicity seen following ingestion of 10% snakeweed (Gutierrezia microcephala) throughout pregnancy. Sixty-two young primiparous female rats born in those studies were paired with adult male Sprague-Dawley rats. After 4 d they were removed and carried their litters to term. Observations were made of the presence and extent of reproductive effects attributable to the 10% snakeweed exposure and differences in fecundity that were attributable to dosing with safflower oil or normal saline during the snakeweed exposure. Of the 62 rats, 50 carried litters to term and approximated the reproductive efficiency of normal primiparous Sprague-Dawley rats. There was no significant difference between the fecundity of females born to rats fed the 10% snakeweed and dosed with safflower oil, those born of rats fed snakeweed dosed with normal saline, or those fed a snakeweed-free diet and dosed with normal saline. Regardless of the diet or treatment administered, dams carrying their litters to parturition gave birth to healthy, normo-reproductive offspring. While the toxic principles in Gutierrezia species plants may act as estrogenic or anti-estrogenic compounds, they did not impair fertility in the female offspring of dosed rats. PMID:8592831

  9. Edible Safety Assessment of Genetically Modified Rice T1C-1 for Sprague Dawley Rats through Horizontal Gene Transfer, Allergenicity and Intestinal Microbiota

    PubMed Central

    Zhao, Kai; Ren, Fangfang; Han, Fangting; Liu, Qiwen; Wu, Guogan; Xu, Yan; Zhang, Jian; Wu, Xiao; Wang, Jinbin; Li, Peng; Shi, Wei; Zhu, Hong; Lv, Jianjun; Zhao, Xiao; Tang, Xueming

    2016-01-01

    In this study, assessment of the safety of transgenic rice T1C-1 expressing Cry1C was carried out by: (1) studying horizontal gene transfer (HGT) in Sprague Dawley rats fed transgenic rice for 90 d; (2) examining the effect of Cry1C protein in vitro on digestibility and allergenicity; and (3) studying the changes of intestinal microbiota in rats fed with transgenic rice T1C-1 in acute and subchronic toxicity tests. Sprague Dawley rats were fed a diet containing either 60% GM Bacillus thuringiensis (Bt) rice T1C-1 expressing Cry1C protein, the parental rice Minghui 63, or a basic diet for 90 d. The GM Bt rice T1C-1 showed no evidence of HGT between rats and transgenic rice. Sequence searching of the Cry1C protein showed no homology with known allergens or toxins. Cry1C protein was rapidly degraded in vitro with simulated gastric and intestinal fluids. The expressed Cry1C protein did not induce high levels of specific IgG and IgE antibodies in rats. The intestinal microbiota of rats fed T1C-1 was also analyzed in acute and subchronic toxicity tests by DGGE. Cluster analysis of DGGE profiles revealed significant individual differences in the rats' intestinal microbiota. PMID:27706188

  10. Life-span exposure to sinusoidal-50 Hz magnetic field and acute low-dose γ radiation induce carcinogenic effects in Sprague-Dawley rats.

    PubMed

    Soffritti, Morando; Tibaldi, Eva; Padovani, Michela; Hoel, David G; Giuliani, Livio; Bua, Luciano; Lauriola, Michelina; Falcioni, Laura; Manservigi, Marco; Manservisi, Fabiana; Panzacchi, Simona; Belpoggi, Fiorella

    2016-01-01

    Background In 2002 the International Agency for Research on Cancer classified extremely low frequency magnetic fields (ELFMF) as a possible carcinogen on the basis of epidemiological evidence. Experimental bioassays on rats and mice performed up to now on ELFMF alone or in association with known carcinogens have failed to provide conclusive confirmation. Objectives To study the carcinogenic effects of combined exposure to sinusoidal-50 Hz (S-50 Hz) magnetic fields and acute γ radiation in Sprague-Dawley rats. Methods We studied groups of male and female Sprague-Dawley rats exposed from prenatal life until natural death to 20 or 1000 μT S-50 Hz MF and also to 0.1 Gy γ radiation delivered as a single acute exposure at 6 weeks of age. Results The results of the study showed significant carcinogenic effects for the mammary gland in males and females and a significant increased incidence of malignant schwannomas of the heart as well as increased incidence of lymphomas/leukemias in males. Conclusions These results call for a re-evaluation of the safety of non-ionizing radiation. PMID:26894944

  11. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    PubMed

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

  12. Effect of chronic treatment with ICI D7114, a selective beta 3-adrenoceptor agonist, on macronutrient selection and brown adipose tissue thermogenesis in Sprague-Dawley rats.

    PubMed

    Santti, E; Rouvari, T; Rouru, J; Huupponen, R; Koulu, M

    1994-01-01

    ICI D7114 is a selective beta 3-agonist which stimulates brown adipose tissue thermogenesis. In the present study the effects of 18 days treatment with ICI D7114 (2 mg/kg/day orally) on macronutrient selection and brown adipose tissue thermogenesis were investigated in Sprague-Dawley rats. The rats were maintained on a free-feeding self-selection paradigm with three pure macronutrient diets of carbohydrate, fat and protein. Treatment with ICI D7114 did not change the macronutrient selection or total calories consumed by the rats. To monitor the thermogenic activation of brown adipose tissue the binding of [3H]GDP to brown adipose tissue mitochondria was measured. The treatment with ICI D7114 increased the binding of GDP both when expressed as total binding per lobe (P < 0.001) and per mg of protein (P < 0.01). It is concluded that ICI D7114, used in doses affecting brown adipose tissue thermogenesis, does not change the macronutrient selection or total energy intake in Sprague-Dawley rats. PMID:7800658

  13. Comparative toxicokinetics of low-viscosity mineral oil in Fischer 344 rats, Sprague-Dawley rats, and humans--implications for an Acceptable Daily Intake (ADI).

    PubMed

    Boogaard, Peter J; Goyak, Katy O; Biles, Robert W; van Stee, Leo L P; Miller, Matthew S; Miller, Mary Jo

    2012-06-01

    Oral repeated-dose studies with low-viscosity mineral oils showed distinct species and strain differences, which are hypothesized to be due to differences in bioavailability, with Fischer 344 rats being more susceptible than Sprague-Dawley rats or dogs. Sensitive analytical methodology was developed for accurate measurement of low levels of mineral hydrocarbons and applied in single-dose toxicokinetics studies in rats and humans. Fischer 344 rats showed a 4-fold higher AUC(0-∞) and consistently higher blood and liver concentrations were found than Sprague-Dawley rats. Hepatic mineral hydrocarbon concentration tracked the blood concentration in both strains, indicating that blood concentrations can serve as functional surrogate measure for hepatic concentrations. In human volunteers receiving 1mg/kg body weight of low-viscosity white oil, all blood concentrations of mineral hydrocarbons were below the detection limit. Comparison with threshold blood concentrations associated with NOAELs in both rat strains, indicate that the margin-of-exposure is at least 37-fold. Using an internal dose metric rather than applied dose reduces the uncertainty around the temporary ADI considerably since it intrinsically accounts for intra- and inter-species differences. The current data support replacement of the temporary ADI of 0.01 mg/kg/day by a (permanent) ADI of at least 1.0mg/kg/day for low- and medium-viscosity mineral oils.

  14. A 90-day subchronic feeding study of genetically modified maize expressing Cry1Ac-M protein in Sprague-Dawley rats.

    PubMed

    Liu, Pengfei; He, Xiaoyun; Chen, Delong; Luo, Yunbo; Cao, Sishuo; Song, Huan; Liu, Ting; Huang, Kunlun; Xu, Wentao

    2012-09-01

    The cry1Ac-M gene, coding one of Bacillus thuringiensis (Bt) crystal proteins, was introduced into maize H99 × Hi IIB genome to produce insect-resistant GM maize BT-38. The food safety assessment of the BT-38 maize was conducted in Sprague-Dawley rats by a 90-days feeding study. We incorporated maize grains from BT-38 and H99 × Hi IIB into rodent diets at three concentrations (12.5%, 25%, 50%) and administered to Sprague-Dawley rats (n=10/sex/group) for 90 days. A commercialized rodent diet was fed to an additional group as control group. Body weight, feed consumption and toxicological response variables were measured, and gross as well as microscopic pathology were examined. Moreover, detection of residual Cry1Ac-M protein in the serum of rats fed with GM maize was conducted. No death or adverse effects were observed in the current feeding study. No adverse differences in the values of the response variables were observed between rats that consumed diets containing GM maize BT-38 and non-GM maize H99 × Hi IIB. No detectable Cry1Ac-M protein was found in the serum of rats after feeding diets containing GM maize for 3 months. The results demonstrated that BT-38 maize is as safe as conventional non-GM maize.

  15. Comparison of spatial learning in the partially baited radial-arm maze task between commonly used rat strains: Wistar, Spargue-Dawley, Long-Evans, and outcrossed Wistar/Sprague-Dawley.

    PubMed

    Gökçek-Saraç, Çiğdem; Wesierska, Malgorzata; Jakubowska-Doğru, Ewa

    2015-03-01

    Strain-related differences in animals' cognitive ability affect the outcomes of experiments and may be responsible for discrepant results obtained by different research groups. Therefore, behavioral phenotyping of laboratory animals belonging to different strains is important. The aim of the present study was to compare the variation in allothetic visuospatial learning in most commonly used laboratory rat strains: inbred Wistar (W) and Sprague-Dawley (SD), outcrossed Wistar/Sprague-Dawley (W/SD), and outbred Long Evans (LE) rats. All rats were trained to the arbitrary performance criterion of 83 % correct responses in the partially baited 12-arm radial maze allowing for simultaneous evaluation of both working and reference memory. In the present study, testing albino versus pigmented and inbred versus outcrossed rats revealed significant strain-dependent differences with the inbred SD rats manifesting lower performance on all learning measures compared to other strains. On the other hand, the outcrossed W/SD rats showed a lower frequency of reference memory errors and faster rate of task acquisition compared to both LE and W rats, with W rats showing a lower frequency of working memory errors compared to other strains. In conclusion, albinism apparently did not reduce the animals' performance in the allothetic visuospatial learning task, while outcrossing improved the spatial learning. A differential effect of strain on the contribution of each error type to the animals' overall performance was observed. The strain-dependent differences were more pronounced between subpopulations of learning-deficient individuals ("poor" learners), and generally the reference memory errors contributed more to the final behavioral output than did the working memory errors. PMID:25537841

  16. Overlapping but distinct effects of genistein and ethinyl estradiol (EE2) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies

    PubMed Central

    Delclos, K. Barry; Weis, Constance C.; Bucci, Thomas J.; Olson, Greg; Mellick, Paul; Sadovova, Natalya; Latendresse, John R.; Thorn, Brett; Newbold, Retha R.

    2009-01-01

    Genistein and ethinyl estradiol (EE2) were examined in multigenerational reproductive and chronic toxicity studies that had different treatment intervals among generations. Sprague-Dawley rats received genistein (0, 5, 100, or 500 ppm) or EE2 (0, 2, 10, or 50 ppb) in a low phytoestrogen diet. Nonneoplastic effects in females are summarized here. Genistein at 500 ppm and EE2 at 50 ppb produced similar effects in continuously exposed rats, including decreased body weights, accelerated vaginal opening, and altered estrous cycles in young animals. At the high dose, anogenital distance was subtly affected by both compounds, and a reduction in litter size was evident in genistein-treated animals. Genistein at 500 ppm induced an early onset of aberrant cycles relative to controls in the chronic studies. EE2 significantly increased the incidence of uterine lesions (atypical focal hyperplasia and squamous metaplasia). These compound-specific effects appeared to be enhanced in the offspring of prior exposed generations. PMID:19159674

  17. Low-dose intragastric administration of Phaseolus vulgaris agglutinin (PHA) does not induce immunoglobulin E (IgE) production in Sprague-Dawley rats.

    PubMed

    Haas, H; Herzig, K H; André, S; Galle, J; Gronow, A; Gabius, H J

    2001-04-01

    Native Phaseolus vulgaris agglutinin (PHA) poses a potential health threat, when ingested with improperly cooked red kidney beans. Since PHA triggers human basophilic granulocytes in culture to rapidly release considerable amounts of interleukin-(IL-)4 and IL-13, key cytokines for inducing immunoglobulin E (IgE) production, the question was addressed whether this lectin can evoke in vivo IgE production. IgE-low-responder (Sprague-Dawley) rats received PHA (6 mg/rat/day) intragastrically by gavage over a period of 10 days. Up to day 35, there was no IgE induction regardless of whether the animals were boostered subcutaneously with PHA or not, indicating that PHA cannot be regarded as a general IgE inducer in rats. PMID:11788794

  18. Maternal separation enhances object location memory and prevents exercise-induced MAPK/ERK signalling in adult Sprague-Dawley rats.

    PubMed

    Makena, Nokuthula; Bugarith, Kishor; Russell, Vivienne A

    2012-09-01

    Early life stress increases the risk of developing psychopathology accompanied by reduced cognitive function in later life. Maternal separation induces anxiety-like behaviours and is associated with impaired memory. On the other hand, exercise has been shown to diminish anxiety-like behaviours and improve cognitive function. The effects of maternal separation and exercise on anxiety, memory and hippocampal proteins were investigated in male Sprague-Dawley rats. Maternal separation produced anxiety-like behaviours which were reversed by exercise. Maternal separation also enhanced object location memory which was not affected by exercise. Exercise did, however, increase synaptophysin and phospho-extracellular signal-regulated kinase (p-ERK) in the hippocampus of non-separated rats and this effect was not observed in maternally separated rats. These findings show that maternal separation selectively enhanced n memory and prevented activation of the MAPK/ERK signalling pathway in the adult rat hippocampus.

  19. Oral Accutane (13-cis-retinoic acid) has no effects on spatial learning and memory in male and female Sprague-Dawley rats.

    PubMed

    Ferguson, Sherry A; Berry, Kimberly J

    2007-01-01

    Descriptions of psychiatric effects with Accutane (13-cis-retinoic acid (13-cis-RA)) use prompted a series of studies in a rodent model to ascertain its cognitive effects. Previously, we reported no effects on measures of anhedonia and depression in rats treated with 7.5, 22.5, or 30 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459 [16]; S.A. Ferguson, F.J., Cisneros, J.P. Hanig, K.J. Berry, Chronic oral treatment with Accutane (13-cis-retinoic acid) does not increase measures of anhedonia or depression in male and female Sprague-Dawley rats, (in preparation) [19

  20. Ovariectomy and chronic stress lead toward leptin resistance in the satiety centers and insulin resistance in the hippocampus of Sprague-Dawley rats

    PubMed Central

    Ivić, Vedrana; Blažetić, Senka; Labak, Irena; Balog, Marta; Vondrak, Luka; Blažeković, Robert; Vari, Sandor G.; Heffer, Marija

    2016-01-01

    Aim To evaluate the changes in the expression level of gonadal steroid, insulin, and leptin receptors in the brain of adult Sprague-Dawley female rats due to ovariectomy and/or chronic stress. Methods Sixteen-week-old ovariectomized and non-ovariectomized female Sprague-Dawley rats were divided in two groups and exposed to three 10-day-sessions of sham or chronic stress. After the last stress-session the brains were collected and free-floating immunohistochemical staining was performed using androgen (AR), progesterone (PR), estrogen-β (ER-β), insulin (IR-α), and leptin receptor (ObR) antibodies. The level of receptors expression was analyzed in hypothalamic (HTH), cortical (CTX), dopaminergic (VTA/SNC), and hippocampal regions (HIPP). Results Ovariectomy downregulated AR in the hypothalamic satiety centers and hippocampus. It prevented or attenuated the stress-specific upregulation of AR in these regions. The main difference in stress response between non-ovariectomized and ovariectomized females was in PR level. Ovariectomized ones had increased PR level in the HTH, VTA, and HIPP. Combination of stressors pushed the hypothalamic satiety centers toward the rise of ObR and susceptibility to leptin resistance. When exposed to combined stressors, the HIPP, SNC and piriform cortex upregulated the expression of IR-α and the possibility to develop insulin resistance. Conclusion Ovariectomy exacerbates the effect of chronic stress by preventing gonadal receptor-specific stress response reflected in the upregulation of AR in the satiety and hippocampal regions, while stress after ovariectomy usually raises PR. The final outcome of inadequate stress response is reflected in the upregulation of ObR in the satiety centers and IR-α in the regions susceptible to early neurodegeneration. We discussed the possibility of stress induced metabolic changes under conditions of hormone deprivation. PMID:27106360

  1. Acute prenatal exposure to ethanol on gestational day 12 elicits opposing deficits in social behaviors and anxiety-like behaviors in Sprague Dawley rats.

    PubMed

    Diaz, Marvin R; Mooney, Sandra M; Varlinskaya, Elena I

    2016-09-01

    Our previous research has shown that in Long Evans rats acute prenatal exposure to a high dose of ethanol on gestational day (G) 12 produces social deficits in male offspring and elicits substantial decreases in social preference relative to controls, in late adolescents and adults regardless of sex. In order to generalize the observed detrimental effects of ethanol exposure on G12, pregnant female Sprague Dawley rats were exposed to ethanol or saline and their offspring were assessed in a modified social interaction (SI) test as early adolescents, late adolescents, or young adults. Anxiety-like behavior was also assessed in adults using the elevated plus maze (EPM) or the light/dark box (LDB) test. Age- and sex-dependent social alterations were evident in ethanol-exposed animals. Ethanol-exposed males showed deficits in social investigation at all ages and age-dependent alterations in social preference. Play fighting was not affected in males. In contrast, ethanol-exposed early adolescent females showed no changes in social interactions, whereas older females demonstrated social deficits and social indifference. In adulthood, anxiety-like behavior was decreased in males and females prenatally exposed to ethanol in the EPM, but not the LDB. These findings suggest that social alterations associated with acute exposure to ethanol on G12 are not strain-specific, although they are more pronounced in Long Evans males and Sprague Dawley females. Furthermore, given that anxiety-like behaviors were attenuated in a test-specific manner, this study indicates that early ethanol exposure can have differential effects on different forms of anxiety. PMID:27154534

  2. Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats

    PubMed Central

    Al-Husseiny, Fatma; Sobh, Mohamed Ahmed; Ashour, Rehab H.; Foud, Samah; Medhat, Tarek; El-Gilany, Abdel-Hady; Elghannam, Doaa; Abdel-Ghaffar, Hassan; Saad, Mohamed-Ahdy; Sobh, Mohamed

    2016-01-01

    Background and objectives Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. Methods 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. Results hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. Conclusion hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity. PMID:27426088

  3. Effect of dietary Ximenia caffra kernel meal on blood and liver metabolic substrate content and the general clinical biochemistry of Sprague Dawley rats.

    PubMed

    Chivandi, E; Moyo, D; Dangarembizi, R; Erlwanger, K

    2016-06-01

    We investigated (at the University of the Witwatersrand: GPS coordinates 26°10' 52.96″S; 28°2' 33.61″E) the effects of substituting soya bean meal (SBM) with Ximenia caffra kernel meal (XCKM) as a dietary protein source on blood and liver metabolic substrates content, serum markers of liver and kidney function and the general clinical biochemistry of Sprague Dawley (SD) rats. Five diets with similar energy and protein content were formulated (D1-D5) where XCKM replaced SBM on a crude protein basis at 0, 25, 50, 75 and 100%. Forty weanling male SD rats were randomly assigned to diets D1-D5, fed for 37 days and weighed twice weekly. The rats were then fasted overnight, and fasting blood glucose and triglyceride concentrations were determined from tail-vein-drawn blood. Immediately thereafter, the rats were euthanised and blood was collected via cardiac puncture. Serum was used to assay for markers of the general health profile. Livers were removed and weighed, and samples were used to determine lipid and glycogen content. Rats fed D4 (75% substitution level) had significantly lower (p < 0.05) blood triglyceride content compared with rats fed D2 (25% level of substitution). The substitution of SBM with XCKM did not affect (p > 0.05) fasting blood glucose and cholesterol concentrations, liver glycogen and lipid content. Additionally, it had no effect (p > 0.05) on serum activity/concentration of surrogate markers of liver (alanine aminotransferase and alkaline phosphatase activity and urea, total bilirubin, globulin and albumin concentrations) and kidney (phosphorus, calcium and creatinine concentrations) function and the general clinical biochemistry of the rats. Defatted XCKM could substitute SBM in rat diets without compromising blood glucose and cholesterol homeostasis, liver and kidney function and the general clinical biochemistry of growing male Sprague Dawley rats.

  4. Sweetpotato- and cereal-based infant foods: protein quality assessment, and effect on body composition using sprague dawley rats as a model.

    PubMed

    Amagloh, Francis Kweku; Chiridza, Tracy; Lemercier, Marie-Eve; Broomfield, Anne; Morel, Patrick C H; Coad, Jane

    2015-01-01

    The Protein Digestibility Corrected Amino Acid Score (PDCAAS) of sweetpotato-based complementary foods (OFSP ComFa and CFSP ComFa) and cereal-based infant products (Weanimix and Cerelac) was assessed using 3 wk-old male Sprague Dawley rats weighing between 53-67 g as a model for human infants. Also, the effect of consumption of the infant formulations on lean mass, bone mass content and fat mass was evaluated by Dual-Energy X-ray Absorptiometry (DEXA) using 6 wk-old Sprague Dawley rats (initial weight, 206-229 g). The ComFa products and Weanimix are household-level formulations, and Cerelac is a commercial infant cereal. The true protein digestibility score for Cerelac was 96.27%, and about 1.8% (P<0.0001) higher than that for OFSP ComFa, CFSP ComFa and Weanimix. However, OFSP ComFa had the highest un-truncated PDCAAS by a difference of 4.1%, than CFSP ComFa, and about 20% difference compared with both the Weanimix and Cerelac. All the products investigated had PDCAAS greater than 70%, the minimum protein quality requirement for complementary foods. Among the rats assigned to the four formulations, their bone mass and fat mass composition were not significantly different (P=0.08 and P=0.85, respectively). However, the rats on CFSP ComFa had higher lean mass than those on Cerelac (321.67 vs. 297.19 g; P=0.03). The findings from the PDCAAS and the DEXA-measured body composition studies indicate that complementary foods could be formulated from readily available agricultural resources at the household-level to support growth as would a nutritionally adequate industrial-manufactured infant cereal. Nonetheless, it should be noted that the findings of our studies are based on an animal model. PMID:25836365

  5. Effects of amphetamine on striatal dopamine release, open-field activity, and play in Fischer 344 and Sprague-Dawley rats.

    PubMed

    Siviy, Stephen M; McDowell, Lana S; Eck, Samantha R; Turano, Alexandra; Akopian, Garnik; Walsh, John P

    2015-12-01

    Previous work from our laboratories has shown that juvenile Fischer 344 (F344) rats are less playful than other strains and also appear to be compromised in dopamine (DA) functioning. To determine whether the dysfunctional play in this strain is associated with deficits in the handling and delivery of vesicular DA, the following experiments assessed the extent to which F344 rats are differentially sensitive to the effects of amphetamine. When exposed to amphetamine, striatal slices obtained from F344 rats showed a small increase in unstimulated DA release when compared with slices from Sprague-Dawley rats; they also showed a more rapid high K+-mediated release of DA. These data provide tentative support for the hypothesis that F344 rats have a higher concentration of cytoplasmic DA than Sprague-Dawley rats. When rats were tested for activity in an open field, F344 rats presented a pattern of results that was consistent with either an enhanced response to amphetamine (3 mg/kg) or a more rapid release of DA (10 mg/kg). Although there was some indication that amphetamine had a dose-dependent differential effect on play in the two strains, play in F344 rats was not enhanced to any degree by amphetamine. Although these results are not consistent with our working hypothesis that F344 rats are less playful because of a deficit in vesicular release of DA, they still suggest that this strain may be a useful model for better understanding the role of DA in social behavior during the juvenile period. PMID:26397758

  6. The pilocarpine model of temporal lobe epilepsy: Marked intrastrain differences in female Sprague-Dawley rats and the effect of estrous cycle.

    PubMed

    Brandt, Claudia; Bankstahl, Marion; Töllner, Kathrin; Klee, Rebecca; Löscher, Wolfgang

    2016-08-01

    Rat strains such as Sprague-Dawley (SD) or Wistar are widely used in epilepsy research, including popular models of temporal lobe epilepsy in which spontaneous recurrent seizures (SRS), hippocampal damage, and behavioral alterations develop after status epilepticus (SE). Such rats are randomly outbred, and outbred strains are known to be genetically heterogeneous populations with a high intrastrain variation. Intrastrain differences may be an important reason for discrepancies between studies from different laboratories, but the extent to which such differences affect the development of seizures, neurodegeneration, and psychopathology in post-SE models of epilepsy has received relatively little attention. In the present study, we induced SE by systemic administration of pilocarpine (following pretreatment with lithium) in SD rats from different breeders (Harlan, Charles River [CRL], Taconic) as well as different breeding locations of the same breeder (Harlan-Winkelmann [HW] in Germany vs. Harlan Laboratories [HL] in the Netherlands). Some experiments were also performed in Wistar rats. Pilocarpine was administered by a ramp-up dosing protocol that allows determining interindividual differences in susceptibility to the convulsant. Marked intrastrain differences in induction of SE and its long-term consequences were found. Sprague-Dawley rats from HW were significantly more sensitive to SE induction than all other SD substrains. The majority of SD rats from different vendors developed SRS after SE except SD rats from HL. The CRL-SD rats markedly differed in basal behavior and SE-induced behavioral alterations from other SD substrains. Susceptibility to pilocarpine was hardly affected by the estrous cycle. The marked intrastrain differences provide an interesting tool to study the impact of genetic and environmental factors on seizure susceptibility, epileptogenesis, and relationship between behavior and epilepsy and vice versa. PMID:27344503

  7. Sweetpotato- and Cereal-Based Infant Foods: Protein Quality Assessment, and Effect on Body Composition Using Sprague Dawley Rats as a Model

    PubMed Central

    Amagloh, Francis Kweku; Chiridza, Tracy; Lemercier, Marie-Eve; Broomfield, Anne; Morel, Patrick C. H.; Coad, Jane

    2015-01-01

    The Protein Digestibility Corrected Amino Acid Score (PDCAAS) of sweetpotato-based complementary foods (OFSP ComFa and CFSP ComFa) and cereal-based infant products (Weanimix and Cerelac) was assessed using 3 wk-old male Sprague Dawley rats weighing between 53–67 g as a model for human infants. Also, the effect of consumption of the infant formulations on lean mass, bone mass content and fat mass was evaluated by Dual-Energy X-ray Absorptiometry (DEXA) using 6 wk-old Sprague Dawley rats (initial weight, 206-229 g). The ComFa products and Weanimix are household-level formulations, and Cerelac is a commercial infant cereal. The true protein digestibility score for Cerelac was 96.27%, and about 1.8% (P<0.0001) higher than that for OFSP ComFa, CFSP ComFa and Weanimix. However, OFSP ComFa had the highest un-truncated PDCAAS by a difference of 4.1%, than CFSP ComFa, and about 20% difference compared with both the Weanimix and Cerelac. All the products investigated had PDCAAS greater than 70%, the minimum protein quality requirement for complementary foods. Among the rats assigned to the four formulations, their bone mass and fat mass composition were not significantly different (P=0.08 and P=0.85, respectively). However, the rats on CFSP ComFa had higher lean mass than those on Cerelac (321.67 vs. 297.19 g; P=0.03). The findings from the PDCAAS and the DEXA-measured body composition studies indicate that complementary foods could be formulated from readily available agricultural resources at the household-level to support growth as would a nutritionally adequate industrial-manufactured infant cereal. Nonetheless, it should be noted that the findings of our studies are based on an animal model. PMID:25836365

  8. The hepatic Igf2/H19 locus is not altered in 1-day old pups born to obese-prone Sprague-Dawley rats fed a low protein diet containing adequate folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gong et al. (Epigenetics, 2010) found, using diets low in folic acid, that compared to an 18% protein diet a 9% protein diet fed to pregnant Sprague-Dawley rats resulted in increased Igf2 and H19 gene expression in the liver of day 0 male offspring. In addition DNA methylation in the Imprinting Cont...

  9. 3,5 Diiodo-L-Thyronine (T2) Does Not Prevent Hepatic Steatosis or Insulin Resistance in Fat-Fed Sprague Dawley Rats.

    PubMed

    Vatner, Daniel F; Snikeris, Jaclyn; Popov, Violeta; Perry, Rachel J; Rahimi, Yasmeen; Samuel, Varman T

    2015-01-01

    Thyroid hormone mimetics are alluring potential therapies for diseases like dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and insulin resistance. Though diiodothyronines are thought inactive, pharmacologic treatment with 3,5- Diiodo-L-Thyronine (T2) reportedly reduces hepatic lipid content and improves glucose tolerance in fat-fed male rats. To test this, male Sprague Dawley rats fed a safflower-oil based high-fat diet were treated with T2 (0.25 mg/kg-d) or vehicle. Neither 10 nor 30 days of T2 treatment had an effect on weight, adiposity, plasma fatty acids, or hepatic steatosis. Insulin action was quantified in vivo by a hyperinsulinemic-euglycemic clamp. T2 did not alter fasting plasma glucose or insulin concentration. Basal endogenous glucose production (EGP) rate was unchanged. During the clamp, there was no difference in insulin stimulated whole body glucose disposal. Insulin suppressed EGP by 60% ± 10 in T2-treated rats as compared with 47% ± 4 suppression in the vehicle group (p = 0.32). This was associated with an improvement in hepatic insulin signaling; insulin stimulated Akt phosphorylation was ~2.5 fold greater in the T2-treated group as compared with the vehicle-treated group (p = 0.003). There was no change in expression of genes thought to mediate the effect of T2 on hepatic metabolism, including genes that regulate hepatic lipid oxidation (ppara, carnitine palmitoyltransferase 1a), genes that regulate hepatic fatty acid synthesis (srebp1c, acetyl coa carboxylase, fatty acid synthase), and genes involved in glycolysis and gluconeogenesis (L-pyruvate kinase, glucose 6 phosphatase). Therefore, in contrast with previous reports, in Sprague Dawley rats fed an unsaturated fat diet, T2 administration failed to improve NAFLD or whole body insulin sensitivity. Though there was a modest improvement in hepatic insulin signaling, this was not associated with significant differences in hepatic insulin action. Further study will be necessary before

  10. Multigeneration reproduction and carcinogenicity studies in Sprague-Dawley rats exposed topically to oxidative hair-colouring formulations containing p-phenylenediamine and other aromatic amines.

    PubMed

    Burnett, C M; Goldenthal, E I

    1988-05-01

    Two-generation reproduction and chronic toxicity-carcinogenicity studies were conducted in Sprague-Dawley rats receiving topical applications of six oxidative hair-colouring formulations. These formulations were prepared as prototypes of permanent hair colourings using the base ingredients and primary intermediates and couplers most often used in this kind of product. Among the dyes included in the various formulations were p-phenylenediamine, p-toluenediamine, p-aminophenol, resorcinol, m-aminophenol, 1-naphthol, 2-amino-4-nitrophenol, 4-chlororesorcinol, p-aminodiphenylamine hydrochloride and N-methyl-p-aminophenol sulphate. The dye solutions were mixed with an equal volume of 6% hydrogen peroxide prior to application. In the reproduction study the samples were applied topically twice weekly throughout the growth, mating, gestation and lactation phases of the F0 parents to the weaning of the F1a and F2b litters. Fertility, gestation and foetal viability indices and body weights were evaluated for the six treatment groups and these were compared with the values for the three concurrent control groups. Weanlings selected from the F1a litters were the subjects for the lifetime carcinogenesis study. For 24 months they received twice-weekly topical applications of the same dyes as were administered to their parents. Clinical chemistry, haematological and urinalysis studies were performed at months 3, 12, 18 and 24, and five animals/sex/group were killed at month 12 and autopsied for histological examination of the rat tissues. All animals in the chronic study were evaluated for incidence of neoplastic and non-neoplastic lesions. In the reproduction phase the application of hair dyes had no adverse effect on the fertility of the males or females, or on gestation, lactation and weaning indices. The average number weaned per litter and the mean body weights of the weanlings were comparable among the treated and control groups. No treatment-related gross lesions were

  11. Magnetic field exposure increases cell proliferation but does not affect melatonin levels in the mammary gland of female Sprague Dawley rats.

    PubMed

    Fedrowitz, Maren; Westermann, Jürgen; Löscher, Wolfgang

    2002-03-01

    In line with the possible relationship between electric power and breast cancer risk as well as the underlying "melatonin hypothesis," we have shown previously (Thun-Battersby et al., Cancer Res., 59: 3627-3633, 1999) that 50-Hz magnetic fields (MFs) of low (100 microTesla) flux density enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene model of breast cancer in female Sprague Dawley rats. On the basis of the melatonin hypothesis and previous observations of induction of ornithine decarboxylase in response to MF, we proposed that the effect of MF exposure on mammary carcinogenesis is related to enhanced proliferation of the mammary epithelium. The objective of the present study was to directly assess this proposal by the use of proliferation markers. Female Sprague Dawley rats were MF or sham exposed for 2 weeks at a flux density of 100 microTesla. Proliferation of epithelial cells in the mammary tissue and adjacent skin was examined by in vivo labeling of proliferating cells with bromodeoxyuridine (BrdUrd) and in situ labeling of the nuclear proliferation-associated Ki-67 protein by the antibody MIB-5. Furthermore, melatonin levels were determined after MF or sham exposure in the pineal gland and directly in the mammary tissue. In additional experiments, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate was used for comparison with the effects of MF exposure. MF exposure significantly enhanced BrdUrd and Ki-67 labeling in the mammary epithelium, indicating a marked increase in cell proliferation. The most pronounced effect on proliferation was seen in the cranial thoracic (or cervical) mammary complexes, in which we previously had seen the most marked effects of MF exposure on mammary carcinogenesis. In contrast to the melatonin hypothesis, melatonin levels in pineal or mammary glands were not affected by MF exposure. Topical application of 12-O-tetradecanoylphorbol-13-acetate increased BrdUrd and Ki-67 labeling in

  12. 3,5 Diiodo-L-Thyronine (T2) Does Not Prevent Hepatic Steatosis or Insulin Resistance in Fat-Fed Sprague Dawley Rats

    PubMed Central

    Vatner, Daniel F.; Snikeris, Jaclyn; Popov, Violeta; Perry, Rachel J.; Rahimi, Yasmeen; Samuel, Varman T.

    2015-01-01

    Thyroid hormone mimetics are alluring potential therapies for diseases like dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and insulin resistance. Though diiodothyronines are thought inactive, pharmacologic treatment with 3,5- Diiodo-L-Thyronine (T2) reportedly reduces hepatic lipid content and improves glucose tolerance in fat-fed male rats. To test this, male Sprague Dawley rats fed a safflower-oil based high-fat diet were treated with T2 (0.25 mg/kg-d) or vehicle. Neither 10 nor 30 days of T2 treatment had an effect on weight, adiposity, plasma fatty acids, or hepatic steatosis. Insulin action was quantified in vivo by a hyperinsulinemic-euglycemic clamp. T2 did not alter fasting plasma glucose or insulin concentration. Basal endogenous glucose production (EGP) rate was unchanged. During the clamp, there was no difference in insulin stimulated whole body glucose disposal. Insulin suppressed EGP by 60% ± 10 in T2-treated rats as compared with 47% ± 4 suppression in the vehicle group (p = 0.32). This was associated with an improvement in hepatic insulin signaling; insulin stimulated Akt phosphorylation was ~2.5 fold greater in the T2-treated group as compared with the vehicle-treated group (p = 0.003). There was no change in expression of genes thought to mediate the effect of T2 on hepatic metabolism, including genes that regulate hepatic lipid oxidation (ppara, carnitine palmitoyltransferase 1a), genes that regulate hepatic fatty acid synthesis (srebp1c, acetyl coa carboxylase, fatty acid synthase), and genes involved in glycolysis and gluconeogenesis (L-pyruvate kinase, glucose 6 phosphatase). Therefore, in contrast with previous reports, in Sprague Dawley rats fed an unsaturated fat diet, T2 administration failed to improve NAFLD or whole body insulin sensitivity. Though there was a modest improvement in hepatic insulin signaling, this was not associated with significant differences in hepatic insulin action. Further study will be necessary before

  13. Modafinil alone and in combination with low dose amphetamine does not establish conditioned place preference in male Sprague-Dawley rats.

