Science.gov

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. 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...

  3. The conduct of a two-generation reproductive toxicity study via dermal exposure in the Sprague-Dawley rat--a case study with KBR 3023 (a prospective insect repellent).

    PubMed

    Astroff, A B; Freshwater, K J; Young, A D; Stuart, B P; Sangha, G K; Thyssen, J H

    1999-01-01

    KBR 3023, 1-(1-methyl-propoxycarbonyl)-2-(2-hydroxyethyl)-piperidine, a prospective insect repellent being developed by the Bayer Corporation, was evaluated for reproductive toxicity in the Sprague-Dawley rat. As the intended human use of the test compound is topical, the test system was also exposed to the compound via the dermal route. Specifically, the adult rats (P generation) were fitted with Elizabethan collars, to reduce the likelihood of oral ingestion, and dermally administered either 0, 50, 100, or 200 mg KBR 3023/kg body weight throughout the study (5 d/week) beginning at the onset of the 10-week premating period and continuing through the mating, gestation, and lactation phases. Clinical signs and changes in body weight and food consumption were assessed throughout the study. All adults and neonates underwent a gross necropsy examination. Tissues retained for microscopic examination from all adult animals included the kidney, liver, pituitary, reproductive organs, and samples of skin from the shaved dose site. In addition to the parameters noted above, the animals were evaluated for the effect of the test compound on estrous cycling, mating, fertility, gestation length, litter size, pup sex ratio, and pup viability. There were no test compound-related clinical signs or effects on body weight or food consumption observed in either the adults or the pups during any phase of the study. There were no compound-related effects on any reproductive or litter parameters. Dermal findings at the dose site (acanthosis and hyperkeratosis) were noted in both generations. Other than the dermal findings, no compound-related necropsy findings were seen in either the adults or the pups. No compound-related histopathologic findings were noted in the reproductive tissues of either the males or females. Based on these results, KBR 3023, administered as described in this study at dose levels as high as 200 mg/kg body weight (the physical limit of dermal application for this

  4. TOXICITY STUDIES OF EPICHLOROHYDRIN IN SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Adult male and female Sprague-Dawley rats received epichlorohydrin via gavage in distilled water for 10 consecutive days at dose levels of 3, 7, 19, and 46 mg/kg-day, and for 90 days at dose levels of 1, 5, and 25 mg/kg-day. Epichlorohydrin did not adversely effect mortality, but...

  5. Neuronal Function in Male Sprague Dawley Rats During Normal Ageing.

    PubMed

    Idowu, A J; Olatunji-Bello, I I; Olagunju, J A

    2017-03-06

    During normal ageing, there are physiological changes especially in high energy demanding tissues including the brain and skeletal muscles. Ageing may disrupt homeostasis and allow tissue vulnerability to disease. To establish an appropriate animal model which is readily available and will be useful to test therapeutic strategies during normal ageing, we applied behavioral approaches to study age-related changes in memory and motor function as a basis for neuronal function in ageing in male Sprague Dawley rats. 3 months, n=5; 6 months, n=5 and 18 months, n=5 male Sprague Dawley Rats were tested using the Novel Object Recognition Task (NORT) and the Elevated plus Maze (EPM) Test. Data was analyzed by ANOVA and the Newman-Keuls post hoc test. The results showed an age-related gradual decline in exploratory behavior and locomotor activity with increasing age in 3 months, 6 months and 18 months old rats, although the values were not statistically significant, but grooming activity significantly increased with increasing age. Importantly, we established a novel finding that the minimum distance from the novel object was statistically significant between 3 months and 18 months old rats and this may be an index for age-related memory impairment in the NORT. Altogether, we conclude that the male Sprague Dawley rat show age-related changes in neuronal function and may be a useful model for carrying out investigations into the mechanisms involved in normal ageing.

  6. Ovarian neoplasia in the Sprague-Dawley rat.

    PubMed Central

    Lewis, D J

    1987-01-01

    Macroscopic and microscopic characteristics of 210 spontaneous ovarian tumors from 7748 Sprague-Dawley rats are described. The tumors were classified as tubular adenoma, anaplastic adenocarcinoma, papillary cystadenoma, papillary cystadenocarcinoma, mesothelioma, sertoliform tubular adenoma, Sertoli's cell tumor, granulosa cell tumor, thecal cell tumor, polycystic sex cord/stromal tumor, and lipoid cell tumor. The histogenesis of the tumor types is discussed. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PLATE 17. PLATE 18. PLATE 19. PLATE 20. PLATE 21. PLATE 22. PLATE 23. PMID:2822382

  7. Pharmacological mechanisms of black cohosh in Sprague-Dawley rats.

    PubMed

    Einbond, Linda Saxe; Soffritti, Morando; Esposti, Davide Degli; Wu, Hsan-Au; Tibaldi, Eva; Lauriola, Michelina; He, Kan; Park, Taesik; Su, Tao; Huggins, Lesley; Wang, Xiaomei; Roller, Marc; Brennan, Richard

    2012-04-01

    Studies indicate that extracts and purified components from black cohosh inhibit the growth of human breast cancer cells, but the molecular targets and signaling pathways have not yet been defined. This study examines the pharmacological mechanisms and toxicological effects in the short term of the herb black cohosh on female Sprague-Dawley rats. To assess effects on gene activity and lipid content, we treated female Sprague-Dawley rats with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 or 0mg/kg. Four animals for each group were sacrificed at 1, 6 and 24h after treatment; liver tissue and serum samples were obtained for gene expression and lipid analysis. Microarray analysis of rat liver tissue indicated that black cohosh markedly downregulated mitochondrial oxidative phosphorylation genes. Phospholipid biosynthesis and remodeling, PI3-Kinase and sphingosine signaling were upregulated, driven largely by an upregulation of several isoforms of phospholipase C. Hierarchical clustering indicated that black cohosh clustered with antiproliferative compounds, specifically tubulin binding vinca alkaloids and DNA alkylators. In support of this, black cohosh repressed the expression of cyclin D1 and ID3, and inhibited the proliferation of HepG2, p53 positive, liver cancer cells. Black cohosh reduced the level of free fatty acids at 6 and 24h and triglycerides at 6h in the serum, but increased the free fatty acid and triglyceride content of the treated livers at 24h. Our results suggest that black cohosh warrants further study for breast cancer prevention and therapy. Copyright © 2011. Published by Elsevier B.V.

  8. Waxholm Space atlas of the Sprague Dawley rat brain

    PubMed Central

    Papp, Eszter A.; Leergaard, Trygve B.; Calabrese, Evan; Johnson, G. Allan; Bjaalie, Jan G.

    2014-01-01

    Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 µm isotropic voxels for the MRI volume and 78 µm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in the brain. Delineation criteria are provided for each structure. We have applied a spatial reference system based on internal brain landmarks according to the Waxholm Space standard, previously developed for the mouse brain, and furthermore connected this spatial reference system to the widely used stereotaxic coordinate system by identifying cranial sutures and related stereotaxic landmarks in the template using contrast given by the active staining technique applied to the tissue. With the release of the present atlasing template and anatomical delineations, we provide a new tool for spatial orientation analysis of neuroanatomical location, and planning and guidance of experimental procedures in the rat brain. The use of Waxholm Space and related infrastructures will connect the atlas to interoperable resources and services for multilevel data integration and analysis across reference spaces. PMID:24726336

  9. Inherited tertiary hypothyroidism in Sprague-Dawley rats.

    PubMed

    Stoica, George; Lungu, Gina; Xie, Xueyi; Abbott, Louise C; Stoica, Heidi M; Jaques, John T

    2007-05-07

    Thyroid hormones (THs) are important in the development and maturation of the central nervous system (CNS). The significant actions of THs during CNS development occur at the time when TH levels are lower than those in the mother and the hypothalamic-thyroid (HPT) axis is not fully functional. In the developing rat nervous system, primarily the cerebellum, the first three postnatal weeks represent a period of significant sensitivity to thyroid hormones. This study presents a spontaneous, inherited recessive hypothyroidism in Sprague-Dawley rats with devastating functional consequences to the development of the CNS. The clinical signs develop around 14 day's postnatal (dpn) and are characterized by ataxia, spasticity, weight loss and hypercholesterolemia. The afflicted rats died at 30 days due to severe neurological deficits. The deterioration affects the entire CNS and is characterized by progressive neuronal morphological and biochemical changes, demyelination and astrogliosis. The cerebellum, brain stem, neocortex, hippocampus and adrenal gland medulla appear to be most affected. Thyroid Stimulating Hormone (TSH), T3 and T4 levels were significantly lower in hypothyroid rats than control. Immunohistochemistry and RT-PCR demonstrated a reduction of Thyrotropin Releasing Hormone (TRH) in the hypothalamus of hypothyroid rats. The weight of both thyroid and pituitary glands were significantly less in hypothyroid rats than the corresponding normal littermate controls. Transmission electron microscopy demonstrates consistent postsynaptic dendritic, synaptic and spine alterative changes in the brain of hypothyroid rats. These data suggest that we discovered a tertiary form of inherited hypothyroidism involving the hypothalamus.

  10. Waxholm Space atlas of the Sprague Dawley rat brain.

    PubMed

    Papp, Eszter A; Leergaard, Trygve B; Calabrese, Evan; Johnson, G Allan; Bjaalie, Jan G

    2014-08-15

    Three-dimensional digital brain atlases represent an important new generation of neuroinformatics tools for understanding complex brain anatomy, assigning location to experimental data, and planning of experiments. We have acquired a microscopic resolution isotropic MRI and DTI atlasing template for the Sprague Dawley rat brain with 39 μm isotropic voxels for the MRI volume and 78 μm isotropic voxels for the DTI. Building on this template, we have delineated 76 major anatomical structures in the brain. Delineation criteria are provided for each structure. We have applied a spatial reference system based on internal brain landmarks according to the Waxholm Space standard, previously developed for the mouse brain, and furthermore connected this spatial reference system to the widely used stereotaxic coordinate system by identifying cranial sutures and related stereotaxic landmarks in the template using contrast given by the active staining technique applied to the tissue. With the release of the present atlasing template and anatomical delineations, we provide a new tool for spatial orientation analysis of neuroanatomical location, and planning and guidance of experimental procedures in the rat brain. The use of Waxholm Space and related infrastructures will connect the atlas to interoperable resources and services for multi-level data integration and analysis across reference spaces. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. 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

  12. Leptin Influences Healing in the Sprague Dawley Rat Fracture Model

    PubMed Central

    Liu, Pengcheng; Cai, Ming

    2017-01-01

    Background Leptin plays a crucial role in bone metabolism, and its level is related to bone callus formation in the fracture repair process. The objective of this study was to evaluate the effect of recombinant leptin on the healing process of femoral fractures in rats. Material/Methods Forty-eight male Sprague Dawley (SD) rats with an average body weight of 389 g (range: 376–398 g) and an average age of 10 weeks were included in this animal research, and all rats were randomly divided into two major groups. Then standardized femur fracture models were implemented in all SD rats. Rats in the control group were treated with only 0.5 mL of physiological saline, and rats in the experimental group were treated with recombinant leptin 5 μg/kg/d along with the same 0.5 mL of physiological saline for 42 days intraperitoneally. At the same time, each major group was evenly divided into three parallel subgroups for each parallel bone evaluation separately at the second, fourth, and sixth weeks. Each subgroup included eight rats. Results The total radiological evaluation results showed that the healing progress of femoral fracture in the experimental group was superior to that in the control group from the fourth week. At the sixth week, experimental group rats began to present significantly better femoral fracture healing progress than that of the control group rats. Results of biomechanics show the ultimate load (N) and deflection ultimate load (mm) of the experimental group rats was significantly increased compared with that of the control group rats from the fourth week. Conclusions Our results suggest that leptin may have a positive effect on SD rat femur fracture healing. PMID:28088810

  13. Effects of Ammonium Perchlorate on the Thyroid Hormone Levels of the Sprague-Dawley Rat.

    DTIC Science & Technology

    1995-12-01

    The purpose of this research was to determine the threshold dose for ammonium perchlorate (AP) in the Sprague-Dawley rat. No dose response data exist...consortium of DoD and industry representatives, believes this provisional reference dose is too conservative. This experiment was executed to provide dose ... response data on which to base a more accurate reference dose. The study consisted of eight groups of 12 Sprague-Dawley rats, six male and six female

  14. 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.

  15. 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.

  16. Comparative effects of X irradiation on the testes of adult Sprague-Dawley and Wistar rats.

    PubMed

    Delic, J I; Schlappack, O K; Harwood, J R; Stanley, J A

    1987-10-01

    The response of the testes of two strains of adult rats (Sprague-Dawley and Wistar) to graded single doses and split doses of 230 kVp X rays has been investigated. A marked difference was noted between the strains in the response of the clonogenic spermatogonia to irradiation, as measured histologically by the repopulation index. Single-dose response curves derived for these cells in the Sprague-Dawley strain had a much larger shoulder (up to about 4-5 Gy) than for the Wistar (less than 2 Gy). Split-dose studies revealed that this difference may partly be explained by a greater repair capacity in the cells of the Sprague-Dawley strain. Changes in serum FSH concentrations mirrored the changes in clonogenic spermatogonial survival following split doses of radiation.

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. Behavioral Effects of Enrichment and Nicotine in Male Sprague Dawley Rats

    DTIC Science & Technology

    2008-10-01

    Sprague Dawley rats. Behavioural Brain Research , 165, 187-196. 89 Faraday, M. M., Elliott, B. M., Phillips, J. M., & Grunberg, N. E...novelty exploration in rats can be explained by habituation. Behavioural Brain Research , 121, 11-20. 96 Appendix A: Housing Pictures

  5. 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...

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

    USDA-ARS?s Scientific Manuscript database

    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...

  7. 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...

  8. 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...

  9. 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 ...

  10. 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 ...

  11. Polysorbate 20 increases oral absorption of digoxin in wild-type Sprague Dawley rats, but not in mdr1a(-/-) Sprague Dawley rats.

    PubMed

    Nielsen, Carsten Uhd; Abdulhussein, Ahmed A; Colak, Dilan; Holm, René

    2016-11-20

    The aim was to investigate the ability of polysorbate 20 to alter oral digoxin absorption in vitro and drug exposure in vivo via modulation of transporter mediated efflux. Transport studies were performed in MDCKII-MDR1 and Caco-2 cells using (3)H-digoxin. Pharmacokinetic studies were performed in wild type and mdr1a deficient Sprague Dawley rats. (3)H-digoxin was quantified using liquid scintillation counting. The results showed an increased absorptive transport and a reduced secretory transport in MDCKII-MDR and Caco-2 cells as a function of polysorbate 20 concentrations. The secretory transport (B-A) of digoxin was reduced by 50% at lower polysorbate 20 concentrations than required to increase the absorptive transport (A-B). In vivo, the oral bioavailability of digoxin in wild type animal was increased by 10-25% (w/v) polysorbate 20. In mdr1a deficient Sprague Dawley rats 25% (w/v) polysorbate 20 did not alter the absorption of digoxin after oral administration, but digoxin exposure was significantly different between wild type and mdr1a deficient rats. In conclusion, polysorbate 20 increased absorptive transport across Caco-2 cell monolayers and in vivo in rats in a concentration dependent manner, most likely via inhibition of P-gp rather than through solubilization of digoxin. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Protection against cisplatin ototoxicity in a Sprague-Dawley rat animal model

    PubMed Central

    Giordano, P; Lorito, G; Ciorba, A; Martini, A; Hatzopoulos, S

    2006-01-01

    Summary Cisplatin (CDDP) is an anti-neoplastic drug extensively used in cases of head and neck cancer. Cisplatin induces numerous untoward side-effects including ototoxicity. In this study, cisplatin ototoxicity in Sprague-Dawley rat animal model has been evaluated and the oto-protection provided by the systemic administration of the antioxidant drug D-methionine has been tested. A total of 12 Sprague-Dawley rats were used: 8 were treated intra-peritoneally with D-methionine (300 mg/kg) and cisplatin (16 mg/kg, slow 30 min-infusion), 4 only with cisplatin. The hearing threshold of the animals was evaluated by electrophysiological procedures as Otoacoustic Emissions and Auditory Brainstem Responses. The effects of protection were evaluated after 72 hours. The data from the Otoacoustic Emissions (in the 4.0–12 kHz band) and Auditory Brainstem Responses recordings suggested that D-methionine can partially protect from Cisplatin ototoxicity. PMID:18236636

  13. Sprague-Dawley and Fischer female rats differ in acute effects of fluoxetine on sexual behavior.

    PubMed

    Miryala, Chandra Suma J; Hiegel, Cindy; Uphouse, Lynda

    2013-02-01

    The selective serotonin reuptake inhibitor (SSRI), fluoxetine, leads to sexual dysfunction in a substantial proportion of women. In studies with the Fischer inbred rat, the 5-HT(1A) receptor has been implicated in this sexual dysfunction. Whether this association with 5-HT(1A) receptors holds for other rat strains is not known. The effects of acute fluoxetine on sexual behavior in two strains of rats that differ in their response to a 5-HT(1A) receptor agonist were examined. Whether the strain difference is comparable in naturally cycling and hormonally primed, ovariectomized rats was determined. Proestrous rats and ovariectomized rats, hormonally primed with estradiol benzoate and progesterone, were treated with varying doses of fluoxetine. Sexual behavior was examined before and after treatment with the SSRI. Lordosis to mount ratios, lordosis quality, and proceptive behaviors were quantified. Sprague-Dawley and Fischer females were compared on each of these measures. The IC(50) for inhibition of lordosis behavior was determined. In both the intact and the hormonally primed, ovariectomized model, Sprague-Dawley females were less sensitive to the effects of fluoxetine on sexual behavior. In both groups, fluoxetine showed dose dependency in behavioral inhibition, but a higher dose was required for Sprague-Dawley than for Fischer females. Naturally cycling, proestrous rats required a higher dose of fluoxetine than hormonally primed ovariectomized rats to produce significant inhibition of sexual behavior. Thus, the strain difference in the response to fluoxetine does not parallel strain differences in the response to a 5-HT(1A) receptor agonist. Acute treatment with fluoxetine inhibits lordosis behavior in both Fischer and Sprague-Dawley females and the strain difference cannot be explained by reported strain differences in the response to a 5-HT(1A) receptor agonist. Fluoxetine's inhibition of female rat sexual behavior may involve effects of the SSRI in addition to

  14. Acute Oral Toxicity of Trimethylolethane Trinitrate (TMETN) in Sprague- Dawley Rats

    DTIC Science & Technology

    1989-07-01

    61 LeTellier et al.--16 Appendix A: CHEMICAL DATA Chemical Name: 1,3- Propanediol , 2-methyl-2 [(nitroxy)methyl]-dinitrate (ester) Other Names: 1,3... Propanediol -2-(hydroxymethyl)-2-methyl-, trinitrate; 1,1,1-trimethylolethane trinitrate (TMETN), metriol trinitrate (MTN); nitropentaglycerin Lot... Propanediol , 2-(hydroxymethyl)- 2-methyl -, trinitrate (TMETN). Species: Rat Strain: Sprague-Dawley. History: See LAIR SOP-OP-STX-36. Animals that

  15. Antidepressants and REM sleep in Wistar-Kyoto and Sprague-Dawley rats.

    PubMed

    Ivarsson, Magnus; Paterson, Louise M; Hutson, Peter H

    2005-10-17

    Compared to other rat strains, the Wistar-Kyoto rats show increased amount of REM sleep, one of the characteristic sleep changes observed in depressed patients. The aims of this study were firstly to validate a simple sleep stage discriminator and then compare the effect of antidepressants on suppression of rapid eye movement (REM) sleep in Wistar-Kyoto rats and an outbred rat strain (Sprague-Dawley). Rats were implanted with telemetry transmitters with electroencephalogram/electromyogram electrodes. Following recovery, the animals were orally dosed at light onset with either desipramine (20 mg/kg), fluoxetine (10 mg/kg), citalopram (10 or 40 mg/kg) or vehicle in a cross-over design. Every 12-s epoch was automatically scored as WAKE, NREM or REM sleep. Results confirm that Wistar-Kyoto rats show increased amount of REM sleep and decreased REM latency compared with Sprague-Dawley rats. All antidepressants significantly suppressed REM sleep in Sprague-Dawley rats, but only the high dose of citalopram suppressed REM sleep in Wistar-Kyoto rats. These findings suggest that the enhanced REM activity in Wistar-Kyoto rats is less sensitive to the effect of antidepressants and therefore does not provide any additional predictive validity for assessing antidepressant efficacy.