    PubMed

    Quisenberry, Amanda J; Prisinzano, Thomas E; Baker, Lisa E

    2013-06-01

    Modafinil is a novel wake-promoting drug with FDA approval for the treatment of narcolepsy, shift work sleep disorder, and sleep apnea. It is also prescribed for many off-label uses such as ADHD and it is currently being assessed as a treatment for psychostimulant dependence. Previous research assessing the abuse liability of modafinil in animals and humans suggests it is less potent and has a low abuse potential compared to traditional psychomotor stimulants. However, modafinil has not been carefully assessed in combination with other psychostimulant drugs. The current study used an unbiased place conditioning procedure simultaneously with locomotor screening procedures to assess the combined behavioral effects of modafinil and d-amphetamine in adult male Sprague-Dawley rats. Eight 30-min conditioning trials were conducted in a 2 compartment apparatus with distinct visual and tactile cues. Drug and vehicle conditioning trials were alternated with 1 trial per day separated by 24 hr. On drug conditioning trials, rats were administered either modafinil (64 mg/kg, i.g.), d-amphetamine (0.3 or 2.0 mg/kg, s.c.), a combination of modafinil (64 mg/kg) and d-amphetamine (0.3 mg/kg), or vehicle injections. On vehicle conditioning trials, all groups received vehicle injections. Preference for either compartment was assessed by recording time spent in each compartment during a 15-min test conducted 24 hr after the last conditioning trial. Results indicated that this low oral dose of modafinil did not significantly increase locomotor activity or establish conditioned place preference (CPP). Moreover, modafinil did not significantly alter the hyperlocomotor or CPP effects of d-amphetamine. To confirm that modafinil is behaviorally active at this low oral dose, a separate assessment of horizontal and vertical activity was conducted with male Sprague-Dawley rats in an open field apparatus. Results confirmed that modafinil increased locomotor activity relative to vehicle, with

  14. Antiarthritic effect of aqueous and ethanolic leaf extracts of Pistia stratiotes in adjuvant-induced arthritis in Sprague-Dawley rats

    PubMed Central

    Kyei, Samuel; Koffuor, George A; Boampong, Johnson N

    2012-01-01

    Background Pistia stratiotes has been used effectively to treat a number of inflammatory conditions. This study aims to determine the antiarthritic effect of aqueous and ethanolic leaf extracts of P. stratiotes. Methods Arthritis was induced in Sprague-Dawley rats, paw swelling was measured, and arthritis indices were estimated in rats treated with aqueous and ethanolic leaf extracts of P. stratiotes (AQ PSE and ET PSE, respectively), methotrexate, diclofenac, dexamethasone, and normal saline-treated rats. Radiologic imaging, hematological assessment of red and white blood cells, C-reactive protein and erythrocyte sedimentation rate, as well as histopathological studies were also done. The data were analyzed using GraphPad Prism 5. Results The 30, 100, and 300 mg/kg doses of AQ PSE and the 30 and 100 mg/kg doses of ET PSE caused a significant (P ≤ 0.05–0.001) reduction in ipsilateral paw swelling, similar to the effects of methotrexate, dexamethasone, and diclofenac. Only the 30 mg/kg dose of AQ PSE caused a significant (P ≤ 0.01) reduction in contralateral paw swelling. Arthritic indices reduced significantly (P ≤ 0.05–0.001) at all drug doses, except for the 100 and 300 mg/kg doses of ET PSE. White blood cell levels decreased significantly (P ≤ 0.05–0.01) in arthritic rats treated with the 30 mg/kg dose of AQ PSE and those treated with methotrexate. Erythrocyte sedimentation rate and C-reactive protein levels were significantly (P ≤ 0.01–0.001) lower in all the treatment groups except for the rats treated with AQ PSE 300 mg/kg and ET PSE 100 and 300 mg/kg doses. The arthritic animals treated with 30 mg/kg of the aqueous extract showed no inflammatory changes in the ipsilateral paw, while the contralateral paw showed only foci of mild chronic inflammatory changes, as seen with the reference drug treatment in histopathological studies. Conclusion This study establishes that aqueous and ethanolic extracts of P. stratiotes have antiarthritic

  15. Long Term Study of Protective Mechanisms of Human Adipose Derived Mesenchymal Stem Cells on Cisplatin Induced Kidney injury in Sprague-Dawley Rats

    PubMed Central

    Elhusseini, Fatma M; Saad, Mohamed-Ahdy A.A; Anber, Nahla; Elghannam, Doaa; Sobh, Mohamed-Ahmed; Alsayed, Aziza; El-dusoky, Sara; Sheashaa, Hussein; Abdel-Ghaffar, Hassan; Sobh, Mohamed

    2016-01-01

    Background/Aims: Long-term evaluation of cisplatin induced nephrotoxicity and the probable renal protective activities of stem cells are lacking up until now. We evaluated the early and long-term role of human adipose derived mesenchymal stem cells (ADMSCs) in prevention or amelioration of cisplatin induced acute kidney injury (AKI) in Sprague-Dawley rats. For this, we determined the kidney tissue level of oxidative stress markers in conjugation with a renal histopathological scoring system of both acute and chronic renal changes. Methods: This study used eighty Sprague-Dawley (SD) rats weighing 250-300g. They were assigned into four equal groups (each group n=20): (I) Negative control group, rats injected with single dose of 1 ml normal saline. (II) Positive control cisplatin, rats injected with a single dose of 5 mg/kg I.P in 1 ml saline. (III) Cisplatin and culture media group, rats injected with 0.5 ml of culture media single dose into the tail vein and (IV) Cisplatin and ADMSCs group, rats injected with a single dose of 0.5 ml of culture media containing 5 x106ADMSCs into the tail vein one day after cisplatin administration. Each main group was further divided according to the timing of sacrifice into four subgroups (each subgroup n=5). Rats in the subgroup A were sacrificed after 4 days; subgroup B were sacrificed after 7 days; subgroup C were sacrificed after 11 days; and subgroup D were sacrificed after 30 days. Before sacrifice, 24 hrs.-urine was collected using a metabolic cage. Renal function was evaluated through blood urea nitrogen (BUN), serum creatinine and creatinine clearance. Kidney tissue homogenate oxidative stress parameters, Malondialdehyde (MDA), Superoxide dismutase (SOD) and Glutathione (GSH) were determined. In addition, histopathological analysis for active injury, regenerative and chronic changes was performed. Results: ADMSCs were characterized and their capability of differentiation was proved. Cisplatin induced a significant increase

  16. Non-linear pharmacokinetics of piperine and its herb-drug interactions with docetaxel in Sprague-Dawley rats.

    PubMed

    Li, Chenrui; Wang, Qian; Ren, Tianjing; Zhang, Yufeng; Lam, Christopher Wai Kei; Chow, Moses S S; Zuo, Zhong

    2016-09-01

    . PIP and DOX exhibited good stabilities under various conditions. PIP was administrated via intravenous bolus at 3.5mg/kg and via oral administration at 35mg/kg and 3.5mg/kg, while DOX was intravenously administrated at 7mg/kg to Sprague-Daley rats. The plasma concentrations of PIP and DOX were determined using the above developed and validated method. At the dose of 3.5mg/kg, the bioavailability of PIP was calculated to be 25.36%. Its AUC0→t was unproportionally increased with doses, indicating a potential non-linear pharmacokinetics profile of PIP. It was found that the AUC0→t and C0 of DOX and t1/2 of PIP were significantly increased after their combination use, suggesting potential enhanced bioavailability of not only DOX but also PIP, which may lead to the overall enhanced pharmacological effects. PMID:27288758

  17. Effects of a Proprietary Standardized Orthosiphon stamineus Ethanolic Leaf Extract on Enhancing Memory in Sprague Dawley Rats Possibly via Blockade of Adenosine A 2A Receptors.

    PubMed

    George, Annie; Chinnappan, Sasikala; Choudhary, Yogendra; Choudhary, Vandana Kotak; Bommu, Praveen; Wong, Hoi Jin

    2015-01-01

    The aim of the study was to explore a propriety standardized ethanolic extract from leaves of Orthosiphon stamineus Benth in improving impairments in short-term social memory in vivo, possibly via blockade of adenosine A2A receptors (A2AR). The ethanolic extract of O. stamineus leaves showed significant in vitro binding activity of A2AR with 74% inhibition at 150 μg/ml and significant A2AR antagonist activity with 98% inhibition at 300 μg/mL. A significant adenosine A1 receptor (A1R) antagonist activity with 100% inhibition was observed at 300 μg/mL. Its effect on learning and memory was assessed via social recognition task using Sprague Dawley rats whereby the ethanolic extract of O. stamineus showed significant (p < 0.001) change in recognition index (RI) at 300 mg/kg and 600 mg/kg p.o and 120 mg/kg i.p., respectively, compared to the vehicle control. In comparison, the ethanolic extract of Polygonum minus aerial parts showed small change in inflexion; however, it remained insignificant in RI at 200 mg/kg p.o. Our findings suggest that the ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in short-term social memory and the possible involvement of adenosine A1 and adenosine A2A as a target bioactivity site in the restoration of memory.

  18. Central administration of oxytocin differentially increases yawning, penile erections and scratching in high- (HY) and low-yawning (LY) sublines of Sprague-Dawley rats.

    PubMed

    Eguibar, Jose R; Cortes, Carmen; Isidro, O; Ugarte, A

    2015-07-01

    Central administration of oxytocin has been shown to induce yawning, penile erection, grooming and scratching. Yawning and penile erections are due to activation of oxytocinergic neurons in the paraventricular nucleus of the hypothalamus. We selectively bred two sublines from Sprague-Dawley rats, one with a high-yawning frequency (HY) of 20yawns/h, and one with a low-yawning (LY) frequency of 2yawns/h. The aim of the current study was to analyze the behavioral effects of centrally-administered oxytocin [15ng-10μg; intracerebroventricularly (i.c.v.)] on yawning, penile erections, grooming and scratching in adult male rats from both sublines. Oxytocin produced a dose-dependent increase in yawning and penile erection frequencies and this effect was significantly higher in the HY, compared to the LY, subline. However, the number of oxytocin-induced scratching bouts was significantly higher in the LY, compared to the HY group. In conclusion, these sublines represent a suitable model for detailed analysis of behavior induced by oxytocin and other neuropeptides in animals with different spontaneous expression of behavioral traits.

  19. Cutaneous Epithelial Lesions Induced by N-Methyl-N-nitrosourea in Male Sprague-Dawley Rats: A Possible Animal Model for Human Keratoacanthoma.

    PubMed

    Yuki, Michiko; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuri, Takashi; Kinoshita, Yuichi; Tsubura, Airo; Kurokawa, Ichiro

    2016-01-01

    A single intraperitoneal injection of 50 or 75 mg/kg N-methyl-N-nitrosourea in male Sprague-Dawley rats at 4 weeks of age, dose-dependently resulted in cutaneous epithelial cysts and tumors of pilosebaceous origin. Cysts were composed of epidermal cysts or mixed epidermal and inner root sheath hybrid cysts. The majority of induced tumors were keratoacanthomas. A few tumors were trichofolliculomas, trichoblastomas, pilomatricomas, or sebaceous adenomas. All tumors were benign pilosebaceous tumors. Keratoacanthomas were crater-shaped tumors with thick infoldings of epithelium containing keratohyalin granules (epidermal lip) that abruptly changed to epithelium containing trichohyalin granules. The morphological similarity and resemblance of keratin 1, 10, and 14 profiles, and p63 and β-catenin expression between mixed epidermal and inner root sheath hybrid cysts and keratoacanthomas suggests that hybrid cysts progressed to keratoacanthomas, and the cells from infundibular cells to inner root sheath cells of the pilar segment seem to be the origin of rat keratoacanthomas. Immunohistochemical localization of keratins 1, 10 and 14, p63, and β-catenin in trichofolliculoma, trichoblastoma, and pilomatricoma, as well as keratoacanthoma, may indicate tumor histogenesis. PMID:26722034

  20. Male Sprague-Dawley rats exposed to in utero di(n-butyl) phthalate: dose dependent and age-related morphological changes in Leydig cell smooth endoplasmic reticulum.

    PubMed

    Shirai, Masaru; Wakui, Shin; Wempe, Michael F; Mutou, Tomoko; Oyama, Noriko; Motohashi, Masaya; Takahashi, Hiroyuki; Kansaku, Norio; Asari, Masao; Hano, Hiroshi; Endou, Hitoshi

    2013-01-01

    When 100 mg/kg/day of di(n-butyl) phthalate (DBP) was intragastrically administered to pregnant Sprague-Dawley rats throughout gestation days 12 to 21, the male pups had similar body weights with no apparent physical differences (e.g., litter size, sex ratio) compared to that of the vehicle group. However, prominent age-related morphological alterations in the smooth endoplasmic reticulum (sER) of testicular Leydig cells (LCs) were observed once these animals reached puberty. At weeks 5 to 7, the abundant sER with non-dilated cisternae was distributed in LCs. Subsequently, although the number of LCs significantly increased, the amount of sER was significantly decreased at 9 to 14 weeks of age and had disappeared at 17 weeks. In contrast, the number of LCs and the amount of sER in LCs of the lower dose groups (10, 30, and 50 mg/kg/day) were similar to those of the vehicle group. Further, serum testosterone levels in the 100 mg/kg dose group were significantly lower during 5 to 17 weeks of age. While their luteinizing hormone (LH) level was significantly lower at 5 to 7 weeks of age, it became significantly higher during 9 to 17 weeks. The amount of sER in LCs decreased with age with the increase in LCs proliferation and serum LH levels in rat exposed in utero to DBP in a dose-dependent manner.

  1. Effect of long-term olanzapine treatment on meal-induced insulin sensitization and on gastrointestinal peptides in female Sprague-Dawley rats.

    PubMed

    Hegedűs, Csaba; Kovács, Diána; Kiss, Rita; Sári, Réka; Németh, József; Szilvássy, Zoltán; Peitl, Barna

    2015-12-01

    Meal-induced insulin sensitization (MIS), an endogenous adaptive mechanism is activated post-prandially. Reduced MIS leads to diabetes, but its activation improves insulin sensitivity. MIS is preserved to single olanzapine administration, therefore we aimed to investigate the chronic effect of olanzapine on fasted-state insulin sensitivity and on MIS in female Sprague-Dawley rats. Daily food and water intake, stool and urine production and body weight were determined. The MIS was characterized by a rapid insulin sensitivity test. Fasting hepatic and peripheral insulin sensitivity were determined by a hyperinsulinaemic euglycaemic glucose clamping supplemented with radiotracer technique. Fasted and post-prandial blood samples were obtained for plasma insulin, leptin, ghrelin, amylin, GLP-1, GIP, PYY and PP determination. Adiposity was characterized by weighing intra-abdominal and inguinal fat pads. Olanzapine caused hepatic insulin resistance and a reduced metabolic clearance rate of insulin, but the MIS retained its function. Body weight and adiposity were enhanced, but olanzapine failed to increase food intake. Fasting insulin and leptin were elevated and the post-prandial reduction in ghrelin level was inhibited by olanzapine.The MIS remained functionally intact after long-term olanzapine treatment. Altered insulin, leptin and ghrelin levels indicate olanzapine-induced metabolic derangements. Pharmacological activation of MIS could potentially be exploited to treat or prevent olanzapine-induced insulin resistance. PMID:26349558

  2. Effect of the combination of gelam honey and ginger on oxidative stress and metabolic profile in streptozotocin-induced diabetic Sprague-Dawley rats.

    PubMed

    Sani, Nur Fathiah Abdul; Belani, Levin Kesu; Sin, Chong Pui; Rahman, Siti Nor Amilah Abdul; Das, Srijit; Chi, Thent Zar; Makpol, Suzana; Yusof, Yasmin Anum Mohd

    2014-01-01

    Diabetic complications occur as a result of increased reactive oxygen species (ROS) due to long term hyperglycaemia. Honey and ginger have been shown to exhibit antioxidant activity which can scavenge ROS. The main aim of this study was to evaluate the antioxidant and antidiabetic effects of gelam honey, ginger, and their combination. Sprague-Dawley rats were divided into 2 major groups which consisted of diabetic and nondiabetic rats. Diabetes was induced with streptozotocin intramuscularly (55 mg/kg body weight). Each group was further divided into 4 smaller groups according to the supplements administered: distilled water, honey (2 g/kg body weight), ginger (60 mg/kg body weight), and honey + ginger. Body weight and glucose levels were recorded weekly, while blood from the orbital sinus was obtained after 3 weeks of supplementation for the estimation of metabolic profile: glucose, triglyceride (TG), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH): oxidized glutathione (GSSG), and malondialdehyde (MDA). The combination of gelam honey and ginger did not show hypoglycaemic potential; however, the combination treatment reduced significantly (P < 0.05) SOD and CAT activities as well as MDA level, while GSH level and GSH/GSSG ratio were significantly elevated (P < 0.05) in STZ-induced diabetic rats compared to diabetic control rats. PMID:24822178

  3. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    PubMed

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies. PMID:24318772

  4. Effects of dietary zinc and copper supplementation on serum triglyceride, total-cholesterol and HDL-cholesterol concentrations on young Sprague Dawley male rats

    SciTech Connect

    Frimpong, N.A.; Magee, A.C.

    1986-03-01

    To determine the effects of the level of zinc (Zn) and copper (Cu) supplementation and of Zn/Cu ratio on serum triglycerides (TG), total-cholesterol (TC), and HDL-cholesterol (HDL-C) concentrations, groups of weanling male Sprague Dawley rats were fed diets containing 4 levels of Cu (0, 0.56, 1.68, and 5.04 ppm) and 4 levels of Zn (0, 5, 10 and 20 ppm) for 6 weeks (Low supplementation, Expt I), or a high Zn and Cu supplements each at 4 levels (0, 5.6, 16.8, and 50.4 ppm Cu, plus 0, 50, 100, and 200 ppm Zn) for 6 weeks (Expt II). The effects of Zn/Cu ratios on the parameters were evaluated by combining data from Expt I and Expt II treatments with the same Zn/Cu ratios but different levels of Zn and Cu. Results of the combined data indicated that an increase in dietary Zn was associated with significant (p less than or equal to 0.01) increase in serum triglyceride concentrations, while an increase in dietary Cu was associated with significant (p less than or equal to 0.01) decrease in serum TC and HDL-C concentrations. Dietary Zn/Cu ratios had no significant effect on serum lipids. There is the indication that the absolute levels of the minerals in the diet may be more important in lipid metabolism. These results are in agreement with previous reports.

  5. Anti-inflammatory effect of egg white-chalcanthite and purple bamboo salts mixture on arthritis induced by monosodium iodoacetate in Sprague-Dawley rats

    PubMed Central

    Lee, Tae-Hee; Song, Hyun-kyung; Jang, Ja-Young; Kim, Dong-Yoon; Park, Hyun-Kyung; Choi, Eun-A

    2016-01-01

    The aim of this study is to investigate the potential of anti-osteoarthritis effects on egg white-chalcanthite (EC), purple bamboo salts (PBS), and a mixture of EC and PBS (EC+PBS). EC is a mixture of egg white and pulverized chalcanthite. PBS has been widely used as one of functional foods in Korea and shows unique features compared with common salt. Osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA, 4mg/kg bw) in Sprague-Dawley (SD) rats. Test substances were administered once daily for 6 weeks at doses of 10 mg EC, EC+100 mg PBS, EC+200 mg PBS before and after MIA injection. Each substance was assessed by blood chemistry parameters, and by serum cytokines including IL-1β and IL-6, and nitric oxide (NO) and prostaglandin-E2 (PGE2). Structural changes of articular cartilage were also evaluated by histopathological examination. As a result, body weight and blood chemistry parameter were not different in all experimental groups. EC+PBS mixture reduced the production of PGE2, NO, IL-1β, and IL-6. In histological grade of osteoarthritis, EC+PBS mixture had a tendency to ameliorate damage of articular cartilage induced by MIA in a dose-dependent manner. In conclusion, EC+PBS mixture was demonstrated to have a potential for anti-inflammatory effect against osteoarthritis induced by MIA in a dose-dependent manner. PMID:27382377

  6. Nonclinical Safety Assessment of Morus alba L. Fruits: Study of 90-D Toxicity in Sprague Dawley Rats and Genotoxicity in Salmonella.

    PubMed

    Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

    2016-05-01

    Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential.

  7. PAMAM dendrimers as nano carriers to investigate inflammatory responses induced by pulmonary exposure of PCB metabolites in Sprague-Dawley rats.

    PubMed

    Wangpradit, Orarat; Adamcakova-Dodd, Andrea; Heitz, Katharina; Robertson, Larry; Thorne, Peter S; Luthe, Gregor

    2016-02-01

    Polychlorinated biphenyls (PCBs) persist and accumulate in the ecosystem depending upon the degree of chlorination of the biphenyl rings. Airborne PCBs are especially susceptible to oxidative metabolism, yielding mono- and di-hydroxy metabolites. We have previously demonstrated that 4-chlorobiphenyl hydroquinones (4-CB-HQs) acted as cosubstrates for arachidonic acid metabolism by prostaglandin H synthase (PGHS) and resulted in an increase of prostaglandin production in vitro. In the present study, we tested the capability of 4-CB-HQ to act as a co-substrate for PGHS catalysis in vivo. BQ and 4-CB-2',5'-HQ were administered intratracheally to male Sprague-Dawley rats (2.5 μmol/kg body weight) using nanosized polyamidoamine (PAMAM) dendrimers as carriers. We found that 24 h post application, PGE2 metabolites in kidney of rats treated with 4-CB-2',5'-HQ were significantly increased compared to the controls. The increase of PGE2 metabolites was correlated with increased alveolar macrophages in lung lavage fluid. The elevation of PGE2 synthesis is of great interest since it plays a crucial role in balancing homeostasis and inflammation where a chronic disturbance may increase risk of cancer. PAMAM dentrimers proved to be an effective transport medium and did not stimulate an inflammatory response themselves. PMID:26400242

  8. Transient Decrease in Circulatory Testosterone and Homocysteine Precedes the Development of Metabolic Syndrome Features in Fructose-Fed Sprague Dawley Rats

    PubMed Central

    Sakamuri, Anil; Pitla, Sujatha; Putcha, Uday Kumar; Jayapal, Sugeedha; Pothana, Sailaja; Vadakattu, Sai Santosh

    2016-01-01

    Background. Increased fructose consumption is linked to the development of metabolic syndrome (MS). Here we investigated the time course of development of MS features in high-fructose-fed Sprague Dawley rats along with circulatory testosterone and homocysteine levels. Methods. Rats were divided into control and experimental groups and fed with diets containing 54.5% starch and fructose, respectively, for 4, 12, and 24 weeks. Plasma testosterone and homocysteine levels were measured along with insulin, glucose, and lipids. Body composition, insulin resistance, and hepatic lipids were measured. Results. Increase in hepatic triglyceride content was first observed in metabolic disturbance followed by hypertriglyceridemia and systemic insulin resistance in fructose-fed rats. Hepatic lipids were increased in time-dependent manner by fructose-feeding starting from 4 weeks, but circulatory triglyceride levels were increased after 12 weeks. Fasting insulin and Homeostatis Model Assessment of Insulin Resistance (HOMA-IR) were increased after 12 weeks of fructose-feeding. Decreased visceral adiposity, circulatory testosterone, and homocysteine levels were observed after 4 weeks of fructose-feeding, which were normalized at 12 and 24 weeks. Conclusions. We conclude that transient decrease in circulatory testosterone and homocysteine levels and increased hepatic triglyceride content are the earliest metabolic disturbances that preceded hypertriglyceridemia and insulin resistance in fructose-fed SD rats.

  9. Genetically mediated resistance to naturally occurring aortic sclerosis in spontaneously hypertensive as against Sprague-Dawley and Wistar-Kyoto breeder rats.

    PubMed Central

    Wexler, B. C.; McMurtry, J. P.

    1982-01-01

    Male and female, normotensive, Sprague-Dawley (S-D), Wistar-Kyoto (WKy), and spontaneously hypertensive rats (SHR) were bred repeatedly until the females had given birth to and nursed 6 litters of pups. At the close of the 2nd, 4th and 6th breeding, breeder males and females, along with celibate males and females of equal age, were killed. S-D and WKy breeder rats manifested progressively increasing adiposity and high blood pressure with each successive breeding; breeder SHR showed mild exacerbation of their pre-existing high blood pressure. Adrenocortical hyperplasia and thymus-gland involution suggested increasing pituitary-adrenal activity in breeder rats. Circulating aldosterone levels decreased with repeated breeding in parallel with increased deoxycorticosterone and corticosterone secretion. The repeatedly bred normotensive rats manifested worsening aortic sclerosis as against little or no aortic sclerosis in the repeatedly bred SHR. Breeder SHR developed fibrinohyalin intimal lesions limited exclusively to the arterioles of the testis and ovary. Virgin rats did not develop any vascular disease. It is suggested that a diverse spectrum of adrenal steroids in breeder HSR combined with genetic direction control the morphogenesis of arterial disease in breeder SHR. Images Fig. 8 Fig. 9 Fig. 6 Fig. 7 Fig. 10 Fig. 11 Fig. 12 PMID:7066185

  10. Maternal low-protein diet causes body weight loss in male, neonate Sprague-Dawley rats involving UCP-1-mediated thermogenesis.

    PubMed

    Claycombe, Kate J; Vomhof-DeKrey, Emilie E; Roemmich, James N; Rhen, Turk; Ghribi, Othman

    2015-07-01

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT thermogenesis and BW of offspring in utero is not yet known. We fed obese-prone Sprague-Dawley dams 8% LP or 20% normal protein (NP) diets for 3 weeks prior to breeding and through pregnancy. BW and gene expression of interscapular BAT (iBAT) thermogenic markers were measured in male fetal (gestation day 18) and neonatal (day 0 or 1) offspring. BW of neonatal LP males was lower than NP males but no difference was observed in females. Gene and protein expression of UCP-1 and transcription factors PRDM16 and PPARα in iBAT were 2- to 6-fold greater in LP than in NP male neonatal offspring. FNDC5, a precursor of irisin and activator of thermogenesis, was expressed 2-fold greater in neonatal LP iBAT than NP males. However, fetal iBAT UCP-1, PRDM16, PPARα and irisin mRNA did not differ between LP and NP groups. Maternal LP diet had no effects on placental irisin and UCP-2 expression. These results suggest that prenatal protein restriction increases the risk for low BW through mechanisms affecting full-term offspring iBAT thermogenesis but not greatly altering fetal iBAT or placental thermogenesis.

  11. Providing Flaxseed Oil but Not Menhaden Oil Protects against OVX Induced Bone Loss in the Mandible of Sprague-Dawley Rats.

    PubMed

    Longo, Amanda B; Ward, Wendy E

    2016-01-01

    Higher intakes of polyunsaturated fatty acids (PUFA) are associated with benefits at several skeletal sites in postmenopausal women and in rodent models, but the effect of PUFA-containing oils on tooth-supporting alveolar bone of the mandible has not been studied. Moreover, direct comparison of the effect of flaxseed oil (a source of alpha-linolenic acid (ALA)) and menhaden oil (a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) is unknown. One-month old female Sprague-Dawley rats (n = 48) were randomized to and fed a diet containing flaxseed oil or menhaden oil from one to six months of age. At three months of age, rats were randomized to receive SHAM or ovariectomy (OVX) surgery (n = 12/diet). The inter-radicular septum below the first molar of the mandible was imaged at 6 months of age (study endpoint) using micro-computed tomography (μCT) at a resolution of 9 μm. As expected, OVX significantly reduced percent bone volume (BV/TV), connectivity density (Conn. D.), trabecular number (Tb. N.), and increased trabecular separation (Tb. Sp.) compared to SHAM rats (p < 0.001). However, post hoc analysis revealed these differences were present in rats fed menhaden oil but not those fed flaxseed oil. These results suggest that providing flaxseed oil, possibly through its high ALA content, provides protection against the OVX-induced alveolar bone loss in rats. PMID:27669296

  12. Prenatal low-protein and postnatal high-fat diets induce rapid adipose tissue growth by inducing Igf2 expression in Sprague Dawley rat offspring.

    PubMed

    Claycombe, Kate J; Uthus, Eric O; Roemmich, James N; Johnson, Luann K; Johnson, W Thomas

    2013-10-01

    Maternal low-protein diets result in lower birth weight followed by accelerated catch-up growth that is accompanied by the development of obesity and glucose intolerance in later life. Whether postnatal high-fat (HF) diets further contribute to the development of obesity and insulin resistance in offspring by affecting adipose tissue metabolism and DNA methylation is currently unknown. Obese-prone Sprague-Dawley rats were fed 8% low protein (LP) or 20% normal protein diets for 3 wk prior to conception and throughout pregnancy and lactation to investigate whether prenatal LP and postnatal HF diets affect the rate of adipose tissue growth, insulin-like growth factor 2 (Igf2) expression, and DNA methylation in male offspring. At weaning, the offspring were fed 10% normal fat or 45% HF diets for 12 wk. The adipose tissue growth rate was increased (up to 26-fold) by the LP prenatal and HF postnatal diets. Adipose tissue Igf2 mRNAs and DNA methylation were increased by the LP prenatal and HF postnatal diets. The LP prenatal and HF postnatal diet increased the number of small adipocytes in adipose tissue and decreased insulin sensitivity. These findings suggest that prenatal LP and postnatal HF intake result in adipose tissue catch-up growth through alterations in the expression of the Igf2 gene and DNA methylation within adipocytes. These alterations in adiposity are accompanied by an increased risk of development of type 2 diabetes.

  13. Dose-dependent effects of sevoflurane exposure during early lifetime on apoptosis in hippocampus and neurocognitive outcomes in Sprague-Dawley rats

    PubMed Central

    Zhou, Xue; Li, Wenda; Chen, Xiaohui; Yang, Xiaoyu; Zhou, Zhibin; Lu, Dihan; Feng, Xia

    2016-01-01

    Sevoflurane has become a main method for induction of anesthesia in pediatric populations. Preclinical evidence suggest the neurotoxic effect of volatile anesthetics on the developing brain including sevoflurane. This study investigates the effect of different doses of sevoflurane on the developing brain. In this study, Sprague-Dawley rats of postnatal (P) day 7 were exposed to 0.3%, 1.3% and 2.3% sevoflurane for 6 hours. 6 hours after exposure, Nissl staining was performed to observe the morphological changes of the hippocampus and western-blot was done to evaluate the expression changes in cytochrome c, cleaved caspase-3, Bcl-2 and Bax. At P28, we used the step-through test and novel object recognition test to evaluate the influence of sevoflurane exposure on learning and memory of juvenile rats. We found that neonatal exposure to 2.3% but neither 0.3% nor 1.3% sevoflurane on P7 induced histopathological damage in the CA1 and CA3 subfields of the hippocampus. Only 2.3% sevoflurane induced hippocampal neural apoptosis via the mitochondrial-dependent pathway. Moreover, 2.3% sevoflurane deteriorated the learning and memory in juvenile rats, but 1.3% sevoflurane showed its positive effect. In conclusions, higher dose of sevoflurane lead to histopathological changes and apoptosis in neonatal rat hippocampus, as well as temporal neurocognition deficits.

  14. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats.

    PubMed

    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14-21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  15. Nonclinical Safety Assessment of Morus alba L. Fruits: Study of 90-D Toxicity in Sprague Dawley Rats and Genotoxicity in Salmonella.

    PubMed

    Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

    2016-05-01

    Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential. PMID:27075529

  16. Cutaneous Epithelial Lesions Induced by N-Methyl-N-nitrosourea in Male Sprague-Dawley Rats: A Possible Animal Model for Human Keratoacanthoma.

    PubMed

    Yuki, Michiko; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuri, Takashi; Kinoshita, Yuichi; Tsubura, Airo; Kurokawa, Ichiro

    2016-01-01

    A single intraperitoneal injection of 50 or 75 mg/kg N-methyl-N-nitrosourea in male Sprague-Dawley rats at 4 weeks of age, dose-dependently resulted in cutaneous epithelial cysts and tumors of pilosebaceous origin. Cysts were composed of epidermal cysts or mixed epidermal and inner root sheath hybrid cysts. The majority of induced tumors were keratoacanthomas. A few tumors were trichofolliculomas, trichoblastomas, pilomatricomas, or sebaceous adenomas. All tumors were benign pilosebaceous tumors. Keratoacanthomas were crater-shaped tumors with thick infoldings of epithelium containing keratohyalin granules (epidermal lip) that abruptly changed to epithelium containing trichohyalin granules. The morphological similarity and resemblance of keratin 1, 10, and 14 profiles, and p63 and β-catenin expression between mixed epidermal and inner root sheath hybrid cysts and keratoacanthomas suggests that hybrid cysts progressed to keratoacanthomas, and the cells from infundibular cells to inner root sheath cells of the pilar segment seem to be the origin of rat keratoacanthomas. Immunohistochemical localization of keratins 1, 10 and 14, p63, and β-catenin in trichofolliculoma, trichoblastoma, and pilomatricoma, as well as keratoacanthoma, may indicate tumor histogenesis.

  17. Feasibility and Safety of Continuous and Chronic Bilateral Deep Brain Stimulation of the Medial Forebrain Bundle in the Naïve Sprague-Dawley Rat

    PubMed Central

    Furlanetti, Luciano L.; Döbrössy, Máté D.; Aranda, Iñigo A.; Coenen, Volker A.

    2015-01-01

    Objective. Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (MFB) has provided rapid and dramatic reduction of depressive symptoms in a clinical trial. Early intracranial self-stimulation experiments of the MFB suggested detrimental side effects on the animals' health; therefore, the current study looked at the viability of chronic and continuous MFB-DBS in rodents, with particular attention given to welfare issues and identification of stimulated pathways. Methods. Sprague-Dawley female rats were submitted to stereotactic microelectrode implantation into the MFB. Chronic continuous DBS was applied for 3–6 weeks. Welfare monitoring and behavior changes were assessed. Postmortem histological analysis of c-fos protein expression was carried out. Results. MFB-DBS resulted in mild and temporary weight loss in the animals, which was regained even with continuing stimulation. MFB-DBS led to increased and long-lasting c-fos expression in target regions of the mesolimbic/mesocortical system. Conclusions. Bilateral continuous chronic MFB-DBS is feasible, safe, and without impact on the rodent's health. MFB-DBS results in temporary increase in exploration, which could explain the initial weight loss, and does not produce any apparent behavioral abnormalities. This platform represents a powerful tool for further preclinical investigation of the MFB stimulation in the treatment of depression. PMID:25960609

  18. Providing Flaxseed Oil but Not Menhaden Oil Protects against OVX Induced Bone Loss in the Mandible of Sprague-Dawley Rats

    PubMed Central

    Longo, Amanda B.; Ward, Wendy E.

    2016-01-01

    Higher intakes of polyunsaturated fatty acids (PUFA) are associated with benefits at several skeletal sites in postmenopausal women and in rodent models, but the effect of PUFA-containing oils on tooth-supporting alveolar bone of the mandible has not been studied. Moreover, direct comparison of the effect of flaxseed oil (a source of alpha-linolenic acid (ALA)) and menhaden oil (a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) is unknown. One-month old female Sprague-Dawley rats (n = 48) were randomized to and fed a diet containing flaxseed oil or menhaden oil from one to six months of age. At three months of age, rats were randomized to receive SHAM or ovariectomy (OVX) surgery (n = 12/diet). The inter-radicular septum below the first molar of the mandible was imaged at 6 months of age (study endpoint) using micro-computed tomography (μCT) at a resolution of 9 μm. As expected, OVX significantly reduced percent bone volume (BV/TV), connectivity density (Conn. D.), trabecular number (Tb. N.), and increased trabecular separation (Tb. Sp.) compared to SHAM rats (p < 0.001). However, post hoc analysis revealed these differences were present in rats fed menhaden oil but not those fed flaxseed oil. These results suggest that providing flaxseed oil, possibly through its high ALA content, provides protection against the OVX-induced alveolar bone loss in rats. PMID:27669296

  19. Short-Term High Fat Intake Does Not Significantly Alter Markers of Renal Function or Inflammation in Young Male Sprague-Dawley Rats.

    PubMed

    Crinigan, Catherine; Calhoun, Matthew; Sweazea, Karen L

    2015-01-01

    Chronic high fat feeding is correlated with diabetes and kidney disease. However, the impact of short-term high fat diets (HFD) is not well-understood. Six weeks of HFD result in indices of metabolic syndrome (increased adiposity, hyperglycemia, hyperinsulinemia, hyperlipidemia, hyperleptinemia, and impaired endothelium-dependent vasodilation) compared to rats fed on standard chow. The hypothesis was that short-term HFD would induce early signs of renal disease. Young male Sprague-Dawley rats were fed either HFD (60% fat) or standard chow (5% fat) for six weeks. Morphology was determined by measuring changes in renal mass and microstructure. Kidney function was measured by analyzing urinary protein, creatinine, and hydrogen peroxide (H2O2) concentrations, as well as plasma cystatin C concentrations. Renal damage was measured through assessment of urinary oxDNA/RNA concentrations as well as renal lipid peroxidation, tumor necrosis factor alpha (TNFα), and interleukin 6 (IL-6). Despite HFD significantly increasing adiposity and renal mass, there was no evidence of early stage kidney disease as measured by changes in urinary and plasma biomarkers as well as histology. These findings suggest that moderate hyperglycemia and inflammation produced by short-term HFD are not sufficient to damage kidneys or that the ketogenic HFD may have protective effects within the kidneys.

  20. Genes in the GABA Pathway Increase in the Lateral Thalamus of Sprague-Dawley Rats During the Proestrus/Estrus Phase.

    PubMed

    Umorin, Mikhail; Stinson, Crystal; Bellinger, Larry L; Kramer, Phillip R

    2016-05-01

    Pain can vary over the estrous cycle as a result of changes in estradiol concentration but the mechanism causing this variation is unclear. Because the thalamus is important in pain control, gene expression in the lateral thalamus (ventral posteromedial, ventral posterolateral, reticular thalamic nuclei) was screened at different phases of the estrous cycle. Gene expression changes in Sprague-Dawley rats were further analyzed by real-time PCR and ELISA and plasma estradiol levels were measured by RIAs at different phases of the estrous cycle. Our results indicated that both the RNA and protein expression of glutamate decarboxylase 1 and 2 (GAD1, GAD2), GABA(A) receptor-associated protein like 1 (GABARAPL1), and vesicular GABA transporter (VGAT) significantly increased in the lateral thalamus when plasma estradiol levels were elevated. Estradiol levels were elevated during the proestrus and estrus phases of the estrous cycle. Estrogen receptor α (ERα) was observed to be co-localized in thalamic cells and thalamic infusion of an ERα antagonist significantly reduced GAD1 and VGAT transcript. GAD1, GAD2, GABARAPL1, and VGAT have been shown to effect neuronal responses suggesting that attenuation of pain during the estrous cycle can be dependent, in part, through estradiol induced changes in thalamic gene expression. PMID:26388520

  1. Effect of PCB's on plasma vitamin A (retinol) and hepatic retinyl palmitate hydrolase (RPH) activity in female Sprague-Dawley rats

    SciTech Connect

    Powers, R.H.; Gilbert, L.C.; Aust, S.D.

    1987-05-01

    A single i.p. dose of 15, 5 or 1 mg/kg 3,4,3',4'-tetrachlorobiphenyl (TCB) caused a dose-dependent depression of plasma retinol levels 24 hours after treatment of female Sprague-Dawley rats. The loss of plasma retinol appeared to be a function of depressed levels of the retinol-retinol binding protein (RBP)-transthyretin ternary complex. No free retinol-RBP was observed in plasma from treated animals. Hepatic RPH activity was also depressed, and highly and positively correlated to the plasma retinol levels. TCB was determined to be a non-competitive inhibitor of partially purified RPH with a KI of 91 uM. Metabolism of TCB by microsomes in vitro decreased the inhibition of RPH. Equimolar doses of either 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) or 3,4,5,3',4',5'-HCB failed to cause a similar depression of plasma retinol of treated female rats. They conclude that, unlike other PCB congeners, TCB causes a depression of plasma retinol by inhibition of hepatic RPH.

  2. Safety and biosimilarity of ior(®) EPOCIM compared with Eprex(®) based on toxicologic, pharmacodynamic, and pharmacokinetic studies in the Sprague-Dawley rat.

    PubMed

    Pucaj, Kresimir; Riddle, Katherine; Taylor, Simon R; Ledon, Nuris; Bolger, Gordon T

    2014-11-01

    This study examined the safety, pharmacodynamic (PD), and pharmacokinetic (PK) biosimilarity of the human recombinant erythropoietin (EPO) products ior(®) EPOCIM and Eprex(®) following a 28-day repeated intravenous dose administration in male and female Sprague-Dawley rats with a 14-day recovery period. Safety profiling was based on clinical observations, clinical pathology, and pathology findings for control rats dosed with vehicle and rats dosed either with 30, 300, and 600 I.U./kg of ior(®) EPOCIM or 600 I.U. of Eprex(®) . Adverse findings for both ior(®) EPOCIM and Eprex(®) were similar and were a consequence of thrombotic events (ulcerative skin lesions, swollen hock joints/lameness, stomach ulcers) and decreased body weight gains, all known adverse reactions to this class of drug in rats. With the exception of stomach ulcers, all other adverse findings were fully reversible. Neither drug stimulated the production of antidrug antibodies. As expected, ior(®) EPOCIM and Eprex(®) both increased reticulocyte, red blood cell, hemoglobin, and hematocrit levels in rats. The PK of EPO following dosing with ior(®) EPOCIM was well behaved and consistent with the literature. The results of this study imply that ior(®) EPOCIM and Eprex(®) had safety profiles, PD responses, and toxicokinetic profiles that were biosimilar.

  3. Effects of a Proprietary Standardized Orthosiphon stamineus Ethanolic Leaf Extract on Enhancing Memory in Sprague Dawley Rats Possibly via Blockade of Adenosine A 2A Receptors.

    PubMed

    George, Annie; Chinnappan, Sasikala; Choudhary, Yogendra; Choudhary, Vandana Kotak; Bommu, Praveen; Wong, Hoi Jin

    2015-01-01

    The aim of the study was to explore a propriety standardized ethanolic extract from leaves of Orthosiphon stamineus Benth in improving impairments in short-term social memory in vivo, possibly via blockade of adenosine A2A receptors (A2AR). The ethanolic extract of O. stamineus leaves showed significant in vitro binding activity of A2AR with 74% inhibition at 150 μg/ml and significant A2AR antagonist activity with 98% inhibition at 300 μg/mL. A significant adenosine A1 receptor (A1R) antagonist activity with 100% inhibition was observed at 300 μg/mL. Its effect on learning and memory was assessed via social recognition task using Sprague Dawley rats whereby the ethanolic extract of O. stamineus showed significant (p < 0.001) change in recognition index (RI) at 300 mg/kg and 600 mg/kg p.o and 120 mg/kg i.p., respectively, compared to the vehicle control. In comparison, the ethanolic extract of Polygonum minus aerial parts showed small change in inflexion; however, it remained insignificant in RI at 200 mg/kg p.o. Our findings suggest that the ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in short-term social memory and the possible involvement of adenosine A1 and adenosine A2A as a target bioactivity site in the restoration of memory. PMID:26649059

  4. A 90-Day Dietary Toxicity Study of Genetically Modified Rice T1C-1 Expressing Cry1C Protein in Sprague Dawley Rats

    PubMed Central

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study. PMID:23300690

  5. Soluble Fiber Dextrin and Soluble Corn Fiber Supplementation Modify Indices of Health in Cecum and Colon of Sprague-Dawley Rats

    PubMed Central

    Knapp, Brenda K.; Bauer, Laura L.; Swanson, Kelly S.; Tappenden, Kelly A.; Fahey, George C.; de Godoy, Maria R. C.

    2013-01-01

    The objective of this study was to evaluate health outcomes resulting from dietary supplementation of novel, low-digestible carbohydrates in the cecum and colon of Sprague-Dawley rats randomly assigned to one of four treatment groups for 21 days: 5% cellulose (Control), Pectin, soluble fiber dextrin (SFD), or soluble corn fiber (SCF). Rats fed Pectin had a higher average daily food intake, but no differences in final body weights or rates of weight gain among treatments were observed. No differences were observed in total short-chain fatty acid (SCFA) or branched-chain fatty acid (BCFA) concentrations in the cecum and colon of rats fed either SFD or SCF. The SFD and SCF treatments increased cecal propionate and decreased butyrate concentrations compared to Control or Pectin. Pectin resulted in increased BCFA in the cecum and colon. Supplementation of SFD and SCF had no effect on cecal microbial populations compared to Control. Consumption of SFD and SCF increased total and empty cecal weight but not colon weight. Gut histomorphology was positively affected by SFD and SCF. Increased crypt depth, goblet cell numbers, and acidic mucin were observed in both the cecum and colon of rats supplemented with SFD, SCF, and Pectin. These novel, low-digestible carbohydrates appear to be beneficial in modulating indices of hindgut morphology when supplemented in the diet of the rat. PMID:23381099

  6. o-p'-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and Sprague-Dawley rats.

    PubMed

    Kwekel, Joshua C; Forgacs, Agnes L; Williams, Kurt J; Zacharewski, Timothy R

    2013-12-15

    1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p'-DDT) is an organochlorine pesticide and endocrine disruptor known to activate the estrogen receptor. Comprehensive ligand- and species-comparative dose- and time-dependent studies were conducted to systematically assess the uterine physiological, morphological and gene expression responses elicited by o,p'-DDT and ethynyl estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague-Dawley rats. Custom cDNA microarrays were used to identify conserved and divergent differential gene expression responses. A total of 1256 genes were differentially expressed by both ligands in both species, 559 of which exhibited similar temporal expression profiles suggesting that o,p'-DDT elicits estrogenic effects at high doses when compared to EE. However, 51 genes exhibited species-specific uterine expression elicited by o,p'-DDT. For example, carbonic anhydrase 2 exhibited species- and ligand-divergent expression as confirmed by quantitative real-time PCR. The identification of comparable temporal phenotypic responses linked to gene expression demonstrates that systematic comparative gene expression assessments are valuable for elucidating conserved and divergent estrogen signaling mechanisms in rodent uterotrophy.

  7. Providing Flaxseed Oil but Not Menhaden Oil Protects against OVX Induced Bone Loss in the Mandible of Sprague-Dawley Rats.

    PubMed

    Longo, Amanda B; Ward, Wendy E

    2016-01-01

    Higher intakes of polyunsaturated fatty acids (PUFA) are associated with benefits at several skeletal sites in postmenopausal women and in rodent models, but the effect of PUFA-containing oils on tooth-supporting alveolar bone of the mandible has not been studied. Moreover, direct comparison of the effect of flaxseed oil (a source of alpha-linolenic acid (ALA)) and menhaden oil (a source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) is unknown. One-month old female Sprague-Dawley rats (n = 48) were randomized to and fed a diet containing flaxseed oil or menhaden oil from one to six months of age. At three months of age, rats were randomized to receive SHAM or ovariectomy (OVX) surgery (n = 12/diet). The inter-radicular septum below the first molar of the mandible was imaged at 6 months of age (study endpoint) using micro-computed tomography (μCT) at a resolution of 9 μm. As expected, OVX significantly reduced percent bone volume (BV/TV), connectivity density (Conn. D.), trabecular number (Tb. N.), and increased trabecular separation (Tb. Sp.) compared to SHAM rats (p < 0.001). However, post hoc analysis revealed these differences were present in rats fed menhaden oil but not those fed flaxseed oil. These results suggest that providing flaxseed oil, possibly through its high ALA content, provides protection against the OVX-induced alveolar bone loss in rats.

  8. Baseline serum cardiac troponin I concentrations in Sprague-Dawley, spontaneous hypertensive, Wistar, Wistar-Kyoto, and Fisher rats as determined with an ultrasensitive immunoassay.

    PubMed

    Herman, Eugene; Knapton, Alan; Rosen, Elliot; Zhang, Jun; Estis, Joel; Agee, Sara J; Lu, Quynh-Anh; Todd, John A; Lipshultz, Steven E

    2011-06-01

    Cardiac troponins have proved to be reliable blood biomarkers for identifying a variety of myocardial alterations in humans and animals. Recently, an ultrasensitive cTnI assay (Erenna IA) has been used to demonstrate increases in baseline cTnI resulting from drug-induced myocardial injury in rats, dogs, and monkeys, as well as to document baseline cTnI ranges in Sprague-Dawley (SD) rats. The present study was initiated to use the Erenna cTnI assay to further document baseline cTnI concentrations in normal control animals from multiple strains, including SD, Spontaneous Hypertensive (SHR), Wistar, Wistar-Kyoto (WKY), and Fisher strains. Baseline cTnI concentrations were quantified in all rats tested, and males had higher mean cTnI concentrations than females of the same strain. SHR males had the highest mean cTnI concentrations and the largest cTnI variability. Interestingly, cTnI concentrations increased in castrated SHR compared with unaltered male SHR, whereas cTnI concentrations decreased in ovariectomized SHR compared with unaltered female SHR. These results show significant differences in cTnI concentrations between strains, sexes, and noncardiac surgical alterations in control animals, and identify these as potential contributing factors to cTnI baseline variability that should be taken into account when using ultrasensitive cTnI as a biomarker to assess preclinical cardiotoxicity.

  9. Induction of apoptosis and downregulation of ERα in DMBA-induced mammary gland tumors in Sprague-Dawley rats by synthetic 3,5-disubstituted isoxazole derivatives.

    PubMed

    Ananda, Hanumappa; Kumar, Kothanahally S Sharath; Hegde, Mahesh; Rangappa, Kanchugarakoppal S

    2016-09-01

    Isoxazole derivatives are an important group of chemotherapeutic prototypes. In the current study, we have synthesized few isoxazole derivatives and tested them for their antiproliferative properties in cancer cell lines such as MCF7 and HeLa. The lead compound, 3-(3,4-dimethoxyphenyl)-5-(thiophen-2-yl)isoxazole (2b), showed considerable inhibition of proliferation of MCF7 and HeLa cells with the IC50 values of 19.5 and 39.2 µM, respectively. Cell cycle analyses and annexin-FITC staining in 2b-treated breast adenocarcinoma cells (MCF7) showed increased sub-G1 population and apoptosis. Furthermore, we tested the tumor inhibitory effect of 2b and estrogen receptor expression profile in DMBA-induced mammary tumors in Sprague-Dawley rats. The gross morphology of tumor studies was investigated by histopathology and ERα protein expression was evaluated by immunohistochemistry, which showed tumor regression and downregulation of ERα in tumor cells. The present results implicate that compound 2b could be used for the further derivatization for the treatment of breast cancer. PMID:27473146

  10. Exocrine pancreatic pathology in female Harlan Sprague-Dawley rats after chronic treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds.

    PubMed Central

    Nyska, Abraham; Jokinen, Micheal P; Brix, Amy E; Sells, Donald M; Wyde, Michael E; Orzech, Denise; Haseman, Joseph K; Flake, Gordon; Walker, Nigel J

    2004-01-01

    We evaluated the effect of chronic exposure to dioxin and dioxin-like compounds on the pancreas in female Harlan Sprague-Dawley rats. This investigation represents part of an ongoing National Toxicology Program initiative to determine the relative potency of chronic toxicity and carcinogenicity of polychlorinated dioxins, furans, and biphenyls. Animals were treated by gavage for up to 2 years with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3,4,4,5-pentachlorobiphenyl (PCB-126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a toxic-equivalency-factor (TEF) mixture of these agents; control animals received corn oil-acetone vehicle alone. A complete necropsy was performed on all animals, and a full complement of tissues was collected and examined microscopically. Administration of each of the four compounds was associated with increased incidences of several nonneoplastic changes in the exocrine pancreas, including cytoplasmic vacuolation, chronic active inflammation, atrophy, and arteritis. Low incidences, but higher than those in the historical database, of pancreatic acinar adenoma and carcinoma were seen in the TCDD, PeCDF, and TEF-mixture groups. These results indicate that the pancreatic acini are target tissues for dioxin and certain dioxin-like compounds. Key words: carcinogenesis, dioxin, furans, inflammation, pancreas, polychlorinated biphenyls. PMID:15175180

  11. Protective effect of alpha glucosyl hesperidin (G-hesperidin) on chronic vanadium induced testicular toxicity and sperm nuclear DNA damage in male Sprague Dawley rats.

    PubMed

    Vijaya Bharathi, B; Jaya Prakash, G; Krishna, K M; Ravi Krishna, C H; Sivanarayana, T; Madan, K; Rama Raju, G A; Annapurna, A

    2015-06-01

    The study was conducted to evaluate the vanadium-induced testicular toxicity and its effect on sperm parameters, sperm nuclear DNA damage and histological alterations in Sprague Dawley rats and to assess the protective effect of G-hesperidin against this damage. Treatment of rats with vanadium at a dose of 1 mg kg bw(-1) for 90 days resulted in significant reduction in serum testosterone levels, sperm count and motility. Further, a parallel increase in abnormal sperm morphology and adverse histopathological changes in testis was also associated with vanadium administration when compared to normal control. Moreover, sperm chromatin dispersion assay revealed that vanadium induces sperm nuclear DNA fragmentation. A marked increase in testicular malondialdehyde levels and decreased activity of antioxidant enzymes such as superoxide dismutase and catalase indicates vanadium-induced oxidative stress. Co-administration of G-hesperidin at a dose of 25 and 50 mg kg bw(-1) significantly attenuated the sperm parameters and histological changes by restoring the antioxidant levels in rat testis. These results suggested that vanadium exposure caused reduced bioavailability of androgens to the tissue and increased free radical formation, thereby causing structural and functional changes in spermatozoa. G-hesperidin exhibited antioxidant effect by protecting the rat testis against vanadium-induced oxidative damage, further ensures antioxidant potential of bioflavonoids.

  12. Subchronic safety evaluation of CMS-1 (a botanical antihypertensive product derived from Semen Cnidium monnieri) in Sprague-Dawley rats and beagle dogs.

    PubMed

    Gong, Xue-Lian; Gao, Ting-Ting; Zhao, Li-Jun; Zhu, Hai; Xia, Zhen-Na; Lu, Wen; Lu, Guo-Cai

    2014-08-01

    CMS-1, mainly composed of imperatorin as its active compound, is a partially purified fraction of a Chinese herbal medicine, Semen Cnidium monnieri. CMS-1 has the potential to be further developed as a new treatment for hypertension. Thus, we studied its toxicity in both Sprague-Dawley rats and beagle dogs. Rats (0-900mg/kg/day) and dogs (0-450mg/kg/day) received CMS-1 orally for 30 consecutive days, followed by a 15-day recovery period. The major target organs of CMS-1 toxicity are the GI (inappetence), liver (hepatocellular necrosis, enzyme elevation), thymus (atrophy), cardiovascular (hypotension), changes in ECG T and P waveforms, elevation of nitrous oxide levels and hematological (RBC parameters disturbances) systems. Most treatment-induced adverse effects were reversible or showed a progressive recovery upon discontinuation of the treatment. The No Observed Adverse Effect Level (NOAEL) was 100mg/kg/day for rats and 50mg/kg/day for dogs. This non-clinical study suggests that clinical monitoring of CMS-1 in patients should focus on the gastrointestinal system, blood tests for liver functions, electrolytes, and blood homeostasis, cardiovascular functions, and immune functions.

  13. Methylglyoxal (MG) and cerebro-renal interaction: does long-term orally administered MG cause cognitive impairment in normal Sprague-Dawley rats?

    PubMed

    Watanabe, Kimio; Okada, Kana; Fukabori, Ryoji; Hayashi, Yoshimitsu; Asahi, Koichi; Terawaki, Hiroyuki; Kobayashi, Kazuto; Watanabe, Tsuyoshi; Nakayama, Masaaki

    2014-01-07

    Methylglyoxal (MG), one of the uremic toxins, is a highly reactive alpha-dicarbonyl compound. Recent clinical studies have demonstrated the close associations of cognitive impairment (CI) with plasma MG levels and presence of kidney dysfunction. Therefore, the present study aims to examine whether MG is a direct causative substance for CI development. Eight-week-old male Sprague-Dawley (SD) rats were divided into two groups: control (n = 9) and MG group (n = 10; 0.5% MG in drinking water), and fed a normal diet for 12 months. Cognitive function was evaluated by two behavioral tests (object exploration test and radial-arm maze test) in early (4-6 months of age) and late phase (7-12 months of age). Serum MG was significantly elevated in the MG group (495.8 ± 38.1 vs. 244.8 ± 28.2 nM; p < 0.001) at the end of study. The groups did not differ in cognitive function during the course of study. No time-course differences were found in oxidative stress markers between the two groups, while, antioxidants such as glutathione peroxidase and superoxide dismutase activities were significantly increased in the MG group compared to the control. Long-term MG administration to rats with normal kidney function did not cause CI. A counter-balanced activation of the systemic anti-oxidant system may offset the toxicity of MG in this model. Pathogenetic significance of MG for CI requires further investigation.

  14. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    PubMed

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies.

  15. Probiotics Lactobacillus rhamnosus GG, Lactobacillus acidophilus suppresses DMH-induced procarcinogenic fecal enzymes and preneoplastic aberrant crypt foci in early colon carcinogenesis in Sprague Dawley rats.

    PubMed

    Verma, Angela; Shukla, Geeta

    2013-01-01

    Diet makes an important contribution to colorectal cancer (CRC) risk implying risks for CRC are potentially reducible. Therefore, the probiotics have been suggested as the prophylactic measure in colon cancer. In this study, different probiotics were used to compare their protective potential against 1,2 dimethylhydrazine dihydrochloride (DMH)-induced chemical colon carcinogenesis in Sprague Dawley rats. Animals belonging to different probiotic groups were fed orally with 1 × 10(9) lactobacilli daily for 1 week, and then a weekly injection of DMH was given intraperitoneally for 6 wks with daily administration of probiotic. Lactobacillus GG and L.acidophilus + DMH-treated animals had maximum percent reduction in ACF counts. A significant decrease (P < 0.05) in fecal nitroreductase activity was observed in L.casei + DMH and L.plantarum + DMH-treated rats whereas β-glucuronidase activity decreased in L.GG + DMH and L.acidophilus + DMH-treated rats. Animals treated with Bifidobacterium bifidum + DMH had significant decreased β-glucosidase activity. However, not much difference was observed in the colon morphology of animals belonging to various probiotic + DMH-treated rats compared with DMH-treated alone. The results indicated that probiotics, L.GG, and L.acidophilus can be used as the better prophylactic agents for experimental colon carcinogenesis. PMID:23368917

  16. REM sleep deprivation induces changes of down regulatory antagonist modulator (DREAM) expression in the ventrobasal thalamic nuclei of sprague-dawley rats.

    PubMed

    Siran, Rosfaiizah; Ahmad, Asma Hayati; Abdul Aziz, Che Badariah; Ismail, Zalina

    2014-12-01

    REM sleep is a crucial component of sleep. Animal studies indicate that rapid eye movement (REM) sleep deprivation elicits changes in gene expression. Down regulatory antagonist modulator (DREAM) is a protein which downregulates other gene transcriptions by binding to the downstream response element site. The aim of this study is to examine the effect of REM sleep deprivation on DREAM expression in ventrobasal thalamic nuclei (VB) of rats. Seventy-two male Sprague-Dawley rats were divided into four major groups consisting of free-moving control rats (FMC) (n = 18), 72-h REM sleep-deprived rats (REMsd) (n = 18), 72-h REM sleep-deprived rats with 72-h sleep recovery (RG) (n = 18), and tank control rats (TC) (n = 18). REM sleep deprivation was elicited using the inverted flower pot technique. DREAM expression was examined in VB by immunohistochemical, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) studies. The DREAM-positive neuronal cells (DPN) were decreased bilaterally in the VB of rats deprived of REM sleep as well as after sleep recovery. The nuclear DREAM extractions were increased bilaterally in animals deprived of REM sleep. The DREAM messenger RNA (mRNA) levels were decreased after sleep recovery. The results demonstrated a link between DREAM expression and REM sleep deprivation as well as sleep recovery which may indicate potential involvement of DREAM in REM sleep-induced changes in gene expression, specifically in nociceptive processing.

  17. Safety assessment of freeze-dried powdered Tenebrio molitor larvae (yellow mealworm) as novel food source: Evaluation of 90-day toxicity in Sprague-Dawley rats.

    PubMed

    Han, So-Ri; Lee, Byoung-Seok; Jung, Kyung-Jin; Yu, Hee-Jin; Yun, Eun-Young; Hwang, Jae Sam; Moon, Kyoung-Sik

    2016-06-01

    Worldwide demand for novel food source has grown and edible insects are a promising food sources for humans. Tenebrio molitor, as known as yellow mealworm, has advantages of being rich in protein, and easy to raise as a novel food source. The objective of this study was to evaluate subchronic toxicity, including potential hypersensitivity, of freeze-dried powdered T. molitor larvae (fdTML) in male and female Sprague-Dawley rats. The fdTML was administered orally once daily at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 90 days. A toxicological assessment was performed, which included mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings, histopathologic examination and allergic reaction. There were no fdTML- related findings in clinical signs, urinalysis, hematology and serum chemistry, gross examination, histopathologic examination or allergic reaction. In conclusion, the No Observed Adverse Effect Level (NOAEL) for fdTML was determined to be in excess of 3000 mg/kg/day in both sexes of rats under the experimental conditions of this study. PMID:26993751

  18. Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats

    PubMed Central

    Yu, Hong-Ren; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Chen, Chih-Cheng; Kuo, Ho-Chang; Hung, Pi-Lien; Hsieh, Kai-Sheng; Huang, Li-Tung

    2016-01-01

    Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14–21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming. PMID:27669212

  19. Reproductive toxicity screen of 1,3,5-trinitrobenzene administered in the diet of sprague-dawley rats. Final report, September 1993-June 1994

    SciTech Connect

    Kinkead, E.R.; Wolfe, R.E.; Flemming, C.D.; Caldwell, D.J.; Miller, C.R.

    1994-10-01

    Several Army installations targeted for restoration have measurable quantities of 1,3,5-trinitrobenzene (TNB) in the soil and ground water. As part of the process to develop environmental and health effects criteria for restoration, a modified Screening Information Data Set (SIDS) reproductive study was performed. Male and female Sprague-Dawley rats received diet containing approximately 300, 150, or 30 mg Th%B/kg diet. Mating occurred following 14 days of treatment. All dams, one-half the males, and representative pups were maintained for a total of 90 days of treatment. No mortality occurred during the study; however, a decrease in mean body weights was noted in both sexes of high-dose rats. A dose-related effect was noted in measurements of sperm function/activity. Sperm depletion and degeneration of the seminiferous tubules were noted histopathologically. Methemoglobinemia and splenic hemosiderosis were common findings in the high- and mid-dose levels of both sexes at necropsy. No adverse effects were noted in mating or fertility indices. No significant treatment-related differences were found in length of gestation, sex ratio, gestation index, or mean number of pups per litter.

  20. A 90-day dietary toxicity study of genetically modified rice T1C-1 expressing Cry1C protein in Sprague Dawley rats.

    PubMed

    Tang, Xueming; Han, Fangting; Zhao, Kai; Xu, Yan; Wu, Xiao; Wang, Jinbin; Jiang, Lingxi; Shi, Wei

    2012-01-01

    In a 90-day study, Sprague Dawley rats were fed transgenic T1C-1 rice expressing Cry1C protein and were compared with rats fed non-transgenic parental rice Minghui 63 and rats fed a basal diet. No adverse effects on animal behavior or weight gain were observed during the study. Blood samples were collected and analyzed, and standard hematological and biochemical parameters were compared. A few of these parameters were found to be significantly different, but were within the normal reference intervals for rats of this breed and age, and were thus not considered to be treatment-related. Following sacrifice, a large number of organs were weighed, and macroscopic and histopathological examinations were performed with no changes reported. The aim of this study was to use a known animal model to determine the safety of the genetically modified (GM) rice T1C-1. The results showed no adverse or toxic effects due to T1C-1 rice when tested in this 90-day study.

  1. A 90-day safety study in Sprague-Dawley rats fed milk powder containing recombinant human lactoferrin (rhLF) derived from transgenic cloned cattle.

    PubMed

    Zhou, Cui; Wang, Jian Wu; Huang, Kun Lun; He, XiaoYun; Chen, Xiu Ping; Sun, Hong; Yu, Tian; Che, Hui Lian

    2011-10-01

    Transgenic cloned animals expressing beneficial human nutritional traits offer a new strategy for large-scale production of some kinds of functional substances. In some cases, the required safety testing for genetically modified (GM) foods do not seem appropriate for human food safety, though regulations do not seem to provide alternatives. A 90-day rat feeding study is the core study for the safety assessment of GM foods. The test material in this 90-day study was prepared nonfat milk powder containing recombinant human lactoferrin (rhLF), which was expressed in transgenic cloned cattle. Groups of 10 male and female Sprague-Dawley rats were given a nutritionally balanced purified diet containing 7.5, 15, or 30% transgenic or conventional milk powder for 90 days. A commercial AIN93G diet was used as an additional control group. Clinical, biological, and pathological parameters were compared between groups. The only significant effect of treatment was higher mean ferritin and Fe(+) concentrations for both male and female rats fed the transgenic milk powder diets, as compared to rats fed nontransgenic milk diets or the commercial diet. The results of the present study are consistent with previous research, which indicates that milk powder containing rhLF derived from healthy transgenic cloned cattle is as safe as conventional milk powder.

  2. A 90-day feeding study of glyphosate-tolerant maize with the G2-aroA gene in Sprague-Dawley rats.

    PubMed

    Zhu, Yaxi; He, Xiaoyun; Luo, Yunbo; Zou, Shiying; Zhou, Xin; Huang, Kunlun; Xu, Wentao

    2013-01-01

    Maize is not only a staple food crop but also an important raw material for feed and industry; however, the threat of weeds leads to a serious decline in its output and quality. The G2-aroA gene confers glyphosate herbicide tolerance to crops. In this study, the food safety of genetically modified (GM), glyphosate-tolerant maize with the G2-aroA gene was evaluated in a 90-day feeding study in Sprague-Dawley (SD) rats. Maize grain from GM or non-GM isogenic control lines were separately formulated into rodent diets at concentrations of 12.5% (low level), 25% (middle level), and 50% (high level). An additional group of rats were fed a commercialized diet as a control. The toxicological response variables, including body weights, food consumption, serum biochemistry, hematology, and absolute and relative organ weights, were compared between rats fed GM maize and those fed non-GM maize after consumption of test diets for 90days. In addition, gross and microscopic pathology were conducted among treatment groups. No adverse effects related to the consumption of GM maize were detected in the subchronic feeding study. These results indicated that the GM glyphosate-tolerant maize was as safe and nutritious as conventional maize.

  3. Effects of a Proprietary Standardized Orthosiphon stamineus Ethanolic Leaf Extract on Enhancing Memory in Sprague Dawley Rats Possibly via Blockade of Adenosine A2A Receptors

    PubMed Central

    Choudhary, Yogendra; Choudhary, Vandana Kotak; Bommu, Praveen; Wong, Hoi Jin

    2015-01-01

    The aim of the study was to explore a propriety standardized ethanolic extract from leaves of Orthosiphon stamineus Benth in improving impairments in short-term social memory in vivo, possibly via blockade of adenosine A2A receptors (A2AR). The ethanolic extract of O. stamineus leaves showed significant in vitro binding activity of A2AR with 74% inhibition at 150 μg/ml and significant A2AR antagonist activity with 98% inhibition at 300 μg/mL. A significant adenosine A1 receptor (A1R) antagonist activity with 100% inhibition was observed at 300 μg/mL. Its effect on learning and memory was assessed via social recognition task using Sprague Dawley rats whereby the ethanolic extract of O. stamineus showed significant (p < 0.001) change in recognition index (RI) at 300 mg/kg and 600 mg/kg p.o and 120 mg/kg i.p., respectively, compared to the vehicle control. In comparison, the ethanolic extract of Polygonum minus aerial parts showed small change in inflexion; however, it remained insignificant in RI at 200 mg/kg p.o. Our findings suggest that the ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in short-term social memory and the possible involvement of adenosine A1 and adenosine A2A as a target bioactivity site in the restoration of memory. PMID:26649059

  4. HIF-1α may provide only short-term protection against ischemia-reperfusion injury in Sprague-Dawley myocardial cultures

    PubMed Central

    WANG, SIYANG; SHAO, XIN; LI, XIAOXUE; SU, XIAOJUAN; HUO, YONGXU; YANG, CHUNLEI

    2016-01-01

    Hypoxia-inducible factor-1 (HIF-1α) exerts an important role in protecting against cardiac tissue damage, for example, following ischemia-reperfusion (I/R), although the time frame during which it acts has yet to be fully elucidated. In the present study, a culture model of myocardial cells from Sprague-Dawley rats was used to examine the expression levels of HIF-1α and various downstream effectors at different times following I/R. The levels of HIF-1α were manipulated by overexpressing HIF-1α prior to I/R. HIF-1α levels peaked at 6 h following I/R, subsequently decreasing to low levels. The levels of downstream effectors peaked at 48 h, and decreased almost to pre-I/R levels by 72 h. These results suggest that HIF-1α and its downstream targets offer only short-term protection following I/R. These results may have implications for the treatment of I/R-associated injury in a variety of clinical contexts. PMID:27073667

  5. Amelioration of oxidative stress by dandelion extract through CYP2E1 suppression against acute liver injury induced by carbon tetrachloride in Sprague-Dawley rats.

    PubMed

    Park, Chung Mu; Cha, Yeon Suk; Youn, Hyun Joo; Cho, Chung Won; Song, Young Sun

    2010-09-01

    The protective effects of common dandelion leaf water extract (DLWE) were investigated by carbon tetrachloride (CCl4) induced hepatitis in Sprague-Dawley rats. The animals were divided into five groups: normal control, DLWE control, CCl4 control, and two DLWE groups (0.5 and 2 g/kg bw). After 1 week of administering corresponding vehicle or DLWE, a single dose of CCl4 (50% CCl4/olive oil; 0.5 mL/kg bw) was administered 24 h before killing in order to produce acute liver injury. The DLWE treatment significantly decreased CCl4-induced hepatic enzyme activities (AST, ALT and LDH) in a dose dependent manner. Also, the obstructed release of TG and cholesterol into the serum was repaired by DLWE administration. Hepatic lipid peroxidation was elevated while the GSH content and antioxidative enzyme activities were reduced in the liver as a result of CCl4 administration, which were counteracted by DLWE administration. Furthermore, the hepatocytotoxic effects of CCl4 were confirmed by significantly elevated Fas and TNF-α mRNA expression levels, but DLWE down-regulated these expressions to the levels of the normal control. Highly up-regulated cytochrome P450 2E1 was also lowered significantly in the DLWE groups. These results indicate that DLWE has a protective effect against CCl4-induced hepatic damage with at least part of its effect being attributable to the attenuation of oxidative stress and inflammatory processes resulting from cytochrome P450 activation by CCl4.