  16. 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

    2015-05-21

    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.

  17. Congenital dystrophic epidermolysis bullosa (DEB) in Sprague Dawley rats: a case series.

    PubMed

    Eden, Kristin B; Peterson, Ashley; Payne, Harold R; Corapi, Wayne V; Mansell, Joanne; Hoffman, Aline Rodrigues

    2016-04-01

    Epidermolysis bullosa is a rare skin disease caused by defects in the basement membrane and/or other dermoepidermal junction components. We describe a series of spontaneous cases of dystrophic epidermolysis bullosa (DEB) in a colony of Sprague Dawley rats investigated with histopathology, transmission electron microscopy (TEM) and inheritance pattern. Four, 4-day-old pups from a litter of Sprague Dawley rats developed blistering, haemorrhagic skin lesions and were euthanized. Age-matched controls from the same litter were normal. Several months later two more litters presented with identical findings. All three litters had the same sire, suggesting a genetic component. Skin from affected and control animals was evaluated histologically and with TEM. Unaffected sibling pairs from affected litters were bred in order to potentially reproduce the disease and determine the mode of inheritance. Histologically, there was significant dermoepidermal clefting below the basement membrane with variable amounts of haemorrhage and cellular debris within the clefts. Ultrastructurally, clefting occurred below the basement membrane with an intact lamina densa and normal hemidesmosomes. Anchoring filaments were strikingly absent. Litters produced from phenotypically unaffected sibling pairs resulted in a total of four more litters with approximately a quarter of pups affected. Based on the gross lesions, histopathological features and TEM determination of separation below the lamina densa and lack of normal anchoring fibrils, these cases are most consistent with DEB. This is the first report of naturally occurring, localized and reproducible recessive DEB in Sprague Dawley rats. © 2016 ESVD and ACVD.

  18. Dose (and Time Dependent) Blockade of Pregnancy in Sprague-Dawley Rats Administered Ammonium Dinitramide in the Drinking Water

    DTIC Science & Technology

    1995-11-01

    hypokalemia was noted in both sexes. The major effect noted in the study was a dose-dependent blockade of pregnancy . Only 9 and 25% of female rats...AL/OE-TR-1995-0181 UNITED STATES AIR FORCE ARMSTRONG LABORATORY DOSE (AND TIME DEPENDENT) BLOCKADE OF PREGNANCY IN SPRAGUE-DAWLEY RATS...TITLE AND SUBTITLE Dose (and Time Dependent) Blockade of Pregnancy in Sprague-Dawley Rats Administered Ammonium Dinitramide in the Drinking Water 6

  19. [Microbiological composition of dental plaque using Sprague Dawley rats as an experimental model].

    PubMed

    Sánchez, F R; Perrone, M; Acevedo, A M

    1990-01-01

    In this study, the microbiological composition of the dental plaque in 12 male Sprague-Dawley rats was determined. Analysis using the light microscope showed the presence of nine colonies which suggested the presence of cocci, (6) diplococci (1) and rods. (2) Five of the bacteria were Gram positive and three were Gram negative. The morphological characteristic suggested the presence of Actinomyces in the case of Gram positive rods; Fusobacterium in the case of Gram negative rods; Neisseria and Veillonella in the of Gram negative cocci and Streptococci for the rest of the colonies. The biochemical characterization of the bacteria suggested the absence of Streptococcus mutans in the dental plaque of this animals.

  20. 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

  1. Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats.

    PubMed

    Weber, Klaus

    2017-01-01

    A substantial quantity of data on Sprague-Dawley (SD) and Hannover Wistar rats strains have been published concerning their source, diet, and housing conditions, as well as the incidences of nonneoplastic lesions and neoplasms observed in different laboratories. Differences between the commonly used rat strains provided by different breeders (i.e., CD (SD) vs. Harlan Sprague-Dawley strain or Crl: WI(Han) vs. Wistar Hannover (Han)-derived strain, continued breeding by RCC Ltd., Switzerland, thereafter continued breeding by Harlan) may include, but are not limited to, body weight, incidence, and onset of major nonneoplastic lesions and neoplasms, and these can impact the development of a nonclinical safety program. Fisher 344 (F344) and SD rat strains generally have the highest tumor incidences, exceeding that in Wistar rats. Certain tumors are more commonly observed in one strain, and for some, the difference in incidence may be so significant that the tumor may even be considered characteristic for a specific strain (e.g., thymoma in Wistar and amphophilic renal adenoma in SD).

  2. Effect of calcium phosphate glass on bone formation in calvarial defects of Sprague-Dawley rats.

    PubMed

    Moon, Hyun-Ju; Kim, Kyoung-Nam; Kim, Kwang-Mahn; Choi, Seong-Ho; Kim, Chong-Kwan; Kim, Kee-Deog; LeGeros, Racquel Z; Lee, Yong-Keun

    2006-09-01

    The purpose of this study was to investigate the bone regenerative effect of calcium phosphate glass in vivo. We prepared two different sizes of calcium phosphate glass powder using the system CaO-CaF2-P2O5-MgO-ZnO; the particle size of the powders were 400 microm and 40 microm. 8 mm calvarial critical-sized defects were created in 60 male Sprague-Dawley rats. The animals were divided into 3 groups of 20 animals each. Each defect was filled with a constant weight of 0.5 g calcium phosphate glass powder mixed with saline. As controls, the defect was left empty. The rats were sacrificed 2 or 8 weeks after postsurgery, and the results were evaluated using radiodensitometric and histological studies; they were also examined histomorphometrically. When the bigger powders with 400 microm particle were grafted, the defects were nearly completely filled with new-formed bone in a clean healing condition after 8 week. When smaller powders with 40 microm particle were transplanted, new bone formation was even lower than the control group due to a lot of inflammatory cell infiltration. It was concluded that the prepared calcium phosphate glass enhanced the new bone formation in the calvarial defect of Sprague-Dawley rats and it is expected to be a good potential materials for hard tissue regeneration. The particle size of the calcium phosphate was crucial; 400 microm particles promoted new bone formation, while 40 microm particles inhibited it because of severe inflammation.

  3. Bone formation in calvarial defects of Sprague-Dawley rats by transplantation of calcium phosphate glass.

    PubMed

    Moon, Hyun-Ju; Kim, Kyoung-Nam; Kim, Kwang-Mahn; Choi, Seong-Ho; Kim, Chong-Kwan; Kim, Kee-Deog; LeGeros, Racquel Z; Lee, Yong-Keun

    2005-09-01

    The purpose of this study was to investigate the bone-regenerative effect of calcium phosphate glass in vivo. We prepared amorphous calcium phosphate glass powder having a mean particle size of 400 microm in the system CaO-CaF2-P2O5-MgO-ZnO. Calvarial critical-sized defects (8 mm) were created in 60 male Sprague-Dawley rats. The animals were divided into an experimental group and control group of 30 animals each. Each defect was filled with a constant weight of 0.5 g calcium phosphate glass powder mixed with saline. As a control, the defect was left empty. The rats were sacrificed 2, 4, or 8 weeks postsurgery, and the results evaluated using radiodensitometric and histological studies; they were also examined histomorphometrically. When the calcium phosphate glass powders with 400-microm particles were grafted, the defects were nearly completely filled with new-formed bone in a clean healing condition after 8 weeks. It was observed that the prepared calcium phosphate glass enhanced new bone formation in the calvarial defect of Sprague-Dawley rats and could be expected to have potential for use as a hard tissue regeneration material.

  4. 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

  5. Chemopreventive potential of black cohosh on breast cancer in Sprague-Dawley rats.

    PubMed

    Einbond, Linda Saxe; Soffritti, Morando; Degli Esposti, Davide; Tibaldi, Eva; Lauriola, Michelina; Bua, Luciano; He, Kan; Genovese, Giannicola; Su, Tao; Huggins, Lesley; Wang, Xiaomei; Roller, Marc; Wu, Hsan-Au

    2012-01-01

    This study examines the chemopreventive potential and action of the herb black cohosh on Sprague-Dawley rats. Female Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 (Group I), 7.14 (Group II), 0.714 (Group III) or 0 mg/kg b.w. for 40 weeks starting from 56 weeks of age and the incidence of benign and malignant mammary tumors was determined at the end of observation. Among female rats treated at 35.7 and 7.14 mg/kg b.w. there was a dose-related reduction (p<0.05) of the incidence of mammary adenocarcinomas when compared to the treatment of 0.714 mg/kg b.w., with a protection index (calculated relative to the group III; PI=[total tumours × 100 animals of group III] - [total tumours × 100 animals of the group I (or group II)]/ [total tumours of group III] × 100) for mammary adenocarcinomas of 87.5 and 48.8%, respectively. Black cohosh reduced Ki-67 and cyclin D1 protein expression in fibroadenomas, by immunohistochemistry. Our results suggest that black cohosh may have chemopreventive potential for mammary cancer.

  6. Three-Dimensional Study of the Terminal Portion in Sprague-Dawley Rat Ejaculatory Ducts.

    PubMed

    Motohashi, M; Inomata, T; Takahashi, H; Ichihara, N; Kansaku, N; Ikegami, M; Asari, M; Mutou, T; Wakui, S

    2016-08-01

    In mammals, a pair of ejaculatory ducts exists in the urethra at the seminal colliculus. The detailed anatomical structures of the distal end of the ejaculatory ducts of Sprague-Dawley rats were investigated by the computer-assisted three-dimensional reconstruction analysis using light-microscopic serial sections. A three-dimensional reconstruction revealed that in adult rats, the ejaculatory sinus pair consists of two parts: the cranial section - a compartment region composed of a fusion of the ampullary gland duct and the seminal vesicle duct, and the caudal section - a grooved region composed of a long slitlike ejaculatory ostium that extends into the urethra on both sides of the seminal colliculus. But the sphincter structure was not observed. The long axis of the compartment region was approximately 58 μm in length, and that of the groove region was approximately 495 μm. Although many epithelial glands ducts were distributed throughout the ejaculatory sinuses, the prostate and coagulation gland ducts did not open in these sinuses. The urethra was composed of transitional epithelium, while the ejaculatory sinuses were composed of single to stratified cuboidal epithelium. The ejaculatory ducts continued to the ejaculatory ostium in male adult Sprague-Dawley rat were composed of the seminal vesicle ducts received the ampullary gland ducts.

  7. Teratogenic effect of the water extract of bitter gourd (Momordica charantia) on the Sprague Dawley rats.

    PubMed

    Uche-Nwachi, Edward O; McEwen, Carol

    2009-10-15

    It has been reported that the water extract of the whole unripe fruit of Momordica charantia can significantly reduce blood glucose levels. However the safety of its use during pregnancy has not been fully investigated. The aim of this investigation is to determine the safety of this extract during pregnancy. The water extract of the unripe fruit was given to pregnant Sprague Dawley rats on days 7, 8, 9, 10, 11, 12, 13 and 14 of gestation. The litter size was determined for each group and the litters were examined for gross malformations. The gross and histological examinations of various organs of the litters were also carried out. Results show that 8.65% of the litters from experimental animals were malformed as against 1.62% of control. It also showed that 31.2% of all the malformed litters had multiple congenital malformations. It also showed that the experimental rats had nine resorption sites while control had none. This demonstrates that the water extract of Momordica charantia is teratogenic in Sprague Dawley rats and should be used with caution in man.

  8. Yawning reduces facial temperature in the high-yawning subline of Sprague-Dawley rats.

    PubMed

    Eguibar, Jose R; Uribe, Carlos A; Cortes, Carmen; Bautista, Amando; Gallup, Andrew C

    2017-01-03

    Yawning is a stereotyped behavior that enhances blood flow to the skull, and the resulting counterflow has been hypothesized as a mechanism for brain cooling. Studies have shown that yawns are strongly associated with physiological and pathological conditions that increase brain temperature, and that they are followed by equivalent decreases in brain temperature. However, measured reductions in cranial or facial temperatures following yawning have yet to be reported, to our knowledge. To accomplish this, we used a subline of Sprague-Dawley rats that yawn at a much greater rate (20 yawns/h) than do outbred Sprague-Dawley rats (2 yawns/h). Using an infrared camera, we effectively evaluated thermal changes in the cornea and concha of these rats before, during, and after yawns. The maximum temperature in both regions significantly decreased 10 s following yawns (concha: -0.3 °C, cornea: -0.4 °C), with a return to basal temperatures after 20 s. This study is the first clear demonstration of yawning-induced thermal cooling on the surface of the face, providing convergent evidence that this behavior plays a functional role in thermoregulation. As other studies have demonstrated that yawning is capable of reducing cortical brain temperature, our current data support the idea that yawning functions as a thermoregulator, affecting all structures within the head.

  9. Chemopreventive effect of quercetin in MNU and testosterone induced prostate cancer of Sprague-Dawley rats.

    PubMed

    Sharmila, Govindaraj; Athirai, Thavadurainathan; Kiruthiga, Balakrishnan; Senthilkumar, Kalimuthu; Elumalai, Perumal; Arunkumar, Ramachandran; Arunakaran, Jagadeesan

    2014-01-01

    Prostate cancer becomes an ideal target for chemoprevention because of its high incidence and extended natural history. The consumption of quercetin (plant flavonoid) in diet is associated with decreased risk of disease and many cancers but then this was not elucidated in prostate malignancy. Hence, a study in which the male Sprague-Dawley rats were induced prostate cancer by hormone (testosterone) and carcinogen (MNU) and simultaneously supplemented with quercetin (200 mg/Kg body weight) thrice a week, was conducted. After the treatment period, rats were killed; ventral and dorsolateral lobes of the prostate were dissected. Histology and oxidative stress markers LPO, H2O2, and antioxidant GSH level were measured in both lobes. The lipid peroxidation, H2O2, in (MNU+T) treated rats were increased and GSH level was decreased, whereas simultaneous quercetin-treated rats reverted back to normal level in both ventral and dorsolateral regions. The different patterns of PIN were observed with associated hyperplasia and dysplasia; changes in these regions and the occurrence of this lesion were reduced in simultaneous quercetin-treated rats. The study concluded that dietary quercetin prevented MNU + T-induced prostate carcinogenesis on both ventral and dorsolateral lobes of Sprague-Dawley rats.

  10. 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.

  11. Toxicological Assessment of the Cochleate Derived from Neisseria meningitidis Proteoliposome in Sprague Dawley Rats

    PubMed Central

    Infante-Bourzac, Juan Francisco; Sifontes-Rodríguez, Sergio; Arencibia-Arrebola, Daniel Francisco; Hernández-Salazar, Tamara; Fariñas-Medina, Mildrey; Pérez, Oliver

    2012-01-01

    Background: The AFCo1 cochleate is a potential novel adjuvant derived from Neisseria meningitidis B proteoliposome. Aim: The aim was to assessing the safety of AFCo1 by single and repeated doses in Sprague Dawley rats. Materials and Methods: Rats were grouped for treatment with AFCo1, placebo formulation or control. The first study was a single intranasal dose of 100 μl and monitoring body weight, water, and food intakes as well as clinical symptoms. Fourteen days later the rats were killed and anatomopathological studies were conducted. In a second study, four similar doses of the test substance were instilled every 5 days. Clinical observations were carried out as for the single dose study and a number of rats from each group were killed 3 and 14 days after the last dose in order to conduct hematological, hemochemical, and anatomopathological studies. Results: No variable showed differences of toxicological relevance; the histological changes found were mild and similarly frequently in the three groups. According to the irritability index calculated form histology of the nasal region, AFCo1 was also classified as nonirritating. Conclusion: AFCo1 is potentially safe for human use by nasal route as evidenced by the absence of local and systemic signs of toxicity in Sprague Dawley rats. PMID:22454827

  12. 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.

  13. An Automated Self-similarity Analysis of the Pulmonary Tree of the Sprague-Dawley Rat

    SciTech Connect

    Einstein, Daniel R.; Neradilak, Blazej; Pollisar, Nayak; Minard, Kevin R.; Wallis, Chris; Fanucchi, M.; Carson, James P.; Kuprat, Andrew P.; Kabilan, Senthil; Jacob, Rick; Corley, Rick

    2008-12-01

    Abstract In this study, we present an automated method for tabulating geometric information of biological trees, based on magnetic resonance imaging data of silicone casts of the pulmonary airway trees of Sprague Dawley rats. From a segmentation of the airway tree, we construct a scale-invariant triangulated surface that is subsequently distilled into a connected graph, representing the airway centerline. Segment statistics are derived from this graph. To validate the method, these statistics are compared to manual measurements of a single lung cast. Subsequently, we analyze the morphometry of the airway tree by assembling individual airway segments into structures that span multiple generations, which we call branches. We show that branches not segments are the fundamental repeating unit in the rat lung and develop a parameterization of these structures for the entire lung. Our analysis shows that airway diameters and lengths have both a deterministic and stochastic character and can be described by a simple set of equations.

  14. 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.

  15. Lack of evidence for an impairment of tuberoinfundibolar dopaminergic neurons in aged male rats of the Sprague-Dawley strain.

    PubMed

    Amoroso, S; Di Renzo, G F; Maurano, F; Maida, P; Taglialatela, M; Annunziato, L

    1987-01-01

    Circulating prolactin (PRL) levels, dopamine (DA) content, in vitro basal and stimulus-evoked endogenous DA release from arcuate-periventricular nuclei median-eminence fragments were studied in young (4 months) and old (24-25 months) male rats of Sprague-Dawley strain. Serum PRL levels did not differ in young and aged animals. In addition DA tissue content, basal and K+- or d-amphetamine evoked endogenous DA release did not show age-related differences. These results suggest that in male rats of the Sprague-Dawley strain the activity of tuberoinfundibular dopaminergic (TIDA) neurons does not change during senescence, unlike what happens in other strains of rats.

  16. Sprague-Dawley rats obtained from different vendors exhibit distinct adrenocorticotropin responses to inflammatory stimuli.

    PubMed

    Turnbull, A V; Rivier, C L

    1999-09-01

    The purpose of this work was to compare the plasma adrenocorticotropin (ACTH), corticosterone and interleukin-6 (IL-6) responses that rats of the outbred Sprague-Dawley strain obtained from two different vendors: Charles River (CR) and Harlan (HSD). Basal plasma ACTH and IL-6 concentrations were similar in rats from either vendor (HSD or CR), while CR animals exhibited slightly elevated corticosterone levels in late afternoon. Inflammatory stimuli such as lipopolysaccharide (LPS) (1 microgram/kg, i.v.) or turpentine (50 microliter/100 g, i.m.) which induce the production of endogenous cytokines, produced a significantly larger ACTH response in CR, compared to HSD rats, while the overall corticosterone responses were comparable in both rat groups. This could probably not be accounted for by a greater ACTH responsiveness in CR rats per se because CR and HSD rats showed similar peak ACTH responses to electrofootshock. Furthermore, in contrast to when the stimulus was one that induced endogenous cytokine production, the administration of exogenous interleukin-1beta (IL-1beta, 200 ng/kg, i.v.) produced a 2-fold greater rise in plasma ACTH concentrations in HSD rats compared to CR rats. The plasma IL-6 responses to the inflammatory stimuli showed a similar pattern to ACTH, with LPS and turpentine tending to pruduce greater IL-6 responses in CR rats, though these differences were not statistically significant. In contrast HSD rats had a significantly greater IL-6 response to IL-1beta than did CR rats. Collectively, these results show that Sprague-Dawley rats obtained from different commercial sources can differ in immune-neuroendocrine responses to inflammatory stimuli.