  6. Differential inducing effect of benzo[a]pyrene on gene expression and enzyme activity of cytochromes P450 1A1 and 1A2 in Sprague-Dawley and Wistar rats.

    PubMed

    Floreani, Maura; Gabbia, Daniela; Barbierato, Massimo; DE Martin, Sara; Palatini, Pietro

    2012-01-01

    The objective of this study was to compare RT-PCR, Western blot and determination of enzyme activity in the assessment of the induction of cytochromes P450 (CYPs) 1A1 and 1A2 by benzo[a]pyrene (BaP) in Sprague-Dawley and Wistar rats. Inhibition studies and kinetic analyses confirmed literature data indicating that methoxyresorufin is a specific CYP1A2 substrate in both uninduced and BaP-treated rats, whereas ethoxyresorufin is a specific CYP1A1 substrate only in BaP-treated rats. BaP treatment increased mRNA and protein expressions of both CYP1A enzymes to a greater extent in Wistar than Sprague-Dawley rats. It consistently caused a higher increase in mRNA and protein expression of the aryl hydrocarbon receptor in the former rats. By contrast, CYP1A2 enzyme activity was much more markedly increased in Sprague-Dawley than Wistar rats and CYP1A1 activity was induced to similar levels. A BaP-induced increase in the turnover number of CYP1A enzymes in Sprague-Dawley rats, relative to Wistar rats, may provide a plausible explanation for the differential effect of BaP on gene expression and enzyme activity. These results have methodological implications, since they show that RT-PCR and Western blot may not provide a quantitative measure of induction of CYP1A activity, which is the actual measure of the change in CYP1A-mediated metabolism.

  7. Assessment of the Toxicity and the Stability of Saeng Mak San by Using Repeated Intravenous Injections in Sprague-Dawley Rats

    PubMed Central

    Lee, Hwa-Young; Kim, Sungchul; Cho, Seung-Hun

    2016-01-01

    Objectives: This study used repeated intravenous injections of Saeng Maek San (SMS) injection in Sprague-Dawley (SD) rats to assess the toxicity and the stability of SMS Methods: Six-week-old male and female SD rats reared by Orient bio Inc were chosen for this pilot study. They were randomly split into four groups: Group 1 (G1), the control group (0.3 mL of normal saline solution/day/animal), and Groups 2, 3 and 4 (G2, G3 and G4), the experimental groups (0.1, 0.2 and 0.3 mL/day/animal of SMS), respectively. Each animal received an intravenous injection of SMS once a day for four weeks. Clinical signs, body weight changes, and food consumption were monitored during the observation period, and urinalysis and hematology were conducted after four weeks of SMS or saline administration. Results: No deaths occurred in any of the four groups during the observation period. Compared to the control group, male and female rats in groups 3 and 4 (0.2 and 0.3 mL/animal/day) showed hemoglobinuria, but the low-dosage group (G2, 0.1 mL/animal/day) showed no significant changes in the clinical signs test. No significant changes due to SMS were observed in the experimental groups regarding body weight changes, food consumption urinalysis, or hematology. Conclusion: During this study, no mortalities were observed in any of the experimental groups and no hemoglobinuria was observed in the low dosage group (0.1 mL/animal/day) while it was intermittently observed in groups 3 and 4 (0.2 and 0.3 mL/animal/day). Thus, we suggest that the no-observed adverse-effect level (NOAEL) is 0.1 mL/animal/day in male and female SD rats. PMID:27695632

  8. Streptozotocin-induced type-1-diabetes disease onset in Sprague-Dawley rats is associated with an altered intestinal microbiota composition and decreased diversity.

    PubMed

    Patterson, Elaine; Marques, Tatiana M; O'Sullivan, Orla; Fitzgerald, Patrick; Fitzgerald, Gerald F; Cotter, Paul D; Dinan, Timothy G; Cryan, John F; Stanton, Catherine; Ross, R Paul

    2015-01-01

    There is a growing appreciation that microbiota composition can significantly affect host health and play a role in disease onset and progression. This study assessed the impact of streptozotocin (STZ)-induced type-1-diabetes (T1D) on intestinal microbiota composition and diversity in Sprague-Dawley rats, compared with healthy controls over time. T1D was induced by injection of a single dose (60 mg STZ kg(-1)) of STZ, administered via the intraperitoneal cavity. Total DNA was isolated from faecal pellets at weeks 0 (pre-STZ injection), 1, 2 and 4 and from caecal content at week 5 from both healthy and T1D groups. High-throughput 16S rRNA sequencing was employed to investigate intestinal microbiota composition. The data revealed that although intestinal microbiota composition between the groups was similar at week 0, a dramatic impact of T1D development on the microbiota was apparent post-STZ injection and for up to 5 weeks. Most notably, T1D onset was associated with a shift in the Bacteroidetes : Firmicutes ratio (P<0.05), while at the genus level, increased proportions of lactic acid producing bacteria such as Lactobacillus and Bifidobacterium were associated with the later stages of T1D progression (P<0.05). Coincidently, T1D increased caecal lactate levels (P<0.05). Microbial diversity was also reduced following T1D (P<0.05). Principle co-ordinate analyses demonstrated temporal clustering in T1D and control groups with distinct separation between groups. The results provide a comprehensive account of how T1D is associated with an altered intestinal microbiota composition and reduced microbial diversity over time.

  9. Effects of (99m)Tc sestamibi on antioxidant defense system and lipid peroxidation in the heart of Sprague Dawley rats.

    PubMed

    Cesur, Gokhan; Doguc, Duygu Kumbul; Yildiz, Mustafa; Ogut, Serdal; Polat, Mumin; Ongel, Kurtulus

    2014-03-01

    Nuclear medicine has been using radiopharmaceuticals for the diagnostic and therapeutic purposes of many diseases. Technetium-(99m) methoxyisobutylisonitrile ((99m)Tc sestamibi) is a lypophilic complex that has a positive-loaded isonitril group. Aim of the study is to investigate whether (99m)Tc sestamibi, which is one of the mostly used radiopharmaceuticals in nuclear medicine field, causes oxidative damage or not in rats' heart after an injection. A total of 16 male Sprague Dawley rats were randomly divided into two groups: group I: (99m)Tc sestamibi group, (99m)Tc sestamibi administered intravenously with the dose of 25MBq; group II: control group, one dose of isotonic sodium chloride was administered intravenous with the same volume as (99m)Tc sestamibi group. Malondialdehyde (MDA) and total oxidant status (TOS) were used as markers of oxidative stress-induced heart impairment. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant status (TAS) activities were studied to evaluate the changes in the antioxidant status. In the (99m)Tc sestamibi group (group I), animals treated with (99m)Tc sestamibi produced a significant decrease in the activities of antioxidant enzymes (SOD and CAT), while MDA level increased when compared with control group (group II) in myocardial tissue (p < 0.05). On the other hand, the GSH-Px activities were significantly increased in the (99m)Tc sestamibi-treated rats compared with the untreated rats (p < 0.05). There was no significant difference in the TAS and TOS levels of plasma.

  10. Behavioral and physiological effects of a single injection of rat interferon-alpha on male Sprague-Dawley rats: a long-term evaluation.

    PubMed

    Kentner, A C; Miguelez, M; James, J S; Bielajew, C

    2006-06-20

    Interferon-alpha (IFN-alpha) is a cytokine used as a first line of defense against diseases such as cancer and hepatitis C. However, reports indicate that its effectiveness as a treatment is countered by central nervous system (CNS) disruptions in patients. Our work explored the possibility that it may also cause long-term behavioral disruptions by chronicling the behavioral and physiological disturbances associated with a single injection of vehicle, 10, 100, or 1,000 units of IFN-alpha in male Sprague-Dawley rats (n = 5/dose). Following 1 day of locomotor baseline collection, we monitored sickness behaviors (ptosis, piloerection, lethargy, and sleep), food and water intake, body weight, temperature, and motor activity. Observations were recorded 4 days prior to and 4 days following the IFN-alpha injection. Temperature and sickness behaviors were recorded three times daily at 9:00, 15:00, and 21:00 h, and all other indices, once daily. On the injection day, temperature values were highest in the animals receiving the 10-unit IFN-alpha dose 15 min and 13 h post-injection. In the case of sickness behaviors, a significant increase was observed in piloerection in all IFN-alpha groups at each time point measured, while the scores of the rats in the vehicle condition remained unchanged between pre- and post-injection days. Analyses of overall sickness behaviors during morning and night observation periods indicated increased scores in all IFN-alpha groups following injection. Cumulatively, these data suggest that a single IFN-alpha exposure may elicit long-term behavioral disruptions and that its consequences should be thoroughly investigated for its use in clinical populations.

  11. Myelotoxicity in genistein-, nonylphenol-, methoxychlor-, vinclozolin- or ethinyl estradiol-exposed F1 generations of Sprague-Dawley rats following developmental and adult exposures.

    PubMed

    Guo, T L; Germolec, D R; Musgrove, D L; Delclos, K B; Newbold, R R; Weis, C; White, K L

    2005-08-01

    The myelotoxicity of five endocrine active chemicals was evaluated in F1 generation of Sprague-Dawley rats following developmental and adult exposures at three concentration levels. Rats were exposed to genistein (GEN: 25, 250 and 1250 ppm), nonylphenol (NPH: 25, 500 and 2000 ppm), methoxychlor (MXC: 10, 100 and 1000 ppm), vinclozolin (VCZ: 10, 150 and 750 ppm) and ethinyl estradiol (EE2: 5, 25 and 200 ppb) gestationally and lactationally through dams from day 7 of gestation and through feed after weaning on postnatal day (PND) 22 to PND 64. The parameters examined included the number of recovered bone marrow cells, DNA synthesis, and colony forming units (CFU) in the presence of granulocyte macrophage-colony stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and erythropoietin. Except for the EE2, the concentrations of other individual chemicals in the diet were in an approximate range that allowed for a comparison to be made in terms of myelotoxic potency. Decreases in the DNA synthesis, CFU-GM and CFU-M seemed to be the common findings among the alterations induced by these compounds. Using the numbers of alterations induced by each chemical in the parameters examined as criteria for comparison, the order of myelotoxic potency in F(1) males was: GEN>MXC>NPH>VCZ; the order in females: GEN>NPH>VCZ. Additionally, some of the functional changes induced by these compounds were gender-specific or dimorphic. Overall, the results demonstrated that developmental and adult exposures of F1 rats to these endocrine active chemicals at the concentrations tested had varied degrees of myelotoxicity with GEN being the most potent. Furthermore, the sex-specific effects of these chemicals in F1 male and female rats suggest that there may be interactions between these compounds and sex hormone in modulating these responses.

  12. Comparative studies of oral administration of marine collagen peptides from Chum Salmon (Oncorhynchus keta) pre- and post-acute ethanol intoxication in female Sprague-Dawley rats.

    PubMed

    Liang, Jiang; Li, Qiong; Lin, Bing; Yu, Yongchao; Ding, Ye; Dai, Xiaoqian; Li, Yong

    2014-09-01

    The present study aimed to evaluate the effect of an oral administration of marine collagen peptides (MCPs) pre- and post-acute ethanol intoxication in female Sprague-Dawley (SD) rats. MCPs were orally administered to rats at doses of 0 g per kg bw, 2.25 g per kg bw, 4.5 g per kg bw and 9.0 g per kg bw, prior to or after the oral administration of ethanol. Thirty minutes after ethanol treatment, the effect of MCPs on motor incoordination and hypnosis induced by ethanol were investigated using a screen test, fixed speed rotarod test (5 g per kg bw ethanol) and loss of righting reflex (7 g per kg bw ethanol). In addition, the blood ethanol concentrations at 30, 60, 90, and 120 minutes after ethanol administration (5 g per kg bw ethanol) were measured. The results of the screen test and fixed speed rotarod test suggested that treatment with MCPs at 4.5 g per kg bw and 9.0 g per kg bw prior to ethanol could attenuate ethanol-induced loss of motor coordination. Moreover, MCP administered both pre- and post-ethanol treatment had significant potency to alleviate the acute ethanol induced hypnotic states in the loss of righting reflex test. At 30, 60, 90 and 120 minutes after ethanol ingestion at 5 g per kg bw, the blood ethanol concentration (BEC) of control rats significantly increased compared with that in the 4.5 g per kg bw and 9.0 g per kg bw MCP pre-treated groups. However, post-treatment with MCPs did not exert a significant inhibitory effect on the BEC of the post-treated groups until 120 minutes after ethanol administration. Therefore, the anti-inebriation effect of MCPs was verified in SD rats with the possible mechanisms related to inhibiting ethanol absorption and facilitating ethanol metabolism. Moreover, the efficiency was better when MCPs were administered prior to ethanol.

  13. EPR studies of in vivo radical production by 3,3',5,5'-tetrabromobisphenol A (TBBPA) in the Sprague-Dawley rat

    SciTech Connect

    Chignell, C.F.; Mouithys-Mickalad, A.; Sik, R.H.; Stadler, K.; Kadiiska, M.B.

    2008-07-01

    Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard and it is of interest to determine the mechanism of their toxicity. Of all the BFRs, 3,3',5,5'-tetrabromobisphenol A (TBBPA) is produced in the largest volume. Previous studies by Szymanska et al. (2000) have shown that TBBPA is hepatotoxic in rats. We report here that when TBBPA (100 or 600 mg/kg) dissolved in DMSO and {alpha}-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN) was administered ip to male Sprague-Dawley rats the POBN/{center_dot}CH{sub 3} spin adduct was detected by electron paramagnetic resonance (EPR) in the bile. When {sup 13}C-DMSO was employed the POBN/{center_dot}C{sup 13}H{sub 3} adduct was observed. Also present in the bile was the 2,6-dibromobenzosemiquinone radical derived from 2,6-dibromohydroquinone, a known metabolite of TBBPA. Reaction of the 2,6-dibromobenzosemiquinone radical with oxygen would generate superoxide from which hydrogen peroxide can form by dismutation. The hydroxyl radical generated via the Fenton reaction from hydrogen peroxide reacts in vivo with DMSO to give the methyl radical which is trapped by POBN. These observations suggest that the hepatotoxicity of TBBPA in rats may be due to the in vivo generation of the hydroxyl radical as a result of redox reactions involving the TBBPA metabolite 2,6-dibromohydroquinone and its corresponding semiquinone radical.

  14. Sub-Acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats.

    PubMed

    Kong, Boon-Hong; Tan, Nget-Hong; Fung, Shin-Yee; Pailoor, Jayalakshmi

    2016-01-01

    Lignosus also known as "Tiger Milk Mushroom," is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD) rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500, and 1000 mg/kg to the SD rats once daily, consecutively for 28-days. Body weight of the rats was recorded and general behavior, adverse effects, and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights, and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology, and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL) dose is more than 1000 mg/kg.

  15. Polychlorinated biphenyls modulated tumorigenesis in Sprague Dawley rats: correlation with mixed function oxidase activities and superoxide (O2* ) formation potentials and implied mode of action.

    PubMed

    Brown, John F; Mayes, Brian A; Silkworth, Jay B; Hamilton, Stephen B

    2007-08-01

    Parallel, chronic (24 months) multidose bioassays of the PCB (polychlorinated biphenyls) Aroclors 1016, 1242, 1254, and 1260 in male and female Sprague-Dawley rats showed sex/Aroclor-dependent increases in hepatic tumors and decreases in extrahepatic tumors. To elucidate the PCB mode of action (MOA) involved, levels of a number of hypothesized mediators were measured in liver specimens collected at 3, 6, 12, 18, and 24 months and screened for correlation with late life hepatotumorigenesis (HT; mostly adenomas). Consistently correlated with HT were (1) tissue accumulations of SigmaPCBs (correlated in both sexes) and of dioxin equivalents (toxic equivalency [TEQ]; correlated in females only); (2) net activities of six groups of mixed function oxidases (MFOs), some PCB-induced, some PCB-repressed, as determined by differential metabolism of PCB congeners; (3) activities of deproteinated, reoxidized hepatic cytosols as catalysts for superoxide (O(2)(*-)) production, such activity having the chemical characteristics of redox-cycling quinones (RCQs), e.g., those derived from the glutathionylated estrogen catechols that were identified in the female rat livers; and (4) increased expression of the indicator of cell proliferation, proliferating cell nuclear antigen. The new findings, along with other recently reported relationships, were indicative of a MOA consisting of (1) SigmaPCB/TEQ accumulation in rat tissues; (2) SigmaPCB/TEQ repression of constitutive MFOs; (3) SigmaPCB/TEQ induction of other MFOs; (4) MFO-mediated formation of RCQs; (5) RCQ-mediated formation of O(2)(*-); (6) O(2)(*-) dismutation to H(2)O(2); and (7) H(2)O(2)-mediated mitotic signaling, resulting in the proliferation of spontaneously or otherwise initiated cells to form hepatic tumors, as in tumor promotion. PMID:17510085

  16. Nutritional and clinical evaluation of a modified soy protein with covalently bound branched-chain amino acids in cirrhotic sprague-dawley rats.

    PubMed

    Rodríguez, M F; Wall, A; Kondrup, J; López-Cervantes, G; Calderón de la Barca, A M

    2003-01-01

    Several studies suggested that branched-chain amino acids (BCAA) improve plasma amino acid imbalance as well as protein metabolism in patients with cirrhosis. However, commercial formulas supplemented with free BCAA have their limitations. We evaluated a modified soy protein diet with covalently bound BCAA (diet M) by comparing it with diets based on casein (diet C) or Hepatic Aid II (diet H; commercial formula) as protein sources. After 3 weeks of bile duct obstruction, 24 Sprague-Dawley rats divided into three groups received diets with 9% (w/w) protein/amino acids for 7 days. Nutritional and clinical parameters were determined. Nitrogen balance and weight gain (g)/protein intake (g) with diet M (0.19 +/- 0.31 and 1.33 +/- 1.43 g, respectively) were significantly higher (p < 0.05) than with diet H (-0.34 +/- 0.20 and -0.34 +/- 1.11 g), but comparable to those with diet C (0.04 +/- 0.38 and 0.20 +/- 0.93 g). Animals on diet M had a significantly (p < 0.05) increased plasma BCAA:aromatic amino acid ratio (1.8 +/- 0.3) as compared with those on diets H (1.3 +/- 0.1) and C (0.8 +/- 0.0). There were no significant differences in organ weight or liver function among the groups. We conclude that the BCAA-modified protein is an attractive option in the nutritional support of patients having cirrhosis.

  17. A high-fat diet enriched with low omega-6 to omega-3 fatty acid ratio reduced fat cellularity and plasma leptin concentration in Sprague-Dawley rats.

    PubMed

    Tekeleselassie, A W; Goh, Y M; Rajion, M A; Motshakeri, M; Ebrahimi, M

    2013-01-01

    This study was aimed to investigate the effects of dietary fatty acids on the accretion pattern of major fat pads, inguinal fat cellularity, and their relation with plasma leptin concentration. Forty Sprague-Dawley rats were randomly assigned into four groups and received the following diets for 22 weeks: (1) standard rat chow diet (CTRL), (2) CTRL + 10% (w/w) butter (HFAR), (3) CTRL + 3.33% (w/w) menhaden fish oil + 6.67% (w/w) soybean oil (MFAR), and (4) CTRL + 6.67% (w/w) menhaden fish oil + 3.33% (w/w) soybean oil (LFAR). Inguinal fat cellularity and plasma leptin concentration were measured in this study. Results for inguinal fat cellularity showed that the mean adipocyte number for the MFAR (9.2 ∗ 10⁵ ± 3.6) and LFAR (8.5 ∗ 10⁵ ± 5.1) groups was significantly higher (P < 0.05) than the rest, while the mean adipocyte diameter of HFAR group was larger (P < 0.05) (46.2 ± 2.8) than the rest. The plasma leptin concentration in the HFAR group was higher (P < 0.05) (3.22 ± 0.32 ng/mL), than the other groups. The higher inguinal fat cellularity clearly indicated the ability of the polyunsaturated fatty acids (PUFA) and butter supplemented diets to induce hyperplasia and hypertrophy of fat cells, respectively, which caused adipocyte remodeling due to hyperleptinemia.

  18. Long-lasting sensitization induced by repeated risperidone treatment in adolescent Sprague-Dawley rats: A possible D2 receptor mediated phenomenon?

    PubMed Central

    Zhang, Qinglin; Hu, Gang; Li, Ming

    2014-01-01

    Rationale Risperidone use in children and adolescents for the treatment of various neuropsychiatric disorders (e.g. schizophrenia, autism, disruptive behavior, etc.) has increased substantially in recent decades. However, its long-term effect on the brain and behavioral functions is not well understood. Objective The present study investigated how a short-term risperidone treatment in adolescence impacts antipsychotic response in adulthood in the conditioned avoidance response and PCP-induced hyperlocomotion tests. Methods Male adolescent Sprague-Dawley rats (postnatal days [P] 40-44 or 43-48) were first treated with risperidone (0.3, 0.5 or 1.0 mg/kg, sc) and tested in the conditioned avoidance or PCP (3.2 mg/kg, sc)-induced hyperlocomotion model daily for 5 consecutive days. After they became adults (~P 76-80), they were challenged with risperidone (0.3 mg/kg, sc) to assess their sensitivity to risperidone re-exposure. A quinpirole (a D2/3 receptor agonist, 1.0 mg/kg, sc)-induced hyperlocomotion test was later conducted to assess the risperidone-induced functional changes in D2 receptor. Results In the risperidone challenge test in adulthood, adult rats previously treated with risperidone in adolescence made significantly fewer avoidance responses and exhibited significantly lower PCP-induced hyperlocomotion than those previously treated with vehicle. They also appeared to be more hyperactive than the vehicle-pretreated ones in the quinpirole-induced hyperlocomotion test. Prepulse inhibition of acoustic startle or fear-induced 22 kHz ultrasonic vocalizations in adulthood was not altered by adolescence risperidone treatment. Conclusions Adolescent risperidone exposure induces a long-term increase in behavioral sensitivity to risperidone that persists into adulthood. This long-lasting change might be due to functional upregulation of D2-mediated neurotransmission. PMID:24363078

  19. The effect of the degree of left renal vein constriction on the development of adolescent varicocele in Sprague-Dawley rats.

    PubMed

    Yao, Bing; Zhou, Wen-Liang; Han, Da-Yu; Ouyang, Bin; Chen, Xu; Chen, Sheng-Fu; Deng, Chun-Hua; Sun, Xiang-Zhou

    2016-01-01

    Experimental models have allowed inquiry into the pathophysiology of varicocele (VC) beyond that possible with human patients. A randomized controlled study in rats was designed to clarify the influence of the degree of left renal vein constriction on the development of adolescent VC. Fifty adolescent male Sprague-Dawley rats (Rattus norvegicus) were randomly assigned to five groups of 10: the experimental groups (I-IV) underwent partial ligation of left renal veins with 0.5-, 0.6-, 0.7-, and 0.8-mm diameter needles, respectively. The control group (V) underwent a sham operation. The diameter of the left spermatic vein (LSV) was measured at baseline and 30 days postoperatively. In addition, the lesion of the left kidney was examined with the naked eye and assessed by Masson's trichrome staining. VC was successfully induced in 2 (20%), 4 (40%), 7 (70%), and 10 (100%) rats in groups I-IV, respectively. The other rats failed to develop VCs primarily due to left renal atrophy. No VC was observed in group V. The postsurgical LSV diameters in VC rats in groups III and IV were 1.54 ± 0.16 and 1.49 ± 0.13 mm, respectively (P > 0.05), and their increments were 1.36 ± 0.10 and 1.31 ± 0.10 mm, respectively (P > 0.05). These results suggest that suitable constriction of the left renal vein is critical for adolescent VC development. In addition, the 0.8-mm diameter needle may be more suitable for inducing left renal vein constriction in adolescent rat models.

  20. Sub-Acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats

    PubMed Central

    Kong, Boon-Hong; Tan, Nget-Hong; Fung, Shin-Yee; Pailoor, Jayalakshmi

    2016-01-01

    Lignosus also known as “Tiger Milk Mushroom,” is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD) rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500, and 1000 mg/kg to the SD rats once daily, consecutively for 28-days. Body weight of the rats was recorded and general behavior, adverse effects, and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights, and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology, and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL) dose is more than 1000 mg/kg. PMID:27555822

  1. Alteration of Kupffer cell function and morphology by low melt point paraffin wax in female Fischer-344 but not Sprague-Dawley rats.

    PubMed

    Hoglen, N C; Regan, S P; Hensel, J L; Younis, H S; Sauer, J M; Steup, D R; Miller, M J; Waterman, S J; Twerdok, L E; Sipes, I G

    1998-11-01

    This study was conducted to compare the effects of 60-day dietary exposure (2%) to low melt point paraffin wax (LMPW) on both general liver morphology and Kupffer cell (KC) function and morphology in female F-344 and Sprague-Dawley (SD) rats. Livers from only F-344 rats fed LMPW had granuloma formation/lymphoid cell aggregates with small areas of necrosis. Significant increases in serum alanine and aspartate aminotransferase as well as gamma-glutamyltransferase activities were detected only in treated F-344 rats. Additionally, detectable amounts of LMPW were present only in livers of treated F-344 rats. Because KC can be involved in granuloma formation, their morphology and function were examined. Electron microscopy revealed the presence of large, irregularly shaped, membrane-associated vacuoles in cells isolated from F-344 rats exposed to LMPW. These vacuoles were not seen in KC from control rats and rarely detected in KC isolated from LMPW-exposed SD rats. Moreover, indices of KC function including phagocytic activity and nitric oxide and superoxide anion production were significantly increased by KC isolated from F-344 rats exposed to LMPW (1.6-, 36-, and 2.2-fold increases, respectively) over untreated controls. In contrast, LPS-stimulated production of TNF and LTB4 was significantly decreased only in KC of LMPW-fed F-344 rats. No significant changes in these functions were observed in KC isolated from SD rats exposed to LMPW or from KC isolated from control F-344 or SD rats. These data provide evidence that dietary LMPW alters the morphology and functional capacity of KC of F-344 but not SD rats and these changes may ultimately lead to granuloma formation.

  2. Pubertal administration of DEHP delays puberty, suppresses testosterone production, and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans rats.

    PubMed

    Noriega, Nigel C; Howdeshell, Kembra L; Furr, Jonathan; Lambright, Christy R; Wilson, Vickie S; Gray, L Earl

    2009-09-01

    Although is clear that exposure to high dosage levels of some phthalates delays the onset of puberty in the male rat, it has been hypothesized that low levels of di(2-ethylhexyl) phthalate (DEHP) accelerate puberty by enhancing testicular androgen synthesis. The current study was designed to determine if the dose response to DEHP was nonmonotonic, as hypothesized. Pubertal administration of DEHP delayed the onset of puberty and reduced androgen-dependent tissue weights in both Long-Evans (LE) and Sprague-Dawley (SD) male rats 300 and 900 mg DEHP/kg/day. These effects were generally of greater magnitude in LE than SD rats. By contrast, alterations in testis histopathology (300 and 900 mg/kg/day) were more severe in SD than in LE rats. Taken together, these results suggest that DEHP may be acting on the pubertal male rat testis via two modes of action; one via the Leydig cells and the other via the Sertoli cells. Treatment with DEHP generally reduced serum testosterone and increased serum luteinizing hormone (LH) levels, demonstrating that the reduction in testosterone was due to the effect of DEHP on the testis and not via an inhibition of LH from hypothalamic-pituitary axis. Testosterone production ex vivo (with and without human chorionic gonadotropin stimulation) was consistently reduced in males at the time of puberty and shortly thereafter. DEHP treatment did not accelerate the age at puberty or enhance testosterone levels at 10 or 100 mg/kg/day in either LE or SD rats, as some have hypothesized. Taken together, these results do not provide any evidence of a nonmonotonic dose response to DEHP during puberty.

  3. Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks.

    PubMed

    Boudreau, Mary D; Imam, Mohammed S; Paredes, Angel M; Bryant, Matthew S; Cunningham, Candice K; Felton, Robert P; Jones, Margie Y; Davis, Kelly J; Olson, Greg R

    2016-03-01

    There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon.

  4. Safety evaluation of the human-identical milk monosaccharide sialic acid (N-acetyl-d-neuraminic acid) in Sprague-Dawley rats.

    PubMed

    Choi, Sharon S H; Baldwin, Nigel; Wagner, Valentine O; Roy, Shambhu; Rose, Jennifer; Thorsrud, Bjorn A; Phothirath, Phoukham; Röhrig, Christoph H

    2014-11-01

    N-Acetyl-d-neuraminic acid (Neu5Ac) is the predominant form of sialic acid (Sia) in humans, while other mammals express Sia as a mixture with N-glycolyl-d-neuraminic acid (Neu5Gc). Neu5Ac occurs in highest levels in the brain and in breast milk, and is therefore, coined a human-specific milk monosaccharide, and is thought to play an important nutritional role in the developing infant. Synthesized human-identical milk monosaccharide (HiMM) Neu5Ac is proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of HiMM Neu5Ac, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague-Dawley rats. Neu5Ac was without maternal toxicity or compound-related adverse effects on female reproduction and on the general growth and development of offspring at a maternal dietary level of up to 2%, equivalent to a dose of 1895mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 2% (highest level tested), corresponding to doses of 974 and 1246mg/kgbw/day in males and females, respectively. Neu5Ac also was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of Neu5Ac both in infant formula and as a food ingredient at levels equivalent to those found naturally in human breast milk. PMID:25111575

  5. Chocolate matrix factors modulate the pharmacokinetic behavior of cocoa flavan-3-ol phase II metabolites following oral consumption by Sprague-Dawley rats.

    PubMed

    Neilson, Andrew P; Sapper, Teryn N; Janle, Elsa M; Rudolph, Ralf; Matusheski, Nathan V; Ferruzzi, Mario G

    2010-06-01

    The impact of carbohydrates and milk on the bioavailability of catechin (C) and epicatechin (EC) from chocolate has been previously studied. However, little data exist regarding potential modulation of the phase II metabolism by these chocolate matrix factors. The objectives of this study were to assess the impact of matrix composition on qualitative and quantitative profiles of circulating catechins and their metabolites following administration of commercially relevant chocolate confections. Sprague-Dawley rats were administered 1.5 g of a confection (reference dark, high sucrose, or milk chocolate) by intragastric gavage, and plasma samples were collected over 8 h. High-performance liquid chromatography-mass spectrometry analysis was performed to quantify C, EC, and their metabolites. The predominant metabolites were O-glucuronides (two metabolites) and O-Me-O-glucuronides (three metabolites). Plasma concentrations of metabolites were generally the highest for high sucrose treatment and lowest for milk treatment, while the reference dark treatment generally resulted in intermediate concentrations. The O-Me-(+/-)-C/EC-O-beta-glucuronide (peak 4) was significantly higher for the high sucrose treatment (2325 nM h) versus the milk treatment (1300 nM h). Additionally, C(MAX) values for (+/-)-C/EC-O-beta-glucuronide (peak 3) and two O-Me-(+/-)-C/EC-O-beta-glucuronides (peaks 4 and 6) were significantly higher for the high sucrose treatment (4012, 518, and 2518 nM, respectively) versus the milk treatment (2590, 240, and 1670 nM, respectively). Milk and sucrose appear to modulate both metabolism and plasma pharmacokinetics and, to a lesser extent, the overall bioavailability of catechins from chocolate confections. PMID:20446738

  6. Effects of early and late adverse experiences on morphological characteristics of Sprague-Dawley rat liver subjected to stress during adulthood

    PubMed Central

    Vásquez, Bélgica; Sandoval, Cristian; Smith, Ricardo Luiz; del Sol, Mariano

    2014-01-01

    The literature indicates that early rupture of the maternal bond and social isolation are variables involved in social and emotional behaviors and in increase in anxiety, particularly in stressful situations. The liver plays a role in the adaptation to stress, yet the possible morphologic changes that its structure can suffer have been studied very little. Therefore, the aim here was to ascertain, through the model of altering the early mother-infant bond and the late social bond through isolation, the effect on the stereologic characteristics of the liver in adult Sprague-Dawley rats subjected to intermittent chronic stress. Twenty-five newborn female rats were used, distributed into 5 groups, under standardized lactation and feeding conditions. The experimental groups were exposed to early (E1), late (E2), and early-late (E3) adverse experiences and then subjected to intermittent chronic stress in adulthood. The liver of each animal was isolated, and the stereologic characteristics of Nv, Vv, and Sv of the hepatocytes were determined. The results from the experimental groups were significantly higher than those obtained in the control groups. The highest values were found in group E3 (Nv = 4.43 ± 0.89 x 105/mm3, Vv = 68.74 ± 2.01%, Sv = 68.78 ± 3.77 mm2/mm3). Considering these results, the hepatic morphology can be affected by exposure to chronic stress; however, when the individuals have been subjected to previous adverse experiences, the changes are more evident. PMID:25197335

  7. Differences in Retinal Structure and Function between Aging Male and Female Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle

    PubMed Central

    Chaychi, Samaneh; Polosa, Anna; Lachapelle, Pierre

    2015-01-01

    Purpose Biological sex and age are considered as two important factors that may influence the function and structure of the retina, an effect that might be governed by sexual hormones such as estrogen. The purpose of this study was to delineate the influence that biological sex and age exert on the retinal function and structure of rodents and also clarify the effect that the estrus cycle might exert on the retinal function of female rats. Method The retinal function of 50 normal male and female albino Sprague-Dawley (SD) rats was investigated with the electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 5–6 male and female rats/age). Following the ERG recording sessions, retinal histology was performed in both sexes. In parallel, the retinal function of premenopausal and menopausal female rats aged P540 were also compared. Results Sex and age-related changes in retinal structure and function were observed in our animal model. However, irrespective of age, no significant difference was observed in ERG and retinal histology obtained from male and female rats. Notwithstanding the above we did however notice that between P60 and P200 there was a gradual increase in ERG amplitudes of female rats compared to males. Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was larger compared to age-matched menopausal female rats as well as that of male rats. Conclusion Our results showed that biological sex and age can influence the retinal function and structure of albino SD rats. Furthermore, we showed that cycled female rats have better retinal function compared to the menopausal female rats suggesting a beneficial effect of the estrus cycle on the retinal function. PMID:26317201

  8. Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

    SciTech Connect

    Fonsart, Julien ||; Menet, Marie-Claude |; Decleves, Xavier ||; Galons, Herve |; Crete, Dominique; Debray, Marcel; Scherrmann, Jean-Michel ||; Noble, Florence ||

    2008-07-01

    The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg{sup -1} sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences.

  9. Pattern of deposition of stainless steel welding fume particles inhaled into the respiratory systems of Sprague-Dawley rats exposed to a novel welding fume generating system.

    PubMed

    Yu, I J; Kim, K J; Chang, H K; Song, K S; Han, K T; Han, J H; Maeng, S H; Chung, Y H; Park, S H; Chung, K H; Han, J S; Chung, H K

    2000-07-27

    In order to investigate occupational diseases related to welding fume exposure, such as nasal septum perforation, pneumoconiosis and manganese intoxication, we built a welding fume exposure system that included a welding fume generator, exposure chamber and fume collector. The fume concentrations in the exposure chamber were monitored every 15 min during a 2-h exposure. Fume (mg/m(3)) concentrations of major metals, including Fe, Mn, Cr, and Ni were found to be consistently maintained. An acute inhalation toxicity study was conducted by exposing male Sprague-Dawley rats to the welding fumes generated in this apparatus by stainless steel arc welding. The rats were exposed in the inhalation chamber to a welding fume with a concentration of 62 mg/m(3) total suspended particulates for 4 h. Animals were sacrificed at 4 h and at 1, 3, 7, 10, and 14 days after exposure. Histopathological examinations were conducted on the animals' upper respiratory tracts, including the nasal pathway and the conducting airway, and on the gas exchange region including the alveolar ducts, alveolar sacs, and alveoli. Diameters of fume particles varied from 0.02 to 0.81 microm and were distributed log normally, with a mean diameter of 0.1 microm and geometric standard deviation of 1.42. Rats exposed to the welding fume for 4 h did not show any significant respiratory system toxicity. The mean particle diameter of 0.1 microm resulted in little adsorption of the welding fume particles in the upper respiratory tract. Particle adsorption took place principally in the lower respiratory tracts, including bronchioles, alveolar ducts, alveolar sacs, and alveoli.

  10. The Effect of Route, Vehicle, and Divided Doses on the Pharmacokinetics of Chlorpyrifos and its Metabolite Trichloropyridinol in Neonatal Sprague-Dawley Rats

    SciTech Connect

    Marty, M. S.; Domoradzki, J. Y.; Hansen, S. C.; Timchalk, Chuck; Bartels, M. J.; Mattsson, Joel L.

    2007-12-01

    There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single vs. divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol (TCP), were measured at multiple times through 24 h. Groups included: single gavage bolus vs. divided gavage doses in corn oil (1 vs 3 times in 24 h), single gavage bolus vs. divided gavage doses in rat milk, and subcutaneous administration in DMSO. These data were compared with lactational exposure of PND 5 pups from dams exposed to CPF in the diet at 5 mg/kg/day for four weeks or published data from dams exposed to daily gavage with CPF at 5 mg/kg/day. Maternal blood CPF levels were an order of magnitude lower from dietary exposure than gavage (1.1 vs 14.8 ng/g), and blood CPF levels in PND 5 pups that nursed dietary-exposed or gavage-exposed dams were below the limit of detection. Single gavage doses of 1 mg/kg CPF in corn oil vehicle in pups resulted in CPF blood levels of 49 ng/g, and in milk vehicle about 9 ng/g. Divided doses led to lower peak CPF levels. A bolus dose of 1 mg/kg CPF in DMSO administered sc appeared to have substantially altered pharmacokinetics from orally administered chlorpyrifos. To be meaningful for risk assessment, neonatal studies require attention to the exposure scenario, since route, vehicle, dose and frequency of administration result in different systemic exposure to the test chemical and its metabolites.

  11. Adverse effects of bisphenol A (BPA) on the dopamine system in two distinct cell models and corpus striatum of the Sprague-Dawley rat.

    PubMed

    Nowicki, Brittney A; Hamada, Matt A; Robinson, Gina Y; Jones, Douglas C

    2016-01-01

    The aim of this study was to examine the effects of bisphenol A (BPA) on the brain dopamine (DA) system utilizing both in vitro models (GH3 cells, a rat pituitary cell line, and SH-SY5Y cells, a human neuroblastoma cell line) and an animal model such as Sprague-Dawley (SD) rats. First, cellular DA uptake was measured 2 or 8 h following BPA exposure (0.1-400 μM) in SH-SY5Y cells, where a significant increase in DA uptake was noted. BPA exerted no marked effect on dopamine active transporter levels in GH3 cells exposed for 8 or 24 h. However, SH-SY5Y cells displayed an increase in dopamine transporter (DAT) levels following 24 h of exposure to BPA. In contrast to DAT levels, BPA exposure produced no marked effect on DA D1 receptor levels in SH-SY5Y cells, yet a significant decrease in GH3 cells following both 8- and 24-h exposure periods was noted, suggesting that BPA exerts differential effects dependent upon cell type. BPA produced no significant effects on prolactin levels at 2 h, but a marked fall occurred at 24 h of exposure in GH3 cells. Finally, to examine the influence of dietary developmental exposure to BPA on brain DA levels in F1 offspring, SD rats were exposed to BPA (0.5-20 mg/kg) through maternal transfer and/or diet and striatal DA levels were measured on postnatal day (PND) 60 using high-performance liquid chromatography (HPLC). Data demonstrated that chronic exposure to BPA did not significantly alter striatal DA levels in the SD rat. PMID:27494678

  12. Comparison of the toxicity profiles of ISIS 1082 and ISIS 2105, phosphorothioate oligonucleotides, following subacute intradermal administration in Sprague-Dawley rats.

    PubMed

    Henry, S P; Grillone, L R; Orr, J L; Bruner, R H; Kornbrust, D J

    1997-01-15

    The systemic toxicity of two phosphorothioate oligonucleotides specific for herpes simplex viruses (ISIS 1082) and human papiloma virus (ISIS 2105) were evaluated following repeated intradermal injections of vehicle control, 0.33, 2.17, or 21.7 mg/kg daily to Sprague-Dawley rats (10/sex/group) for 14 days. Animals were sacrificed 1 day after the last dose, except for a portion of the ISIS 1082-treated animals (5/sex/group) which were maintained for an additional 14-day recovery period. The profile of alterations noted for both compounds was very similar. Other than local signs of irritation at the site of injection, there were no clinical signs of toxicity or treatment-related mortality, but there was a slight decrease in body weight gain for the 21.7 mg/kg dose groups. Alterations in hematology parameters included dose-dependent thrombocytopenia and anemia. Alterations in serum chemistry parameters were suggestive of mild alterations in hepatic metabolism, with increases in liver transaminases and bilirubin, along with decreases in albumin and cholesterol. Both spleen and liver weights were significantly elevated in a dose-dependent fashion. Histopathological alterations noted in liver, kidney, lung, injection site skin, and spleen were characterized as perivascular and interstitial infiltrates of macrophages and monocytes. Additional microscopic alterations in the spleen included mild lymphoid hyperplasia (seen in lymph nodes as well), and extramedullary hematopoiesis. Treatment-related cytopenias were likely related to mild, focal hypocellularity in the bone marrow. Alterations in ISIS 1082-treated animals were only partially reversed following the 14-day treatment-free period. In conclusion, repeated intradermal administration of ISIS 1082 and ISIS 2105 produced a similar spectrum of toxicities, with liver, kidney, spleen, and bone marrow being identified as target tissues.

  13. Adenosine protects Sprague Dawley rats from high-fat diet and repeated acute restraint stress-induced intestinal inflammation and altered expression of nutrient transporters.

    PubMed

    Lee, C Y

    2015-04-01

    This study investigated the effect of repeated acute restraint stress and high-fat diet (HFD) on intestinal expression of nutrient transporters, concomitant to intestinal inflammation. The ability of adenosine to reverse any change was examined. Six-week-old male Sprague Dawley rats were divided into eight groups: control or non-stressed (C), rats exposed to restraint stress for 6 h per day for 14 days (S), control rats fed with HFD (CHF) and restraint-stressed rats fed with HFD (SHF); four additional groups received the same treatments and were also given 50 mg/l adenosine dissolved in drinking water. Fasting blood glucose, plasma insulin, adiponectin and corticosterone were measured. Intestinal expression of SLC5A1, SLC2A2, NPC1L1 and TNF-α was analysed. Histological evaluation was conducted to observe for morphological and anatomical changes in the intestinal tissues. Results showed that HFD feeding increased glucose and insulin levels, and repeated acute restraint stress raised the corticosterone level by 22%. Exposure to both stress and HFD caused a further increase in corticosterone to 41%, while decreasing plasma adiponectin level. Restraint stress altered intestinal expression of SLC5A1, SLC2A2 and NPC1L1. These changes were enhanced in SHF rats. Adenosine was found to alleviate HFD-induced increase in glucose and insulin levels, suppress elevation of corticosterone in S rats and improve the altered nutrient transporters expression profiles. It also prevented upregulation of TNF-α in the intestine of SHF rats. In summary, a combination of stress and HFD exaggerated stress- and HFD-induced pathophysiological changes in the intestine, and biochemical parameters related to obesity. Adenosine attenuated the elevation of corticosterone and altered expression of SLC5A1, NPC1L1 and TNF-α.

  14. Differential Effects of Silver Nanoparticles and Silver Ions on Tissue Accumulation, Distribution, and Toxicity in the Sprague Dawley Rat Following Daily Oral Gavage Administration for 13 Weeks.

    PubMed

    Boudreau, Mary D; Imam, Mohammed S; Paredes, Angel M; Bryant, Matthew S; Cunningham, Candice K; Felton, Robert P; Jones, Margie Y; Davis, Kelly J; Olson, Greg R

    2016-03-01

    There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon. PMID:26732888

  15. Brain-targeted distribution and high retention of silver by chronic intranasal instillation of silver nanoparticles and ions in Sprague-Dawley rats.

    PubMed

    Wen, Ruoxi; Yang, Xiaoxi; Hu, Ligang; Sun, Cheng; Zhou, Qunfang; Jiang, Guibin

    2016-03-01

    The wide applications of silver nanoparticles (AgNPs) have been concerned regarding their unintentional toxicities. Different exposure modes may cause distinct accumulation, retention and elimination profiles, which are closely related with their toxicities. Unlike silver accumulation profiles through other regular administration modes, the biodistribution, accumulation and elimination of AgNPs by intranasal instillation are not fully understood. This study conducted intranasal instillation of polyvinylpyrrolidone-coated AgNPs in neonatal Sprague-Dawley rats at doses of 1 and 0.1 mg kg(-1) day(-1) for 4 and 12 weeks, respectively. The 4-week recovery was also designed after the 12-week exposure. Silver concentrations in the main tissues or organs were periodically monitored. Parallel exposures using silver ion were performed for the comparative studies. No physiological alterations were observed in AgNP exposures. In comparison, 1 mg kg(-1) day(-1) silver ions decreased body weight gain and caused mortality of 18.2%, showing ionic silver had a relatively higher toxicity than AgNPs. A relatively higher silver accumulation was observed in silver ion groups than AgNP groups. The silver ion release could not fully explain silver accumulation in AgNP exposures, showing silver distribution caused by particulate silver occurred in vivo. The highest silver concentration was in the liver at week 4, while it shifted to the brain after a 12-week exposure. Dose-related silver accumulation occurred for both AgNP and silver ion groups. The time course revealed a uniquely high concentration and retention of brain silver, implying chronic intranasal instillation caused brain-targeted silver accumulation. These findings provided substantial evidence on the potential neuronal threat from the intranasal administration of AgNPs or silver colloid-based products.

  16. Evaluation of memory enhancing clinically available standardized extract of Bacopa monniera on P-glycoprotein and cytochrome P450 3A in Sprague-Dawley rats.

    PubMed

    Singh, Rajbir; Panduri, Jagadeesh; Kumar, Devendra; Kumar, Deepak; Chandsana, Hardik; Ramakrishna, Rachumallu; Bhatta, Rabi Sankar

    2013-01-01

    Bacopa monniera is a traditional Ayurvedic herbal medicine used to treat various mental ailments from ancient times. Recently, chemically standardized alcoholic extract of Bacopa monniera (BM) has been developed and currently available as over the counter herbal remedy for memory enhancement in children and adults. However, the consumption of herbal drugs has been reported to alter the expression of drug metabolizing enzymes and membrane transporters. Present study in male Sprague-Dawley rat was performed to evaluate the effect of memory enhancing standardized extract of BM on hepatic and intestinal cytochrome P450 3A and P-glycoprotein expression and activity. The BM (31 mg/kg/day) was orally administered for one week in BM pre-treated group while the control group received the same amount of vehicle for the same time period. The BM treatment decreased the cytochrome P450 3A (CYP3A) mediated testosterone 6β-hydroxylation activity of the liver and intestine by 2 and 1.5 fold, respectively compared to vehicle treated control. Similarly pretreatment with BM extract decreased the expression of intestinal P-glycoprotein (Pgp) as confirmed by Western blot analysis but did not alter the expression of hepatic Pgp. To investigate whether this BM pretreatment mediated decrease in activity of CYP3A and Pgp would account for the alteration of respective substrate or not, pharmacokinetic study with carbamazepine and digoxin was performed in BM pre-treated rats and vehicle treated rats. Carbamazepine and digoxin were used as CYP3A and Pgp probe drugs, respectively. Significant increase in AUC and Cmax of carbamazepine (4 and 1.8 fold) and digoxin (1.3 and 1.2 fold), respectively following the BM pre-treatment confirmed the down regulation of CYP3A and Pgp.

  17. The effect of ACE inhibition on the pulmonary vasculature in combined model of chronic hypoxia and pulmonary arterial banding in Sprague Dawley rats

    NASA Astrophysics Data System (ADS)

    Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert

    2010-03-01

    Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular

  18. Adverse effects of bisphenol A (BPA) on the dopamine system in two distinct cell models and corpus striatum of the Sprague-Dawley rat.

    PubMed

    Nowicki, Brittney A; Hamada, Matt A; Robinson, Gina Y; Jones, Douglas C

    2016-01-01

    The aim of this study was to examine the effects of bisphenol A (BPA) on the brain dopamine (DA) system utilizing both in vitro models (GH3 cells, a rat pituitary cell line, and SH-SY5Y cells, a human neuroblastoma cell line) and an animal model such as Sprague-Dawley (SD) rats. First, cellular DA uptake was measured 2 or 8 h following BPA exposure (0.1-400 μM) in SH-SY5Y cells, where a significant increase in DA uptake was noted. BPA exerted no marked effect on dopamine active transporter levels in GH3 cells exposed for 8 or 24 h. However, SH-SY5Y cells displayed an increase in dopamine transporter (DAT) levels following 24 h of exposure to BPA. In contrast to DAT levels, BPA exposure produced no marked effect on DA D1 receptor levels in SH-SY5Y cells, yet a significant decrease in GH3 cells following both 8- and 24-h exposure periods was noted, suggesting that BPA exerts differential effects dependent upon cell type. BPA produced no significant effects on prolactin levels at 2 h, but a marked fall occurred at 24 h of exposure in GH3 cells. Finally, to examine the influence of dietary developmental exposure to BPA on brain DA levels in F1 offspring, SD rats were exposed to BPA (0.5-20 mg/kg) through maternal transfer and/or diet and striatal DA levels were measured on postnatal day (PND) 60 using high-performance liquid chromatography (HPLC). Data demonstrated that chronic exposure to BPA did not significantly alter striatal DA levels in the SD rat.

  19. Evaluation of Memory Enhancing Clinically Available Standardized Extract of Bacopa monniera on P-Glycoprotein and Cytochrome P450 3A in Sprague-Dawley Rats

    PubMed Central

    Singh, Rajbir; Panduri, Jagadeesh; Kumar, Devendra; Kumar, Deepak; Chandsana, Hardik; Ramakrishna, Rachumallu; Bhatta, Rabi Sankar

    2013-01-01

    Bacopa monniera is a traditional Ayurvedic herbal medicine used to treat various mental ailments from ancient times. Recently, chemically standardized alcoholic extract of Bacopa monniera (BM) has been developed and currently available as over the counter herbal remedy for memory enhancement in children and adults. However, the consumption of herbal drugs has been reported to alter the expression of drug metabolizing enzymes and membrane transporters. Present study in male Sprague-Dawley rat was performed to evaluate the effect of memory enhancing standardized extract of BM on hepatic and intestinal cytochrome P450 3A and P-glycoprotein expression and activity. The BM (31 mg/kg/day) was orally administered for one week in BM pre-treated group while the control group received the same amount of vehicle for the same time period. The BM treatment decreased the cytochrome P450 3A (CYP3A) mediated testosterone 6β-hydroxylation activity of the liver and intestine by 2 and 1.5 fold, respectively compared to vehicle treated control. Similarly pretreatment with BM extract decreased the expression of intestinal P-glycoprotein (Pgp) as confirmed by Western blot analysis but did not alter the expression of hepatic Pgp. To investigate whether this BM pretreatment mediated decrease in activity of CYP3A and Pgp would account for the alteration of respective substrate or not, pharmacokinetic study with carbamazepine and digoxin was performed in BM pre-treated rats and vehicle treated rats. Carbamazepine and digoxin were used as CYP3A and Pgp probe drugs, respectively. Significant increase in AUC and Cmax of carbamazepine (4 and 1.8 fold) and digoxin (1.3 and 1.2 fold), respectively following the BM pre-treatment confirmed the down regulation of CYP3A and Pgp. PMID:24015255

  20. The impact of cafeteria diet feeding on physiology and anxiety-related behaviour in male and female Sprague-Dawley rats of different ages.

    PubMed

    Warneke, Wiebke; Klaus, Susanne; Fink, Heidrun; Langley-Evans, Simon C; Voigt, Jörg-Peter

    2014-01-01

    There is emerging experimental evidence that hyper-energetic diets not only cause obesity but also impact on behaviour in rodents. A hyper-energetic comfort diet/cafeteria diet (CD) fed during early development programmes anxiety-related behaviour in adult age, but little is known how an obesogenic CD impacts on behaviour when fed at a later age. To this end we fed CD to Sprague-Dawley rats of both sexes at either 6 weeks or 12 months old, for a period of 6 weeks. Anxiety-related behaviour was assessed in the elevated plus maze (EPM) and the open field (OF). A glucose tolerance test was performed and metabolic indices, body weight and fat were measured. CD-fed young adult females, but not males, had a higher energy intake, due to an overconsumption of carbohydrates and fats. Only in adult CD-fed rats of both sexes did this overconsumption led to increased weight gain. Protein intake was reduced in all CD groups. Fat mass (subcutaneous, perirenal, gonadal) increased in most CD groups, whereas brown fat increased only in adults. Triacylglycerol, free fatty acid and total cholesterol concentrations increased predominantly in adult CD-fed rats. Glucose tolerance was only impaired in adult males. CD-fed adult males showed fewer entries into the aversive open arms and groomed more on the EPM, whereas adult females spent more time on these arms. In the OF, CD-fed females of both ages visited the inner zone more frequently and travelled a longer distance. The behavioural data suggests anxiolysis in CD-fed females and signs of increased anxiety in adult males. In conclusion, this study demonstrates that feeding CD leads to both obesity and behavioural changes in rats. Overall, these effects were more pronounced in older rats, with the behavioural effects being particularly gender dependent.

  1. Development and application of an analytical method for curdione quantification in pregnant Sprague-Dawley rats by LC-MS/MS.

    PubMed

    Meng, Xiang; Zhang, Ting; Li, Ying; Pan, Qi; Jiang, Juan; Luo, Yongwei; Chong, Liming; Yang, Yang; Xu, Sichong; Zhou, Li; Sun, Zuyue

    2015-10-01

    The vaginal administration route suffers from relatively low absorption efficiency, which may hinder the identification of the toxicokinetics of curdione in pregnant women. A sensitive analytical method for determining the plasma concentration of curdione was developed and applied in the determination of curdione in pregnant Sprague-Dawley rats as a simulated model. Glimepiride was used as an internal standard and chromatographic separation was achieved on a Capcell Pak C18 MGIII column. A gradient elution profile with 0.5% formic acid (A)-0.5% formic acid-acetonitrile (B) was selected as mobile phase. The selected reaction monitoring mode was used for quantification based on the target fragment ions m/z 237.2 to m/z 135.1 for curdione and m/z 491.3 to m/z 352.1 for the glimepiride. The standard curve was linear over the range of 0.5-500 ng/mL for curdione in rat plasma and yielded a consistent peak pattern, even at the lower limit of quantitation of 0.5 ng/mL. The retention times of curdione and IS were 6.55 and 6.59 min, respectively. The mean recovery of curdione in rat plasma was 95.5-101.1%. The intra-day and inter-day precisions were between 2.35 and 9.08%. This LC-MS/MS method provides a simple and sensitive means for determining the plasma concentration. PMID:25736727

  2. Individual differences in cocaine-induced locomotor activity of male Sprague-Dawley rats are not explained by plasma corticosterone levels

    PubMed Central

    Nelson, Anna M.; Kleschen, Melissa J.; Zahniser, Nancy R.

    2010-01-01

    Humans differ in their initial response to, and subsequent abuse of, addictive drugs like cocaine. Rodents also exhibit marked individual differences in responsiveness to cocaine. Previously, we classified male Sprague-Dawley rats as either low or high cocaine responders (LCRs or HCRs, respectively), based on their acute low-dose cocaine-induced locomotor activity, and found that with repeated drug exposure LCRs exhibit greater cocaine locomotor sensitization, reward and reinforcement than HCRs. Differential cocaine-induced increases in striatal dopamine help to explain the LCR/HCR phenotypes. Differential levels of stress and/or anxiety could also contribute but have not been explored. Here we measured open-field activity and plasma corticosterone levels both pre- and post-cocaine treatment in LCRs, HCRs, and saline-treated controls. The three groups did not differ in baseline locomotor activity or corticosterone levels. Importantly, LCR/HCR differences in corticosterone levels were also not observed following acute cocaine (10 mg/kg, i.p.), when cocaine induced approximately 3.5-fold greater locomotor activity in HCRs than LCRs. Additionally, there were no LCR/HCR differences in plasma corticosterone levels following five days of once-daily cocaine, during which time LCRs developed locomotor sensitization such that their cocaine-induced locomotor activity no longer differed from that of HCRs. Likewise, there were no group activity differences in any of four concentric zones within the open-field chamber. In summary, neither plasma corticosterone levels nor thigmotaxis-type anxiety appears to be a factor that contributes to the observed cocaine-induced LCR/HCR behavioral differences. PMID:20302913

  3. Manifestation of the Se, Cd and Mo levels in different components of the peripheral blood of Sprague-Dawley rats poisoned via the respiratory tract.

    PubMed

    Wang, Dong-Fang; Sun, Xuan; Cao, Bing; Wen, Hua; Zhang, Yu; Liu, Duo-Jian; Yan, Lai-Lai; Liu, Ya-Qiong; Lu, Qing-Bin; Wang, Jing-Yu

    2015-01-01

    This study aimed to explore the effects of exogenous element exposure via the respiratory tract on the Se, Cd and Mo concentrations in different components of the peripheral blood in rats as well as to determine the correlations of the three trace elements concentrations among the components. The Sprague-Dawley rats were randomly divided into a control group and several experimental groups treated with different doses. The rats were exposed to a mixed trace element solution through 10 days of intratracheal instillation. The whole blood of all rats was collected and separated into three parts with Percoll density gradient centrifugation. The Se, Cd and Mo levels in whole blood, plasma, red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were determined by inductively coupled plasma mass spectrometry. The concentrations of the three trace elements increased together with the increase of the given doses (P<0.05), except Cd and Mo in the PBMCs. The three trace elements lacked linearity with the exposure doses in the PBMCs (r, 0.249-0.508), while the opposite was the case for the other components of the peripheral blood (r, 0.806-0.934). The correlation coefficients were higher (0.842-0.962) among the whole blood, plasma and RBCs than between PBMCs and other components, such as Se (0.376-0.529), Cd (0.495-0.604) and, especially, Mo (0.160-0.257). In conclusion, PBMCs might provide information about endogenous factors, and whole blood could more accurately reflect the effects of exogenous factors compared to other blood components. PMID:26770359

  4. The effect of the degree of left renal vein constriction on the development of adolescent varicocele in Sprague-Dawley rats.

    PubMed

    Yao, Bing; Zhou, Wen-Liang; Han, Da-Yu; Ouyang, Bin; Chen, Xu; Chen, Sheng-Fu; Deng, Chun-Hua; Sun, Xiang-Zhou

    2016-01-01

    Experimental models have allowed inquiry into the pathophysiology of varicocele (VC) beyond that possible with human patients. A randomized controlled study in rats was designed to clarify the influence of the degree of left renal vein constriction on the development of adolescent VC. Fifty adolescent male Sprague-Dawley rats (Rattus norvegicus) were randomly assigned to five groups of 10: the experimental groups (I-IV) underwent partial ligation of left renal veins with 0.5-, 0.6-, 0.7-, and 0.8-mm diameter needles, respectively. The control group (V) underwent a sham operation. The diameter of the left spermatic vein (LSV) was measured at baseline and 30 days postoperatively. In addition, the lesion of the left kidney was examined with the naked eye and assessed by Masson's trichrome staining. VC was successfully induced in 2 (20%), 4 (40%), 7 (70%), and 10 (100%) rats in groups I-IV, respectively. The other rats failed to develop VCs primarily due to left renal atrophy. No VC was observed in group V. The postsurgical LSV diameters in VC rats in groups III and IV were 1.54 ± 0.16 and 1.49 ± 0.13 mm, respectively (P > 0.05), and their increments were 1.36 ± 0.10 and 1.31 ± 0.10 mm, respectively (P > 0.05). These results suggest that suitable constriction of the left renal vein is critical for adolescent VC development. In addition, the 0.8-mm diameter needle may be more suitable for inducing left renal vein constriction in adolescent rat models. PMID:26262773

  5. Safety evaluation of the human-identical milk monosaccharide sialic acid (N-acetyl-d-neuraminic acid) in Sprague-Dawley rats.

    PubMed

    Choi, Sharon S H; Baldwin, Nigel; Wagner, Valentine O; Roy, Shambhu; Rose, Jennifer; Thorsrud, Bjorn A; Phothirath, Phoukham; Röhrig, Christoph H

    2014-11-01

    N-Acetyl-d-neuraminic acid (Neu5Ac) is the predominant form of sialic acid (Sia) in humans, while other mammals express Sia as a mixture with N-glycolyl-d-neuraminic acid (Neu5Gc). Neu5Ac occurs in highest levels in the brain and in breast milk, and is therefore, coined a human-specific milk monosaccharide, and is thought to play an important nutritional role in the developing infant. Synthesized human-identical milk monosaccharide (HiMM) Neu5Ac is proposed for use in infant formulas to better simulate the free saccharides present in human breast milk. As part of the safety evaluation of HiMM Neu5Ac, a subchronic dietary toxicity study preceded by an in utero phase was conducted in Sprague-Dawley rats. Neu5Ac was without maternal toxicity or compound-related adverse effects on female reproduction and on the general growth and development of offspring at a maternal dietary level of up to 2%, equivalent to a dose of 1895mg/kg body weight (bw)/day. During the subchronic phase, no compound-related adverse effects were observed in first generation rats at dietary levels of up to 2% (highest level tested), corresponding to doses of 974 and 1246mg/kgbw/day in males and females, respectively. Neu5Ac also was non-genotoxic in a series of in vitro genotoxicity/mutagenicity tests. These results support the safe use of Neu5Ac both in infant formula and as a food ingredient at levels equivalent to those found naturally in human breast milk.

  6. The effect of cloudy apple juice on hepatic and mammary gland phase I and II enzymes induced by DMBA in female Sprague-Dawley rats.

    PubMed

    Szaefer, Hanna; Krajka-Kuźniak, Violetta; Ignatowicz, Ewa; Adamska, Teresa; Markowski, Jarosław; Baer-Dubowska, Wanda

    2014-10-01

    Apples abundant in phenolic compounds show a variety of biological activities that may contribute to health beneficial effects against cardiovascular diseases, diabetes, obesity and cancer. We investigated the effect of cloudy apple juice (CAJ) on the hepatic and mammary gland carcinogen metabolizing enzymes, DNA damage and liver injury, altered by 7,12-dimethylbenz[a]anthracene (DMBA). Sprague-Dawley female rats were gavaged with CAJ (10 ml/kg b.w.) for 28 consecutive days. DMBA was administered i.p. on the 27th and the 28th days. In the liver, feeding with CAJ decreased the activities of CYP1A1 and 1A2 and increased phase II enzymes. The activities of all enzymes tested were enhanced in the animals treated with DMBA alone and in combination with CAJ. The most significant changes in the level of the hepatic enzymes tested were observed for GST alpha and NQO1. In mammary gland CAJ induced an increase in the level of GST mu and GST pi, while DMBA and CAJ combined administration elevated GST pi only. This may be beneficial as GST pi is involved in the DMBA detoxification. Additionally, pretreatment with CAJ reduced the level of most of the blood biochemical liver and kidney markers elevated as a result of DMBA treatment. These findings indicate that CAJ may interfere with enzyme system involved in carcinogen metabolism. However, this effect seems to be dependent on tissue and carcinogen and is moderately effective in the case of DMBA. Moreover, CAJ can also provide some protection against the liver and kidney damage.

  7. Early ethanol and water intake: choice mechanism and total fluid regulation operate in parallel in male alcohol preferring (P) and both Wistar and Sprague Dawley rats.

    PubMed

    Azarov, Alexey V; Woodward, Donald J

    2014-01-17

    The goal of this study was to clarify similar and distinctly different parameters of fluid intake during early phases of ethanol and water choice drinking in alcohol preferring P-rat vs. non-selected Wistar and Sprague Dawley (SD) rats. Precision information on the drinking amounts and timing is needed to analyze micro-behavioral components of the acquisition of ethanol intake and to enable a search for its causal activity patterns within individual CNS circuits. The experiment followed the standard ethanol-drinking test used in P-rat selective breeding, with access to water, then 10% ethanol (10E) as sole fluids, and next to ethanol/water choice. The novelty of the present approach was to eliminate confounding prandial elevations of fluid intake, by time-separating daily food from fluid access. P-rat higher initial intakes of water and 10E as sole fluids suggest adaptations to ethanol-induced dehydration in P vs. Wistar and SD rats. P-rat starting and overall ethanol intake during the choice period were the highest. The absolute extent of ethanol intake elevation during choice period was greatest in Wistar and their final intake levels approached those of P-rat, contrary to the hypothesis that selection would produce the strongest elevation of ethanol intake. The total daily fluid during ethanol/water choice period was strikingly similar between P, Wistar and SD rats. This supports the hypothesis for a universal system that gauges the overall intake volume by titrating and integrating ethanol and water drinking fluctuations, and indicates a stable daily level of total fluid as a main regulated parameter of fluid intake across the three lines in choice conditions. The present findings indicate that a stable daily level of total fluid comprises an independent physiological limit for daily ethanol intake. Ethanol drinking, in turn, stays under the ceiling of this limit, driven by a parallel mechanism of ethanol/water choice.

  8. Early ethanol and water consumption: accumulating experience differentially regulates drinking pattern and bout parameters in male alcohol preferring (P) vs. Wistar and Sprague Dawley rats.

    PubMed

    Azarov, Alexey V; Woodward, Donald J

    2014-01-17

    Alcohol-preferring (P) rats develop high ethanol intake over several weeks of water/10% ethanol (10E) choice drinking. However, it is not yet clear precisely what components of drinking behavior undergo modification to achieve higher intake. Our concurrent report compared precisely measured daily intake in P vs. non-selected Wistar and Sprague Dawley (SD) rats. Here we analyze their drinking patterns and bouts to clarify microbehavioral components that are common to rats of different genetic backgrounds, vs. features that are unique to each. Under sole-fluid conditions P, Wistar and SD rats all consumed water at a high initial rate followed by a slow maintenance phase, but 10E - in a distinctly different step-like pattern of evenly distributed bouts. During choice period, 10E vs. water patterns for P rat appeared as an overlap of sole-fluid patterns. The SD rat choice patterns resembled sole-fluid patterns but were less regular. Choice patterns in Wistar differed from both P and SD rats, by consisting of intermixed small frequent episodes of drinking both 10E and water. Wistar and SD rats increased choice ethanol intake by elevating the number of bouts. A key finding was that P rat increased choice ethanol intake through a gradual increase of the bout size and duration, but kept bout number constant. This supports the hypothesis that genetic selection modifies microbehavioral machinery controlling drinking bout initiation, duration, and other pattern features. Precision analysis of drinking patterns and bouts allows differentiation between genetic lines, and provides a venue for study of localized circuit and transmitter influences mediating mesolimbic control over ethanol consumption.

  9. Prenatal stress and early life febrile convulsions compromise hippocampal genes MeCP2/REST function in mid-adolescent life of Sprague-Dawley rats.

    PubMed

    Cassim, Sadiyah; Qulu, Lihle; Mabandla, Musa V

    2015-11-01

    Early life neuronal insults exacerbate the development of febrile seizures and can result in epigenetic changes in the hippocampus. The MeCP2 and REST genes play a pivotal role in cognition as both contribute to neuronal function. In this study, cognitive function and expression of the MeCP2 and REST genes in the hippocampus were investigated in four groups of Sprague Dawley rats offspring viz. (1) Normally reared treated with saline (NSS). (2) Prenatally stressed treated with saline (SS). (3) Normally reared with febrile seizures (NSFS). (4) Prenatally stressed with febrile seizures (SFS). Pregnant dams were subjected to 1h of restraint stress for 7days starting on gestational day 14. Following birth, a once-off exposure to saline injections or febrile seizure induction was conducted on postnatal day (PND) 14. Behavioural tests were conducted using the Morris-Water maze on PND 21 and 30. Our results showed a febrile seizure effect on learning and memory in the non-stressed animals. However, febrile seizures did not exacerbate learning deficits in the prenatally stressed animals. Gene analysis found a down-regulation in MeCP2 gene expression and an up-regulation of the REST gene in prenatally stressed animals. Exposure to febrile seizure resulted in down-regulation of both MeCP2 and REST gene expression in the non-stressed animals, but febrile seizures did not exacerbate the stress effect on gene expression. This suggests that exposure to prenatal stress (SS) and febrile seizures (NSFS) may impair cognitive behavioural function. However, in the NSFS animals, there seems to be an attempt to counteract the effects of febrile seizures with time. PMID:26358644

  10. The Effect of Atrazine Administered by Gavage or in Diet on the LH Surge and Reproductive Performance in Intact Female Sprague-Dawley and Long Evans Rats

    PubMed Central

    Foradori, Chad D; Sawhney Coder, Prägati; Tisdel, Merrill; Yi, Kun Don; Simpkins, James W; Handa, Robert J; Breckenridge, Charles B

    2014-01-01

    Atrazine (ATR) blunts the hormone-induced luteinizing hormone (LH) surge, when administered by gavage (50–100 mg/kg/day for 4 days), in ovariectomized rats. In this study, we determined if comparable doses delivered either by gavage (bolus dose) or distributed in diet would reduce the LH surge and subsequently affect fertility in the intact female rat. ATR was administered daily to intact female Sprague-Dawley (SD) or Long Evans (LE) rats by gavage (0, 0.75 1.5, 3, 6, 10, 12, 50, or 100 mg/kg/day) or diet (0, 30, 100, 160, 500, 660, or 1460 ppm) during one complete 4-day estrous cycle, starting on day of estrus. Estrous status, corpora lutea, ova, and LH plasma concentrations were evaluated. A second cohort of animals was mated on the fourth treatment day. Fertility metrics were assessed on gestational day 20. A higher portion of LE rats had asynchronous estrous cycles when compared to SD rats both during pretreatment and in response to ATR (≥50 mg/kg). In contrast, bolus doses of ATR (≥50 mg/kg) inhibited the peak and area under the curve for the preovulatory LH surge in SD but not LE animals. Likewise, only bolus-treated SD, not LE, rats displayed reduced mean number of corpora lutea and ova. There were no effects of ATR administered by gavage on mating, gravid number, or fetus number. Dietary administration had no effect on any reproductive parameter measured. These findings indicate that short duration, high-bolus doses of ATR can inhibit the LH surge and reduce the number of follicles ovulated; however, dietary administration has no effect on any endocrine or reproductive outcomes PMID:24831581

  11. Alcohol consumption increases basal extracellular glutamate in the nucleus accumbens core of Sprague-Dawley rats without increasing spontaneous glutamate release.