  17. 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.

  18. 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

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

    PubMed

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

    2012-11-01

    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.

  20. Ameliorative Effect of Curcumin on Olanzapine-induced Obesity in Sprague-Dawley Rats.

    PubMed

    Parasuraman, Subramani; Zhen, Khor Ming; Banik, Urmila; Christapher, Parayil Varghese

    2017-01-01

    To evaluate the effect of curcumin on olanzapine-induced obesity in rats. Sprague-Dawley (SD) rats were used for experiments. The animals were divided into six groups, namely, normal control, olanzapine control, betahistine (10 mg/kg), and curcumin 50, 100, and 200 mg/kg treated groups. Except the normal control group, all other animals were administered with olanzapine 4 mg/kg intraperitoneally to induce obesity. The drugs were administered once daily, per oral for 28 days. During the experiment, body weight changes and behavior alterations were monitored at regular intervals. At the end of the experiment, blood sample was collected from all the experimental animals for biochemical analysis. Part of the liver and kidney tissues was harvested from the sacrificed animals and preserved in neutral formalin for histopathological studies. Curcumin showed a significant reduction in olanzapine-induced body weight gain on the rats and improved the locomotor effects. The effect of curcumin on olanzapine-induced body weight gain is not comparable with that of betahistine. This study has shown metabolic alteration effect of curcumin on olanzapine, an antipsychotic drug, treated SD rats. Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia and bipolar disorder. Obesity is an adverse effect of olanzapine, and the present study was made an attempt to study the effect of curcumin on olanzapine-induced obesity in rats. In this present study, curcumin significantly reduced olanzapine-induced body weight gain in rats. Abbreviations Used: 5HT: 5-hydroxytryptamine, ALP: Alkaline phosphatase, ALT: Alanine transaminase, ANOVA: Analysis of variance, AST: Aspartate transaminase, CMC: Carboxymethyl cellulose, D: Dopamine, H and E: Hematoxylin and Eosin stain, H: Histamine, HDL-C: Highdensity lipoprotein cholesterol, IP: Intraperitoneal, MAO: Monoamine oxidase, NaOH: Sodium hydroxide, SD rats: Sprague Dawley rats, TCs: Total cholesterols, TG: Triglyceride.

  1. 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

  2. Metformin, but not exercise training, increases insulin responsiveness in skeletal muscle of Sprague-Dawley rats.

    PubMed

    Borst, S E; Snellen, H G

    2001-08-17

    We assessed the effects of combined metformin treatment and exercise training on body composition, on insulin concentration following glucose loading, on insulin-stimulated glucose transport in skeletal muscle, and on muscle glycogen content. Male Sprague-Dawley rats were treated for 35 days with or without metformin (320 mg/kg/day) and/or treadmill exercise training (20 min at 20 m/min, 5 days/wk). Because metformin reduces food intake, pair-fed controls were included. Metformin, training, and pair-feeding all decreased food intake, body weight, and insulin concentration following glucose loading. Metformin and training reduced intra-abdominal fat, but pair feeding did not. In isolated strips derived from soleus, epitrochlearis and extensor carpi ulnaris muscles, metformin increased insulin-stimulated transport of [3H]-2-deoxyglucose by 90%, 89% and 125%, respectively (P < 0.02) and training increased [3H]-2-deoxyglucose transport in the extensor carpi ulnaris muscle only (66%, P < 0.05). Pair-feeding did not alter [3H]-2-deoxyglucose transport. Training increased gastrocnemius muscle glycogen by 100% (P < 0.001). Metformin and pair-feeding did not alter muscle glycogen. We conclude that metformin reverses the maturation-induced impairment of insulin responsiveness in Sprague-Dawley rats by increasing insulin-stimulated glucose transport in skeletal muscle and that this effect is not secondary to reduced food intake. We also conclude that metformin and exercise training may increase insulin sensitivity by different mechanisms, with training causing increased glucose transport only in some muscles and also causing increased muscle glycogen storage.

  3. Mephedrone (4-methylmethcathinone) supports intravenous self-administration in Sprague-Dawley and Wistar rats

    PubMed Central

    Aarde, S. M.; Angrish, D.; Barlow, D.J.; Wright, M. J.; Vandewater, S. A.; Creehan, K.M.; Houseknecht, K. L.; Dickerson, T. J.; Taffe, M. A.

    2013-01-01

    Recreational use of the drug 4-methylmethcathinone (mephedrone; 4-MMC) became increasingly popular in the United Kingdom in recent years, spurred in part by the fact it was not criminalized until April of 2010. Although several fatalities have been associated with consumption of 4-MMC and cautions for recreational users about its addictive potential have appeared on Internet forums, very little information about abuse liability for this drug is available. This study was conducted to determine if 4-MMC serves as a reinforcer in a traditional intravenous self-administration model. Groups of male Wistar and Sprague-Dawley rats were prepared with intravenous catheters and trained to self-administer 4-MMC in one hour sessions. Per infusion doses of 0.5 and 1.0 mg/kg were consistently self-administered resulting in greater than 80% discrimination for the drug-paired lever and mean intakes of about 2–3 mg/kg/hr. Dose-substitution studies after acquisition demonstrated that the number of responses and/or the total amount of drug self-administered varied as a function of dose. In addition, radiotelemetry devices were employed to show that self-administered 4-MMC was capable of increasing locomotor activity (Wistar) and decreasing body temperature (Sprague-Dawley). Pharmacokinetic studies found the T1/2 of 4-MMC was about an hour in vivo in rat plasma and 90 minutes using in vitro liver microsomal assays. This study provides evidence of stimulant-typical abuse liability for 4-MMC in the traditional preclinical self-administration model. PMID:23363010

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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 ...

  9. 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...

  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. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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 ...

  16. 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 ...

  17. 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...

  18. Anticancer Potential of Nutraceutical Formulations in MNU-induced Mammary Cancer in Sprague Dawley Rats

    PubMed Central

    Pitchaiah, Gummalla; Akula, Annapurna; Chandi, Vishala

    2017-01-01

    Background: Nutraceuticals help in combating some of the major health problems of the century including cancer, and ‘nutraceutical formulations’ have led to the new era of medicine and health. Objective: To develop different nutraceutical formulations and to assess the anticancer potential of nutraceutical formulations in N-methyl-N-nitrosourea (MNU)-induced mammary cancer in Sprague Dawley rats. Materials and Methods: Different nutraceutical formulations were prepared using fine powders of amla, apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed. The anticancer potential of nutraceutical formulations was evaluated against MNU-induced mammary cancer in female Sprague Dawley rats. Results: Improvement in total phenolic content was significant (P < 0.001) after self-fortification process. Toxicity studies showed that the nutraceutical formulations were safe to use in animals. Microbial load was within the limits. Significant longer tumor-free days (P < 0.01), lower tumor incidence (P < 0.01), lower tumor multiplicity (P < 0.05) and tumor burden (P < 0.01) were observed for nutraceutical formulation-treated groups. Conclusion: Combination of whole food-based nutraceuticals acted synergistically in the prevention of mammary cancer. Further, the process of fortification is novel and enhanced the anticancer potential of nutraceutical formulations. SUMMARY Nutraceuticals help in combating some of the major health problems of the century including cancer, and ‘nutraceutical formulations’ have led to the new era of medicine and health. In this study, different nutraceutical formulations using fine powders of amla, apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate. Total phenolic content, acute oral toxicity, and microbial load of nutraceutical formulations were assessed

  19. Effects of handling and vehicle injections on adrenocorticotropic and corticosterone concentrations in Sprague-Dawley compared with Lewis rats.

    PubMed

    Deutsch-Feldman, Molly; Picetti, Roberto; Seip-Cammack, Katharine; Zhou, Yan; Kreek, Mary Jeanne

    2015-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a key factor in the trajectory of the addiction-like cycle (a pattern of behavior characterized by escalating drug use, withdrawal, and relapse) in preclinical and clinical studies. Concentrations of HPA hormones change in laboratory animals in response to standard experimental procedures, including handling and vehicle injections. We compared HPA activity in adult male Lewis (inbred) and Sprague-Dawley (outbred) rats, 2 common strains in rodent models of addiction, after different schedules of handling and saline injections, to explore the extent to which HPA responses differ by strain and whether interindividual differences underlie addiction vulnerability. The 4 treatment conditions were no, short, or long handling and saline injections. In handled groups, rats were handled for 1 to 2 min for 3 times daily and were euthanized after 7 d (short handling) or 14 d (long handling). The injection schedule in the saline injection group mimicked that in a model of binge-like cocaine exposure. Across all treatment groups, concentrations of adrenocorticotropic hormone were higher in Sprague-Dawley than in Lewis rats. In Sprague-Dawley rats, corticosterone concentrations decreased after continued handling but remained constant in Lewis rats. Interindividual variability in hormone levels was greater in Sprague-Dawley than Lewis rats, although corticosterone variability decreased after continued handling. Prolactin did not differ between groups of either Sprague-Dawley and Lewis rats before or after handling. This study underscores the importance of prolonged handling before experimenter-provided drug-administration paradigms and of strain-associated differences that may affect study outcomes.

  20. The Antinociceptive Effects of Tualang Honey in Male Sprague-Dawley Rats: A Preliminary Study

    PubMed Central

    Aziz, Che Badariah Abd; Ismail, Che Aishah Nazariah; Hussin, Che Maraina Che; Mohamed, Mahaneem

    2014-01-01

    Tualang honey (蜂蜜 Fēng Mì) is known to have anti-inflammatory property, but its antinociceptive property has not been extensively investigated. In this study, we examined the preemptive effects on administering different doses of Tualang honey and prednisolone on the nociceptive response in male Sprague-Dawley rats. Thirty-five male Sprague-Dawley rats were randomized into five groups (n = 7) and each group received either distilled water, Tualang honey (0.2, 1.2 or 2.4 g/kg) or prednisolone (10 mg/kg) for 10 days. The response to noxious thermal stimulus was assessed using tail flick test on Day 10. The well-being of the rats was also assessed by monitoring their food intake and body weight. Data were analyzed using one-way Analysis of Variance (ANOVA) with post-hoc Scheffe's test and P value less than 0.05 was considered significant. In tail flick test, the tail flick latency time was significantly higher in the groups that received 1.2 g/kg and 2.4 g/kg of Tualang honey and 10 mg/kg of prednisolone, compared to the control group (P < 0.05). There was significant reduction in the total food pellet intake in the groups receiving prednisolone and Tualang honey (1.2 g/kg and 2.4 g/kg) compared to controls; however, the body weight gain was only significantly reduced in the prednisolone group. All the parameters were not significantly affected in the group receiving 0.2 g/kg of Tualang honey. In conclusion, preemptive administration of Tualang honey (1.2 g/kg and 2.4 g/kg) and prednisolone (10 mg/kg) had reduced the pain responses. The reduced weight gain in the prednisolone group is an unwanted effect due to its metabolic and central actions. Further studies are required to confirm the antinociceptive effects and elucidate the mechanism of antinociceptive action of Tualang honey in the rats. PMID:25379476

  1. The antinociceptive effects of tualang honey in male sprague-dawley rats: a preliminary study.

    PubMed

    Aziz, Che Badariah Abd; Ismail, Che Aishah Nazariah; Hussin, Che Maraina Che; Mohamed, Mahaneem

    2014-10-01

    Tualang honey ( Fēng Mì) is known to have anti-inflammatory property, but its antinociceptive property has not been extensively investigated. In this study, we examined the preemptive effects on administering different doses of Tualang honey and prednisolone on the nociceptive response in male Sprague-Dawley rats. Thirty-five male Sprague-Dawley rats were randomized into five groups (n = 7) and each group received either distilled water, Tualang honey (0.2, 1.2 or 2.4 g/kg) or prednisolone (10 mg/kg) for 10 days. The response to noxious thermal stimulus was assessed using tail flick test on Day 10. The well-being of the rats was also assessed by monitoring their food intake and body weight. Data were analyzed using one-way Analysis of Variance (ANOVA) with post-hoc Scheffe's test and P value less than 0.05 was considered significant. In tail flick test, the tail flick latency time was significantly higher in the groups that received 1.2 g/kg and 2.4 g/kg of Tualang honey and 10 mg/kg of prednisolone, compared to the control group (P < 0.05). There was significant reduction in the total food pellet intake in the groups receiving prednisolone and Tualang honey (1.2 g/kg and 2.4 g/kg) compared to controls; however, the body weight gain was only significantly reduced in the prednisolone group. All the parameters were not significantly affected in the group receiving 0.2 g/kg of Tualang honey. In conclusion, preemptive administration of Tualang honey (1.2 g/kg and 2.4 g/kg) and prednisolone (10 mg/kg) had reduced the pain responses. The reduced weight gain in the prednisolone group is an unwanted effect due to its metabolic and central actions. Further studies are required to confirm the antinociceptive effects and elucidate the mechanism of antinociceptive action of Tualang honey in the rats.

  2. A 90-day toxicity study of GmTMT transgenic maize in Sprague-Dawley rats.

    PubMed

    Fang, Jin; Feng, Yongquan; Zhi, Yuan; Zhang, Lan; Yu, Zhou; Jia, Xudong

    2017-04-01

    GmTMT transgenic maize is a genetically modified maize plant that overexpresses the γ-tocopherol methyltransferase (γ-TMT) from Glycine max (Gm). The γ-TMT gene was introduced into maize line Zhen58 to encode the GmTMT2a protein which can convert γ-tocopherol into α-tocopherol. Overexpression of GmTMT2a significantly increased the α-tocopherol content in transgenic maize. The present study was designed to investigate any potential effects of GmTMT maize grain in a 90-day subchronic rodent feeding study. Maize grains from GmTMT or Zhen58 were incorporated into rodent diets at low (12.5%), medium (25%) or high (50%) concentrations and administered to Sprague-Dawley rats (n = 10/sex/group) for 90 days. The negative control group of rats (n = 10/sex/group) were fed with common maize diets. Results from body weights, feed consumption, clinical chemistry, hematology, absolute and relative organ weights indicated no treatment-related side effects of GmTMT maize grain on rats in comparison with rats consuming diets containing Zhen58 maize grain. In addition, no treatment-related changes were found in necropsy and histopathology examinations. Altogether, our data indicates that GmTMT transgenic maize is as safe and nutritious as its conventional non-transgenic maize.

  3. Biopersistence of silver nanoparticles in tissues from Sprague-Dawley rats.

    PubMed

    Lee, Ji Hyun; Kim, Yong Soon; Song, Kyung Seuk; Ryu, Hyun Ryol; Sung, Jae Hyuck; Park, Jung Duck; Park, Hyun Min; Song, Nam Woong; Shin, Beom Soo; Marshak, Daniel; Ahn, Kangho; Lee, Ji Eun; Yu, Il Je

    2013-08-01

    Silver nanoparticles are known to be distributed in many tissues after oral or inhalation exposure. Thus, understanding the tissue clearance of such distributed nanoparticles is very important to understand the behavior of silver nanoparticles in vivo. For risk assessment purposes, easy clearance indicates a lower overall cumulative toxicity. Accordingly, to investigate the clearance of tissue silver concentrations following oral silver nanoparticle exposure, Sprague-Dawley rats were assigned to 3 groups: control, low dose (100 mg/kg body weight), and high dose (500 mg/kg body weight), and exposed to two different sizes of silver nanoparticles (average diameter 10 and 25 nm) over 28 days. Thereafter, the rats were allowed to recover for 4 months. Regardless of the silver nanoparticle size, the silver content in most tissues gradually decreased during the 4-month recovery period, indicating tissue clearance of the accumulated silver. The exceptions were the silver concentrations in the brain and testes, which did not clear well, even after the 4-month recovery period, indicating an obstruction in transporting the accumulated silver out of these tissues. Therefore, the results showed that the size of the silver nanoparticles did not affect their tissue distribution. Furthermore, biological barriers, such as the blood-brain barrier and blood-testis barrier, seemed to play an important role in the silver clearance from these tissues.

  4. Creatine monohydrate increases bone mineral density in young Sprague-Dawley rats.

    PubMed

    Antolic, Anamaria; Roy, Brian D; Tarnopolsky, Mark A; Zernicke, Ronald F; Wohl, Gregory R; Shaughnessy, Stephen G; Bourgeois, Jacqueline M

    2007-05-01

    Creatine kinase, found in osteoblasts, is an enzyme that is upregulated in response to interventions that enhance bone mass accretion. Creatine monohydrate supplementation can increase fat-free mass in young healthy men and women and can reduce markers of bone breakdown in boys with Duchenne muscular dystrophy. The objective of this study was to determine the influence of supplementation with creatine monohydrate on bone structure and function in growing rats, to establish a therapeutic model. Creatine monohydrate (2% w.w.) (CR; N = 16) or standard rat chow (CON; N = 16) was fed to Sprague-Dawley rats beginning at 5 wk of age, for 8 wk. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy x-ray absorptiometry at the beginning and end of the protocol. The rats were sacrificed, and one femur was removed for the determination of mechanical properties. The CR-treated rats showed greater lumbar BMD and femoral bending load at failure compared with the CON rats (P < 0.05). Together, these data suggest that creatine monohydrate potentially has a beneficial influence on bone function and structure; further investigation is warranted into its effect on bone functional properties and its effects in disorders associated with bone loss.

  5. Luteolin Supplementation Prevents Selenite-Induced Cataractogenesis in Sprague Dawley Rat Pups.

    PubMed

    Sreelakshmi, Vasudevanpillai; Sasikala, Vilasini; Abraham, Annie

    2015-12-01

    Luteolin, a flavonoid present in leaves and stems of many plants finds mention in literature for beneficial effects on eyes. Presently, no reports are available on the in vivo anticataractogenic effect of luteolin. The current study was designed to evaluate the efficacy of luteolin on selenite-induced cataract models in vivo. The study consisted of three groups of Sprague Dawley rat pups 8-10 d old (Group I (Normal), Group II (Cataract induced), and Group III (Treatment)). Cataract was induced in Group II and Group III by a subcutaneous injection of sodium selenite (4 μg/g body weight) on the 10th day. Luteolin was administered orally from 8th day up to 12th day at a concentration of 1 μg/g body weight in Group III. After 30 d, lenses of treated animals showed normal morphology. Activities of antioxidant enzymes were increased and levels of reactive oxygen species were decreased in the luteolin-treated group when compared to the cataract-induced group. Increased Ca(2+) ATPase activity and lowered calcium level, caspase 3 activity and down-regulation of caspase 3 expression were seen in the treatment group when compared to the selenite group. Luteolin enhances the antioxidant potential and thereby lowers the oxidative damages to the lens. It also stabilizes the membrane integrity of the lens and maintains the ionic balance.

  6. Anti-profibrotic effects of artesunate on bleomycin-induced pulmonary fibrosis in Sprague Dawley rats.

    PubMed

    Wang, Changming; Xuan, Xiuping; Yao, Wenmin; Huang, Guojin; Jin, Junfei

    2015-07-01

    The present study aimed to determine whether artesunate has beneficial effects on bleomycin-induced pulmonary fibrosis in rats and to examine the possible mechanisms underlying these effects. All experiments were performed with male Sprague Dawley rats weighing 180-250 g. Animals were randomly divided into four experimental groups that were administered either saline alone, artesunate alone, bleomycin alone or bleomycin + artesunate. Lung histopathology was investigated by hematoxylin and eosin staining and Masson staining. Lung profibrotic molecules were analyzed by reverse transcription polymerase chain reaction, immunoblotting and immunohistochemistry. In rats treated with artesunate, pulmonary fibrosis induced by bleomycin was significantly reduced. Administration of artesunate significantly improved bleomycin-induced morphological alterations. Profibrotic molecules, including transforming growth factor-β1, Smad3, heat shock protein 47, α-smooth muscle actin and collagen type I were also reduced by artesunate. These findings suggest that artesunate improves bleomycin-induced pulmonary fibrosis pathology in rats possibly by inhibiting profibrotic molecules associated with pulmonary fibrosis.