    PubMed

    Pati, Dipanwita; Kelly, Kyle; Stennett, Bethany; Frazier, Charles J; Knackstedt, Lori A

    2016-07-01

    Glutamate neurotransmission in the nucleus accumbens core (NAc) mediates ethanol consumption. Previous studies using non-contingent and voluntary alcohol administration in inbred rodents have reported increased basal extracellular glutamate levels in the NAc. Here, we assessed basal glutamate levels in the NAc following intermittent alcohol consumption in male Sprague-Dawley rats that had access to ethanol for 7 weeks on alternating days. We found increased basal NAc glutamate at 24 h withdrawal from ethanol and thus sought to identify the source of this glutamate. To do so, we employed a combination of microdialysis, slice electrophysiology and western blotting. Reverse dialysis of the voltage-gated sodium channel blocker tetrodotoxin did not affect glutamate levels in either group. Electrophysiological recordings in slices made after 24 h withdrawal revealed a decrease in spontaneous excitatory postsynaptic current (sEPSC) frequency relative to controls, with no change in sEPSC amplitude. No change in metabotropic glutamate receptor 2/3 (mGlu2/3) function was detected as bath application of the mGlu2/3 agonist LY379268 decreased spontaneous and miniature EPSC frequency in slices from both control and ethanol-consuming rats. The increase in basal glutamate was not associated with changes in the surface expression of GLT-1, however, a decrease in slope of the no-net-flux dialysis function was observed following ethanol consumption, indicating a potential decrease in glutamate reuptake. Taken together, these findings indicate that the increase in basal extracellular glutamate occurring after chronic ethanol consumption is not mediated by an increase in action potential-dependent glutamate release or a failure of mGlu2/3 autoreceptors to regulate such release. PMID:27207718

  12. A physiologically based pharmacokinetic/pharmacodynamic model for carbofuran in Sprague-Dawley rats using the exposure-related dose estimating model.

    PubMed

    Zhang, Xiaofei; Tsang, Andy M; Okino, Miles S; Power, Frederick W; Knaak, James B; Harrison, Lynda S; Dary, Curtis C

    2007-12-01

    Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl-N-methylcarbamate), a broad spectrum N-methyl carbamate insecticide, and its metabolite, 3-hydroxycarbofuran, exert their toxicity by reversibly inhibiting acetylcholinesterase (AChE). To characterize AChE inhibition from carbofuran exposure, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was developed in the Exposure-Related Dose Estimating Model (ERDEM) platform for the Sprague-Dawley (SD) rat. Experimental estimates of physiological, biochemical, and physicochemical model parameters were obtained or based on data from the open literature. The PBPK/PD model structure included carbofuran metabolism in the liver to 16 known metabolites, enterohepatic circulation of glucuronic acid conjugates, and excretion in urine and feces. Bolus doses by ingestion of 50 microg/kg and 0.5 mg/kg carbofuran were simulated for the blood and brain AChE activity. The carbofuran ERDEM simulated a half-life of 5.2 h for urinary clearance, and the experimental AChE activity data were reproduced for the blood and brain. Thirty model parameters were found influential to the model outputs and were chosen for perturbation in Monte Carlo simulations to evaluate the impact of their variability on the model predictions. Results of the simulation runs indicated that the minimum AChE activity in the blood ranged from 29.3 to 79.0% (as 5th and 95th percentiles) of the control level with a mean of 55.9% (standard deviation = 15.1%) compared to an experimental value of 63%. The constructed PBPK/PD model for carbofuran in the SD rat provides a foundation for extrapolating to a human model that can be used for future risk assessment.

  13. Nordihydroguaiaretic acid ameliorates cisplatin induced nephrotoxicity and potentiates its anti-tumor activity in DMBA induced breast cancer in female Sprague-Dawley rats.

    PubMed

    Mundhe, Nitin Arunrao; Kumar, Parveen; Ahmed, Sahabuddin; Jamdade, Vinayak; Mundhe, Sanjay; Lahkar, Mangala

    2015-09-01

    Cisplatin is a widely used antineoplastic drug, but its clinical usefulness is limited due to dose dependent nephrotoxicity. Nordihydroguaiaretic acid (NDGA) is a natural compound with broad pharmacological properties like antioxidant, anti-inflammatory and anticancer activity. The present study was undertaken to evaluate the possible beneficial effects of NDGA on cisplatin induced nephrotoxicity as well as its anticancer activity in rats bearing DMBA induced mammary tumors. The effect of NDGA on cisplatin induced nephrotoxicity was evaluated by checking serum nephrotoxicity markers, antioxidant enzymes and inflammatory markers level and kidney histopathology. NDGA induced amelioration of cisplatin nephrotoxicity was clearly visible from significant reductions in serum blood urea nitrogen (86.51 g/dl) and creatinine (5.30 g/dl) levels and significant improvement in body weight change (-10.34 g) and kidney weight (728 mg/kg). The protective effect of NDGA against cisplatin induced nephrotoxicity in the rats was further confirmed by significant restoration of antioxidant enzymes like SOD (86.28% inhibition), inflammatory markers like TNF-α (34.6 pg/ml) and histopathological examination. Moreover, our results showed that NDGA potentiated anti-breast cancer activity of cisplatin through an increment in the expression of antioxidant enzymes like SOD (85.35% inhibition) in breast cancer tissue. These results indicated that NDGA potentiated the anti-breast cancer activity of cisplatin, which was clearly evident from the tumor volume and % tumor inhibition in breast cancer rats. The current study demonstrated that NDGA may modify the therapeutic effect of cisplatin in DMBA induced breast cancer in female Sprague-Dawley rats. PMID:26247680

  14. Effects of subchronic exposure of silver nanoparticles on intestinal microbiota and gut-associated immune responses in the ileum of Sprague-Dawley rats.

    PubMed

    Williams, Katherine; Milner, Jessica; Boudreau, Mary D; Gokulan, Kuppan; Cerniglia, Carl E; Khare, Sangeeta

    2015-05-01

    Silver nanoparticles (AgNP) are widely used for their antibacterial properties. Incorporation of AgNP into food-related products and health supplements represents a potential route for oral exposure to AgNP; however, the effects of such exposure on the gastrointestinal system are mostly unknown. This study evaluated changes in the populations of intestinal-microbiota and intestinal-mucosal gene expression in Sprague-Dawley rats (both male and female) that were gavaged orally with discrete sizes of AgNP (10, 75 and 110 nm) and silver acetate. Doses of AgNP (9, 18 and 36 mg/kg body weight/day) and silver acetate (100, 200 and 400 mg/kg body weight/day) were divided and administered to rats twice daily (∼10 h apart) for 13 weeks. The results indicate that AgNP prompted size- and dose-dependent changes to ileal-mucosal microbial populations, as well as, intestinal gene expression and induced an apparent shift in the gut microbiota toward greater proportions of Gram-negative bacteria. DNA-based analyses revealed that exposure to 10 nm AgNP and low-dose silver acetate caused a decrease in populations of Firmicutes phyla, along with a decrease in the Lactobacillus genus. Analysis of host gene expression demonstrated that smaller sizes and lower doses of AgNP exposure prompted the decreased expression of important immunomodulatory genes, including MUC3, TLR2, TLR4, GPR43 and FOXP3. Gender-specific effects to AgNP exposure were more prominent for the gut-associated immune responses. These results indicate that the oral exposure to AgNP alter mucosa-associated microbiota and modulate the gut-associated immune response and the overall homeostasis of the intestinal tract. PMID:24877679

  15. A 4-week Repeated dose Oral Toxicity Study of Mecasin in Sprague-Dawley Rats to Determine the Appropriate Doses for a 13-week, Repeated Toxicity Test

    PubMed Central

    Cha, Eunhye; Lee, Jongchul; Lee, Seongjin; Park, Manyong; Song, Inja; Son, Ilhong; Song, Bong-Keun; Kim, Dongwoung; Lee, Jongdeok

    2015-01-01

    Objectives: In this study, we investigated the 4-week repeated-dose oral toxicity of gami-jakyak gamcho buja decoction (Mecasin) to develop safe treatments. Methods: In order to investigate the 4-week oral toxicity of Mecasin, we administered Mecasin orally to rats. Sprague-Dawley (SD) rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of Mecasin of 500, 1,000, and 2,000 mg/kg of body weight were administered to the experimental groups, and a dose of normal saline solution of 10 mL/kg was administered to the control group. We examined the survival rate, weight, clinical signs, and gross findings for four weeks. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths occurred in any of the four groups. No significant changes in weights or food consumption between the control group and the experimental groups were observed. Serum biochemistry revealed that some groups showed significant decrease in inorganic phosphorus (IP) (P < 0.05). During necropsy on the rats, one abnormal macroscopic feature, a slight loss of fur, was observed in the mid dosage (1,000 mg/ kg) male group. No abnormalities were observed in any other rats. In histopathological findings, the tubular basophilia and cast of the kidney and extramedullary hematopoiesis of the spleen were found. However, those changes were minimal and had occurred naturally or sporadically. No other organ abnormalities were observed. Conclusion: During this 4-week, repeated, oral toxicity test of Mecasin in SD rats, no toxicity changes due to Mecasin were observed in any of the male or the female rats in the high dosage group. Thus, we suggest that the doses in a 13-week, repeated test should be 0, 500, 1,000, and 2,000 mg/kg respectively. PMID:26998389

  16. Acute and 28-day sub-acute oral toxicity evaluation of two dietary bamboo charcoal powders in Sprague-Dawley rats.

    PubMed

    Jia, Zhen-chao; Luo, Sha; Zhong, Yu-ting; Li, Xiao; Chen, Jin-yao; Zhang, Li-shi

    2015-04-01

    No data were available on the acute oral toxicity, short-term oral toxicity of vegetable carbon in animals. This study was designed to evaluate the safety of two commercially available dietary bamboo charcoal powders (BCP1 and BCP2). The size distribution of the two powders was determined by a Mastersizer 2000 laser particle size analyzer prior to the in vivo safety studies. For the acute toxicity study, a single dose of 11.24 g/kg body weight of BCP1 and BCP2 was given once orally to healthy Sprague-Dawley (SD) rats. Mortality and clinical symptoms were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. In the repeated dose 28-day oral toxicity study, BCP1 and BCP2 were administered orally at doses of 2.81, 5.62, and 11.24 g/kg body weight for 28 days to SD rats. Animals were sacrificed and organs and blood samples were analyzed. Results showed that both BCP1 and BCP2 were micro-sized and various in size. In the acute toxicity and the repeated dose 28-day oral toxicity studies, BCP caused neither mortality nor visible signs of toxicity in rats. No significant differences were found in the relative organ weights or in biochemical parameters in BCP treated groups compared to a control group. No treatment-related histological changes were observed in the organs of these animals. Based on these data, it is concluded that the median lethal dose (LD50) of BCP for both male and female rats is more than 11.24 g/kg body weight and the no-observed-adverse-effect level (NOAEL) is >11.24 g/kg body weight for 28 days.

  17. Effect of Age, Duration of Exposure, and Dose of Atrazine on Sexual Maturation and the Luteinizing Hormone Surge in the Female Sprague-Dawley Rat.

    PubMed

    Breckenridge, Charles B; Sawhney Coder, Pragati; Tisdel, Merrill O; Simpkins, James W; Yi, Kun Don; Foradori, Chad D; Handa, Robert J

    2015-10-01

    Atrazine (ATZ) was administered daily by gavage to pregnant female Sprague Dawley rats at doses of 0, 6.25, 25 or 50 mg/kg/day, either during gestation, lactation and post-weaning (G/L/PW cohort) to F1 generation female offspring or only from postnatal day (PND 21) until five days after sexual maturation (vaginal opening) when the estrogen-primed, luteinizing hormone (LH) surge was evaluated (PW cohort). Additional subgroups of F1 females received the vehicle or ATZ from PND 21-133 or from PND 120-133. Slight reductions in fertility and the percentage of F1 generation pups surviving to PND 21 in the gestationally exposed 50 mg/kg dose group were accompanied by decreased food intake and body weight of dams and F1 generation offspring. The onset of puberty was delayed in of the F1 generation G/L/PW females at doses of 25 and 50 mg/kg/day. F1 generation females in the PW high-dose ATZ group also experienced a delay in the onset of puberty. ATZ had no effect on peak LH or LH AUC in ovariectomized rats 5 days after sexual maturation, irrespective of whether the F1 generation females were treated from gestation onward or only peripubertally. There was no effect of ATZ treatment on the estrous cycle, peak LH or LH AUC of F1 generation females exposed from gestation through to PND 133 or only for two weeks from PND 120-133. These results indicate that developing females exposed to ATZ are not more sensitive compared to animals exposed to ATZ as young adults.

  18. Lactation deficit in OFA hr/hr rats may be caused by differential sensitivity to stress compared with Wistar and Sprague Dawley rats.

    PubMed

    Valdez, Susana R; Bonafede, Melisa M; Carreño, Norma B; Deis, Ricardo P; Jahn, Graciela A

    2012-07-01

    OFA hr/hr (OFA) rats present a major lactation deficit that impairs offspring survival. To explore whether abnormal stress responsiveness causes this deficit, we compared their hormonal (prolactin, progesterone, and corticosterone) responses to stress (room change and 2-min ether exposure) with those of Wistar and Sprague Dawley (SD) rats. We tested responses during the estrous cycle, pregnancy, lactation, after ovariectomy, and ovarian steroid hormone priming, and responses to suckling. We evaluated hypothalamic expression of receptors for prolactin (PRLRlong) and the isoforms of receptors for progesterone (PRA and B) and estrogen (ERα and β) in late pregnancy. We tested whether administration of an anxiolytic (diazepam) improved lactation. Ether exposure increased circulating levels of the three hormones in the three strains of rats, cycling and ovariectomized, but was less effective in pregnancy and lactation. Elevated estrogen level (estrus and estradiol-treated ovariectomized rats) potentiated the prolactin response more in SD and OFA rats than in Wistar rats. Elevated progesterone level (late pregnancy, lactation, progesterone-treated ovariectomized rats) inhibited the prolactin response less in OFA than in SD or Wistar rats. Ether exposure inhibited the prolactin and oxytocin responses to suckling only in OFA rats. Diazepam treatment increased pup survival rate and the prolactin response to suckling. Hypothalamic total PR mRNA content, assayed by RT-PCR, was higher in pregnant OFA rats compared with SD and Wistar rats, but the PRB/PRA protein ratio determined by Western blot was lowest in Wistar rats, intermediate in OFA rats, and highest in SD rats. The heightened sensitivity to stress of lactating OFA rats may contribute to their lactational deficit and be caused by a combination of hypoprolactinemia and reduced inhibitory capacity of progesterone.

  19. Dose-independent pharmacokinetics of a new peroxisome proliferator-activated receptor-γ agonist, KR-62980, in Sprague-Dawley rats and ICR mice.

    PubMed

    Park, Jong-Shik; Kim, Min-Sun; Song, Jin Sook; Choi, Sung Heum; Lee, Byung Hoi; Woo, Jaechun; Ahn, Jin Hee; Bae, Myung Ae; Ahn, Sung-Hoon

    2011-12-01

    The pharmacokinetics of a novel peroxisome proliferator-activated receptor-γ agonist, KR-62980, were characterized in vitro with respect to liver metabolic stability, cell permeability, and plasma protein binding and in vivo using Sprague-Dawley rats and ICR mice. The metabolic half-life of 0.1-10 μM KR-62980 was 11.5-15.2 min in rat liver microsomes and 25.8-28.8 min in human liver microsomes. KR-62980 showed high permeability across MDCK cell monolayers, with apparent permeability coefficients of 20.4 × 10(-6) to 30.8 × 10(-6) cm/sec. The plasma protein binding rate of KR-62980 was 89.4%, and most was bound to serum albumin. After intravenous administration of KR-62980 (2 mg/kg), the systemic clearance was 2.50 L/h/kg, and the volume of distribution at steady-state was 9.16 L/kg. The bioavailability after oral administration was approximately 60.9%. The dose-normalized AUC values were 0.50 ± 0.09, 0.41 ± 0.20, and 0.62 ± 0.08 h · μg/mL after oral administration of 2, 5, and 10 mg/kg KR-62980, respectively, showing no dose-dependency. The in vivo pharmacokinetic parameters in ICR mice were also dose independent. These data suggest that KR-62980 is not significantly dose dependent in rats or mice, although it may disappear rapidly from the systemic circulation via metabolism in the liver.

  20. Deleterious impacts of a 900-MHz electromagnetic field on hippocampal pyramidal neurons of 8-week-old Sprague Dawley male rats.

    PubMed

    Şahin, Arzu; Aslan, Ali; Baş, Orhan; İkinci, Ayşe; Özyılmaz, Cansu; Sönmez, Osman Fikret; Çolakoğlu, Serdar; Odacı, Ersan

    2015-10-22

    Children are at potential risk due to their intense use of mobile phones. We examined 8-week-old rats because this age of the rats is comparable with the preadolescent period in humans. The number of pyramidal neurons in the cornu ammonis of the Sprague Dawley male rat (8-weeks old, weighing 180-250 g) hippocampus following exposure to a 900 MHz (MHz) electromagnetic field (EMF) were examined. The study consisted of control (CN-G), sham exposed (SHM-EG) and EMF exposed (EMF-EG) groups with 6 rats in each. The EMF-EG rats were exposed to 900 MHz EMF (1h/day for 30 days) in an EMF jar. The SHM-EG rats were placed in the EMF jar but not exposed to the EMF (1h/day for 30 days). The CN-G rats were not placed into the exposure jar and were not exposed to the EMF during the study period. All animals were sacrificed at the end of the experiment, and their brains were removed for histopathological and stereological analysis. The number of pyramidal neurons in the cornu ammonis of the hippocampus was estimated on Cresyl violet stained sections of the brain using the optical dissector counting technique. Histopathological evaluations were also performed on these sections. Histopathological observation showed abundant cells with abnormal, black or dark blue cytoplasm and shrunken morphology among the normal pyramidal neurons. The largest lateral ventricles were observed in the EMF-EG sections compared to those from the other groups. Stereological analyses showed that the total number of pyramidal neurons in the cornu ammonis of the EMF-EG rats was significantly lower than those in the CN-G (p<0.05) and the SHM-EG (p<0.05). In conclusion, our results suggest that pyramidal neuron loss and histopathological changes in the cornu ammonis of 8-week-old male rats may be due to the 900-MHz EMF exposure.

  1. Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats

    PubMed Central

    Han, Chung-Tack; Kim, Myoung-Jun; Moon, Seol-Hee; Jeon, Yu-Rim; Hwang, Jae-Sik; Nam, Chunja; Park, Chong-Woo; Lee, Sun-Ho; Na, Jae-Bum; Park, Chan-Sung; Park, Hee-Won; Lee, Jung-Min; Jang, Ho-Song; Park, Sun-Hee; Han, Kyoung-Goo; Choi, Young Whan

    2015-01-01

    Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes. PMID:26877842

  2. Sub-Acute Toxicity Study of Tiger Milk Mushroom Lignosus tigris Chon S. Tan Cultivar E Sclerotium in Sprague Dawley Rats.

    PubMed

    Kong, Boon-Hong; Tan, Nget-Hong; Fung, Shin-Yee; Pailoor, Jayalakshmi

    2016-01-01

    Lignosus also known as "Tiger Milk Mushroom," is classified in the family Polyporaceae and mainly consumed for its medicinal properties in Southeast Asia and China. The sclerotium is known as the part with medicinal value and often used by the natives to treat a variety of ailments. Lignosus tigris Chon S. Tan, one of the species of the Malaysia Tiger Milk mushroom, has recently been successfully cultivated in laboratory. Earlier studies have demonstrated the L. tigris cultivar E sclerotia exhibited beneficial biomedicinal properties. This study evaluated the potential toxicity of L. tigris E sclerotia in a 28-day sub-acute oral administration in Sprague Dawley (SD) rats. L. tigris E sclerotial powder was administered orally at three different doses of 250, 500, and 1000 mg/kg to the SD rats once daily, consecutively for 28-days. Body weight of the rats was recorded and general behavior, adverse effects, and mortality were observed daily throughout the experimental period. At the end of the experiment, blood hematology and biochemistry, relative organ weights, and histopathological analysis were performed. Results showed that there were no mortality nor signs of toxicity throughout the 28-day sub-acute toxicity study. Oral administration of the L. tigris E sclerotial powder at daily dose up to 1000 mg/kg had no significant effects in body weight, relative organ weight, blood hematological and biochemistry, gross pathology, and histopathology of the organs. L. tigris E sclerotial powder did not cause any treatment-related adverse effect in the rats at different treatment dosages up to 1000 mg/kg. As the lethal dose for the rats is above 1000 mg/kg, the no-observed-adverse-effect level (NOAEL) dose is more than 1000 mg/kg. PMID:27555822

  3. Evaluation of the Reproductive Toxicity, Glycometabolism, Glycometabolism-Related Enzyme Levels and Lipid Metabolism of Chromium Malate Supplementation in Sprague-Dawley Rats.

    PubMed

    Feng, Weiwei; Zhang, Weijie; Zhao, Ting; Mao, Guanghua; Wang, Wei; Wu, Xueshan; Zhou, Zhaoxiang; Huang, Jing; Bao, Yongtuan; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the reproductive toxicity of chromium malate in Sprague-Dawley rats and then inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, and lipid metabolism. The results showed that no pathological, toxic feces and urine changes were observed in clinical signs of parental and fetal rats in chromium malate groups. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of chromium malate groups have no significant change compared with control group and chromium picolinate group. The serum and organ contents of Cr in chromium malate groups have no significant change when compared with control group. No measurable damage on liver, brain, kidney, and testis/uterus of chromium malate groups was found. No significant change in body mass, absolute and relative organ weights, and hematological and biochemical changes of rats were observed compared with the control and chromium picolinate groups. The results indicated that supplements with chromium malate does not cause obvious damage and has no obvious effect on glycometabolism, glycometabolism-related enzyme, and lipid metabolism on female and male rats. The results of this study suggested that chromium malate is safe for human consumption and has the potential for application as a functional food ingredient and dietary supplement. PMID:25876088

  4. Apigenin prevents development of medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumors in Sprague-Dawley rats

    PubMed Central

    Mafuvadze, Benford; Benakanakere, Indira; Lopez, Franklin; Besch-Williford, Cynthia; Ellersieck, Mark R.; Hyder, Salman M.

    2011-01-01

    The use of progestins as a component of hormone replacement therapy has been linked to an increase in breast cancer risk in postmenopausal women. We have previously shown that medroxyprogesterone acetate (MPA), a commonly administered synthetic progestin, increases production of the potent angiogenic factor vascular endothelial growth factor (VEGF) by tumor cells, leading to the development of new blood vessels and tumor growth. We sought to identify nontoxic chemicals that would inhibit progestin-induced tumorigenesis. We used a recently developed progestin-dependent mammary cancer model in which tumors are induced in Sprague-Dawley rats by 7,12-dimethylbenz(a)anthracene (DMBA) treatment. The flavonoid apigenin, which we previously found to inhibit progestin-dependent VEGF synthesis in human breast cancer cells in vitro, significantly delayed the development of, and decreased the incidence and multiplicity of, MPA-accelerated DMBA-induced mammary tumors in this animal model. Whereas apigenin decreased the occurrence of such tumors, it did not block MPA-induced intraductal and lobular epithelial cell hyperplasia in the mammary tissue. Apigenin blocked MPA-dependent increases in VEGF, and suppressed VEGF receptor-2 (VEGFR-2) but not VEGFR-1 in regions of hyperplasia. No differences were observed in estrogen or progesterone receptor levels, or the number of estrogen receptor-positive cells, within the mammary gland of MPA-treated animals administered apigenin, MPA-treated animals, and placebo treated animals. However, the number of progesterone receptor-positive cells was reduced in animals treated with MPA or MPA and apigenin compared with those treated with placebo. These findings suggest that apigenin has important chemopreventive properties for those breast cancers that develop in response to progestins. PMID:21505181

  5. Subchronic feeding study of grain from herbicide-tolerant maize DP-Ø9814Ø-6 in Sprague-Dawley rats.

    PubMed

    Appenzeller, Laura M; Munley, Susan M; Hoban, Denise; Sykes, Greg P; Malley, Linda A; Delaney, Bryan

    2009-09-01

    This 13-week feeding study conducted in Sprague-Dawley rats evaluated the potential health effects from long-term consumption of a rodent diet formulated with grain from genetically modified (GM), herbicide-tolerant maize DP-Ø9814Ø-6 (98140; trade name Optimum GAT (Optimum GAT is a registered trademark of Pioneer Hi-Bred)). Metabolic inactivation of the herbicidal active ingredient glyphosate was conferred by genomic integration and expression of a gene-shuffled acetylase coding sequence, gat4621, from Bacillus licheniformis; tolerance to acetolactate synthase (ALS) inhibiting herbicides was conferred by overexpression of a modified allele (zm-hra) of the endogenous maize ALS enzyme that is resilient to inactivation. Milled maize grain from untreated (98140) and herbicide-treated (98140+Gly/SU) plants, the conventional non-transgenic, near-isogenic control (091), and three commercial non-transgenic reference hybrids (33J56, 33P66, and 33R77) was substituted at concentrations of 35-38% w/w into a common rodent chow formula (PMI) Nutrition International, LLC Certified Rodent LabDiet 5002) and fed to rats (12/sex/group) for at least 91 consecutive days. Compared with rats fed diets containing grain from the conventional near-isogenic control maize, no adverse effects were observed in rats fed diets containing grain from 98140 or 98140+Gly/SU maize with respect to standard nutritional performance metrics and OECD 408-compliant toxicological response variables [OECD, 1998. Section 4 (Part 408), Health Effects: Repeated Dose 90-Day Oral Toxicity Study in Rodents, Guideline for the Testing of Chemicals. Organisation of Economic Co-operation and Development, Paris, France]. These results support the comparative safety and nutritional value of maize grain from genetically modified Optimum GAT and conventional, non-transgenic hybrid field corn.

  6. Combined effects of dietary phytoestrogen and synthetic endocrine-active compound on reproductive development in Sprague-Dawley rats: genistein and methoxychlor.

    PubMed

    You, Li; Casanova, Mercedes; Bartolucci, Erika J; Fryczynski, Mary W; Dorman, David C; Everitt, Jeffrey I; Gaido, Kevin W; Ross, Susan M; Heck Hd, Henry d'A

    2002-03-01

    Humans and wildlife are frequently exposed to mixtures of endocrine active-compounds (EAC). The objective of the present study was to investigate the potential of the phytoestrogen genistein to influence the reproductive developmental toxicity of the endocrine-active pesticide methoxychlor. Three levels of genistein (0, 300, or 800 ppm) and two levels of methoxychlor (0 or 800 ppm) were used in this study. Sprague-Dawley rats were exposed to the two compounds, either alone or in combinations, through dietary administration to dams during pregnancy and lactation and to the offspring directly after weaning. Both compounds, methoxychlor in particular, were associated with reduced body growth at 800 ppm, but pregnancy outcome was not affected by either treatment. An acceleration of vaginal opening (VO) in the exposed female offspring was the only observed effect of genistein at 300 ppm. Exposure to 800 ppm genistein or 800 ppm methoxychlor caused accelerated VO and also altered estrous cyclicity toward persistent estrus in the female offspring. The estrogenic responses to genistein and methoxychlor administered together were apparently accumulative of the effects associated with each compound alone. Methoxychlor, but not genistein, delayed preputial separation (PPS) in the male rats. When administered with methoxychlor, genistein at 800 ppm enhanced the effect of methoxychlor on delaying PPS. Genistein and methoxychlor treatment did not change gender-specific motor activity patterns in either sex. To explore possible mechanisms for interaction between the two compounds on development, we performed estrogen receptor (ER)- and androgen receptor (AR)-based in vitro transcriptional activation assays using genistein and the primary methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE). While the in vitro assays supported the estrogenic effects of genistein and methoxychlor and the antiandrogenic effects of methoxychlor, the reactivity of these

  7. Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague-Dawley rats.

    PubMed

    Pattananandecha, Thanawat; Sirilun, Sasithorn; Duangjitcharoen, Yodsawee; Sivamaruthi, Bhagavathi Sundaram; Suwannalert, Prasit; Peerajan, Sartjin; Chaiyasut, Chaiyavat

    2016-09-01

    Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9- and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOM-treated rats fed with inulin-supplemented diet showed ∼1.3- and ∼2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as β-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary

  8. Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats

    PubMed Central

    Ferguson, Sherry A.; Law, Charles Delbert; Kissling, Grace E.

    2014-01-01

    The developing central nervous system may be particularly sensitive to bisphenol A (BPA)-induced alterations. Here, pregnant Sprague Dawley rats (n = 11–12/group) were gavaged daily with vehicle, 2.5 or 25.0 μg/kg BPA, or 5.0 or 10.0 μg/kg ethinyl estradiol (EE2) on gestational days 6–21. The BPA doses were selected to be below the no-observed-adverse-effect level (NOAEL) of 5 mg/kg/day. On postnatal days 1–21, all offspring/litter were orally treated with the same dose. A naïve control group was not gavaged. Body weight, pubertal age, estrous cyclicity, and adult serum hormone levels were measured. Adolescent play, running wheel activity, flavored solution intake, female sex behavior, and manually elicited lordosis were assessed. No significant differences existed between the vehicle and naïve control groups. Vehicle controls exhibited significant sexual dimorphism for most behaviors, indicating these evaluations were sensitive to sex differences. However, only EE2 treatment caused significant effects. Relative to female controls, EE2-treated females were heavier, exhibited delayed vaginal opening, aberrant estrous cyclicity, increased play behavior, decreased running wheel activity, and increased aggression toward the stimulus male during sexual behavior assessments. Relative to male controls, EE2-treated males were older at testes descent and preputial separation and had lower testosterone levels. These results suggest EE2-induced masculinization/defeminization of females and are consistent with increased volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) at weaning in female siblings of these subjects (He, Z., Paule, M. G. and Ferguson, S. A. (2012) Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21. Neurotoxicol. Teratol. 34, 331–337). Although EE2 treatment caused pubertal delays and decreased testosterone levels in males, their

  9. Effects of early and late adverse experiences on morpho-quantitative characteristics of Sprague-Dawley rat spleen subjected to stress during adulthood

    PubMed Central

    Vásquez, Bélgica; Sandoval, Cristian; Smith, Ricardo Luiz; del Sol, Mariano

    2015-01-01

    Morpho-quantitative studies of the spleen indicate that the proportions of the compartments and sub-compartments are stable in normal conditions. However, disorders due to stress can influence the number and function of the immune cells in this organ. The aim of this study was to determine, through the model of altering the early mother-infant bond and altering the late social bond through isolation, the effect on the morpho-quantitative characteristics of the spleen in adult Sprague-Dawley rats subjected to intermittent chronic stress in adulthood. Twenty-five newborn female rats were used, kept under the standardized lactation and feeding conditions. The rats were assigned randomly to 2 control groups (C1 and C2) and 3 experimental groups, exposed to early (E1), late (E2) or early-late (E3) adverse experiences and then subjected to intermittent chronic stress in adulthood (C2, E1, E2 and E3). The spleen of each animal was isolated and its morphometric characteristics were determined: volume density (Vv) of the red pulp, white pulp, marginal zone, splenic lymph nodule, periarterial lymphatic sheath and germinal center; areal number density (Na), surface density (Sv), number density (Nv), diameter (D) and total number of splenic lymph nodules. The mass of each compartment was also determined. A one-way analysis of variance (ANOVA) and Scheffé’s post hoc test were used for the statistical analysis. The p values were considered significant when they were less than 0.05 (*) and very significant at less than 0.025 (**). There were significant differences in the Vv of the red pulp, white pulp and their sub-compartments between the control and experimental groups. The white pulp increased significantly (P = 0.000) in E1, E2 and E3 compared to C1 and C2. The average Na and D values of the splenic lymph nodules were also higher in the experimental groups. The ANOVA for the mass of the spleen and the red pulp revealed no differences between the groups. The mass of the

  10. Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague-Dawley rats.

    PubMed

    Pattananandecha, Thanawat; Sirilun, Sasithorn; Duangjitcharoen, Yodsawee; Sivamaruthi, Bhagavathi Sundaram; Suwannalert, Prasit; Peerajan, Sartjin; Chaiyasut, Chaiyavat

    2016-09-01

    Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9- and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOM-treated rats fed with inulin-supplemented diet showed ∼1.3- and ∼2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as β-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary

  11. Protective effect of palm vitamin E and α-tocopherol against gastric lesions induced by water immersion restraint stress in Sprague-Dawley rats

    PubMed Central

    Ibrahim, Ibrahim Abdel Aziz; Yusof, Kamisah; Ismail, Nafeeza Mohd; Fahami, Nur Azlina Mohd

    2008-01-01

    Objective: Stress can lead to various changes in the gastrointestinal tract of rats. The present study was designed to compare the effect of palm vitamin E (PVE) and α-tocopherol (α-TF) supplementations on the gastric parameters important in maintaining gastric mucosal integrity in rats exposed to water immersion restraint stress (WRS). These parameters include gastric acidity, plasma gastrin level, gastric prostaglandin E2 (PGE2), and gastric lesions. Materials and Methods: Sixty male Sprague-Dawley rats (200-250 g) were divided into three equal groups: a control group, which received a normal rat diet (RC), and two treatment groups, receiving oral supplementation of either PVE or α-TF at 60 mg/kg body weight for 28 days. Each group was further divided into two groups: the nonstress and stress groups. The stress groups were subjected to 3.5 h of WRS once at the end of the treatment period. Blood samples were then taken to measure the gastrin level, after which the rats were killed. Gastric juice was collected for measurement of gastric acidity and gastric tissue was taken for measurement of gastric mucosal lesions and PGE2. Results: Exposure to stress resulted in the production of gastric lesions. PVE and α-TF lowered the lesion indices as compared to the stress control group. Stress reduced gastric acidity but pretreatment with PVE and α-TF prevented this reduction. The gastrin levels in the stress group were lower as compared to that in the nonstress control. However, following treatment with PVE and α-TF, gastrin levels increased and approached the normal level. There was also a significant reduction in the gastric PGE2 content with stress exposure, but this reduction was blocked with treatment with both PVE and α-TF. Conclusion: In conclusion, WRS leads to a reduction in the gastric acidity, gastrin level, and gastric PGE2 level and there is increased formation of gastric lesions. Supplementation with either PVE or α-TF reduces the formation of gastric

  12. Toxic Effects of Titanium Dioxide Nanoparticles and Titanium Dioxide Bulk Salt in the Liver and Blood of Male Sprague-Dawley Rats Assessed by Different Assays.

    PubMed

    Shakeel, Muhammad; Jabeen, Farhat; Qureshi, Naureen Aziz; Fakhr-E-Alam, Muhammad

    2016-10-01

    This study evaluated the toxic effects of titanium dioxide (TiO2) bulk salt as well as its nanoparticles (NPs) in anatase phase with mean crystallite size of 36.15 nm in male Sprague-Dawley rats by subcutaneous injections at four different dose levels of either control (0), 50, 100 or 150 mg/kg of body weight (BW) of rat for 28 days on alternate days. Animal mortality, haematology, micronucleus assay, liver histology and activities of liver tissue damage markers like, alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), as well as oxidative stress indicators like superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) were investigated. The study revealed significant differences (P < 0.05) among control and experimental groups in all the haematological parameters at the end of experiment. Significantly elevated levels (P < 0.05) of ALT, AST and ALP were found for the group treated with TiO2 NPs at the dose of 150 mg/kg of body weight as compared to control. TiO2 and TiO2 NPs caused dose-dependent genotoxicity in the blood cells of the treated rat as revealed by micronuclei test. The highest frequency of micronuclei was observed in rats treated with NPs at the dose of 150 mg/kg BW which was significantly different (P < 0.001) from all other experimental groups after 28 days of exposure. Similarly, all the treatments showed dose-dependent oxidative stress in the treated rats. However, the significantly high decline in the activities of CAT, SOD, and GST as well as elevation in malondialdehyde and GSH was observed in the group receiving NPs at the rate of 150 mg/kg BW. TiO2 also caused histological alterations in the liver. The study revealed that higher dose of TiO2 NPs exerted significantly harmful effects on liver and blood as compared to its lower doses as well as from all other doses of their bulk counterparts.