  7. Protective effect of cordycepin-enriched Cordyceps militaris on alcoholic hepatotoxicity in Sprague-Dawley rats.

    PubMed

    Cha, Jae-Young; Ahn, Hee-Young; Cho, Young-Su; Je, Jae-Young

    2013-10-01

    This study was to investigate the protective effect of cordycepin-enriched Cordyceps militaris against alcohol-induced hepatotoxicity in Sprague-Dawley rats. Alcohol-feeding rats were fed diets with Paecilomyces japonica as CPJ group, C. militaris as CCM group, cordycepin-enriched C. militaris as CCMα group at the 3% (w/w) level and silymarin at the 0.1% (w/w) level for 4 weeks. Alcohol administration resulted in a significant increase in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and the levels of blood alcohol and acetaldehyde in serum. However, CCMα group markedly prevented from alcohol-induced elevation of these parameters in serum. CCMα group showed the increased both hepatic activities of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). Unlike the action of alcohol treatment on alcoholic fatty liver, CCMα group was also attenuated lipid droplet accumulation in the hepatocytes. Present study was also confirmed the beneficial roles of silymarin (hepatoprotective agent) against alcohol-induced liver injury in rats. Therefore, cordycepin-enriched C. militaris can be a promising candidate to prevent from alcohol-induced hepatotoxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats

    PubMed Central

    Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha

    2013-01-01

    Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-α, and IL-1β in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-α, and IL-1β, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo. PMID:23964314

  11. Dietary supplementation of bitter gourd reduces the risk of hypercholesterolemia in cholesterol fed sprague dawley rats.

    PubMed

    Naz, Rabia; Anjum, Faqir Muhammad; Butt, Masood Sadiq; Mahr-Un-Nisa, -

    2016-09-01

    Functional and health endorsing benefits of various foods are often attributed to their phytochemistry. The bitter gourd holds potential in improving the health of the individuals owing to its incredible versatility in phytochemistry. However, the efficacy of different parts of bitter gourd needs attention of the researchers. In the current exploration, different parts of bitter gourd were evaluated for their cholesterol lowering potential in cholesterol fed Sprague dawley rats. For the purpose, four types of bitter gourd part i.e. whole fruit, seedless fruit, seeds, and seed extracts were used and compared with placebo in hypercholesterolemic rats. In placebo, momentous increase in serum cholesterol, triglycerides and LDL levels was observed. All parts attenuate the cholesterol 18.79 to 40.17% triglycerides 25.97 to 37.01% and LDL 14.49 to 26.09%. However, 1% extract powder was most effective in reducing the cholesterol and triglycerides. From the present study, it is deduced that bitter gourd extract can be supplemented in food products for the management of hypercholesterolemia. However, future studies in human subjects needs to be conducted for meticulousness of the present findings.

  12. 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.

  13. Teratogenic and Embryocidal Effects of Zidovudine (AZT) in Sprague-Dawley Rats

    PubMed Central

    Christmas, James T.; Knoll, Kraig A.; Bawdon, Roger E.; Gilstrap III, Larry C.

    1995-01-01

    Objective: The purpose of the present investigation was to analyze the effets of zidovudine on the postimplantation embryo and fetus. Methods: Pregnant Sprague-Dawley rats were given various doses (10 mg/kg, 30 mg/kg, 150 mg/kg) of zidovudine or saline by an endotracheal tube during the period of embryogenesis (days 6–8, 9–11, 6–11 postconception). The animals were sacrificed on days 18–19 of pregnancy, and their fetuses were removed by hysterotomy. Autopsies under low (15×) and high (40×) power light microscopy were performed on all fetuses. Results: There was no statistically significant difference among the groups with respect to maternal weight gain. There were more pregnancy resorptions in the group receiving high-dose zidovudine (150 mg/kg/day) throughout embryogenesis than in the control group (P = 0.001, respectively). Four major structural anomalies were noted among the 689 fetuses examined, but zidovudine was not associated with an increased frequency of congenital anomalies in rats when it was administered in doses similar to, 3-, and 15-fold higher than the regimen recommended for adult humans. The drug, however, was embryocidal in the high-dose group (P = 0.002). Conclusions: These findings are consistent with previous studies of preimplantation mouse embryos that demonstrated an embryocidal effect on preimplantation conceptuses. In summary, post-implantation embryonic zidovudine exposure was associated with significantly increased pregnancy losses (resorptions and intrauterine deaths). PMID:18475397

  14. 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

  15. 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.

  16. 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

  17. Physiological and pharmacokinetic effects of multilevel caging on Sprague Dawley rats under ketamine-xylazine anesthesia

    PubMed Central

    Dodelet-Devillers, Aurore; Zullian, Chiara; Beaudry, Francis; Gourdon, Jim; Chevrette, Julie; Hélie, Pierre; Vachon, Pascal

    2016-01-01

    While the cage refinement is a necessary step towards improving the welfare of research rats, increasing the complexity and surface area of the living space of an animal may have physiological impacts that need to be taken into consideration. In this study, ketamine (80 mg/kg) and xylazine (10 mg/kg) caused a short duration anesthesia that was significantly decreased in Sprague-Dawley rats housed in multilevel cages (MLC), compared to rats housed in standard cages (SDC). The withdrawal reflex, the palpebral reflexes and the time-to-sternal all occurred earlier in MLC housed rats, suggesting an effect of housing on the physiology of the rats. In addition, during anesthesia, cardiac frequencies were increased in animals housed in the smaller SDC. Respiratory frequencies, the blood oxygen saturation and rectal temperatures during anesthesia did not vary between conditions during the anesthesia. While xylazine pharmacokinetics were unchanged with caging conditions, the clearance and half-lives of ketamine and its metabolite, norketamine, were altered in the rats housed in MLC. Finally, while no difference was ultimately seen in rat body weights, isolated liver and adrenal gland weights were significantly lighter in rats housed in the MLC. Increasing cage sizes, while having a positive impact on wellbeing in rats, can alter anesthetic drug metabolism and thus modify anesthesia parameters and associated physiological processes. PMID:27263962

  18. 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.

  19. Advantame Sweetener Preference in C57BL/6J Mice and Sprague-Dawley Rats

    PubMed Central

    Ackroff, Karen

    2015-01-01

    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

  20. 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.

  1. 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.

  2. 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.

  3. Electrolyzed-reduced water inhibits acute ethanol-induced hangovers in Sprague-Dawley rats.

    PubMed

    Park, Seung-Kyu; Qi, Xu-Feng; Song, Soon-Bong; Kim, Dong-Heui; Teng, Yung-Chien; Yoon, Yang-Suk; Kim, Kwang-Yong; Li, Jian-Hong; Jin, Dan; Lee, Kyu-Jae

    2009-10-01

    Ethanol consumption disturbs the balance between the pro- and anti-oxidant systems of the organism, leading to oxidative stress. Electrolyzed-reduced water (ERW) is widely used by people in East Asia for drinking purposes because of its therapeutic properties including scavenging effect of reactive oxygen species. This study was performed to investigate the effect of ERW on acute ethanol-induced hangovers in Sprague-Dawley rats. Alcohol concentration in serum of ERW-treated rats showed significant difference at 1 h, 3 h and 5 h respectively as compared with the rats treated with distilled water. Both alcohol dehydrogenase type 1 and acetaldehyde dehydrogenase related with oxidation of alcohol were significantly increased in liver tissue while the level of aspartate aminotransferase and alanine aminotransferase in serum was markedly decreased 24 h after pre-oral administration of ERW. Moreover, oral administration of ERW significantly activated non-ezymatic (glutathione) and enzymatic (glutathione peroxidase, glutathione-S-transferase, Cu/Zn-superoxide dismutase and catalase) antioxidants in liver tissues compared with the control group. These results suggest that drinking ERW has an effect of alcohol detoxification by antioxidant mechanism and has potentiality for relief of ethanol-induced hangover symptoms.

  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. 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.

  6. Subcutaneous and intraperitoneal lipogranulomas following subcutaneous injection of olive oil in Sprague-Dawley rats.

    PubMed

    Ramot, Yuval; Ben-Eliahu, Shmulik; Kagan, Leonid; Ezov, Nathan; Nyska, Abraham

    2009-12-01

    Olive oil is commonly employed as a solubilizing agent for lipophilic materials in preclinical studies in rodents. Here we report that following subcutaneous (SC) injection of olive oil to Sprague-Dawley (SD) rats, local SC lipogranulomas formed, which were associated with an unusual location of the same changes in the peritoneum. Macroscopically, multifocal white spots were found over the liver and mesentery. Histologically, lipid granulomas were seen in the SC injection site, as well as on the capsular or serosal surface of the abdominal organs. No abnormal clinical signs were noted except for swelling at the injection site. The olive oil may have reached the peritoneal cavity from the SC tissue passively via the lymphatic vessels or actively after engulfment by antigen-presenting cells via the lymphatic or blood vessels. These findings are of particular importance for drug safety assessments, as the occurrence of lipogranulomas in locations distant from the site of administration may lead to misinterpretation of histological results. We suggest that these aberrations may be induced by the administration of olive oil as a vehicle.

  7. Subchronic Oral Toxicity of Sodium Tungstate in Sprague-Dawley Rats.

    PubMed

    McCain, Wilfred C; Crouse, Lee C B; Bazar, Mathew A; Roszell, Laurie E; Leach, Glenn J; Middleton, John R; Reddy, Gunda

    2015-01-01

    The subchronic toxicity of sodium tungstate dihydrate aqueous solution in male and female Sprague-Dawley rats was evaluated by daily oral gavage of 0, 10, 75, 125, or 200 mg/kg/d for 90 days. Measured parameters included food consumption, body weight measurements, hematology, clinical chemistry, and histopathological changes. There was a significant decrease in food consumption and body weight gain in males at 200 mg/kg/d from days 77 to 90; however, there was no effect in food consumption and body weights in females. There were no changes in the hematological and clinical parameters studied. Histopathological changes were seen in kidney of male and female and epididymis of male rats. Histopathological changes were observed in the kidneys of male and female rats dosed at 125 or 200 mg/k/d consisting of mild to severe cortical tubule basophilia in 2 high-dose groups. Histological changes in epididymides included intraluminal hypospermia with cell debris in the 200 mg/kg/d dosed male rats. Histopathological changes were observed in the glandular stomach including inflammation and metaplasia in the high-dose groups (125 or 200 mg/kg/d) of both sexes of rats. Based on histopathology effects seen in the kidneys, the lowest observable adverse effect level was 125 mg/kg/d and the no observable adverse effect level was 75 mg/kg/d in both sexes of rats for oral subchronic toxicity.

  8. Acute and chronic effects of ferret odor exposure in Sprague-Dawley rats.

    PubMed

    Campeau, S; Nyhuis, T J; Sasse, S K; Day, H E W; Masini, C V

    2008-09-01

    This manuscript describes several behavioral and functional studies evaluating the capacity of ferret odors to elicit a number of acute and long-term responses in male Sprague-Dawley rats. Acute presentation elicits multiple responses, suggesting that ferret odor, likely from skin gland secretions, provides an anxiogenic-like stimulus in this strain of rats. Compared to cat odor, however, ferret odor did not produce rapid fear conditioning, a result perhaps attributable to methodological factors. Inactivation of the olfactory system and medial nucleus of the amygdala, combined with induction of the immediate-early gene c-fos, suggest the necessity of the accessory olfactory system in mediating the effects of ferret odor. Repeated exposures to ferret odor produce variable habituation of neuroendocrine and behavioral responses, perhaps indicative of the lack of control over the exact individual origin or concentration of ferret odor. Ferret odor induces rapid and long-term body weight regulation, thymic involution, adrenal hyperplasia and facilitation of the neuroendocrine response to additional challenges. It is argued that the use of such odors is exquisitely suited to investigate the brain regions coordinating anxiety-like responses and the long-term changes elicited by such stimuli.

  9. Subchronic Hepatotoxicity Evaluation of 2,3,4,6-Tetrachlorophenol in Sprague Dawley Rats

    PubMed Central

    Dodd, Darol E.; Pluta, Linda J.; Sochaski, Mark A.; Banas, Deborah A.; Thomas, Russell S.

    2012-01-01

    Male Sprague Dawley rats were exposed to 2,3,4,6-tetrachlorophenol (TCP) for 5 days, 2 weeks, 4 weeks, or 13 weeks. TCP was administered by gavage at doses of 0, 10, 25, 50, 100, or 200 mg/kg/day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood TCP, gross pathology, and liver histopathology. There were no TCP exposure-related clinical signs of toxicity. Mean body weight decreased 12–22% compared to control in the 100 and 200 mg/kg/day groups. Serum ALT concentrations were increased in rats of the 200 mg/k/day. Liver weight increases were both dose- and exposure time-related and statistically significant at ≥25 mg/kg/day. Incidence and severity of centrilobular hepatocytic vacuolation, hepatocyte hypertrophy, and single cell hepatocytic necrosis were related to dose and exposure time. Following 13 weeks of exposure, bile duct hyperplasia and centrilobular and/or periportal fibrosis were observed in rats primarily of the highest TCP dose group. Blood TCP concentrations increased with dose and at 13 weeks ranged from 1.3 to 8.5 μg/mL (10 to 200 mg/kg/day). A NOAEL of 10 mg/kg/day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥25 mg/kg/day. PMID:22666246

  10. 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

  11. Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats.

    PubMed

    Wallisch, Michael; El Rody, Nehad M; Huang, Baohua; Koop, Dennis R; Baker, James R; Olsen, George D

    2012-01-15

    Respiratory depression is the main obstacle for the safe administration of morphine for acute pain after injury. Due to this complication, new delivery methods are needed to insure that safe and effective doses of opioid analgesics are administered during emergencies. A depot formulation containing a naloxone pro-drug was designed to release the antidote when morphine causes dangerous hypoxic conditions in the blood. The aim of this work was to test the naloxone release in vivo in response to a severe overdose of morphine in the Sprague-Dawley rat model. Non-invasive two-chamber plethysmography was used to monitor and record respiration and to test the capability of the naloxone pro-drug to respond to and rescue morphine-induced respiratory depression in the animal. We show that the pro-drug formulation can both prevent and reverse severe morphine induced respiratory depression. The animal model demonstrates that co-administration of the naloxone pro-drug reliably antagonizes profound respiratory depressive effects of morphine.

  12. Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.

    PubMed

    Radad, Khaled; Hassanein, Khaled; Al-Shraim, Mubarak; Moldzio, Rudolf; Rausch, Wolf-Dieter

    2014-01-01

    The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions. Thus the current study shed some light on the beneficial effects of thymoquinone against neurotoxic effects of lead in rats.

  13. Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats

    PubMed Central

    Hodges, Matthew R.; Echert, Ashley E.; Puissant, Madeleine M.; Mouradian, Gary C.

    2013-01-01

    The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7 % CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10 mg/kg/day) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p>0.05), although tidal volume (VT) was reduced in BN rats (p<0.05). There were also minimal effects of fluoxetine on CO2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and VT during hypercapnia in BN rats (p<0.05). The augmented CO2 response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (p<0.05) consistent with selective and effective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO2 sensitivity in the BN rat. PMID:23454023

  14. 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.

  15. 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.

  16. Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats.

    PubMed

    Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha; Park, Kun-Young

    2013-08-01

    Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-α, and IL-1β in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-α, and IL-1β, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo.

  17. Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats.

    PubMed

    Hodges, Matthew R; Echert, Ashley E; Puissant, Madeleine M; Mouradian, Gary C

    2013-04-01

    The Brown Norway (BN; BN/NHsdMcwi) rat exhibits a deficit in ventilatory CO2 sensitivity and a modest serotonin (5-HT) deficiency. Here, we tested the hypothesis that the selective serotonin reuptake inhibitor fluoxetine would augment CO2 sensitivity in BN but not Sprague Dawley (SD) rats. Ventilation during room air or 7% CO2 exposure was measured before, during and after 3 weeks of daily injections of saline or fluoxetine (10mg/(kgday)) in adult male BN and SD rats. Fluoxetine had minimal effects on room air breathing in BN and SD rats (p>0.05), although tidal volume (VT) was reduced in BN rats (p<0.05). There were also minimal effects of fluoxetine on CO2 sensitivity in SD rats, but fluoxetine increased minute ventilation, breathing frequency and VT during hypercapnia in BN rats (p<0.05). The augmented CO2 response was reversible upon withdrawal of fluoxetine. Brain levels of biogenic amines were largely unaffected, but 5-HIAA and the ratio of 5-HIAA/5-HT were reduced (p<0.05) consistent with selective and effective 5-HT reuptake inhibition. Thus, fluoxetine increases ventilatory CO2 sensitivity in BN but not SD rats, further suggesting altered 5-HT system function may contribute to the inherently low CO2 sensitivity in the BN rat.

  18. Spontaneous Age-related Lesions of the Kidney Fornices in Sprague-Dawley Rats.

    PubMed

    Tomonari, Yuki; Kurotaki, Tetsuro; Sato, Junko; Doi, Takuya; Kokoshima, Hiroko; Kanno, Takeshi; Tsuchitani, Minoru; Seely, John Curtis

    2016-02-01

    The upper portion of the rat kidney pelvis has specialized anatomic structures referred to as fornices. Fornices have a role in urine concentration. Spontaneous lesions including mineralization, epithelial hyperplasia, and inflammatory cell infiltration may occur in the area of the fornices. However, little information regarding specific historical control data or the spontaneous development of these findings in male and female fornices is known. Understanding spontaneous age-related lesions in the area of the fornices versus other portions of the kidney pelvis may be relevant in the identification of test article-induced changes. A retrospective study was conducted of male and female Sprague-Dawley rat kidney fornices over several time points to determine the incidence and severity of mineralization, epithelial hyperplasia, and inflammatory cell infiltration. Based on this investigation, these lesions appeared to increase over time and, in general, occurred earlier and with a greater incidence in females. Regarding those chemicals that may result in lesions of the kidney pelvis, it may be important for pathologists to separately diagnose lesions of the fornices from other portions of the kidney pelvis to help differentiate between any spontaneous age-related and induced changes.

  19. 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.

  20. 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.

  1. Histology surrounding cystotomy healing in a Sprague-Dawley rat model.

    PubMed

    Bilbao, Michelle; Spaniol, Alison; Bearss, Jeremy; Schellhase, Chris; Shippey, Stuart; Aungst, Matthew

    2014-01-01

    The purpose of this study was to histologically chronicle wound healing following cystotomy repair using a small animal model. Thirty female Sprague-Dawley rats were included in this study. Twenty-eight rats underwent a vertical cystotomy in the bladder dome, which was repaired in a single continuous fashion. Two rats served as histological controls. Following cystotomy repair, groups of three to four rats were studied at single day intervals for 4 days, then at 2-day intervals until 10 days post-repair. The animal bladders were harvested and examined for inflammation, scar formation, and bladder healing. Thirty rat bladders were histologically examined. An inflammatory wound phase was observed during the first 4 days after wounding. Transition from acute to chronic inflammation was observed at day 2 with chronic inflammation persisting through day 10. Inflammation severity peaked 4 days post-wounding without regression through day 10. Evidence of proliferative phase wound healing was first observed 4 days post-wounding. Early increases in wound healing are due to inflammatory events such as fibrin plugging of the wound. Later developments after day 4 are due to wound proliferation, collagen deposition, and re-epithelialization. Additionally, wound healing in the rat bladder is observed on a continuum and not necessarily in discrete stages observed on precisely the same postoperative day in each animal.

  2. Pan-colonic pharmacokinetics of catechins and procyanidins in male Sprague-Dawley rats.

    PubMed

    Goodrich, Katheryn M; Smithson, Andrew T; Ickes, Anne K; Neilson, Andrew P

    2015-10-01

    Poor absorption and bioavailability of procyanidins from the upper gastrointestinal tract result in the majority of the dose reaching the colon. During colonic transit, progressive microbial metabolism likely produces gradients of procyanidins and microbial metabolites along the length of the colon, suggesting that proximal and distal regions are exposed to different profiles of procyanidins and metabolites. However, previous studies have largely treated the colon as a single organ or looked at fecal profiles, and differences in the profiles of native and metabolite compounds between regions have not been observed. The metabolism kinetics of procyanidins larger than trimers and formation of metabolites in the colon have not been well characterized. Therefore, the objective of this study was to determine the kinetics of delivery and microbial metabolism of monomeric, dimeric and oligomeric procyanidins in the cecum and proximal, mid and distal colon. Sprague-Dawley rats were gavaged grape seed extract and sacrificed over 18 h. Analysis of luminal contents showed distinct native and metabolite profiles for each region. Procyanidins had maximum concentrations at approximately 3h postgavage for all sections. Metabolites reached maximum concentrations from 3 to 18 h postgavage. The appearance of metabolites was highly dependent on species: larger metabolites were found at earlier times in the more proximal segments, and smaller metabolites were found at later times in more distal regions. This study allowed for the observation of regions in the lower gastrointestinal tract, giving insight into the distribution and delivery of procyanidins and their microbial metabolites throughout the colon.

  3. 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.

  4. Effects of Preconceptional Ethanol Consumption on ADHD-Like Symptoms in Sprague-Dawley Rat Offsprings

    PubMed Central

    Choi, Inah; Kim, Pitna; Joo, So Hyun; Kim, Min Kyeong; Park, Jin Hee; Kim, Hee Jin; Ryu, Jong Hoon; Cheong, Jae Hoon; Shin, Chan Young

    2012-01-01

    Ethanol exposure during gestational period is related to growth retardation, morphological abnormality, and even in neurological abnormalities including attention deficit/hyperactivity disorder (ADHD)-like behaviors on offspring. However, relatively little is known about the effects of maternal ethanol consumption prior to conception on their offspring. In this study, we investi-gated whether maternal ethanol administration during preconceptional phase produces ADHD-like behaviors in the rat offspring. Sprague-Dawley (SD) female rats were administrated ethanol via intragastric intubation with dosing regimen of 6 g/kg daily for 10 consecutive days and treated female rats then mated with non-treated male SD rats after 8 weeks. Another group subjected to the same procedure as those conducted on ethanol treated group except the saline administration instead of ethanol. Offspring was tested for their ADHD-like behaviors using open field test, Y maze test and impulsivity test that is performed in the aversive electronic foot shock paradigm. Offspring of preconceptional ethanol treated (EtOH) group showed hyperlocomotive activity, attention deficit and impulsivity. And reduction of striatal dopamine transporter (DAT) level was observed by Western blot in the EtOH group, compared to control (Con) group, while the immunohistochemical analysis exhibited increased expression of norepinephrine transporter (NET) in the frontal cortex. These results suggest that maternal ethanol consumption in the preconceptional phase induces ADHD-like behaviors in offspring that might be related to the abnormal expression of DAT and NET in rat. PMID:24116300

  5. Toxicokinetics of short-chain chlorinated paraffins in Sprague-Dawley rats following single oral administration.

    PubMed

    Geng, Ningbo; Zhang, Haijun; Xing, Liguo; Gao, Yuan; Zhang, Baoqin; Wang, Feidi; Ren, Xiaoqian; Chen, Jiping

    2016-02-01

    Short-chain chlorinated paraffins (SCCPs) have attracted considerable attention for their characteristic of persistent organic pollutants. However, very limited information is available for their toxicokinetic characteristics, limiting the evaluation of their health risks. In this study, we performed a toxicokinetics study to explore the absorption and excretion processes of SCCPs (a mixture of C10-, C11-, C12- and C13-CPs) after a single oral administration to the Sprague-Dawley rats. The toxicokinetic results showed that peak blood concentration of total SCCPs was attained at 2.8 day with Cmax value of 2.3 mg L(-1). The half-lives of total SCCPs in blood for the absorption t1/2 (ka), distribution t1/2 (α) and elimination phases t1/2 (β) were calculated to be 1.0, 1.7 and 6.6 days, respectively. During the 28 days post-dosing, about 27.9% and 3.5% of orally administrated SCCPs were excreted through feces and urine without metabolism, respectively. Congener group abundance profiles indicate a relative increase of Cl5-SCCPs in blood and urine in the elimination stage, and a higher accumulation of Cl8-10-SCCPs in feces. The distribution discrepancies of SCCPs congener groups in blood and excreta were more dependent on chlorine contents than on carbon chain lengths.

  6. 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.

  7. Decreased oral colonization of Streptococcus mutans during aging of Sprague-Dawley rats.

    PubMed

    Van Houte, J; Upeslacis, V N; Edelstein, S

    1977-04-01

    The colonization by streptomycin-resistant Streptococcus mutans strains of the teeth of conventional and ex-germfree Sprague-Dawley rats of various ages fed either a high-sucrose or a high-glucose diet was studied. Bacterial colonization occurred with increasingly greater difficulty as the rats became older. This was observed in studies of the implantation of the test organism after oral inoculation with different cell numbers as well as its transmission between infected and uninfected rats. With rat fed sucrose diet, the effect of age could not be demonstrated until they were age 3 months or older; the results from rats fed a glucose diet suggest that changes may already have occurred early after weaning. Changes in susceptibility to colonization during aging manifested themselves as a decrease in the proportions of rats which became infected as well as lower population levels in infected rats. The possible mechanism(s) involved as well as the possible significance of the findings was discussed.

  8. Toxicity of bryostatin-1 on the embryo-fetal development of Sprague-Dawley rats.

    PubMed

    Jiangbo, Zhu; Xuying, Wan; Yuping, Zhu; Xili, Ma; Yiwen, Zheng; Tianbao, Zhang

    2010-06-01

    Bryostatin-1, a highly oxygenated marine macrolide with a unique polyacetate backbone isolated from the marine animal Bugula neritina (Linnaeus), is now being developed as an anti-cancer drug for treating malignancy. In the present study, developmental toxicity of bryostatin-1 was evaluated in Sprague-Dawley rats. Bryostatin-1 was intravenously administered to rats on gestation days 6-15 at 4.0, 8.0, and 16.0 microg/kg on a daily basis. Then the reproductive parameters were determined in animals, and fetuses were examined for external, visceral, and skeletal malformations. The total weight gains were significantly different in animals between the control group and 8.0 and 16.0 microg/kg bryostatin-1 groups during and after treatment. The resorption and death fetus rates were significantly different between the bryostatin-1 group (16 microg/kg) and the control group. The fetal weight and fetal crown-rump length in the bryostatin-1 groups were significantly lower than that in the control group. Our results indicated that maternal toxicity occurred when the dose of bryostatin-1 was at 8.0 microg/kg, embryotoxicity at 16.0 microg/kg, and fetotoxicity at 4.0 microg/kg; but bryostatin-1 showed no teratogenic effect in rats. In light of our findings, bryostatin-1 should be used with caution in pregnant women with cancer, if they would like to continue the pregnancy.

  9. Syndactyly lethal: new mutation with multiple malformations occurring in Sprague Dawley rats.

    PubMed

    Fujii, Sakiko; Yabe, Kaoru; Kimura, Yuki; Ito, Yukie; Rokukawa, Masumi; Furukawa, Masatoshi; Ito, Kouta; Matsuura, Masao; Kiguchi, Masao

    2009-12-01

    We previously found newborns exhibiting syndactyly of both fore- and hindlimbs in a litter from a pair of Sprague Dawley rats. Continuous breeding of the parental animals yielded pups with the same anomaly in following litters, suggesting that the syndactyly was genetic in origin. In the present study, as all the syndactylous pups died on postnatal day 0, we conducted genetic analyses using 30 phenotypically normal female progeny and the sire. The females were subjected to caesarean section on day 20 of gestation and the fetuses were examined for the phenotypes. The results of the mating experiments suggest that the mutant phenotype is caused by a single autosomal recessive gene at a homozygous condition. As homozygous mutants are lethal at the neonatal stage, the mutant gene was named syndactyly lethal, gene symbol syl. The mutant rats have multiple abnormalities, such as syndactyly, micrognathia, fused/absent/small lung lobes, absent kidney and ureter, small spleen, small uterus, fused phalanges, sternoschisis, absent/detached rib, and splitting/fused/absent/small thoracic vertebra, some of which must be the cause of death on postnatal day 0. This mutant is considered to be useful for investigating the mechanisms and/or pathogenesis of syndactyly, as well as the accompanying malformations.

  10. A 6-Week Oral Toxicity Study of Oral Cholera Vaccine in Sprague-Dawley Rats

    PubMed Central

    Baek, Yeong-Ok; Choi, Seuk-Keun; Shin, Seo-Ho; Koo, Kyo-Hwan; Choi, Ho-Young; Cha, Seung-Bum; Li, Yong-Chun; Yoo, Hyeon-Jeong; Lee, Joo-Young; Kil, Ki-Hyun; Kim, Hak-Soo; Kang, Min-Soo; Kang, Boo-Hyun; Kim, Kap-Ho

    2012-01-01

    The present study was carried out to examine the toxicity and target organs of oral cholera vaccine (OCV) after repeated oral administration in Sprague-Dawley rats for 6 weeks (3 administrations, once every 2 weeks). OCV is an inactivated oral cholera vaccine that contains Vibrio cholerae and confers protection against cholera caused by V. cholera serogroups O1 (Inaba and Ogawa serotypes) and O139 (strain 4260B). The animals were orally administered either OCV placebo (negative control) or OCV at a dose equivalent to 240 times the anticipated human dose. Throughout the administration period, no significant change was detected in clinical signs, body weight, food or water consumption, urinalysis results, hematological and clinical biochemistry test results, organ weights, necropsy, or histopathological examination results. Minor changes were found in hematological and clinical biochemistry tests; however, these changes were within normal ranges. The above results suggest that oral administration of OCV in rats did not induce any toxicologically meaningful changes, and the target organs could not be determined. This study was conducted in accordance with the guidelines established by Good Laboratory Practice (2009-183, KFDA, December 22, 2009) and the OECD Principles of Good Laboratory Practice (1997). PMID:24278614

  11. Genotoxicity study of silver nanoparticles in bone marrow cells of Sprague-Dawley rats

    PubMed Central

    Patlolla, Anita K.; Hackett, Diahanna; Tchounwou, Paul B.

    2015-01-01

    The antimicrobial properties of silver nanoparticles (Ag-NPs) have resulted in their extensive application in consumer and health care products. Although Ag-NPs have great potential benefits, their side effects are unknown and seem inevitable due to their ability to reach the nucleus and damage genetic material. This study aimed to determine genotoxic potential of Ag-NPs using mitotic index (MI), DNA damage (comet assay), structural chromosome aberrations (SCA), micronuclei (MN) formation as genetic endpoints and induction of reactive oxygen species (ROS) as oxidative stress endpoint in bone marrow of Sprague-Dawley rats. Four groups of five male rats were orally administered Ag-NPs, once a day for five days with doses of 5, 25, 50, 100, mg/Kg. A control group was also made of five rats. Bone marrow samples were collected 24 h after the last treatment following standard protocols. Ag-NPs exposure significantly increased (p<0.05) the induction of ROS, number of SCA, the frequency of micro-nucleated cells, damaged the DNA and decreased the mitotic index compared to negative control. The results suggest that Ag-NPs may have the potential to induce oxidative stress mediated genotoxicity in rats. Further characterization of their genotoxicity and also their potential health implications should be monitored regularly. PMID:26032631

  12. 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

  13. 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.

  14. Pharmacology and toxicology of an oral tablet whole cells inactivated cholera vaccine in Sprague Dawley rats.

    PubMed

    López, Yulieé; Infante, Juan Francisco; Sifontes, Sergio; Díaz, Daiyana; Pérez, Viviana; Año, Gemma; Hernández, Tamara; Fernández, Sonsire; Castaño, Jorge Luis; Cedré, Bárbara; Oliva, Reynaldo; García, Luis; Solís, Rosa L; Talavera, Arturo

    2011-04-27

    Here we further investigate the pharmacological and toxicological properties of a cholera vaccine based on inactivated whole cells presented in either enteric coated (COA) or uncoated (U/C) tablet formulation from Vibrio cholerae C7258 strain. Tablets were dispersed in 2mL drinking water and administered orally to Sprague Dawley rats distributed in five groups (I COA7, II U/C7 immunized at 0, 7, 69days and III COA14, IV U/C14 immunized at 0, 14, 69days and V control group). Serum vibriocidal antibody response was measured after the administration of two doses with an interval of 7-14days. To further investigate the toxicological aspects a third dose was applied 10 weeks after the initial one. Animals were observed daily and water and food consumption was measured every other day. Periodic blood extractions were performed for hematology, biochemistry, and the titer of serum vibriocidal antibodies was determined. Anatomopathological analysis was performed at days 3 or 14 after the third dose. Results from clinical observations, as well as from water and food consumption and body weigh indicated no toxicity of the vaccine product. Meanwhile, no biological differences were found among different groups in hematological, hemo-chemistry, and anatomopathological studies. Moreover, enteric coated and uncoated tablets against human cholera were found to induce an immune response in rats. Copyright © 2011. Published by Elsevier Ltd.

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

    PubMed

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

    2016-03-29

    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.

  16. Study on the potential toxicity of a thymoquinone-rich fraction nanoemulsion in Sprague Dawley rats.

    PubMed

    Tubesha, Zaki; Imam, Mustapha Umar; Mahmud, Rozi; Ismail, Maznah

    2013-06-26

    Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure.

  17. 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.

  18. An Assessment of MDPV-induced Place Preference in Adult Sprague-Dawley Rats

    PubMed Central

    King, Heather E.; Wetzell, Bradley; Rice, Kenner C.; Riley, Anthony L.

    2017-01-01

    OBJECTIVE Most drugs of abuse have both aversive and rewarding effects, and the use and abuse potential of such drugs is thought to be a function of a balance of these affective properties. Characterizing these effects and their relative balance may provide insight into abuse vulnerability. One drug that has received recent attention is methylenedioxyparavalerone (MDPV), a monoamine transport inhibitor similar to, but significantly more potent than, cocaine. MDPV is self-administered and has been shown to produce aversive and rewarding effects in adult rats. The present study extended this characterization of the affective properties of MDPV by examining its ability to support place conditioning at a range of doses known to produce taste avoidance. METHODS Male Sprague-Dawley rats were injected with MDPV (1, 1.8 or 3.2 mg/kg) or saline and placed on the non-preferred side of a place conditioning apparatus for 30 min. On the next day, they were given an injection of saline and placed on the preferred side. This was repeated three times for a total of four conditioning cycles, and side preference was assessed on a final test. RESULTS All doses of MDPV produced significant increases in time spent in the drug-paired chamber, an effect not seen in vehicle-treated animals. CONCLUSIONS That the same doses of MDPV induced both taste avoidance and place preference allows assessments of how other factors might impact these effects and how they may, in turn, contribute to its abuse liability. PMID:25468817

  19. Sevoflurane anesthesia deteriorates pulmonary surfactant promoting alveolar collapse in male Sprague-Dawley rats.

    PubMed

    Malacrida, Leonel; Reta, Germán; Piriz, Héctor; Rocchiccioli, Fabiana; Botti, Horacio; Denicola, Ana; Briva, Arturo

    2014-08-01

    General anesthesia is frequently associated to transient hypoxemia and lung atelectasis. Although volatile anesthetics are safe and widely used, their potential role on anesthesia-induced pulmonary impairment has not been fully explored. In this study, we investigated the effect of volatile anesthetic sevoflurane on pulmonary surfactant composition and structure that could contribute to atelectasis. After 30 min of sevoflurane anesthesia, Sprague-Dawley rats showed increased levels of lyso-phosphatidylcholine and decreased levels of phosphatidylcholine associated with significant impairment in lung mechanics and alveolar collapse, but showed no deterioration of alveolar fluid reabsorption when compared to control group of rats anesthetized with pentobarbital. Exposure to sevoflurane altered the thermotropic profile of surfactant model membranes, as detected by fluorescence anisotropy. In this sense, sevoflurane-promoted fluidification of condensed phases could potentially impair the ability of surfactant films to sustain the lowest surface tensions. In conclusion, the observed changes in surfactant composition and viscosity properties suggest a direct effect of sevoflurane on surfactant function, a factor potentially involved in anesthetic-induced alterations in lung mechanics. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Cloning and sequence analysis of the LOC339524 gene in Sprague-Dawley rats.

    PubMed

    Long, Z H; Li, H; Chen, F; Zou, L Y

    2015-12-11

    We cloned the LOC339524 gene in Sprague-Dawley (SD) rats and analyzed the structure and function of the protein encoded by it. Based on the known human LOC339524 gene sequences, the full-length coding sequence of the LOC339524 gene in SD rats was cloned and amplified by the polymerase chain reaction using the complementary DNA of SD rats as a template. Bioinformatics analysis showed that the length of the cloned LOC339524 gene (GenBank accession No. KM224520) was 831 bp and it encoded a deduced protein of 276 amino acids. Sequence analysis revealed that the coded protein was identical to that produced in humans and its functional domain was located in the 138-236 amino acid fragments, a proline-rich region. Our results suggest that the encoded protein may be a significant regulator of the inflammatory response and may provide sufficient information to justify an in-depth investigation of the role of the LOC339524 gene.

  1. Acute and subchronic (13-week) toxicity of fermented Acanthopanax koreanum extracts in Sprague Dawley rats.

    PubMed

    Cho, MyoungLae; Shin, Gi-Hae; Kim, Jae-Min; Lee, Jin-Ha; Park, Sun-Ok; Lee, Sang-Jong; Shin, HyunMu; Lee, Boo-Yong; Kang, Il-Jun; Lee, Ok-Hwan

    2016-06-01

    The biological fermentation of plants is usually used to improve their product properties, including their biological activity. Acanthopanax koreanum is a plant indigenous to Jeju, Korea; however, fermented A. koreanum (FAK) has not been guaranteed to be safe. Therefore, in this study, a safety evaluation of aqueous extracts of FAK was performed using Sprague Dawley rats. The acute toxicity of FAK did not influence animal mortality, body weight changes or the animals' clinical appearance at a concentration of 5000 mg/kg body weight. Using doses of 500, 1000 and 2000 mg/kg/day in a subchronic (13-week) toxicity study, the administration of FAK in male rats increased their body weight, food consumption, absolute liver weight, liver-associated enzymes and total cholesterol content. However, these effects of FAK were not considered toxic because the changes were not accompanied by any evidence of clinical signs or any change in the histopathological examination. On the other hand, the FAK-treated female rats did not exhibit significant changes in their body weight, food consumption, absolute and relative organ weights or liver enzymes. These results suggest that the acute oral administration of FAK is non-toxic to rats, and 13 weeks of repeated dosing demonstrated no FAK-related toxicity at a concentration of 2000 mg/kg. Therefore, the no-observed-adverse-effect level (NOAEL) of FAK was determined to be 2000 mg/kg/day for both male and female rats.

  2. 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.

  3. 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.

  4. 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.

  5. Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.

    PubMed

    Hill Gallant, Kathleen M; Gallant, Maxime A; Brown, Drew M; Sato, Amy Y; Williams, Justin N; Burr, David B

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.