  13. A 90-day study of sub-chronic oral toxicity of 20 nm positively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Kim, Seon-Ju; Lee, Taek-Jin; Kim, Geon-Yong; Meang, EunHo; Hong, Jeong-Sup; Kim, Su-Hyon; Koh, Sang-Bum; Hong, Seung-Guk; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The study reported here was conducted to determine the systemic oral toxicity and to find the no-observed-adverse-effect level of 20 nm positively charged zinc oxide (ZnOSM20(+)) nanoparticles in Sprague Dawley rats for 90 days. Methods For the 90-day toxicity study, the high dose was set as 500 mg per kg of body weight (mg/kg) and the middle and low dose were set to 250 mg/kg and 125 mg/kg, respectively. The rats were held for a 14-day recovery period after the last administration, to observe for the persistence or reduction of any toxic effects. A distributional study was also carried out for the systemic distribution of ZnOSM20(+) NPs. Results No rats died during the test period. There were no significant clinical changes due to the test article during the experimental period in functional assessment, body weight, food and water consumption, ophthalmological testing, urine analysis, necropsy findings, or organ weights, but salivation was observed immediately after administration in both sexes. The total red blood cell count was increased, and hematocrit, albumin, mean cell volume, mean cell hemoglobin, and mean cell hemoglobin concentration were decreased significantly compared with control in both 500 mg/kg groups. Total protein and albumin levels were decreased significantly in both sexes in the 250 and 500 mg/kg groups. Histopathological studies revealed acinar cell apoptosis in the pancreas, inflammation and edema in stomach mucosa, and retinal atrophy of the eye in the 500 mg/kg group. Conclusion There were significant parameter changes in terms of anemia in the hematological and blood chemical analyses in the 250 and 500 mg/kg groups. The significant toxic change was observed to be below 125 mg/kg, so the no-observed-adverse-effect level was not determined, but the lowest-observed-adverse-effect level was considered to be 125 mg/kg in both sexes and the target organs were found to be the pancreas, eye, and stomach. PMID:25565829

  14. Deleterious impacts of a 900-MHz electromagnetic field on hippocampal pyramidal neurons of 8-week-old Sprague Dawley male rats.

    PubMed

    Şahin, Arzu; Aslan, Ali; Baş, Orhan; İkinci, Ayşe; Özyılmaz, Cansu; Sönmez, Osman Fikret; Çolakoğlu, Serdar; Odacı, Ersan

    2015-10-22

    Children are at potential risk due to their intense use of mobile phones. We examined 8-week-old rats because this age of the rats is comparable with the preadolescent period in humans. The number of pyramidal neurons in the cornu ammonis of the Sprague Dawley male rat (8-weeks old, weighing 180-250 g) hippocampus following exposure to a 900 MHz (MHz) electromagnetic field (EMF) were examined. The study consisted of control (CN-G), sham exposed (SHM-EG) and EMF exposed (EMF-EG) groups with 6 rats in each. The EMF-EG rats were exposed to 900 MHz EMF (1h/day for 30 days) in an EMF jar. The SHM-EG rats were placed in the EMF jar but not exposed to the EMF (1h/day for 30 days). The CN-G rats were not placed into the exposure jar and were not exposed to the EMF during the study period. All animals were sacrificed at the end of the experiment, and their brains were removed for histopathological and stereological analysis. The number of pyramidal neurons in the cornu ammonis of the hippocampus was estimated on Cresyl violet stained sections of the brain using the optical dissector counting technique. Histopathological evaluations were also performed on these sections. Histopathological observation showed abundant cells with abnormal, black or dark blue cytoplasm and shrunken morphology among the normal pyramidal neurons. The largest lateral ventricles were observed in the EMF-EG sections compared to those from the other groups. Stereological analyses showed that the total number of pyramidal neurons in the cornu ammonis of the EMF-EG rats was significantly lower than those in the CN-G (p<0.05) and the SHM-EG (p<0.05). In conclusion, our results suggest that pyramidal neuron loss and histopathological changes in the cornu ammonis of 8-week-old male rats may be due to the 900-MHz EMF exposure. PMID:26239913

  15. Metabonomics evaluations of age-related changes in the urinary compositions of male Sprague Dawley rats and effects of data normalization methods on statistical and quantitative analysis

    PubMed Central

    Schnackenberg, Laura K; Sun, Jinchun; Espandiari, Parvaneh; Holland, Ricky D; Hanig, Joseph; Beger, Richard D

    2007-01-01

    Background Urine from male Sprague-Dawley rats 25, 40, and 80 days old was analyzed by NMR and UPLC/MS. The effects of data normalization procedures on principal component analysis (PCA) and quantitative analysis of NMR-based metabonomics data were investigated. Additionally, the effects of age on the metabolic profiles were examined by both NMR and UPLC/MS analyses. Results The data normalization factor was shown to have a great impact on the statistical and quantitative results indicating the need to carefully consider how to best normalize the data within a particular study and when comparing different studies. PCA applied to the data obtained from both NMR and UPLC/MS platforms reveals similar age-related differences. NMR indicated many metabolites associated with the Krebs cycle decrease while citrate and 2-oxoglutarate, also associated with the Krebs cycle, increase in older rats. Conclusion This study compared four different normalization methods for the NMR-based metabonomics spectra from an age-related study. It was shown that each method of normalization has a great effect on both the statistical and quantitative analyses. Each normalization method resulted in altered relative positions of significant PCA loadings for each sample spectra but it did not alter which chemical shifts had the highest loadings. The greater the normalization factor was related to age, the greater the separation between age groups was observed in subsequent PCA analyses. The normalization factor that showed the least age dependence was total NMR intensity, which was consistent with UPLC/MS data. Normalization by total intensity attempts to make corrections due to dietary and water intake of the individual animal, which is especially useful in metabonomics evaluations of urine. Additionally, metabonomics evaluations of age-related effects showed decreased concentrations of many Krebs cycle intermediates along with increased levels of oxidized antioxidants in urine of older rats

  16. Feeding and metabolic consequences of scheduled consumption of large, binge-type meals of high fat diet in the Sprague-Dawley rat.

    PubMed

    Bake, T; Morgan, D G A; Mercer, J G

    2014-04-10

    Providing rats and mice with access to palatable high fat diets for a short period each day induces the consumption of substantial binge-like meals. Temporal food intake structure (assessed using the TSE PhenoMaster/LabMaster system) and metabolic outcomes (oral glucose tolerance tests [oGTTs], and dark phase glucose and insulin profiles) were examined in Sprague-Dawley rats given access to 60% high fat diet on one of 3 different feeding regimes: ad libitum access (HF), daily 2 h-scheduled access from 6 to 8 h into the dark phase (2 h-HF), and twice daily 1 h-scheduled access from both 1-2 h and 10-11 h into the dark phase (2×1 h-HF). Control diet remained available during the scheduled access period. HF rats had the highest caloric intake, body weight gain, body fat mass and plasma insulin. Both schedule-fed groups rapidly adapted their feeding behaviour to scheduled access, showing large meal/bingeing behaviour with 44% or 53% of daily calories consumed from high fat diet during the 2 h or 2×1 h scheduled feed(s), respectively. Both schedule-fed groups had an intermediate caloric intake and body fat mass compared to HF and control (CON) groups. Temporal analysis of food intake indicated that schedule-fed rats consumed large binge-type high fat meals without a habitual decrease in preceding intake on control diet, suggesting that a relative hypocaloric state was not responsible or required for driving the binge episode, and substantiating previous indications that binge eating may not be driven by hypothalamic energy balance neuropeptides. In an oGTT, both schedule-fed groups had impaired glucose tolerance with higher glucose and insulin area under the curve, similar to the response in ad libitum HF fed rats, suggesting that palatable feeding schedules represent a potential metabolic threat. Scheduled feeding on high fat diet produces similar metabolic phenotypes to mandatory (no choice) high fat feeding and may be a more realistic platform for mechanistic study

  17. Citrus auraptene suppresses cyclin D1 and significantly delays N-methyl nitrosourea induced mammary carcinogenesis in female Sprague-Dawley rats

    PubMed Central

    2009-01-01

    Background Breast cancer is a major problem in the United States leading to tens of thousands of deaths each year. Although citrus auraptene suppresses cancer in numerous rodent models, its role in breast cancer prevention previously has not been reported. Thus, our goal was to determine the anticarcinogenic effects of auraptene against breast cancer. Methods The effects of auraptene on cell proliferation of MCF-7 and MDA-MB-231 human breast carcinoma cells in culture was assessed by measuring metabolism of a substrate to a formazan dye. Dietary effects of auraptene on tumor incidence, multiplicity and latency were studied in the N-methyl nitrosourea (MNU) induced mammary carcinogenesis model in female Sprague Dawley rats. The concentration of auraptene in rat tissues was analyzed by reverse phase HPLC. Cyclin D1 expression in MCF-7 cells and rat tumors was measured by western blot. Results Auraptene (500 ppm) significantly delayed median time to tumor by 39 days compared to the MNU only group (p < 0.05, n = 24–26). Auraptene (10 μM) reduced Insulin like Growth Factor-1 (IGF-1, 10 ng/mL)-induced cyclin D1 expression by 40% in MCF-7 cells. In comparison, western blot analysis of rat mammary tumors (n = 10 per group) confirmed that auraptene (500 ppm) significantly reduced (p < 0.05) cyclin D1 expression by 49% compared to the MNU only group. Analysis of rat mammary tissue extract by HPLC with fluorescence detection indicated an average concentration (means ± S.E.) of 1.4 ± 0.5 μM and 1.8 ± 0.3 μM in the normal mammary glands of the auraptene 200 ppm and 500 ppm groups, respectively. The concentration (means ± S.E.) of auraptene in the mammary tumors of the auraptene 200 ppm group was 0.31 ± 0.98 μM. Conclusion Overall, these observations suggest that the predominant effect of auraptene was to delay the development of tumors possibly through the suppression of cyclin D1 expression. These results point to the potential chemopreventive effects of auraptene

  18. Hypothalamic energy balance gene responses in the Sprague-Dawley rat to supplementation of high-energy diet with liquid ensure and subsequent transfer to chow.

    PubMed

    Archer, Z A; Rayner, D V; Barrett, P; Balik, A; Duncan, J S; Moar, K M; Mercer, J G

    2005-11-01

    Energy dense, high fat, high sugar, foods and beverages in our diet are a major contributor to the escalating global obesity problem. Here, we examine the physiological and neuroendocrine effects of feeding rats a solid high-energy (HE) diet with or without a liquid supplement (Ensure) and the consequence of subsequently transferring animals back to chow (C). Outbred Sprague-Dawley rats were fed C until 49-56 days of age, and then transferred a HE diet for 3 weeks before allocation to one of two weight-matched groups. Over the next 10 weeks, one group remained on HE diet, whereas the other had access to the liquid diet, chocolate Ensure (EN), in addition to HE diet (HE + EN). Half the rats from each group were then killed, and the remainder were returned to C for 3 weeks. Supplementation of the HE diet with EN accelerated weight gain and increased daily energy intake, adipose tissue mass, and circulating leptin levels. Transferring animals back to C caused a decrease in bodyweight in the HE + EN group, whereas HE animals were weight stable. Both groups also exhibited voluntary hypophagia, although the magnitude and duration of this response was greater in HE + EN animals. The only effect of Ensure on the hypothalamic genes studied was on tyrosine kinase B expression in the ventromedial hypothalamic nucleus (VMH), which was increased in rats given the supplement. Withdrawal of the obesogenic diets decreased gene expression for cocaine-and-amphetamine regulated transcript (CART) and dynorphin (DYN) in the arcuate nucleus (ARC), and DYN and brain-derived neurotrophic factor (BDNF) in the VMH, whereas neuropeptide Y (NPY) gene expression in the ARC was increased. These changes were independent of previous dietary history. EN supplementation generates distinct physiological responses, yet has a minimal effect on hypothalamic neuropeptide or receptor gene expression, possibly due to the development of leptin resistance. Withdrawal of obesogenic diets induces changes in

  19. Developmental treatment with ethinyl estradiol, but not bisphenol A, causes alterations in sexually dimorphic behaviors in male and female Sprague Dawley rats.

    PubMed

    Ferguson, Sherry A; Law, Charles Delbert; Kissling, Grace E

    2014-08-01

    The developing central nervous system may be particularly sensitive to bisphenol A (BPA)-induced alterations. Here, pregnant Sprague Dawley rats (n = 11-12/group) were gavaged daily with vehicle, 2.5 or 25.0 μg/kg BPA, or 5.0 or 10.0 μg/kg ethinyl estradiol (EE2) on gestational days 6-21. The BPA doses were selected to be below the no-observed-adverse-effect level (NOAEL) of 5 mg/kg/day. On postnatal days 1-21, all offspring/litter were orally treated with the same dose. A naïve control group was not gavaged. Body weight, pubertal age, estrous cyclicity, and adult serum hormone levels were measured. Adolescent play, running wheel activity, flavored solution intake, female sex behavior, and manually elicited lordosis were assessed. No significant differences existed between the vehicle and naïve control groups. Vehicle controls exhibited significant sexual dimorphism for most behaviors, indicating these evaluations were sensitive to sex differences. However, only EE2 treatment caused significant effects. Relative to female controls, EE2-treated females were heavier, exhibited delayed vaginal opening, aberrant estrous cyclicity, increased play behavior, decreased running wheel activity, and increased aggression toward the stimulus male during sexual behavior assessments. Relative to male controls, EE2-treated males were older at testes descent and preputial separation and had lower testosterone levels. These results suggest EE2-induced masculinization/defeminization of females and are consistent with increased volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) at weaning in female siblings of these subjects (He, Z., Paule, M. G. and Ferguson, S. A. (2012) Low oral doses of bisphenol A increase volume of the sexually dimorphic nucleus of the preoptic area in male, but not female, rats at postnatal day 21. Neurotoxicol. Teratol. 34, 331-337). Although EE2 treatment caused pubertal delays and decreased testosterone levels in males, their

  20. Azoreductase activity of Sprague Dawley and Wistar-derived rats towards both carcinogenic and non-carcinogenic analogues of 4-dimethylaminophenylazobenzene (DAB).

    PubMed

    Elliott, B M

    1984-08-01

    Azoreductase activity towards the hepatocarcinogen p-dimethylaminophenylazobenzene (DAB) and four analogues has been measured in vitro in the liver and caecum of Sprague Dawley (Alpk/SD) and Alderley Park (Alpk/AP Wistar-derived) rats. Two carcinogenic DAB analogues, 3'-methyl-p-dimethylaminophenylazobenzene (3M) and 6-p-dimethylaminophenylazobenzothiazole (6BT) and two non-carcinogenic analogues, 4-N-pyrrolidinylazobenzene (4N) and 5-p-dimethylaminophenylazoindazole (5I) have been examined. The azoreductase activity towards DAB of a 9000 g supernatant of liver homogenate was greater in the SD than the AP strain between 6 and 13 weeks of age, but comparable to that of AP rats at 4 weeks of age. The activity towards DAB fell in both strains with increasing age. Animals of both strains fed a riboflavin-low diet (2-3 mg kg-1) had reduced azoreductase activity with DAB when compared to a standard diet at all ages studied, although the difference was less marked in the AP rats. 3M and 4N were azoreduced by the livers of both strains of rat fed a standard diet at a rate of approximately 50% of that of DAB, whereas 5I and 6BT were cleaved at a much lower rate (5-20%). All the chemicals were reduced by an oxygen-insensitive enzyme in the liver preparation, as has previously been reported for DAB. DAB, 3M and 6BT were reduced at a similar rate to each other by a fraction containing caecal contents, both in and between the two strains of rat. Similarly, 4N and 5I were reduced by a caecal preparation at a similar rate to each other in and between both strains of rat, but at a rate of only 30-50% that shown by DAB, 3M and 6BT. In contrast to the conditions required by the liver azoreductase enzyme, anaerobic conditions were required for maximal activity of the caecal preparation. Liver azoreductase activity towards all the DAB analogues was reduced in both strains of rat maintained on a riboflavin-low diet, while the caecal azoreductase activity was unaffected. Neither the

  1. A novel 4 S [3H]beta-naphthoflavone-binding protein in liver cytosol of female Sprague-Dawley rats treated with aryl hydrocarbon receptor agonists.

    PubMed Central

    Brauze, D; Malejka-Giganti, D

    2000-01-01

    beta-Naphthoflavone (beta-NF) is a widely used inducer of phase-I and phase-II enzymes controlled by aryl hydrocarbon receptor (AhR). Studies of competitive binding with (3)H-labelled 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3-MC) and benzo[a]pyrene (B[a]P) have shown that beta-NF is a high-affinity ligand for AhR and also for polycyclic aromatic hydrocarbon (PAH)-binding protein, both soluble proteins of rat liver in 8 S and 4 S fractions, respectively, of sucrose gradients. This study examined binding of [(3)H]beta-NF to liver cytosolic proteins of female Sprague-Dawley rats. Treatment of rats with beta-NF, 3-MC, TCDD or alpha-naphthoflavone (alpha-NF) increased the specific [(3)H]beta-NF binding to liver cytosol up to 125-fold that of vehicle (corn oil)-treated rats (<100 fmol/mg of protein). Sucrose gradients revealed a large 4 S and a small 8 S peak of radioactivity from [(3)H]beta-NF binding to cytosols of beta-NF-, 3-MC-, TCDD- or alpha-NF-treated rats. Whereas co-incubation with the unlabelled beta-NF eliminated both peaks, co-incubation with 2,3, 7,8-tetrachlorodibenzofuran (TCDF) eliminated only the 8 S peak. The sucrose density gradient from [(3)H]TCDD binding to cytosol of beta-NF- or TCDD-treated rats yielded a small 4 S and a larger 8 S peak; only the latter was abolished by co-incubation with TCDF. Thus, the patterns of sedimentation, distribution and elimination of radioactivity from the 8 S fraction of the liver cytosols from beta-NF-, 3-MC-, TCDD- or alpha-NF-treated rats were characteristic for the AhR, whereas those from the 4 S fraction appeared specific for [(3)H]beta-NF binding. The data indicate that potent AhR agonists, TCDD, 3-MC and beta-NF, and to a lesser extent alpha-NF, a weak AhR agonist, induce a 4 S [(3)H]beta-NF-binding protein in liver cytosol of female rats. alpha-NF, beta-NF and 3-MC were effective competitors (80-85% inhibition) of the [(3)H]beta-NF-specific binding to the beta-NF-, 3 MC- or TCDD

  2. NTP toxicity report of reproductive dose range-finding study of Genistein (CAS No. 446-72-0) administered in feed to Sprague-Dawley rats.

    PubMed

    Delclos, K B; Newbold, Retha

    2007-11-01

    Genistein is a naturally occurring isoflavone that interacts with estrogen receptors and multiple other molecular targets. Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements. A series of short-term studies with genistein was conducted with two goals: 1) to obtain data necessary to establish dose levels for subsequent multigeneration reproductive and chronic toxicity studies and 2) to evaluate the effects of genistein on endpoints outside the reproductive tract. The data generated from these studies have been reported previously in the peer-reviewed literature or in technical reports (Appendix C). In addition, selected data from these studies were analyzed and discussed in the National Toxicology Program's Report of the Endocrine Disruptors Low-Dose Peer Review (NTP, 2001). The present report focuses on the reproductive and general toxicology endpoints evaluated. Data obtained in separate evaluations of behavioral, neuroanatomical, neurochemical, and immunological endpoints, as well as the assessment of serum genistein levels, are also discussed to put in better perspective the selection of doses for the multigenerational and chronic studies. Genistein was administered in an irradiated soy- and alfalfa-free diet (Purina 5K96) at exposure concentrations of 0, 5, 25, 100, 250, 625, or 1,250 ppm to 10 vaginal plug-positive, female Sprague-Dawley rats starting on gestation day 7 and continuing throughout pregnancy. These dietary exposure concentrations resulted in ingested doses of approximately 0.3, 1.7, 6.4, 16, 38, and 72 mg genistein/kg body weight to dams in the 5, 25, 100, 250, 625, and 1,250 ppm groups, respectively. Dietary exposure of the dams continued through lactation, during which time ingested doses were approximately 0.6, 3.5, 14, 37, 84, and 167 mg/kg per day. Pups from five litters, culled to eight per litter with an equal sex distribution on postnatal day (PND) 2

  3. Dietary methoxychlor exposure modulates splenic natural killer cell activity, antibody-forming cell response and phenotypic marker expression in F0 and F1 generations of Sprague Dawley rats.

    PubMed

    White, K L; Germolec, D R; Booker, C D; Hernendez, D M; McCay, J A; Delclos, K B; Newbold, R R; Weis, C; Guo, T L

    2005-02-14

    Methoxychlor, a chlorinated hydrocarbon pesticide, is a persistent environmental contaminant that has been identified in human reproductive tissues. Methoxychlor has been shown to be estrogenic in both in vivo and in vitro studies. As an endocrine disrupter, it may have the potential to adversely affect endocrine, reproductive, and immune systems in animals. The present study evaluated methoxychlor's immunotoxic potential in F0 (dams) and F1 generations of Sprague Dawley rats exposed to an isoflavone-free diet containing methoxychlor at concentrations of 10, 100, and 1000 ppm. In dams, exposure to methoxychlor from gestation day 7 to postpartum day 51 (65 days total exposure) produced a significant increase in the NK activity (1000 ppm) and the percentages of T cells (1000 ppm), helper T cells (1000 ppm) and macrophages (100 and 1000 ppm). In contrast, a decrease in the numbers of splenocytes and B cells was observed at the 100 and 1000 ppm concentrations. In F1 males, exposure to methoxychlor gestationally, lactationally and through feed from postnatal day 22-64 (78 days total exposure) produced an increase in the spleen IgM antibody-forming cell response to sheep red blood cells (100 and 1000 ppm) and the activity of NK cells (1000 ppm). However, there was a decrease in the terminal body weight (1000 ppm), spleen weight (1000 ppm), thymus weight (100 and 1000 ppm), and the numbers of splenocytes (1000 ppm), B cells (100 and 1000 ppm), cytotoxic T cells (1000 ppm) and NK cells (100 and 1000 ppm). In F1 females, exposure to methoxychlor produced a decrease in the terminal body weight (1000 ppm) and the percentages of cytotoxic T cells (10, 100 and 1000 ppm). These results demonstrate that developmental and adult dietary exposure to methoxychlor modulates immune responses in Sprague Dawley rats. Immunological changes were more pronounced in the F1 generation male rats that were exposed during gestation and postpartum, when compared to the F0 and F1 generation

  4. Dopamine D1 and D2 agonist effects on prepulse inhibition and locomotion: comparison of Sprague-Dawley rats to Swiss-Webster, 129X1/SvJ, C57BL/6J, and DBA/2J mice.

    PubMed

    Ralph, Rebecca J; Caine, S Barak

    2005-02-01

    D2 receptors have been studied in relation to therapeutic uses of dopaminergic drugs, and psychomotor stimulant effects [as manifested by decreased prepulse inhibition (PPI) of startle and increased locomotor activity] are hallmark behavioral effects of D2 agonists in rats. Genetic studies with mutant mice might be useful in this line of investigation; however, recent studies suggest that mice differ from rats with respect to D2 agonist effects. Accordingly, we studied a wide range of doses of the D2-like agonist quinelorane (0.0032-5.6 mg/kg) and the D1-like agonist R-6-Br-APB [R(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] (0.032-5.6 mg/kg) in outbred Sprague-Dawley rats, outbred Swiss-Webster mice, and inbred 129X1/SvJ, C57BL/6J, and DBA/2J mice. Whereas the D2 agonist dose-dependently decreased PPI and increased locomotion in rats, neither of these effects was observed in outbred or inbred mice. In contrast, the D1 agonist reduced PPI and increased locomotion in Sprague-Dawley rats and in Swiss-Webster, 129X1/SvJ, and C57BL/6J mice. Neither agonist decreased PPI in DBA/2J mice, although PPI was increased in this strain by a D2 antagonist. Pretreatment with either the D2 antagonist eticlopride (1 mg/kg) or the D1 antagonist SCH39166 [(-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo[d]naptho-(2,1-b)azepine] (1 mg/kg) prevented the PPI-disruptive effects of quinelorane in rats and R-6-Br-APB in mice, suggesting receptor interactions in both species. In summary, psychomotor stimulant effects of a D2 agonist that were robustly observed in outbred rats were absent in several outbred and inbred strains of mice. These results may have implications for the study of mutant mice to investigate genes involved in psychomotor function in humans.

  5. Long-term dysregulation of circadian and 17-beta estradiol-induced LH, prolactin and corticosterone secretion after dimethylbenz (a) anthracene administration in the Sprague-Dawley female rat.

    PubMed

    Yon de Jonage-Canonico, M Beau; Lenoir, V; Scholler, R; Kerdelhué, B

    2005-07-01

    A single intragastric administration of 7,12-dimethylbenz (a) anthracene (DMBA) has been shown, when given at 55-60 days of age, to induce mammary tumors in young cycling female Sprague-Dawley rats. The appearance of the tumors is preceded by a series of neuroendocrine disturbances of the hypothalamo-pituitary-gonadal (HPG) axis, including attenuation of the preovulatory Luteinizing Hormone (LH) and Gonadotropin-Releasing Hormone (GnRH) release and amplification of the preovulatory 17beta-Estradiol (E(2)) surge. In this study, we examined the hypothesis that a single administration of DMBA could also, in the long range, induce disturbances of others neuroendocrine axis, like the Hypothalamic-Pituitary-Adrenal (HPA) axis and/or the Lactotroph axis. Sprague-Dawley rats, 55-60 days of age, received, on the day of Estrous of the Estrous cycle, a single administration of 15 mg of DMBA delivered by intragastric intubation. Then, they were ovariectomized 5 days later. One month later, (1) Two groups of animal were sacrificed by decapitation at 09:00 a.m. and 05:00 p.m. to record the circadian rhythm of plasma LH, Prolactin (PRL) and corticosterone, (2) Three other groups of animal were sacrificed by decapitation at three different times after a morning subcutaneous administration of 50 microg/kg of Estradiol Benzoate (EB), to induce a negative and positive feed-back of the secretion of LH. Then, plasma LH, PRL and corticosterone concentrations were measured. After DMBA administration, (1) the negative--but not the positive--LH feed-back was seen, (2) the PRL circadian rhythm was blunted and the corticosterone circadian rhythm was almost absent, (3) the increase in PRL or Corticosterone plasma concentration was significantly reduced. In conclusion, a single administration of DMBA provokes a long-term dysregulation of not only the HPG axis but also of the lactotroph and HPA axis. These dysregulations, along with the already evidenced long-term inhibition of DMBA upon

  6. Ntp technical report on toxicity, reproductive, and developmental studies of 60-Hz magnetic fields, administered by whole body exposure to F344/N rats, Sprague-Dawley rats, and B6C3F1 mice. Toxicity report series

    SciTech Connect

    Boorman, G.A.

    1996-09-01

    Electric and magnetic fields are associated with the production, transmission, and use of electricity; thus the potential for human exposure is high. These electric and magnetic fields are predominantly of low frequency (60 Hz) and generally of low intensity. The prevailing view among physicists is that exposure to these low-frequency, low-intensity fields does not pose a health hazard. However, this view has been challenged by reports linking magnetic field exposure to the development of leukemia and other cancers. Because multiple epidemiologic studies suggested a potential for increased cancer rates with increasing exposure, and because of public concern, the effects of 60-Hz magnetic field exposure were examined in F344/N rats and B6C3F1 mice in 8-week full-body-exposure studies. Animals were evaluated for hematology and clinical chemistry (rats only) parameters, pineal gland hormone concentrations, and histopathology. Additional studies were performed in Sprague-Dawley rats to examine teratologic and reproductive effects of magnetic field exposure.

  7. Effects of oral exposure to bisphenol A on gene expression and global genomic DNA methylation in the prostate, female mammary gland, and uterus of NCTR Sprague-Dawley rats

    PubMed Central

    Camacho, Luísa; Basavarajappa, Mallikarjuna S.; Chang, Ching-Wei; Han, Tao; Kobets, Tetyana; Koturbash, Igor; Surratt, Gordon; Lewis, Sherry M.; Vanlandingham, Michelle M.; Fuscoe, James C.; da Costa, Gonçalo Gamboa; Pogribny, Igor P.; Delclos, K. Barry

    2015-01-01

    Bisphenol A (BPA), an industrial chemical used in the manufacture of polycarbonate and epoxy resins, binds to the nuclear estrogen receptor with an affinity 4–5 orders of magnitude lower than that of estradiol. We reported previously that “high BPA” (100,000 and 300,000 μg/kg body weight (bw)/day), but not “low BPA” [2.5–2700 μg/kg bw/day], induced clear adverse effects in NCTR Sprague-Dawley rats gavaged daily from gestation day 6 through postnatal day 90. The “high BPA” effects partially overlapped those of ethinyl estradiol (EE2, 0.5 and 5.0 μg/kg bw/day). To evaluate further the potential of “low BPA” to induce biological effects, here we assessed the global genomic DNA methylation and gene expression in the prostate and female mammary glands, tissues identified previously as potential targets of BPA, and uterus, a sensitive estrogen-responsive tissue. Both doses of EE2 modulated gene expression, including of known estrogen-responsive genes, and PND 4 global gene expression data showed a partial overlap of the “high BPA” effects with those of EE2. The “low BPA” doses modulated the expression of several genes; however, the absence of a dose response reduces the likelihood that these changes were causally linked to the treatment. These results are consistent with the toxicity outcomes. PMID:25862956

  8. Relevance of a Hypersaline Sodium-Rich Naturally Sparkling Mineral Water to the Protection against Metabolic Syndrome Induction in Fructose-Fed Sprague-Dawley Rats: A Biochemical, Metabolic, and Redox Approach

    PubMed Central

    Pereira, Cidália Dionísio; Severo, Milton; Araújo, João Ricardo; Guimarães, João Tiago; Pestana, Diogo; Santos, Alejandro; Ferreira, Rita; Ascensão, António; Magalhães, José; Azevedo, Isabel; Monteiro, Rosário; Martins, Maria João

    2014-01-01

    The Metabolic Syndrome increases the risk for atherosclerotic cardiovascular disease and type 2 Diabetes Mellitus. Increased fructose consumption and/or mineral deficiency have been associated with Metabolic Syndrome development. This study aimed to investigate the effects of 8 weeks consumption of a hypersaline sodium-rich naturally sparkling mineral water on 10% fructose-fed Sprague-Dawley rats (Metabolic Syndrome animal model). The ingestion of the mineral water (rich in sodium bicarbonate and with higher potassium, calcium, and magnesium content than the tap water used as control) reduced/prevented not only the fructose-induced increase of heart rate, plasma triacylglycerols, insulin and leptin levels, hepatic catalase activity, and organ weight to body weight ratios (for liver and both kidneys) but also the decrease of hepatic glutathione peroxidase activity and oxidized glutathione content. This mineral-rich water seems to have potential to prevent Metabolic Syndrome induction by fructose. We hypothesize that its regular intake in the context of modern diets, which have a general acidic character interfering with mineral homeostasis and are poor in micronutrients, namely potassium, calcium, and magnesium, could add surplus value and attenuate imbalances, thus contributing to metabolic and redox health and, consequently, decreasing the risk for atherosclerotic cardiovascular disease. PMID:24672546

  9. Relevance of a Hypersaline Sodium-Rich Naturally Sparkling Mineral Water to the Protection against Metabolic Syndrome Induction in Fructose-Fed Sprague-Dawley Rats: A Biochemical, Metabolic, and Redox Approach.

    PubMed

    Pereira, Cidália Dionísio; Severo, Milton; Araújo, João Ricardo; Guimarães, João Tiago; Pestana, Diogo; Santos, Alejandro; Ferreira, Rita; Ascensão, António; Magalhães, José; Azevedo, Isabel; Monteiro, Rosário; Martins, Maria João

    2014-01-01

    The Metabolic Syndrome increases the risk for atherosclerotic cardiovascular disease and type 2 Diabetes Mellitus. Increased fructose consumption and/or mineral deficiency have been associated with Metabolic Syndrome development. This study aimed to investigate the effects of 8 weeks consumption of a hypersaline sodium-rich naturally sparkling mineral water on 10% fructose-fed Sprague-Dawley rats (Metabolic Syndrome animal model). The ingestion of the mineral water (rich in sodium bicarbonate and with higher potassium, calcium, and magnesium content than the tap water used as control) reduced/prevented not only the fructose-induced increase of heart rate, plasma triacylglycerols, insulin and leptin levels, hepatic catalase activity, and organ weight to body weight ratios (for liver and both kidneys) but also the decrease of hepatic glutathione peroxidase activity and oxidized glutathione content. This mineral-rich water seems to have potential to prevent Metabolic Syndrome induction by fructose. We hypothesize that its regular intake in the context of modern diets, which have a general acidic character interfering with mineral homeostasis and are poor in micronutrients, namely potassium, calcium, and magnesium, could add surplus value and attenuate imbalances, thus contributing to metabolic and redox health and, consequently, decreasing the risk for atherosclerotic cardiovascular disease. PMID:24672546

  10. Food intake is inversely correlated with central nervous system histamine receptor (H1) concentrations in male Sprague-Dawley rats fed normal, low protein, low energy or poor quality protein diets.

    PubMed

    Haq, A U; Bundrant, H M; Mercer, L P

    1996-12-01

    The reported studies were designed to examine relationships between whole-brain histamine receptors (H1) and food intake in male Sprague-Dawley rats. Three different experiments were conducted. In each experiment, control rats were fed normal protein (25 g casein/100 g food) and normal metabolizable energy (16.21 kJ/100 g food) diets. Feeding low protein diets (1 g casein/100 g food) elevated central H1 receptor concentrations (P < 0.0027) and reduced voluntary food intake (P < 0.007) compared with normal diets. Feeding low energy diets lowered H1 receptor concentrations (P < 0.0089) and increased voluntary food intake (P < 0.0012). Low quality protein diets also affected the central nervous histaminergic system. Whole-brain H1 receptor concentrations were significantly higher for rats fed low quality protein (25 g gelatin/100 g food) compared with rats fed casein (P < 0.0001). Rats fed medium quality protein (25 g wheat gluten/100 g food) or low quality protein ate significantly less food (P < 0.0001). In all experiments, dietary manipulation affected central histamine receptors. Elevated concentrations of H1 receptors were associated with a decrease in food intake whereas lowered concentrations of H1 receptors were associated with an increase in food intake (P < 0.001). The results of these experiments support the hypothesis that central histamine H1 receptor concentrations in male rats are inversely correlated with voluntary food intake and affected by dietary composition.

  11. In vivo effects of diabetes, insulin and oleanolic acid on enzymes of glycogen metabolism in the skin of streptozotocin-induced diabetic male Sprague-Dawley rats.