  6. Antifertility activity of Thevetia peruviana (Pers.) K. Schum leaf in female Sprague-Dawley rat

    PubMed Central

    Samanta, Jhuma; Bhattacharya, Snehendu; Rana, Avtar C.

    2016-01-01

    Objectives: Thevetia peruviana (Pers.) K. Schum. (Apocynaceae) is known to possess cardioactive glycoside such as thevetin A, thevetin B, neriifolin, peruvoside, thevetoxin, and ruvoside. Traditionally, T. peruviana leaves are used as abortifacient. The aim of the present study is to evaluate antifertility potential of T. peruviana leaves. Subjects and Methods: Cardiac glycoside freed leaves of T. peruviana were extracted with methanol using maceration method. The dried cardiac glycoside-free methanolic extract of T. peruviana leaves (TPL-Me-G) was screened for phytoconstituents and evaluated for its effect on estrogen-primed female Sprague-Dawley rat uterus model. It was further studied for effects on the estrous cycle, implantation, and effect on estrogen and progesterone. Statistical Analysis Used: Statistical analysis was done by ANOVA followed by Dunnett's t-test. Results: Alkaloids, flavonoids, essential oils, carbohydrates, and amino acids were found to be present in the glycoside-free extract. Thin-layer chromatography (TLC) in n-butanol: acetone: water (4:1:5) revealed the presence of quercetin and kaempferol. The presence of flavonoids (quercetin 0.0326% and kaempferol 0.138% on dry weight basis) was reconfirmed by high-performance TLC analysis. The extract was able to induce uterine contractions (EC50, 0.170 mg/ml) in a dose-dependent manner. Further investigation showed significant (P < 0.001) extension of estrous cycle and anti-implantation activity of the extract by reduction of the progesterone level. Conclusions: Methanolic extract of T. peruviana leaves (TPL-Me-G) containing quercetin 0.0326% and kaempferol 0.138% possesses a significant (P < 0.001) antifertility potential by virtue of decreasing the progesterone level. PMID:28066105

  7. Population-averaged diffusion tensor imaging atlas of the Sprague Dawley rat brain.

    PubMed

    Veraart, Jelle; Leergaard, Trygve B; Antonsen, Bjørnar T; Van Hecke, Wim; Blockx, Ines; Jeurissen, Ben; Jiang, Yi; Van der Linden, Annemie; Johnson, G Allan; Verhoye, Marleen; Sijbers, Jan

    2011-10-15

    Rats are widely used in experimental neurobiological research, and rat brain atlases are important resources for identifying brain regions in the context of experimental microsurgery, tissue sampling, and neuroimaging, as well as comparison of findings across experiments. Currently, most available rat brain atlases are constructed from histological material derived from single specimens, and provide two-dimensional or three-dimensional (3D) outlines of diverse brain regions and fiber tracts. Important limitations of such atlases are that they represent individual specimens, and that finer details of tissue architecture are lacking. Access to more detailed 3D brain atlases representative of a population of animals is needed. Diffusion tensor imaging (DTI) is a unique neuroimaging modality that provides sensitive information about orientation structure in tissues, and is widely applied in basic and clinical neuroscience investigations. To facilitate analysis and assignment of location in rat brain neuroimaging investigations, we have developed a population-averaged three-dimensional DTI atlas of the normal adult Sprague Dawley rat brain. The atlas is constructed from high resolution ex vivo DTI images, which were nonlinearly warped into a population-averaged in vivo brain template. The atlas currently comprises a selection of manually delineated brain regions, the caudate-putamen complex, globus pallidus, entopeduncular nucleus, substantia nigra, external capsule, corpus callosum, internal capsule, cerebral peduncle, fimbria of the hippocampus, fornix, anterior commisure, optic tract, and stria terminalis. The atlas is freely distributed and potentially useful for several purposes, including automated and manual delineation of rat brain structural and functional imaging data.

  8. 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.

  9. Chronic, Severe Hypertension Does Not Impair Spatial Learning and Memory in Sprague-Dawley Rats

    PubMed Central

    Kadish, Inga; van Groen, Thomas; Wyss, J. Michael

    2001-01-01

    This study tested the hypothesis that long-term hypertension impairs spatial learning and memory in rats. In 6-wk-old Sprague-Dawley rats, chronic hypertension was induced by placing one of three sizes of stainless steel clips around the descending aorta (above the renal artery), resulting in a 20–80-mm Hg increase of arterial pressure in all arteries above the clip, that is, the upper trunk and head. Ten months later, the rats were tested for 5 d in a repeated-acquisition water maze task, and on the fifth day, they were tested in a probe trial; that is, there was no escape platform present. At the end of the testing period, the nonsurgical and sham control groups had similar final escape latencies (16 ± 4 sec and 23 ± 9 sec, respectively) that were not significantly different from those of the three hypertensive groups. Rats with mild hypertension (140–160 mm Hg) had a final escape latency of 25 ± 6 sec, whereas severely hypertensive rats (170–199 mm Hg) had a final escape latency of 21 ± 7 sec and extremely hypertensive rats (>200 Hg) had a final escape latency of 19 ± 5 sec. All five groups also displayed a similar preference for the correct quadrant in the probe trial. Together, these data suggest that sustained, severe hypertension for over 10 mo is not sufficient to impair spatial learning and memory deficits in otherwise normal rats. PMID:11274256

  10. 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. Published by Elsevier Inc.

  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. Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats.

    PubMed

    Calik, Michael W; Carley, David W

    2017-09-01

    There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing. Adult male Sprague-Dawley rats were anesthetized and implanted with bilateral stainless steel screws into the skull for electroencephalogram recording and bilateral wire electrodes into the nuchal muscles for electromyogram recording. Each animal was recorded by polysomnography on multiple occasions separated by at least 3 days. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections: vehicle; vehicle and CB1 antagonist (AM 251); vehicle and CB2 antagonist (AM 630); vehicle and CB1/CB2 antagonist; dronabinol; dronabinol and CB1 antagonist; dronabinol and CB2 antagonist; and dronabinol and CB1/CB2 antagonist. Dronabinol decreased the percent time spent in rapid eye movement (REM) sleep. CB receptor antagonists did not reverse this effect. Dronabinol also decreased apneas during sleep, and this apnea suppression was reversed by CB1 or CB1/CB2 receptor antagonism. Dronabinol's effects on apneas were dependent on CB1 receptor activation, while dronabinol's effects on REM sleep were CB receptor-independent.

  13. 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.

  14. 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.

  15. 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.

  16. Changes in cross-fostered Sprague-Dawley rat litters exposed to perchlorate.

    PubMed

    Mahle, Deirdre A; Yu, Kyung O; Narayanan, Latha; Mattie, David R; Fisher, Jeffrey W

    2003-01-01

    Ammonium perchlorate is used as an oxidizer in rocket fuel. It has become a groundwater contaminant, dissociating to ammonium cation and perchlorate anion. The perchlorate ion competes with iodide for uptake into the thyroid, reducing thyroid hormone production. Pregnant Sprague-Dawley rats were given either untreated or perchlorate (1 mg/kg-day) treated drinking water beginning on gestation day 2. One set of control and exposed dams was sacrificed on gestation day 20. The litters from the second set of control and exposed dams were crossed immediately after parturition and were sacrificed at postnatal day 10. Dam serum and thyroid, pooled fetal sera, and male and female pup sera were collected and analyzed for perchlorate, thyroid-stimulating hormone (TSH), triiodothyronine (T(3)), and thyroxine (T(4)). Control pups receiving perchlorate through lactation had serum levels at postnatal day 10 of 0.54 microg/ml and 0.56 microg/ml for male and female pups, respectively, whereas exposed fetuses had serum perchlorate levels of 0.38 +/- 0.04 microg/ml. Female pups receiving perchlorate lactationally had significantly lower levels of serum T(4) than control pups and prenatally exposed pups. Serum T(4) levels in male pups were not affected by perchlorate. Serum thyroid hormone levels from gestational perchlorate exposure were restored to control values by postnatal day 10. In utero perchlorate-exposure decreased serum T(4) levels in the fetus. Gestational studies in conjunction with a cross-fostering study design helped discern thyroid hormonal changes caused by perchlorate exposure during the perinatal period.

  17. Spontaneous Peripheral Ameloblastic Odontoma in a Male Sprague-Dawley Rat

    PubMed Central

    Li, Yinghua; Bae, Han-Ik; Kim, Hak-Soo; Kang, Min-Soo; Gong, Bo-Ho; Jung, Won-Hee; Lee, Sranna; Bae, Jin-Sook; Kim, Kap-Ho; Song, Si-Whan; Lee, Jae-Hyun; Kang, Boo-Hyon

    2017-01-01

    Peripheral ameloblastic odontoma is a rare variant of odontogenic tumor occurring in the extraosseous region. The present report describes a spontaneous tumor in male Sprague-Dawley (SD) rats. The clinically confirmed nodule in the right mandibular region was first observed when the rat was 42 weeks and remained until the terminal sacrifice date when the animal was 48 weeks of age. At necropsy, a well demarcated nodule, approximately 2.5 × 2.0 × 2.0 cm, protruded from the ventral area of the right mandible. The nodule was not attached to mandibular bone and was not continuous with the normal teeth. Histopathologically, the tumor was characterized by the simultaneous occurrence of an ameloblastomatous component and composite odontoma-like elements within the same tumor. The epithelial portion formed islands or cords resembling the follicle or plexiform pattern typical of ameloblastoma and was surrounded by mesenchymal tissue. Formation of eosinophilic and basophilic hard tissue matrix (dentin and enamel) resembling odontoma was observed in the center of the tumor. Mitotic figures were rare, and areas of cystic degeneration were present. Immunohistochemically, the epithelial component was positive for cytokeratin AE1/AE3 (CK AE1/AE3), and the mesenchymal component and odontoblast-like cells were positive for vimentin, in the same manner as in normal teeth. On the basis of these findings, the tumor was diagnosed as a peripheral ameloblastic odontoma in an extraosseous mandibular region in a SD rat. In the present study, we report the uncommon spontaneous peripheral ameloblastic odontoma in the SD rat. We also discuss here the morphological characteristics, origin, histochemical, and immunohistochemical features for the diagnosis of this tumor. PMID:28503263

  18. 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.

  19. Biological fractionation of lead isotopes in Sprague-Dawley rats lead poisoned via the respiratory tract.

    PubMed

    Wu, Jing; Liu, Duojian; Xie, Qing; Wang, Jingyu

    2012-01-01

    It was considered that lead isotope ratios did not change during physical, chemical, or biological processes. Thus, lead isotope ratios have been used as fingerprints to identify possible lead sources. However, recent evidence has shown that the lead isotope ratios among different biological samples in human are not always identical from its lead origins in vitro. An animal experiment was conducted to explore the biological fractionation of lead isotopes in biological systems. 24 male Sprague-Dawley (SD) rats were divided into groups that received acute lead exposure (0, 0.02, 0.2, or 2 mg/kg body weight of lead acetate) via the respiratory route every day for 5 days. Biological samples (i.e., blood, urine, and feces) were collected for comparison with the lead acetate (test substance) and the low-lead animal feed (diet) administered to the rats. The lead isotope ratios were determined by inductively coupled plasma mass spectrometry (ICP-MS). There are significant differences (p<0.05) in lead isotope ratios between blood, urine, and feces. Moreover, a nonlinear relationship between the blood lead concentration and the blood lead isotope ratios was observed. There is also a threshold effect to the fractionation function. Only the blood isotope ratio of (204)Pb/(206)Pb matches the test substance well. As for feces, when (204)Pb/(206)Pb ratio is considered, there is no significant difference between feces-test substance pairs in medium and high dose group. The biological fractionation of lead isotopes in SD rats was observed. Moreover, there might be a threshold for the biological fractionation of lead isotopes which is depending on whole blood lead level. It is considered to be more reliable that we compared the isotope ratios of potential lead hazards with both blood and feces lead fingerprints especially for (204)Pb/(206)Pb ratio under high-dose exposure.

  20. Biological Fractionation of Lead Isotopes in Sprague-Dawley Rats Lead Poisoned via the Respiratory Tract

    PubMed Central

    Wu, Jing; Liu, Duojian; Xie, Qing; Wang, Jingyu

    2012-01-01

    Objectives It was considered that lead isotope ratios did not change during physical, chemical, or biological processes. Thus, lead isotope ratios have been used as fingerprints to identify possible lead sources. However, recent evidence has shown that the lead isotope ratios among different biological samples in human are not always identical from its lead origins in vitro. An animal experiment was conducted to explore the biological fractionation of lead isotopes in biological systems. Methods 24 male Sprague-Dawley (SD) rats were divided into groups that received acute lead exposure (0, 0.02, 0.2, or 2 mg/kg body weight of lead acetate) via the respiratory route every day for 5 days. Biological samples (i.e., blood, urine, and feces) were collected for comparison with the lead acetate (test substance) and the low-lead animal feed (diet) administered to the rats. The lead isotope ratios were determined by inductively coupled plasma mass spectrometry (ICP-MS). Results There are significant differences (p<0.05) in lead isotope ratios between blood, urine, and feces. Moreover, a nonlinear relationship between the blood lead concentration and the blood lead isotope ratios was observed. There is also a threshold effect to the fractionation function. Only the blood isotope ratio of 204Pb/206Pb matches the test substance well. As for feces, when 204Pb/206Pb ratio is considered, there is no significant difference between feces-test substance pairs in medium and high dose group. Conclusions The biological fractionation of lead isotopes in SD rats was observed. Moreover, there might be a threshold for the biological fractionation of lead isotopes which is depending on whole blood lead level. It is considered to be more reliable that we compared the isotope ratios of potential lead hazards with both blood and feces lead fingerprints especially for 204Pb/206Pb ratio under high-dose exposure. PMID:23300678

  1. Hematological Alterations on Sub-acute Exposure to Flubendiamide in Sprague Dawley Rats

    PubMed Central

    Vemu, Bhaskar; Dumka, Vinod Kumar

    2014-01-01

    Background: Pesticide poisoning is a common occurrence around the world. Pesticides can act on various body systems resulting in toxicity. Flubendiamide is a new generation pesticide, reported to have better activity against Lepidopteran insects. The present study was carried out with an objective to analyze the effects of flubendiamide sub-acute exposure on hematology of rats. Materials and Methods: Male and female Sprague Dawley (SD) rats (9–11 weeks) were divided into five groups with six animals in each group. First group served as control, while the rest were exposed to ascending oral doses of flubendiamide (125, 250, 500 and 1000 mg/kg) for 28 days. After the trial period, blood was collected in heparinized vials and analyzed using Siemens ADVIA 2120® autoanalyzer. Various erythrocytic, platelet and leukocyte parameters were measured and analyzed using statistical tests by one-way analysis of variance (ANOVA) and t-test using Statistical Package for Social Sciences (SPSS)® 20 software. Results: After processing the data through statistical analysis, it was observed that the effect of flubendiamide exposure on female rats was negligible. The only significant change observed in the female rats was that in total erythrocytic count, while rest of the parameters showed non-significant bidirectional changes. In males, many parameters viz., total leukocyte count (TLC), total erythrocyte count (TEC), packed cell volume (PCV), mean corpuscular volume (MCV), platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), hemoglobin distribution width (HDW), large platelets (LPT) and plateletcrit (PCT) expressed significant difference when compared to control. Conclusion: Many of the changes were dose independent, but sex specific. This lead to the hypothesis that saturation toxicokinetics might be one of the reasons for this varied response, which can only be evaluated after further testing. PMID:25948968

  2. Acrylonitrile-Induced Oxidative Stress and Oxidative DNA Damage in Male Sprague-Dawley Rats

    PubMed Central

    Kamendulis, Lisa M.; Klaunig, James E.

    2009-01-01

    Studies have demonstrated that the induction of oxidative stress may be involved in brain tumor induction in rats by acrylonitrile. The present study examined whether acrylonitrile induces oxidative stress and DNA damage in rats and whether blood can serve as a valid surrogate for the biomonitoring of oxidative stress induced by acrylonitrile in the exposed population. Male Sprague-Dawley rats were treated with 0, 3, 30, 100, and 200 ppm acrylonitrile in drinking water for 28 days. One group of rats were also coadministered N-acetyl cysteine (NAC) (0.3% in diet) with acrylonitrile (200 ppm in drinking water) to examine whether antioxidant supplementation was protective against acrylonitrile-induced oxidative stress. Direct DNA strand breakage in white blood cells (WBC) and brain was measured using the alkaline comet assay. Oxidative DNA damage in WBC and brain was evaluated using formamidopyrimidine DNA glycosylase (fpg)-modified comet assay and with high-performance liquid chromatography-electrochemical detection. No significant increase in direct DNA strand breaks was observed in brain and WBC from acrylonitrile-treated rats. However, oxidative DNA damage (fpg comet and 8′hydroxyl-2-deoxyguanosine) in brain and WBC was increased in a dose-dependent manner. In addition, plasma levels of reactive oxygen species (ROS) increased in rats administered acrylonitrile. Dietary supplementation with NAC prevented acrylonitrile-induced oxidative DNA damage in brain and WBC. A slight, but significant, decrease in the GSH:GSSG ratio was seen in brain at acrylonitrile doses > 30 ppm. These results provide additional support that the mode of action for acrylonitrile-induced astrocytomas involves the induction of oxidative stress and damage. Significant associations were seen between oxidative DNA damage in WBC and brain, ROS formation in plasma, and the reported tumor incidences. Since oxidative DNA damage in brain correlated with oxidative damage in WBC, these results suggest

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

    PubMed Central

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

    2015-01-01

    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. PMID:25791204

  4. 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

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

    PubMed

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

    2013-01-01

    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. 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. 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-a in the uterine tissues of the Genistein-treated animals compared to the control animals. 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.

  6. Immune responses in sprague-dawley rats exposed to dibutyltin dichloride in drinking water as adults.

    PubMed

    DeWitt, Jamie C; Copeland, Carey B; Luebke, Robert W

    2005-07-01

    Organotins are used commercially as agricultural pesticides, antifouling agents, and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted methyl and butyltins, used in PVC pipe production, are of concern as they leach from supply pipes into drinking water and have been reported to cause multisystem toxicity, including immunotoxicity. As part of an ongoing study to evaluate immunotoxic effects of organotins, we assessed immune function in adult Sprague-Dawley (CD) rats after exposure to dibutyltin dichloride (DBTC). Individually-housed adult male and female CD rats were given drinking water containing 0, 10, or 25 mg DBTC/L (final concentration) in 0.5% Alkamuls for 28 days. Water bottles were changed and water consumption was monitored twice weekly and body weights (BW) were recorded weekly. Delayed-type hypersensitivity (DTH), primary and secondary antibody responses to sheep red blood cells, and natural killer (NK) cell activity were evaluated in separate groups of treated and control animals on day 29 of exposure. Water consumption was significantly decreased in both sexes at 25 mg DBTC/L. BW, immune organ weights, the DTH response, and NK cell activity did not vary by dose. Different results for antibody responses in male rats were obtained in two experimental replicates. In the first replicate, IgG was elevated at the highest dose whereas in the second replicate, IgM was suppressed. However, as these effects occurred at the high dose of 25 mg DBTC/L, which is a concentration a million times higher than levels of DBTC reported in drinking water, our data suggest that DBTC is unlikely to cause immunotoxicity at concentrations found in drinking water supplies.

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

    PubMed

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

    2004-03-01

    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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Extremely weak magnetic field exposure may inhibit hippocampal neurogenesis of Sprague Dawley rats

    NASA Astrophysics Data System (ADS)

    Zhang, B.; Tian, L.; Cai, Y.; Xu, H.; Pan, Y.

    2016-12-01

    Hippocampal neurogenesis occurs throughout life in mammals brains and can be influenced by animals' age as well as environmental factors. Lines of evidences have shown that the magnetic field is an important physics environmental factor influencing many animals' growth and development, and extremely weak magnetic field exposures have been proved having serious adverse effects on the metabolism and behaviors in some animals, but few studies have examined the response of hippocampal neurogenesis to it. In the present study, we experimentally examined the extremely weak magnetic field effects on neurogenesis of the dentate gyrus (DG) of hippocampus of adult Sprague Dawley (SD) rats. Two types of magnetic fields were used, an extremely weak magnetic field (≤ 0.5μT) and the geomagnetic fields (strength 31-58μT) as controls. Thirty-two SD rats (3-weeks old) were used in this study. New cell survival in hippocampus was assessed at 0, 14, 28, and 42 days after a 7-day intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Meanwhile, the amounts of immature neurons and mature neurons which are both related to hippocampal neurogenesis, as documented by labeling with doublecortin (DCX) and neuron (NeuN), respectively, were also analyzed at 0, 14, 28, and 42 days. Compared with geomagnetic field exposure groups, numbers of BrdU-, DCX-positive cells of DG of hippocampus in tested rats reduces monotonously and more rapidly after 14 days, and NeuN-positive cells significantly decreases after 28days when exposed in the extremely weak magnetic field condition. Our data suggest that the exposure to an extremely weak magnetic field may suppress the neurogenesis in DG of SD rats.

  14. 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.

  15. Hypolipidaemic effect and mechanism of paprika seed oil on Sprague-Dawley rats.

    PubMed

    Chen, Xuhui; Ding, Yongbo; Song, Jiaxin; Kan, Jianquan

    2017-09-01

    Details regarding the functional properties of paprika seed oil are relatively scarce. In this study the hypolipidaemic effects and mechanisms of paprika seed oil on Sprague-Dawley rats are explored, which may improve the usage of paprika seed source and provide a theoretical basis of paprika seed oil for the alleviation of hyperlipidaemia. In capsaicin and paprika seed oil (PSO) groups, total cholesterol (TC) and total triglyceride (TG) in serum and liver lipids of rats were significantly decreased (P < 0.05). The contents of serum HDL cholesterol were increased and the contents of serum LDL cholesterol were decreased (P < 0.05). Real-time PCR analyses revealed that the hepatic mRNA expression of fatty acid synthetase (FAS) is decreased and the expression levels of HSL is increased (P < 0.05). The mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) is decreased and the expression levels of low-density lipoprotein receptor (LDLR) is significantly improved (P < 0.05). The cholesterol 7-hydroxylase (CYP7A1) expression is regulated to control the cholesterol-to-bile acid transformation and cholesterol excretion is promoted. Capsaicin and unsaturated fatty acid PSO can activate and improve the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and peroxisome proliferators-activated receptors (PPARα). The hypolipidaemic effects of paprika seed oil (PSO) may be attributed to the inhibition of lipid synthesis via suppressing the expression of HMG-CoAR, CYP7A1 and FAS, meanwhile, promoting the metabolism and excretion of lipids via up-regulating the expression of LDLR, HSL, TRPV1 and PPARα. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  16. Continuous exposure to dizocilpine facilitates escalation of cocaine consumption in male Sprague-Dawley rats.

    PubMed

    Allen, Richard M

    2014-01-01

    Although the escalation of cocaine consumption is a hallmark of cocaine dependence, the neurobiological mechanisms that underlie this change in behavior are not well understood. This study used an extended access version of the drug self-administration procedure to explore how N-methyl-d-aspartate (NMDA) receptors are involved in escalation of cocaine consumption. Male Sprague-Dawley rats (n=59) were first trained to self-administer cocaine (0.33 mg/infusion, i.v.) under a fixed-ratio 1 (FR1) schedule of reinforcement. After training, rats were implanted with subcutaneous osmotic minipumps filled with vehicle or the non-competitive NMDAR antagonist, dizocilpine (0.2 or 0.4 mg/kg/d), and subsequently allowed to self-administer cocaine in 2h or 6h self-administration sessions. In the 6h groups, vehicle-treated rats escalated cocaine self-administration across 15 self-administration sessions; rats treated with dizocilpine escalated cocaine self-administration at a greater rate and to a greater degree. Rats that self-administered cocaine during 2h sessions did not escalate consumption of cocaine under any treatment condition. Discontinuation of dizocilpine treatment in the 6h access condition led to a substantial decrease in cocaine consumption, down to pre-escalation levels, and then control rates of escalation thereafter. Despite large differences in intake under the FR1 schedule, post-escalation break point under a progressive ratio schedule of reinforcement did not differ between groups. These data suggest that glutamate tone through NMDA receptors can play a dynamic role in regulating cocaine intake and escalation of consumption. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Increased Methylglyoxal Formation with Upregulation of Renin Angiotensin System in Fructose Fed Sprague Dawley Rats

    PubMed Central

    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

  18. 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

  19. Morinda citrifolia fruit juice augments insulin action in Sprague-Dawley rats with experimentally induced diabetes.

    PubMed

    Horsfall, A U; Olabiyi, O; Aiyegbusi, A; Noronha, C C; Okanlawon, A O

    2008-01-01

    The use of additional medicines by patients with chronic medical illness like diabetes mellitus is on the increase. We investigated the effect of fruit juice of Morinda citrifolia on blood glucose of diabetic rats alone or when combined with insulin. Twenty adult male Sprague Dawley rats with body weights 140-210 g were used for the experiments. They were randomly allocated into groups of five, with five rats in each group. The first group, (Group A) served as control and received standard rat chow and water, throughout the duration of the study. Group B received noni juice treatment, after induction of diabetes, for 4 weeks. Group C rats received fixed dose insulin treatment (Humilin 70/30) in two divided doses, at a dose of 0.6 units/Kg body weight/day, following induction of diabetes, for 4 weeks. The Group D rats received fixed dose insulin as well as noni juice, following induction of diabetes for 4 weeks. We monitored blood glucose level by measuring fasting blood sugar weekly. The result of the experiments show that after an initial hyperglycemia, following alloxan induced diabetes, treatment with noni juice restored reduced blood sugar but euglycaemia was not achieved (Group B). At the end of 4 weeks of experimentation. The mean fasting blood sugar level of 8.0 +/- 0.8 mmol/L following combination therapy, in which insulin treatment was combined with noni juice for 4 weeks, was lower than when either noni juice 15.4 +/- 1.5 mmol/L or insulin was used alone (P < 0.05). 12.9 +/- 1.6 mmol/L. In this study, a synergistic action with insulin was demonstrated by fruit juice of Morinda citrifolia.

  20. 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.; hide

    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.

  1. 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

  2. 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.

  3. 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.

  4. An assessment of MDPV-induced place preference in adult Sprague-Dawley rats.

    PubMed

    King, Heather E; Wetzell, Bradley; Rice, Kenner C; Riley, Anthony L

    2015-01-01

    Most drugs of abuse have both aversive and rewarding effects, and the use and abuse potential of such drugs is thought to be a function of a balance of these affective properties. Characterizing these effects and their relative balance may provide insight into abuse vulnerability. One drug that has received recent attention is methylenedioxypyrovalerone (MDPV), a monoamine transport inhibitor similar to, but significantly more potent than, cocaine. MDPV is self-administered and has been shown to produce aversive and rewarding effects in adult rats. The present study extended this characterization of the affective properties of MDPV by examining its ability to support place conditioning at a range of doses known to produce taste avoidance. Male Sprague-Dawley rats were injected with MDPV (1, 1.8 or 3.2mg/kg) or saline and placed on the non-preferred side of a place conditioning apparatus for 30 min. On the next day, they were given an injection of saline and placed on the preferred side. This was repeated three times for a total of four conditioning cycles, and side preference was assessed on a final test. All doses of MDPV produced significant increases in time spent in the drug-paired chamber, an effect not seen in vehicle-treated animals. That the same doses of MDPV induced both taste avoidance and place preference allows assessments of how other factors might impact these effects and how they may, in turn, contribute to its abuse liability. Copyright © 2014. Published by Elsevier Ireland Ltd.

  5. Sexual maturation data for Crl Sprague-Dawley rats: criteria and confounding factors.

    PubMed

    Lewis, Elise M; Barnett, John F; Freshwater, Les; Hoberman, Alan M; Christian, Mildred S

    2002-11-01

    Considerable concern exists in the scientific community regarding potential effects of endocrine disruptive or modulating environmental agents on male and female reproductive development and capacity. Existing data show that in utero and postnatal exposure of rodents to endocrine modulating chemicals can influence the timing and progression of sexual differentiation and/or maturation (e.g., balanopreputial separation and vaginal opening). Sexual maturation data from various types of littering studies using International Gold Standard (IGS) Crl Sprague-Dawley rats were evaluated for consistency with both historical observations and published values from other laboratories. In addition, litters from two developmental neurotoxicology studies were statistically analyzed to identify whether increasing the numbers of pups per litter evaluated affected the interpretation of sexual maturation data sets. Control values for preputial separation and vaginal opening ages ranged from PD 45.0 to 48.0 and from PD 32.0 to 34.0, respectively, regardless of the number of pups evaluated per litter. However, statistically significant delays in sexual maturation were present when three rats/sex/litter were evaluated that were not present when only one randomly selected rat/sex/litter was evaluated. Standardized procedures and criteria are required to provide consistent intra-laboratory values and reduce inter-laboratory differences in sexual maturation observations. When such criteria are used, these endpoints provide sensitive measures for detecting alterations in sexual maturation. However, our analyses demonstrate that the ability to detect statistically significant and biologically important differences in these endpoints is sometimes impaired by the currently common practice of evaluating only one randomly selected rat/sex/litter. Evaluation of three rats/sex/litter improved the sensitivity of the statistical analysis in detection of treatment-related effects and reduced the

  6. 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.

  7. Low-dose, Chronic Exposure to Silver Nanoparticles Causes Mild Mitochondrial Alterations in the Liver of Sprague-Dawley Rat

    DTIC Science & Technology

    2014-05-10

    AFRL-AFOSR-UK-TR-2014-0032 Low-dose, chronic exposure to silver nanoparticles causes mild mitochondrial alterations in the liver...TITLE AND SUBTITLE Low-dose, chronic exposure to silver nanoparticles causes mild mitochondrial alterations in the liver of Sprague-Dawley rat 5a...Approved for public release; distribution is unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Nanoparticles (NPs) are, by definition

  8. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Acute exhaustive aerobic exercise training impair cardiomyocyte function and calcium handling in Sprague-Dawley rats

    PubMed Central

    Ljones, Kristine; Ness, Henning Ofstad; Solvang-Garten, Karin; Gaustad, Svein Erik; Andre Høydal, Morten

    2017-01-01

    Introduction Recent data from long-distance endurance participants suggest that cardiac function is impaired after completion. Existing data further indicate that right ventricular function is more affected than left ventricular function. The cellular mechanisms underpinning cardiac deterioration are limited and therefore the aim of this study was to examine cardiomyocyte and molecular responses of the right and left ventricle to an acute bout of exhaustive endurance exercise. Materials and methods Male Sprague-Dawley rats were assigned to sedentary controls or acute exhaustive endurance exercise consisting of a 120 minutes long forced treadmill run. The contractile function and Ca2+ handling properties in isolated cardiomyocytes, protein expression levels of sarcoplasmic reticulum Ca2+-ATPase and phospholamban including two of its phosphorylated states (serine 16 and threonine 17), and the mitochondrial respiration in permeabilized cardiac muscle fibers were analyzed. Results The exercise group showed a significant reduction in cardiomyocyte fractional shortening (right ventricle 1 Hz and 3 Hz p<0.001; left ventricle 1 Hz p<0.05), intracellular Ca2+ amplitude (right ventricle 1 and 3 Hz p<0.001; left ventricle 1 Hz p<0.01 and 3 Hz p<0.05) and rate of diastolic Ca2+ decay (right ventricle 1 Hz p<0.001 and 3 Hz p<0.01; left ventricle 1 and 3 Hz p<0.01). Cardiomyocyte relaxation during diastole was only significantly prolonged at 3 Hz in the right ventricle (p<0.05) compared to sedentary controls. We found an increase in phosphorylation of phospholamban at serine 16 and threonine 17 in the left (p<0.05), but not the right, ventricle from exhaustively exercised animals. The protein expression levels of sarcoplasmic reticulum Ca2+-ATPase and phospholamban was not changed. Furthermore, we found a reduction in maximal oxidative phosphorylation and electron transport system capacities of mitochondrial respiration in the right (p<0.01 and p<0.05, respectively), but not the

  10. 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

  11. 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

  12. 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

  13. [Pathologic changes of spontaneous tumors in Sprague-Dawley and Wistar rats].

    PubMed

    He, Y N; Zhang, S C; Zhang, H M

    2017-04-08

    Objective: To investigate the spontaneous neoplastic lesions and their incidences in Sprague-Dawley (SD) and Wistar rats, and to accumulate background data for carcinogenicity studies. Methods: One hundred and eighty SD rats and 240 Wistar rats (4-week old) , half in each sex, were used in this study. The rats were housed routinely under specific pathogen-free environment and euthanized after 104 weeks. Histopathological examination was undertaken for all animals including deaths and scheduled euthanasia. The types and incidences of spontaneous tumors were gathered statistically. Results: Total 411 rats (176 SD rats and 235 Wistar rats) were examined in this study. The total tumor incidence of the 411 rats was 57.7%(237/411). The total tumor incidence in SD rats was 55.7%(98/176), benign tumor incidence was 48.9%(86/176) and malignant tumor incidence was 15.9%(28/176). The total tumor incidence in Wistar rats was 59.1%(139/235), benign tumor incidence was 51.5%(121/235) and malignant tumor incidence was 14.5%(34/235). The main benign tumors were pituitary adenoma (23.3% in SD rats, 12.3% in Wistar rats), breast fibroadenoma (21.3% in SD rats, 12.9% in Wistar rats) and breast adenoma (16.9% in SD rats, 9.5% in Wistar rats) in females; testis Leydig cell tumor (0 in SD rats, 14.3% in Wistar rats) in males. The main malignant tumors were breast carcinoma (10.1% in SD rats, 3.4% in Wistar rats) and uterine leiomyosarcoma (0 in SD rats, 2.6% in Wistar rats) in females; squamous cell carcinoma of skin (2.3% in SD rats, 0.9% in Wistar rats); subcutaneous fibrosarcoma (1.1% in SD rats, 2.1% in Wistar rats); brain malignant glioma (1.1% in SD rats, 1.7% in Wistar rats). Conclusions: In the study, a high incidence of spontaneous tumors is reported in both SD and Wistar rats housed for 2 years. The incidence of benign tumors is higher than that of malignant rumors. The benign tumors mainly are pituitary adenoma, breast fibroadenoma and breast adenoma in females, and testis

  14. 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

  15. 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

  16. A subchronic toxicity study of elemental Nano-Se in Sprague-Dawley rats.

    PubMed

    Jia, X; Li, N; Chen, J

    2005-03-11

    The subchronic toxicity of Nano-Se was compared with selenite and high-selenium protein in rats. Groups of Sprague-Dawley rats (12 males and 12 females per group) were fed diets containing Nano-Se, selenite and high-selenium protein at concentrations of 0, 2, 3, 4 and 5 ppm Se, respectively, for 13 weeks. Clinical observations were made and body weight 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 hematology and clinical chemistry determination. Histopathological examination was performed on selected tissues. At the two higher doses (4 and 5 ppm Se), significant abnormal changes were found in body weight, hematology, clinical chemistry, relative organ weights and histopathology parameters. However, the toxicity was more pronounced in the selenite and high-selenium protein groups than the Nano-Se group. At the dose of 3 ppm Se, significant growth inhibition and degeneration of liver cells were found in the selenite and high-selenium protein groups. No changes attributable to administration of Nano-Se at the dose of 3 ppm Se were found. Taken together, the no-observed-adverse-effect level (NOAEL) of Nano-Se in male and female rats was considered to be 3 ppm Se, equivalent to 0.22 mg/kg bw/day for males and 0.33 mg/kg bw/day for females. On the other hand, the NOAELs of selenite and high-selenium protein in males and females were considered to be 2 ppm Se, equivalent to 0.14 mg/kg bw/day for males and 0.20 mg/kg bw/day for females. In addition, studies have shown that Nano-Se has a similar bioavailability in rat, and much less acute toxicity in mice compared with selenite. In conclusion, Nano-Se is less toxic than selenite and high-selenium protein in the 13-week rat study.

  17. Electrophysiological findings in the Sprague-Dawley rat induced by moderate-dose carboplatin.

    PubMed

    Hatzopoulos, Stavros; Petruccelli, Joseph; Laurell, Goran; Previati, Maurizio; Martini, Alessandro

    2003-08-01

    Carboplatin is a second generation platinum-containing anti-tumor drug which selectively alters the micromechanical function of the inner hair cells (IHCs) of the organ of Corti in the chinchilla. Data from a recent study [Wake et al., Acta Otolaryngol. 116 (1996) 374-381], using the chinchilla model, have suggested that a moderate dose of carboplatin alters the efferent feedback loop gain of the OHCs. The present study was designed to evaluate the possible 'efferent feedback alteration mechanism' in the Sprague-Dawley rat using distortion product otoacoustic emissions (DPOAEs). A moderate dose of carboplatin (50 mg/kg body weight) was administered by a 30 min i.p. infusion. Pre- and 72-h post-treatment DPOAE and auditory brainstem response (ABR) recordings were acquired from a group of 12 rats. The animals were anesthetized with a ketamine-atropin anesthesia administered in two consecutive phases. The DPOAE responses (cubic distortion products) were recorded with four asymmetrical protocols: P1=60-50, P2=50-40, P3=40-30 and P4=30-20 dB SPL (sound pressure level), in the frequency range from 4.0 to 16 kHz. ABR responses were obtained for bipolar clicks and tone pips at the frequencies 8.0, 10.0, 20.0 and 30 kHz using stimuli in the range from 100 to 30 dB SPL. Significant ABR threshold shifts of 15 dB were observed at 30 kHz, and shifts of 10 dB at 20, 16 and 10 kHz. The comparison of pre- and post-treatment DPOAE responses did not reveal any significant changes for protocols P1, P2 and P4. Data from the P3 protocol indicated a decrease of the DPOAE amplitude. The findings from the rat model suggest that (a) moderate doses of carboplatin do not affect the efferent feedback loop OHC function and (b) the cochlear susceptibility to carboplatin across species is different, even at moderate-dose regimes.