    PubMed

    Mukundwa, Andrew; Langa, Silvana O; Mukaratirwa, Samson; Masola, Bubuya

    2016-03-01

    The skin is the largest organ in the body and diabetes induces pathologic changes on the skin that affect glucose homeostasis. Changes in skin glycogen and glucose levels can mirror serum glucose levels and thus the skin might contribute to whole body glucose metabolism. This study investigated the in vivo effects of diabetes, insulin and oleanolic acid (OA) on enzymes of glycogen metabolism in skin of type 1 diabetic rats. Diabetic and non-diabetic adult male Sprague-Dawley rats were treated with a single daily dose of insulin (4 IU/kg body weight), OA (80 mg/kg body weight) and a combination of OA + insulin for 14 days. Glycogen phosphorylase (GP) expression; and GP, glycogen synthase (GS) and hexokinase activities as well glycogen levels were evaluated. The results suggest that diabetes lowers hexokinase activity, GP activity and GP expression with no change in GS activity whilst the treatments increased GP expression and the activities of hexokinase, GP and GS except for the GS activity in OA treated rats. Glycogen levels were increased slightly by diabetes as well as OA treatment. In conclusion diabetes, OA and insulin can lead to changes in GS and GP activities in skin without significantly altering the glycogen content. We suggest that the skin may contribute to whole body glucose homeostasis particularly in disease states.

  12. A thirteen-week oral toxicity study of annatto extract (norbixin), a natural food color extracted from the seed coat of annatto (Bixa orellana L.), in Sprague-Dawley rats.

    PubMed

    Hagiwara, A; Imai, N; Ichihara, T; Sano, M; Tamano, S; Aoki, H; Yasuhara, K; Koda, T; Nakamura, M; Shirai, T

    2003-08-01

    A subchronic oral toxicity study of annatto extract (norbixin), a natural food color, was conducted. Groups of 10 male and 10 female Sprague-Dawley rats were fed annatto extract at dietary levels of 0, 0.1, 0.3 and 0.9% for 13 weeks. There were no treatment-related adverse effects on body weight, food and water consumption, ophthalmology and hematology data. Blood biochemical analysis revealed changes in rats of both sexes confined to the 0.9% and 0.3% groups, including increased alkaline phosphatase, phospholipid, total protein, albumin and albumin/globulin ratio. Marked elevation in absolute and relative liver weights was also found in both sexes of the 0.9% and 0.3% groups, but not the 0.1% group. Hepatocyte hypertrophy was evident and an additional electron microscopic examination demonstrated this to be linked to abundant mitochondria after exposure to a dietary level of 0.9% annatto extract for 2 weeks. Thus, the No-Observed-Adverse-Effect-Level (NOAEL) was judged to be a dietary level of 0.1% (69 mg/kg body weight/day for males, 76 mg/kg body weight/day for females) of annatto extract (norbixin) under the present experimental conditions. PMID:12842184

  13. Toxicity of aerosols of nicotine and pyruvic acid (separate and combined) in Sprague-Dawley rats in a 28-day OECD 412 inhalation study and assessment of systems toxicology.

    PubMed

    Phillips, Blaine; Esposito, Marco; Verbeeck, Jan; Boué, Stéphanie; Iskandar, Anita; Vuillaume, Gregory; Leroy, Patrice; Krishnan, Subash; Kogel, Ulrike; Utan, Aneli; Schlage, Walter K; Bera, Monali; Veljkovic, Emilija; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2015-01-01

    Toxicity of nebulized nicotine (Nic) and nicotine/pyruvic acid mixtures (Nic/Pyr) was characterized in a 28-day Organization for Economic Co-operation and Development 412 inhalation study with additional transcriptomic and lipidomic analyses. Sprague-Dawley rats were nose-only exposed, 6 h/day, 5 days/week to filtered air, saline, nicotine (50 µg/l), sodium pyruvate (NaPyr, 33.9 µg/l) or equimolar Nic/Pyr mixtures (18, 25 and 50 µg nicotine/l). Saline and NaPyr caused no health effects, but rats exposed to nicotine-containing aerosols had decreased body weight gains and concentration-dependent increases in liver weight. Blood neutrophil counts were increased and lymphocyte counts decreased in rats exposed to nicotine; activities of alkaline phosphatase and alanine aminotransferase were increased, and levels of cholesterol and glucose decreased. The only histopathologic finding in non-respiratory tract organs was increased liver vacuolation and glycogen content. Respiratory tract findings upon nicotine exposure (but also some phosphate-buffered saline aerosol effects) were observed only in the larynx and were limited to adaptive changes. Gene expression changes in the lung and liver were very weak. Nic and Nic/Pyr caused few significant changes (including Cyp1a1 gene upregulation). Changes were predominantly related to energy metabolism and fatty acid metabolism but did not indicate an obvious toxicity-related response. Nicotine exposure lowered plasma lipids, including cholesteryl ester (CE) and free cholesterol and, in the liver, phospholipids and sphingolipids. Nic, NaPyr and Nic/Pyr decreased hepatic triacylglycerol and CE. In the lung, Nic and Nic/Pyr increased CE levels. These data suggest that only minor biologic effects related to inhalation of Nic or Nic/Pyr aerosols were observed in this 28-day study.

  14. Astragalus polysaccharides affect insulin resistance by regulating the hepatic SIRT1-PGC-1α/PPARα-FGF21 signaling pathway in male Sprague Dawley rats undergoing catch-up growth.

    PubMed

    Gu, Chengying; Zeng, Yipeng; Tang, Zhaosheng; Wang, Chaoxun; He, Yanju; Feng, Xinge; Zhou, Ligang

    2015-11-01

    The present study investigated the effects of Astragalus polysaccharides (APS) on insulin resistance by modulation of hepatic sirtuin 1 (SIRT1)‑peroxisome proliferator‑activated receptor (PPAR)‑γ coactivator (PGC)‑1α/PPARα‑fibroblast growth factor (FGF)21, and glucose and lipid metabolism. Thirty male Sprague Dawley rats were divided into three groups: A normal control group, a catch‑up growth group and an APS‑treated (APS-G) group. The latter two groups underwent food restriction for 4 weeks, prior to being provided with a high fat diet, which was available ad libitum. The APS‑G group was orally treated with APS for 8 weeks, whereas the other groups were administered saline. Body weight was measured and an oral glucose tolerance test (OGTT) was conducted after 8 weeks. The plasma glucose and insulin levels obtained from the OGTT were assayed, and hepatic morphology was observed by light and transmission electron microscopy. In addition, the mRNA expression levels of PGC‑1α/PPARα, and the protein expression levels of SIRT1, FGF21 and nuclear factor‑κB were quantified in the liver and serum. APS treatment suppressed abnormal glycolipid metabolism and insulin resistance following 8 weeks of catch‑up growth by improving hepatic SIRT1‑PPARα‑FGF21 intracellular signaling and reducing chronic inflammation, and by partially attenuating hepatic steatosis. The suppressive effects of APS on liver acetylation and glycolipid metabolism‑associated molecules contributed to the observed suppression of insulin resistance. However, the mechanism underlying the effects of APS on insulin resistance requires further research in order to be elucidated. Rapid and long‑term treatment with APS may provide a novel, safe and effective therapeutic strategy for type 2 diabetes. PMID:26323321

  15. The selective dopamine D₃ receptor antagonist SB-277011A attenuates drug- or food-deprivation reactivation of expression of conditioned place preference for cocaine in male Sprague-Dawley rats.

    PubMed

    Ashby, Charles R; Rice, Onarae V; Heidbreder, Christian A; Gardner, Eliot L

    2015-06-01

    We determined the effect of the selective dopamine D3 receptor antagonist SB-277011A on reactivation of conditioned place preference (CPP) to cocaine elicited by priming injections of cocaine or exposure to food deprivation stress (21 h) in male Sprague-Dawley rats. Animals paired with the cocaine-associated chamber displayed a robust and consistent CPP response. This CPP was extinguished after repeated pairings of the conditioned stimuli (cocaine-paired chamber contextual cues) in the absence of the unconditioned stimulus (cocaine). Twenty-four hours later, the administration of 5 mg kg(-1) i.p. of cocaine (immediately before the test) or exposure to 21 h of food deprivation reactivated the expression of the cocaine-induced CPP. In contrast, administration of 1 ml kg(-1) i.p. of vehicle did not reactivate the CPP response. Administration of the selective dopamine D3 receptor antagonist SB-277011A (3-24 mg kg(-1) i.p.) 30 min before cocaine administration on the test day produced a significant attenuation of CPP reactivation. Reactivation of the CPP response produced by food deprivation was also significantly attenuated by SB-277011A (6 or 12 mg kg(-1) i.p.) given 30 min before the test session. SB-277011A (12 or 24 mg kg(-1) i.p.) did not itself produce reactivation of the CPP response. Overall, these results suggest that the reactivation of the incentive value of drug-associated cues by cocaine or food deprivation is attenuated by selective antagonism of D3 receptors. PMID:25851636

  16. Onion peel extract increases hepatic low-density lipoprotein receptor and ATP-binding cassette transporter A1 messenger RNA expressions in Sprague-Dawley rats fed a high-fat diet.

    PubMed

    Lee, Seung-Min; Moon, Jiyoung; Do, Hyun Ju; Chung, Ji Hyung; Lee, Kyung-Hea; Cha, Yong-Jun; Shin, Min-Jeong

    2012-03-01

    In the present study, we hypothesized that onion peel extract (OPE) alters hepatic gene expression to improve blood cholesterol profiles. To investigate the effect of OPE to test our hypothesis, Sprague-Dawley rats were fed ad libitum for 8 weeks with the control, high-fat diet (HFD) or the high-fat diet with 0.2% OPE supplementations (HFD + OPE). Messenger RNA (mRNA) levels of genes in cholesterol metabolism and fatty acid metabolism were examined by semiquantitative reverse transcriptase polymerase chain reaction. The OPE in HFD reverted high fat-induced reduction in mRNA levels of sterol regulatory element-binding protein-2, low-density lipoprotein receptor, and hydroxyl-3-methylglutaryl coenzyme reductase genes in the liver comparable with the levels of the control group. Onion peel extract slightly increased stearoyl-coA desaturase 1 (SCD-1) expression compared with high-fat feeding. However, sterol regulatory element-binding protein-1c and fatty acid synthase were not affected by high-fat or OPE feeding. Onion peel extract also enhanced expression of ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor γ2 and scavenger receptor class B type I genes when compared with high-fat feeding. However, OPE did not influence high fat-triggered changes in apolipoprotein A1 mRNA levels and liver X receptor α were not affected by either high-fat or OPE feeding. Our results suggest that OPE changes the expression of genes associated with cholesterol metabolism in favor of lowering blood low-density lipoprotein cholesterol and enhancing high-density lipoprotein cholesterol through increasing mRNA abundance of low-density lipoprotein receptor and ATP-binding cassette transporter A1 genes. PMID:22464808

  17. Sub-chronic testosterone treatment increases the levels of epithelial sodium channel (ENaC)-α, β and γ in the kidney of orchidectomized adult male Sprague-Dawley rats.

    PubMed

    Loh, Su Yi; Giribabu, Nelli; Salleh, Naguib

    2016-01-01

    Testosterone has been reported to cause blood pressure to increase. However mechanisms that underlie the effect of this hormone on this physiological parameter are currently not well understood. The aims of this study were to investigate effects of testosterone on expression of α, β and γ-epithelial sodium channel (ENaC) proteins and messenger RNAs (mRNAs) in kidneys, the channel known to be involved in Na(+) reabsorption, which subsequently can affect the blood pressure. Methods. Adult male Sprague-Dawley (SD) rats were orchidectomized fourteen days prior to receiving seven days treatment with testosterone propionate (125 µg/kg/day or 250 µg/kg/day) with or without flutamide (androgen receptor blocker) or finasteride (5α-reductase inhibitor). Following sacrifice, the kidneys were removed and were subjected for α, β and γ-ENaC protein and mRNA expression analyses by Western blotting and Real-time PCR (qPCR) respectively. The distribution of α, β and γ-ENaC proteins in kidneys were observed by immunofluorescence. Results. The α, β and γ-ENaC proteins and mRNA levels in kidneys were enhanced in rats which received testosterone-only treatment. In these rats, α, β and γ-ENaC proteins were distributed in the distal tubules and collecting ducts of the nephrons. Co-treatment with flutamide or finasteride resulted in the levels of α, β and γ-ENaC proteins and mRNAs in kidneys to decrease. In conclusions, increases in α, β and γ-ENaC protein and mRNA levels in kidneys mainly in the distal tubules and collecting ducts under testosterone influence might lead to enhance Na(+) reabsorption which subsequently might cause an increase in blood pressure. PMID:27413634

  18. Effects of neutrophils peptide-1 transgenic Chlorella ellipsoidea on the gut microbiota of male Sprague-Dawley rats, as revealed by high-throughput 16S rRNA sequencing.

    PubMed

    Guo, Mingzhang; Bao, Qi; Chen, Siyuan; Cui, Xingtian; Xu, Wentao; He, Xiaoyun; Luo, Yunbo; Qi, Xiaozhe; Huang, Kunlun

    2016-03-01

    Rabbit neutrophils peptide-1 (NP-1) is a type of defensin that possesses a broad spectrum of antimicrobial activity. Chlorella ellipsoidea is a new eukaryotic expression system for exogenously producing NP-1. The NP-1 transgenic C. ellipsoidea can be directly added into feed as antimicrobial agent without any purification procedure for the NP-1 peptide. However, the effects of C. ellipsoidea and NP-1 on the host gut microbiota should be explored before application. In this study, diets containing different concentrations (1.25, 2.5, and 5%) of C. ellipsoidea and NP-1 transgenic C. ellipsoidea were administered to male Sprague-Dawley rats. Compared with the chow diet control group, none of the experimental groups showed any significant differences in their growth indices, and no histopathological damage was observed. The phylotypes of gut microbiota in the control group, the 5% C. ellipsoidea diet group and the 5% NP-1 transgenic C. ellipsoidea diet group were determined by 16S rRNA sequencing. The results showed that both 5% experimental groups had shifted community memberships of gut microbiota. In particular, the 5% NP-1 transgenic C. ellipsoidea diet exhibited an increased abundance of most Gram-positive bacterial taxa and a reduced abundance of most Gram-negative bacterial taxa, and it promoted the growth of some lactic acid bacterial genera. Lactic acid bacteria, especially the Bifidobacterium and Lactobacillus, have been widely reported to be benefic effects on the host. Thus NP-1 transgenic C. ellipsoidea is promising feed additive and gut regulator, as it have the potential to increase the abundance of Bifidobacterium and Lactobacillus in gut microbiota of animal.

  19. Toxicology and carcinogenesis studies of 3,3',4,4'-tetrachloroazobenzene (TCAB) (CAS No. 14047-09-7) in Harlan Sprague-Dawley rats and B6C3F1 mice (gavage studies).

    PubMed

    2010-11-01

    3,3',4,4'-Tetrachloroazobenzene (TCAB) is not commercially manufactured but is formed as an unwanted by-product in the manufacture of 3,4-dichloroaniline and its herbicidal derivatives Propanil, Linuron, and Diuron. It occurs from the degradation of chloroanilide herbicides (acylanilides, phenylcarbamates, and phenylureas) in soil by peroxide-producing microorganisms; and is formed by the photolysis and biolysis of 3,4-dichloroaniline. Humans may be exposed to TCAB during the manufacture as well as the application of herbicides containing TCAB as a contaminant. TCAB was nominated by the United States Environmental Protection Agency for toxicity and carcinogenicity testing based on its structural and biological similarity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the potential for human exposure from the consumption of crops contaminated with 3,4-dichloroaniline-derived herbicides. Male and female Harlan Sprague-Dawley rats and B6C3F1 mice were administered TCAB (at least 97.8% pure) in corn oil:acetone (99:1) by gavage for 3 months (rats only) or 2 years. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female Harlan Sprague-Dawley rats were administered 0.1, 0.3, 1, 3, 10, 30, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 14 weeks; groups of 10 male and 10 female rats received the corn oil:acetone vehicle alone. Special study groups of 30 (dosed groups) or 6 (vehicle control group) female Harlan Sprague-Dawley rats were administered 0.1, 3, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 13 weeks; vehicle controls received the corn oil:acetone vehicle alone. All male and female rats survived to the end of the study. Terminal mean body weights of males were not significantly different from vehicle controls in any group. Terminal mean body weights of females administered 10 mg/kg or greater were significantly less than those of the vehicle controls. Mean body weight gains of all

  20. Toxicology and carcinogenesis studies of 3,3',4,4'-tetrachloroazobenzene (TCAB) (CAS No. 14047-09-7) in Harlan Sprague-Dawley rats and B6C3F1 mice (gavage studies).

    PubMed

    2010-11-01

    3,3',4,4'-Tetrachloroazobenzene (TCAB) is not commercially manufactured but is formed as an unwanted by-product in the manufacture of 3,4-dichloroaniline and its herbicidal derivatives Propanil, Linuron, and Diuron. It occurs from the degradation of chloroanilide herbicides (acylanilides, phenylcarbamates, and phenylureas) in soil by peroxide-producing microorganisms; and is formed by the photolysis and biolysis of 3,4-dichloroaniline. Humans may be exposed to TCAB during the manufacture as well as the application of herbicides containing TCAB as a contaminant. TCAB was nominated by the United States Environmental Protection Agency for toxicity and carcinogenicity testing based on its structural and biological similarity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the potential for human exposure from the consumption of crops contaminated with 3,4-dichloroaniline-derived herbicides. Male and female Harlan Sprague-Dawley rats and B6C3F1 mice were administered TCAB (at least 97.8% pure) in corn oil:acetone (99:1) by gavage for 3 months (rats only) or 2 years. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female Harlan Sprague-Dawley rats were administered 0.1, 0.3, 1, 3, 10, 30, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 14 weeks; groups of 10 male and 10 female rats received the corn oil:acetone vehicle alone. Special study groups of 30 (dosed groups) or 6 (vehicle control group) female Harlan Sprague-Dawley rats were administered 0.1, 3, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 13 weeks; vehicle controls received the corn oil:acetone vehicle alone. All male and female rats survived to the end of the study. Terminal mean body weights of males were not significantly different from vehicle controls in any group. Terminal mean body weights of females administered 10 mg/kg or greater were significantly less than those of the vehicle controls. Mean body weight gains of all

  1. Hepatocellular hypertrophy and cell proliferation in Sprague-Dawley rats following dietary exposure to ammonium perfluorooctanoate occurs through increased activation of the xenosensor nuclear receptors PPARα and CAR/PXR.

    PubMed

    Elcombe, Clifford R; Elcombe, Barbara M; Foster, John R; Farrar, David G; Jung, Reinhard; Chang, Shu-Ching; Kennedy, Gerald L; Butenhoff, John L

    2010-10-01

    Ammonium perfluorooctanoate (APFO), a processing aid used in the production of fluoropolymers, produces hepatomegaly and hepatocellular hypertrophy in rodents. In mice, APFO-induced hepatomegaly is associated with increased activation of the xenosensor nuclear receptors, PPARα and CAR/PXR. Although non-genotoxic, chronic dietary treatment of Sprague-Dawley (S-D) rats with APFO produced an increase in benign tumours of the liver, acinar pancreas, and testicular Leydig cells. Most of the criteria for establishing a PPARα-mediated mode of action for the observed hepatocellular tumours have been previously established with the exception of the demonstration of increased hepatocellular proliferation. The present study evaluates the potential roles for APFO-induced activation of PPARα and CAR/PXR with respect to liver tumour production in the S-D rat and when compared to the specific PPARα agonist, 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy 14,643). Male S-D rats were fed APFO (300 ppm in diet) or Wy 14,643 (50 ppm in diet) for either 1, 7, or 28 days. Effects of treatment with APFO included: decreased body weight; hepatomegaly, hepatocellular hypertrophy, hepatocellular hyperplasia (microscopically and by BrdU labelling index), and hepatocellular glycogen loss; increased activation of PPARα (peroxisomal β-oxidation and microsomal CYP4A1 protein); decreased plasma triglycerides, cholesterol, and glucose; increased activation of CAR (CYP2B1/2 protein) and CAR/PXR (CYP3A1 protein). Responses to treatment with Wy 14,643 were consistent with increased activation of PPARα, specifically: increased CYP4A1 and peroxisomal β-oxidation; increased hepatocellular hypertrophy and cell proliferation; decreased apoptosis; and hypolipidaemia. With the exception of decreased apoptosis, the effects observed with Wy 14,643 were noted with APFO, and APFO was less potent. These data clearly demonstrate an early hepatocellular proliferative response to APFO

  2. Systemic uptake, albumin and hemoglobin binding of [(14)C]2,3-butanedione administered by intratracheal instillation in male Harlan Sprague Dawley rats and oropharyngeal aspiration in male B6C3F1/N mice.

    PubMed

    Fennell, Timothy R; Morgan, Daniel L; Watson, Scott L; Dhungana, Suraj; Waidyanatha, Suramya

    2015-02-01

    2,3-Butanedione (BD) is a reactive diketone in artificial butter flavors that is thought to cause bronchiolitis obliterans in workers in microwave popcorn manufacturing. Bronchiolitis obliterans is generally not diagnosed until irreversible damage has occurred; therefore a biomarker of early exposure is needed. The potential systemic uptake of BD from inhalation exposure has not been evaluated. The objective here was to evaluate the systemic exposure of BD and binding to hemoglobin and albumin. [(14)C]BD was administered to male Harlan Sprague Dawley rats (100 mg/kg, intratracheal instillation) and B6C3F1/N mice (157 mg/kg, oropharyngeal aspiration). Blood and plasma was collected 24 h after administration and analyzed for (14)C content. At 24h, 0.88±0.07% of the administered dose was in rat blood, 0.66±0.06% in rat plasma, 0.38±0.13% in mouse blood and 0.17±0.05% in mouse plasma. Albumin binding in rats was 269±24.2 ng equiv./mg, which accounts for 38% of the radioactivity in plasma. In mice, binding was 85.0±22.3 ng equiv./mg albumin, which accounts for 51% of the radioactivity in plasma. The binding to hemoglobin in rats was 38.2±17.6 ng equiv./mg, and to globin was 29.1±3.96 ng equiv./mg. In mice, the binding to hemoglobin was 16.2±9.0 ng equiv./mg. The site(s) of adduction on hemoglobin and albumin was investigated by mass spectrometry. In rat globin, arginine adducts were detected at R-30 and R-104 of the beta chain in vitro and in vivo. In rat albumin, adducts were detected in vitro on R-219/221, R-360, and R-368, and in vivo on a variety of arginine residues. This study demonstrated that BD enters the systemic circulation and reacts with arginine on hemoglobin and albumin. These results indicate that hemoglobin and albumin adducts may be useful as biomarkers of BD exposure in humans. PMID:25559854

  3. Effect of Fe(2)O(3) on the capacity of benzo(a)pyrene to induce polycyclic aromatic hydrocarbon-metabolizing enzymes in the respiratory tract of Sprague-Dawley rats.

    PubMed

    Garçon, Guillaume; Gosset, Pierre; Zerimech, Farid; Grave-Descampiaux, Béatrice; Shirali, Pirouz

    2004-04-21

    In this work, the question that needs to be answered was whether concurrent exposure to iron oxides and polycyclic aromatic hydrocarbons (PAHs) could affect the induction of PAH-metabolizing enzymes. Male Sprague-Dawley rats were intratracheally instilled with hematite (Fe(2)O(3); 3mg), benzo(a)pyrene (B(a)P; 3mg), or B(a)P (3mg)-coated onto Fe(2)O(3) particles (3mg). Forty-eight hours later, we investigated mRNA expressions of cytochrome p4501a1 (cyp1a1), microsomal epoxide hydrolase (meh), and glutathione-S-transferase-ya and -yc (gst-ya and gst-yc, respectively), protein concentrations of CYP1A1, and 7-ethoxyresorufin O-deethylase (EROD) activities in lungs. Exposure to B(a)P alone or coated-onto Fe(2)O(3) particles induced cyp1a1 gene transcription (P < 0.01) and increased both the CYP1A1 protein levels (P < 0.01) and the EROD activities (P < 0.001). However, in this work, we focused our attention on the potential of Fe(2)O(3) in B(a)P/Fe(2)O(3) mixtures to affect the capacity of B(a)P to induce PAH-metabolizing enzymes. Exposure to B(a)P-coated onto Fe(2)O(3) particles increased meh mRNA expressions (1.15-fold, P < 0.05), CYP1A1 protein concentrations (1.85-fold, P < 0.05), and EROD activities (1.95-fold, P < 0.01), versus exposure to B(a)P alone. Hence, animal short-term exposure to B(a)P-coated onto Fe(2)O(3) particles favored dramatically the induction of PAH-bioactivating enzymes to the detriment of PAH-inactivating enzymes in lungs. Taken together, these results support the hypothesis that the Fe(2)O(3)-induced increase of the metabolic activation of B(a)P might rely on several properties of Fe(2)O(3), including its capacity to enhance the rate of CYP1A1 hemoprotein elaboration. The influence of Fe(2)O(3) in B(a)P/Fe(2)O(3) mixtures on the ability of B(a)P to induce PAH-metabolizing enzymes will also be one of the fundamental ways that Fe(2)O(3) can affect B(a)P carcinogenicity in lungs.

  4. Distribution of radio-labeled N-Acetyl-L-Cysteine in Sprague-Dawley rats and its effect on glutathione metabolism following single and repeat dosing by oral gavage.

    PubMed

    Arfsten, Darryl P; Johnson, Eric W; Wilfong, Erin R; Jung, Anne E; Bobb, Andrew J

    2007-01-01

    The distribution of radio-labeled N-Acetyl-L-Cysteine (NAC) and its impact on glutathione (GSH) metabolism was studied in Sprague-Dawley rats following single and multiple dosing with NAC by oral gavage. Radioactivity associated with administration of (14)C-NAC distributed to most tissues examined within 1 hour of administration with peak radioactivity levels occurring within 1 hour to 4 hours and for a majority of the tissues examined, radioactivity remained elevated for up to 12 hours or more. Administration of a second dose of 1,200 mg/kg NAC + (14)C-NAC 4 hours after the first increased liver, kidney, skin, thymus, spleen, eye, and serum radioactivity significantly beyond levels achieved following 1 dose. Administration of a third dose of 1,200 mg/kg NAC + (14)C-NAC 4 hours after the second dose did not significantly increase tissue radioactivity further except in the skin. GSH concentrations were increased 20% in the skin and 50% in the liver after one dose of 1,200 mg/kg NAC whereas lung and kidney GSH were unaffected. Administration of a second and third dose of 1,200 mg/kg NAC at 4 hours and 8 hours after the first did not increase tissue GSH concentrations above background with the exception that skin GSH levels were elevated to levels similar to those obtained after a single dose of NAC. Glutathione-S-transferase (GST) activity was increased 150% in the kidney and 10% in the liver, decreased 60% in the skin, and had no effect on lung GST activity following a single dose of 1,200 mg/kg NAC. Administration of a second dose of 1,200 mg/kg NAC 4 hours after the first decreased skin GST activity a further 20% whereas kidney GST activity remained elevated at levels similar to those obtained after 1 dose of NAC. Administration of a third dose of NAC 4 hours after the second dose increased liver GST activity significantly as compared to background but did not affect skin, kidney, or lung GST activity. Transient decreases in glutathione reductase (GR) activity

  5. Evaluation of the role of oxidative stress, inflammation and apoptosis in the pulmonary and the hepatic toxicity induced by cerium oxide nanoparticles following intratracheal instillation in male Sprague-Dawley rats

    NASA Astrophysics Data System (ADS)

    Nalabotu, Siva Krishna

    The field of nanotechnology is rapidly progressing with potential applications in the automobile, healthcare, electronics, cosmetics, textiles, information technology, and environmental sectors. Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. With increased applications of nanotechnology, there are increased chances of exposure to manufactured nanomaterials. Recent reports on the toxicity of engineered nanomaterials have given scientific and regulatory agencies concerns over the safety of nanomaterials. Specifically, the Organization for Economic Co-operation and Development (OECD) has identified fourteen high priority nanomaterials for study. Cerium oxide (CeO2) nanoparticles are one among the high priority group. Recent data suggest that CeO2 nanoparticles may be toxic to lung cell lines in vitro and lung tissues in vivo. Other work has proposed that oxidative stress may play an important role in the toxicity; however, the exact mechanism of the toxicity, has to our knowledge, not been investigated. Similarly, it is not clear whether CeO2 nanoparticles exhibit systemic toxicity. Here, we investigate whether pulmonary exposure to CeO2 nanoparticles is associated with oxidative stress, inflammation and apoptosis in the lungs and liver of adult male Sprague-Dawley rats. Our data suggest that the intratracheal instillation of CeO2 nanoparticles can cause an increased lung weight to body weight ratio. Changes in lung weights were associated with the accumulation of cerium in the lungs, elevations in serum inflammatory markers, an increased Bax to Bcl-2 ratio, elevated caspase-3 protein levels, increased phosphorylation of p38-MAPK and diminished phosphorylation of ERK1/2-MAPK. Our findings from the study evaluating the possible translocation of CeO2 nanoparticles from the lungs to the liver suggest that CeO 2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase

  6. Differential susceptibilities of Holtzman and Sprague-Dawley rats to fetal death and placental dysfunction induced by 2,3,7,8-teterachlorodibenzo-p-dioxin (TCDD) despite the identical primary structure of the aryl hydrocarbon receptor

    SciTech Connect

    Kawakami, Takashige; Ishimura, Ryuta; Nohara, Keiko; Takeda, Ken; Tohyama, Chiharu . E-mail: ctohyama@m.u-tokyo.ac.jp; Ohsako, Seiichiroh

    2006-05-01

    A single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioin (TCDD) administered to pregnant Holtzman (HLZ) rats on gestational days 15 (GD15) caused placental dysfunction, resulting in fetal death (Ishimura, R., Ohsako, S., Miyabara, Y., Sakaue, M., Kawakami, T., Aoki, Y., Yonemoto, J., Tohyama, C., 2002a. Increased glycogen content and glucose transporter 3 mRNA level in the placenta of Holtzman rats after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 178, 161-171; Ishimura, R., Ohsako, S., Kawakami, T., Sakaue, M., Aoki, Y., Tohyama, C., 2002b. Altered protein profile and possible hypoxia in the placenta of 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed rats. Toxicol. Appl. Pharmacol. 185, 197-206). In order to investigate the mechanism underlying the TCDD-induced fetal death, we compared two outbred strains of rats, namely, the HLZ and the Sprague-Dawley International Genetic Standard rats (SD-IGS), a strain with characteristics resembling those of the HLZ rats. Pregnant HLZ and SD-IGS rats were administered TCDD as a single dose by gavage on GD15, as described within the parentheses (HLZ, 0, 1.6 {mu}g TCDD/kg; SD-IGS, 0, 2, 5, 10 {mu}g TCDD/kg). Whereas a high incidence (14%) of fetal death was observed on GD20 in the HLZ rats, no fetal deaths occurred in the SD-IGS rats, even at the highest dose of TCDD. A histological marker of cellular abnormality at the placental junctional zone, i.e., delay in the disappearance of the glycogen cells and cysts filled with an eosinophilic material (GC-EM), which normally disappear by GD20, was observed in the HLZ rats after exposure to the lowest dose of TCDD (1.6 {mu}g TCDD/kg), but not in the SD-IGS rats even after exposure to the highest dose of TCDD. Furthermore, maternal blood sinusoids in the labyrinth zone were constricted following exposure to TCDD in the HLZ, but not SD-IGS rats. These observations indicate that HLZ rats are more susceptible to the adverse effects of TCDD on fetal growth and

  7. NTP technical report on the toxicology and carcinogenesis studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (CAS No. 1746-01-6) in female Harlan Sprague-Dawley rats (Gavage Studies).

    PubMed

    2006-04-01

    DIOXIN TOXIC EQUIVALENCY FACTOR EVALUATION OVERVIEW: Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized, they accumulate in body tissue, mainly adipose, resulting in chronic lifetime human exposure. Since human exposure to DLCs always involves a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. TCDD is not manufactured commercially other than for scientific research purposes. The main sources of TCDD releases into the environment are from combustion and incineration; metal smelting, refining, and processing; chemical

  8. NTP toxicology and carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (Gavage Studies).

    PubMed

    2006-01-01

    DIOXIN TOXIC EQUIVALENCY FACTOR EVALUATION OVERVIEW: Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as "dioxin-like compounds" (DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized they accumulate in adipose tissue resulting in chronic lifetime human exposure. Since human exposure to DLCs always occurs as a complex mixture, the Toxic Equivalency Factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD that is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation, because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally-related polychlorinated biphenyls (PCBs) and mixtures of these compounds. 3,3',4,4',5-Pentachlorobiphenyl (PCB 126) was produced commercially before 1977 for the electric industry as a dielectric insulating fluid for transformers and capacitors. Manufacture and use of the chemical was stopped because of increased

  9. Repeated dose toxicity and relative potency of 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for induction of CYP1A1, CYP1A2 and thymic atrophy in female Harlan Sprague-Dawley rats.

    PubMed

    Hooth, Michelle J; Nyska, Abraham; Fomby, Laurene M; Vasconcelos, Daphne Y; Vallant, Molly; DeVito, Michael J; Walker, Nigel J

    2012-11-15

    In this study we assessed the relative toxicity and potency of the chlorinated naphthalenes 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) and 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chemicals were administered in corn oil:acetone (99:1) by gavage to female Harlan Sprague-Dawley rats at dosages of 0 (vehicle), 500, 1500, 5000, 50,000 and 500,000 ng/kg (PCN 66 and PCN 67) and 1, 3, 10, 100, and 300 ng/kg (TCDD) for 2 weeks. Histopathologic changes were observed in the thymus, liver and lung of TCDD treated animals and in the liver and thymus of PCN treated animals. Significant increases in CYP1A1 and CYP1A2 associated enzyme activity were observed in all animals exposed to TCDD, PCN 66 and PCN 67. Dose response modeling of CYP1A1, CYP1A2 and thymic atrophy gave ranges of estimated relative potencies, as compared to TCDD, of 0.0015-0.0072, for PCN 66 and 0.00029-0.00067 for PCN 67. Given that PCN 66 and PCN 67 exposure resulted in biochemical and histopathologic changes similar to that seen with TCDD, this suggests that they should be included in the WHO toxic equivalency factor (TEF) scheme, although the estimated relative potencies indicate that these hexachlorinated naphthalenes should not contribute greatly to the overall human body burden of dioxin-like activity.

  10. Disposition and excretion of 14C-AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) and 14c-hhcb (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-gamma-2-benzopyran) after intravenous administration to Sprague-Dawley rats and domestic pigs.

    PubMed

    Api, Anne Marie; Ritacco, Gretchen; Sipes, I Glenn

    2013-07-01

    7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN ) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB) are polycyclic musks widely used as fragrance ingredients in consumer products. Because their metabolic fate following systemic exposure is not fully characterized, disposition and excretion of (14)C-AHTN- and (14)C-HHCB-derived radioactivity were studied in Sprague-Dawley rats and domestic pigs following a single intravenous dose. Rats administered with AHTN or HHCB excreted 21% or 28% of the radioactivity in urine and 67% or 61% in feces, respectively, within 7 days. In pigs administered AHTN or HHCB, 86% or 74% of the dose was excreted in the urine, and 12% or 15% in feces, respectively, during the 14-day collection period. Radioactivity in the whole blood and plasma of both species and tissues of rats declined steadily until the end of the study (28 days) for both the materials. Radioactivity in rat adipose tissue reached peak at 2 hours after dosing, decreasing steadily thereafter. Radioactivity in pig blood declined rapidly from 70 ng equivalents/g at 10 minutes to 1 ng equivalent/g or less by 28 days after administration of either AHTN or HHCB. Radioactivity in pig skin and adipose tissue decreased to below the limit of detection by 28 days for both the materials. Thin-layer chromatography showed multiple radioactive components in both species' urine after administration of either material. Components found in the urine of the 2 species were qualitatively similar but quantitatively different. Both AHTN and HHCB were completely metabolized and excreted. No unchanged parent compound was detected in rat or pig urine.

  11. Suppression of early stages of neoplastic transformation in