  18. Role of sucrose in colonization of Streptococcus mutans in conventional Sprague-Dawley rats.

    PubMed

    Van Houte, J; Upeslacis, V N; Jordan, H V; Skobe, Z; Green, D B

    1976-01-01

    The role of sucrose in the colonization of S mutans strain 6715 in conventional Sprague-Dawley rats was studied. A diet with 56% sucrose favored the oral colonization of the test strain compared to diets with 56% glucose or fructose or to laboratory chow as determined by recoveries from extracted teeth ground in tissue grinders. S mutans strain 6715 cells became well established in all rats fed a high sucrose diet with cell inoculums ranging from 10(8) to the lowest effective dose of 10(5) CFU once orally administered; in rats on nonsucrose diets, inoculation with even the highest dose only infrequently resulted in the establishment of S mutans strain 6715. Sucrose- and glucose- grown cells appeared to behave similarly. Colonization of S mutans strain 6715 occurred in all rats fed diets with a sucrose content ranging from 56 to as low as 1%. The establishment of S mutans strain 6715 on the teeth of rats fed diets with a sucrose concentration of 0.1 or 0.01% was impaired and comparable to the diet containing 56% glucose. In rats fed a high glucose diet, uniform establishment and persistence of the test strain occurred after frequent inoculations with about 5 X 10(8) CFU. The colonization under these conditions appeared to be independent of the intestinal canal as a bacterial cell source. These data suggest the possibility that S mutans can establish itself in the human mouth in the absence of dietary sucrose. In rats fed a high glucose diet and inoculated with 10(7) CFU or less, the cells gradually disappeared from the teeth; in contrast, the test strain implanted well in rats fed the sucrose favors firmer attachment of initially weakly attached cells via in situ new glucan synthesis. S mutans strain 6715 also appeared to have some affinity for teeth in the absence of dietary sucrose that may be of ecological significance. Once firmly established in rats fed a high sucrose diet, S mutans strain 6715 maintained itself in high numbers on the teeth after a switch to a

  19. Effects of Didecyldimethylammonium Chloride (DDAC) on Sprague-Dawley Rats after 13 Weeks of Inhalation Exposure

    PubMed Central

    Kim, Yong-Soon; Lee, Sung-Bae; Lim, Cheol-Hong

    2017-01-01

    Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were 0.63 μm, 0.81 μm, and 1.65 μm, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low (0.11 ± 0.06 mg/m3), the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high (1.41 ± 0.71 mg/m3) male group and 15% lower in the high (1.41 ± 0.71 mg/m3) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle (0.36 ± 0.20 mg/m3) and the high (1.41 ± 0.71 mg/m3) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is 0.11 mg/m3. PMID:28133508

  20. Effects of nicotine exposure on in vitro metabolism of chlorpyrifos in male Sprague-Dawley rats.

    PubMed

    Lee, S; Busby, A L; Timchalk, C; Poet, T S

    2009-01-01

    The routine use of tobacco products may modify key metabolizing systems, which will further impact the metabolism of environmental contaminants. The objective of this study was to quantify the effect of repeated in vivo exposures to nicotine, a major pharmacologically active component of cigarette smoke, on in vitro metabolism of chlorpyrifos (CPF). CPF is an organophosphorus (OP) insecticide that is metabolized by cytochrome P-450 (CYP450) to its major metabolites, chlorpyrifos-oxon (CPF-oxon) and 3,5,6-trichloro-2-pyridinol (TCP). Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg for 1, 7, or 10 d. Rats were sacrificed 4 or 24 h after the last nicotine treatment, and liver microsomes were prepared. The microsomes were incubated with varying concentrations of CPF and the production of the metabolites CPF-oxon and TCP were measured. The metabolism of CPF to the active oxon metabolite did not show significant changes following repeated nicotine treatments, evidenced by the unchanged pseudo first-order clearance rate of V(max)/K(mapp). The V(max) describing the metabolism of CPF to the inactive metabolite, TCP was increased in 24-h postdosing groups, after both single and repeated treatments of nicotine. In contrast, the metabolism to TCP was unchanged in groups evaluated at 4 h (single or repeated) post nicotine dosing. Some basic marker substrate activities were also investigated to ensure that nicotine exerted effects on CYP450 activities. Total P450 reduced spectra were not altered by nicotine treatment, but marker substrate activities for CYP1A and CYP2E1 were increased at 24 h after the single treatment, and marker substrate activity for CYP2B was decreased 4 h after 7 d of treatment. Results of this in vitro study suggest that repeated nicotine exposure may result in altered metabolism of CPF. Future in vivo experiments based on these results need to be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in

  1. Toxicological characterisation of two novel selective aryl hydrocarbon receptor modulators in Sprague-Dawley rats.

    PubMed

    Mahiout, Selma; Lindén, Jere; Esteban, Javier; Sánchez-Pérez, Ismael; Sankari, Satu; Pettersson, Lars; Håkansson, Helen; Pohjanvirta, Raimo

    2017-07-01

    The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). They represent, as diacetyl prodrugs, AHR-active metabolites of the drug compounds laquinimod and tasquinimod, respectively, which are intended for the treatment of autoimmune diseases and cancer. Here, we toxicologically assessed the novel compounds in Sprague-Dawley rats, after a single dose (8.75-92.5mg/kg) and 5-day repeated dosing at the highest doses achievable (IMA-08401: 100mg/kg/day; and IMA-07101: 75mg/kg/day). There were no overt clinical signs of toxicity, but body weight gain was marginally retarded, and the treatments induced minimal hepatic extramedullary haematopoiesis. Further, both the absolute and relative weights of the thymus were significantly decreased. Cyp1a1 gene expression was substantially increased in all tissues examined. The hepatic induction profile of other AHR battery genes was distinct from that caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The only marked alterations in serum clinical chemistry variables were a reduction in triglycerides and an increase in 3-hydroxybutyrate. Liver and kidney retinol and retinyl palmitate concentrations were affected largely in the same manner as reported for TCDD. In vitro, the novel compounds activated CYP1A1 effectively in H4IIE cells. Altogether, these novel compounds appear to act as potent activators of the AHR, but lack some major characteristic toxicities of dioxins. They therefore represent promising new selective AHR modulators. Copyright © 2017 Elsevier

  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. 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...

  4. Colony-Specific Differences in Endocrine and Immune Responses to an Inflammatory Challenge in Female Sprague Dawley Rats

    PubMed Central

    Hill, Lesley A.; Taves, Matthew D.; Yu, Wayne; Soma, Kiran K.; Hammond, Geoffrey L.; Weinberg, Joanne

    2015-01-01

    Sprague Dawley rats from different vendor colonies display divergent responses in a variety of experimental paradigms. An adjuvant-induced arthritis (AA) model of human rheumatoid arthritis was used to examine immune and endocrine responses to inflammatory challenge in Sprague Dawley rats from Charles River and Harlan colonies. Rats were injected with either complete Freund's adjuvant or physiological saline (control), weights, and paw volumes measured over 15 days, and blood and tissue were collected 16 days post-injection. Overall, Harlan rats developed more severe AA than Charles River rats. In addition, despite comparable corticosterone levels, corticosteroid binding globulin levels were lower in Harlan compared with Charles River rats in the absence of inflammation, suggesting that a lower corticosterone reservoir in Harlan rats may underlie their greater susceptibility to inflammation. With increasing AA severity, there was an increase in plasma corticosterone (total and free) and a decrease in corticosteroid binding globulin in both Charles River and Harlan rats. However, contrasting patterns of cytokine activation were observed in the hind paw, suggesting a reliance on different cytokine networks at different stages of inflammation, with Charles River rats exhibiting increased TNF-α, monocyte chemotactic protein-1 (MCP-1), keratinocyte chemoattractant/growth-regulated oncogene (KC/GRO), and IL-1β in the absence of clinical signs of arthritis, whereas Harlan had increased TNF-α, monocyte chemotactic protein-1, and IL-6 with mild to moderate arthritis. These colony-specific differences in endocrine and immune responses to AA in Sprague Dawley rats must be considered when comparing data from different laboratories and could be exploited to provide insight into physiological changes and therapeutic outcomes in arthritis and other inflammatory disorders. PMID:26402842

  5. Developmental neurotoxicity evaluation of the avermectin pesticide, emamectin benzoate, in Sprague-Dawley rats.

    PubMed

    Wise, L D; Allen, H L; Hoe, C M; Verbeke, D R; Gerson, R J

    1997-01-01

    The potential of emamectin benzoate (EB) to cause developmental neurotoxicity in Sprague-Dawley rats was assessed using a study design by the US EPA. Dosages of 0 (deionized water), 0.1, 0.6, or 3.6 mg/kg/day were administered at 5 ml/kg by oral gavage from gestational day (GD) 6 to lactational day (LD) 20 to groups of 25 mated females each. Between GD 17 and 20 the high dose was reduced to 2.5 mg/kg/day because of pup tremors observed at this dose level in a concurrent two-generation study. Females were allowed to deliver and the young were evaluated for survival, growth, development, behavior, and histological changes to brain, spinal cord, peripheral nerve, and skeletal muscle. Behavioral assessment of the offspring consisted of open field motor activity, auditory startle habituation, and passive avoidance tests; each was conducted on weanling and adult animals (one animal/sex/litter). Histopathological examination of the CNS and PNS was conducted on one animal/sex/litter on postnatal days (PND) 11 and 60. There were significant increases in average F0 maternal body weight gains during gestation in the 0.6 and 3.6/2.5 mg/kg/day groups, but no other effects were observed in pregnant females of these or the low-dose groups during the study. Beginning on PND 6, tremors were observed in high-dose pups, and this was followed by hindlimb splay in all high-dose pups by PND 15-26. Both of these physical signs disappeared by PND 34 (i.e., 10-11 days after weaning). There were no compound-related deaths in F1 offspring. Beginning on PND 11, progressive decreases in preweaning average weights were observed in the high-dose group (to 42% below control in females on PND 21). Average weight gain during the postweaning period was significantly decreased in the 3.6/2.5 mg/kg/day group. There were EB-related effects in behavioral tests only in the high-dose group. A significant increase in PND 13 average horizontal motor activity was due to stereotypical movements. Average

  6. Hyperhomocysteinemia exacerbates the development of intimal hyperplasia in Sprague-Dawley rats: Alleviation by rosiglitazone

    PubMed Central

    Murthy, SN; Fonseca, VA; McNamara, DB

    2005-01-01

    The amino acid intermediate homocysteine (Hcy) is formed during the metabolism of methionine to cysteine. Hyperhomocysteinemia (HHcy) is recognized as an independent risk factor for coronary atherosclerosis. The circulating levels of total Hcy (tHcy) can increase due to intake of foods rich in methionine or deficiencies of vitamins such as folate, pyridoxine and cyanocobalamin, which are required for the metabolism of Hcy. In addition, mutations in the genes coding for Hcy metabolizing enzymes can contribute to an increase in tHcy levels. Clinical and epidemiological studies have shown that an elevated level of tHcy measured in serum or plasma is a strong predictor of cardiovascular disease risk, which appears to be greatest in patients who have HHcy following a methionine load. Intimal hyperplasia (IH) (intima/media [I/M] ratio) is the universal response of a vessel to injury and may result in vasoconstriction when left unattended. The effect of dietary HHcy on balloon catheter-injured carotid artery and its modulation (if any) by the peroxisome proliferator-activated receptor agonist gamma rosiglitazone was evaluated in 12-week-old female Sprague-Dawley rats fed either a control diet or a diet containing 1% L-methionine. Once the rats were established on the diet, the group that was fed 1% L-methionine was further subdivided and either given an aqueous preparation of 3 mg/kg/day rosiglitazone or the vehicle via oral gavage for one week. This was followed by surgically injuring the left carotid artery using a Maverick Over-The-Wire catheter (2.0 mm × 20 mm, 3.2F; Boston Scientific, USA). The rats were continued on their respective diets and drug regimen for 21 days postsurgery. On day 22 of the procedure, the rats were sacrificed for collection of blood, the carotid arteries and liver for biochemical and histological evaluation. Compared with controls there was a significant increase in both tHcy levels and I/M ratio in the rats fed 1% L-methionine (5.4±0.28

  7. 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.

  8. 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.

  9. Low and High Locomotor Responsiveness to Cocaine Predicts Intravenous Cocaine Conditioned Place Preference in Male Sprague-Dawley Rats

    PubMed Central

    Allen, Richard M.; Everett, Carson V.; Nelson, Anna M.; Gulley, Joshua M.; Zahniser, Nancy R.

    2009-01-01

    Outbred, male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on cocaine-induced locomotor activity in an open-field arena. This difference reflects cocaine’s ability to inhibit the striatal dopamine transporter and predicts development of sensitization. To investigate the relationship between initial cocaine locomotor responsiveness and cocaine reward, here we first classified rats as either LCRs or HCRs in a conditioned place preference (CPP) apparatus. Subsequently, we conducted cocaine conditioning trials, twice daily over four days with vehicle and cocaine (10 mg/kg, i.p. or 1 mg/kg, i.v.). When cocaine was administered by the i.p. route, similar to previous findings in the open-field, LCRs and HCRs were readily classified and locomotor sensitization developed in LCRs, but not HCRs. However, cocaine CPP was not observed. In contrast, when cocaine was administered by the i.v. route, the LCR/HCR classification not only predicted sensitization, but also CPP, with only LCR rats exhibiting sensitization and cocaine conditioning. Our findings show that the initial locomotor response to cocaine can predict CPP in male Sprague-Dawley rats under conditions when place conditioning develops, and that LCRs may be more prone to develop conditioning in the context of cocaine reward. PMID:17250883

  10. Charles River Sprague Dawley Rats Lack Early Age-Dependent Susceptibility to DMBA-Induced Mammary Carcinogenesis

    PubMed Central

    Gear, R.B.; Yan, M.; Schneider, J.; Succop, P.; Heffelfinger, S.C.; Clegg, D.J.

    2007-01-01

    Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The “window of susceptibility” to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this “window”. We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CDR IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CDR IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent. PMID:17940635

  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. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. 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.

  13. Rapid induction of malignant tumor in Sprague-Dawley rats by injection of RK3E-ras cells.

    PubMed

    Kim, Soo-A; Kim, Hyun-Woo; Kim, Do-Kyung; Kim, Su-Gwan; Park, Joo-Cheol; Kang, Dong-Wan; Kim, Si-Wouk; Ahn, Sang-Gun; Yoon, Jung-Hoon

    2006-04-08

    Several tumor animal models have been provided as a tool for developing cancer therapy. Here, we developed rapid, easy-to use, and cost-effective new rat animal model for invasion and metastasis of cancer using genetically k-ras-induced rat kidney cells (RK3E-ras). We observed tumor as early as 3 days after injection of RK3E-ras cells in subcutaneous of Sprague-Dawley rats. Tumor size and volume were increased exponentially for 2 weeks. The tail vein injected rats obtained the lethal infiltration in the lung within 2 weeks. This tumor animal model has great potential for studying cancer processes and short-term screening of variable cancer therapy strategy.

  14. Aloe-emodin affects the levels of cytokines and functions of leukocytes from Sprague-Dawley rats.

    PubMed

    Yu, Chun-Shu; Yu, Fu-Shun; Chan, Jack Kai-Sheng; Li, Te-Mao; Lin, Song-Shei; Chen, Ssu-Ching; Hsia, Te-Chun; Chang, Yung-Hsien; Chung, Jing-Gung

    2006-01-01

    Aloe-emodin has shown anti-neoplastic activity against some human cancer cell lines. This study aimed to explore the effects of aloe-emodin on the phagocytosis of macrophages, the activity of natural killer (NK) cells and the expression of cytokines in leukocytes from Sprague-Dawley rats. Leukocytes were collected, placed into culture plates and the functions of macrophages and NK cells and the percentage of viable cells were determined by flow cytometric analysis. Incubation of leukocytes with various concentrations of aloe-emodin caused a dose-dependent decrease of viable cells, a decrease of phagocytosis by macrophages, and a decrease of the activity of NK cells. Evaluation of cytokines in leukocytes by ELISA indicated that aloe-emodin increased the levels of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. The results were also confirmed by PCR assay for the mRNA expression of the examined cytokines.

  15. 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.

  16. Acute oral toxicity of ja-2 solid propellant in sprague-dawley rats. Report for 12 November-19 December 1985

    SciTech Connect

    Brown, L.D.; Justus, J.D.; Wheeler, C.R.; Korte, D.W.

    1989-12-01

    The acute oral toxicity of JA-2 Solid Propellant was determined in male and female Sprague-Dawley rats by using an oral gavage split-dose method. The MLD was 3990.6 + or - 349.7 mg/kg for male rats and 2545.9 + or - 421.1 mg/kg for female rats. JA-2 produced clinical signs that were attributed to its nitrate ester components, diethyleneglycol dinitrate and nitroglycerin. These signs included tremors and twitching, cyanosis, and increases in respiratory rate and depth. Other clinical signs observed were associated with the general malaise of the animals following dosing and included hunched posture, rough coat, reddish stains around the eyes and nose, and perianal staining. Most animals exhibited signs by 4 hours after dosing and either had died or the signs had cleared by 96 hours after dosing. According to the classification scheme of Hodge and Sterner, these results place JA-2 in the slightly toxic class.

  17. 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. © 2015 by The Author(s).

  18. [Free radical modification of proteins in brain structure of Sprague-Dawley rats and some behaviour indicators after prenatal stress].

    PubMed

    V'iushina, A V; Pritvorova, A V; Flerov, M A

    2012-08-01

    We studied the influence of late prenatal stress on free radical oxidation processes in Sprague-Dawley rats cortex, striatum, hippocampus, hypothalamus proteins. It was shown that after prenatal stress most changes were observed in hypothalamus and hippocampus. It was shown that in hypothalamus spontaneous oxidation level increased, but level of induced oxidation decreased, the opposite changes were found in hippocampus. Simultaneously minor changes of protein modification were observed in cortex and striatum. It was shown that prenatal stress changed both correlation of proteins free radical oxidation in studied structures and values of these data regarding to control. In test of "open field" motor activity in rats after prenatal stress decreased and time of freezing and grooming increased; opposite, in T-labyrinth motor activity and time of grooming in rats after prenatal stress increased, but time of freezing decreased.

  19. 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.

  20. Urothelial changes of the renal papillae in Sprague-Dawley rats induced by long term feeding of phenacetin.

    PubMed

    Johansson, S; Angervall, L

    1976-09-01

    Thirty female Sprague-Dawley rats were fed 0.535 per cent phenacetin in the diet for up to 110 weeks. Twenty-six of these rats developed urothelial hyperplasia, partly papillary, of the renal papillae. Twenty-eight rats showed dilatation of the vasa recta frequently associated with thrombus formation and calcification. One phenacetin fed rat had epithelial hyperplasia associated with chronic pyelitis. In 2 of the 30 control rats urothelial hyperplasia was found to be associated with chronic pyelitis. The hyperplastic urothelial changes and vascular changes were often, but not always, present simultaneously. One control rat developed a mammary carcinoma, as compared with 5 rats in the phenacetin group. Four phenacetin fed rats developed carcinoma of the ear duct. The results of the present investigation provide evidence that phenacetin can induce proliferative lesions of the urothelium of the rat renal pelvis with weak carcinogenic activity in the ear duct and mammary glands.

  1. 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.

  2. The Impact of Adult Vitamin D Deficiency on Behaviour and Brain Function in Male Sprague-Dawley Rats

    PubMed Central

    Turner, Karly M.; Eyles, Darryl W.; McGrath, John J.; Burne, Thomas H. J.

    2013-01-01

    Background Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Methods Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. Results AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8–10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. Conclusions AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour. PMID:23951200

  3. LC-MS/MS method for the determination of melamine in rat plasma: toxicokinetic study in Sprague-Dawley rats.

    PubMed

    Yang, Feng; Mao, Yu; Zhang, Xiaodong; Ma, Zhiqiang; Zhang, Xinrong

    2009-09-01

    Most recently, melamine has raised international concern for its catastrophic health effects stemming from tainted infant formula. So far there is limited information concerning the pharmacokinetics of melamine in mammals. The present report concerns the development and validation of a sensitive HPLC-ESI-MS/MS method for the pharmacokinetic study of melamine in rat. The method employed a simple liquid-liquid extraction process for plasma sample cleanup, and the extraction recoveries of melamine from plasma were consistent at different concentrations. There was a linear relationship between chromatographic area and concentration over the range of 10-5000 ng/mL for melamine in plasma (R = 0.995). In this work, for the first time, melamine was administered intravenously and orally to Sprague-Dawley rats and the pharmacokinetic characteristics of this contaminant were investigated. The mean values of major pharmacokinetic parameters of oral availability, the mean steady-state distribution volume (V(ss)), clearance, and plasma elimination half-life (T(1/2)) of melamine in Sprague-Dawley rats were 72.9 +/- 13.2%, 102.5 +/- 12.5 mL/kg, 20.1 +/- 3.8 mL/h/kg, and 4.9 +/- 0.5 h, respectively. The rats pharmacokinetic study results suggested that melamine was predominantly restricted to blood or extracellular fluid and is not extensively distributed to most organ tissues. Meanwhile, melamine should be primarily eliminated by renal filtration for rats and does not undergo significant metabolism. These data should be useful to regulatory for risk assessment.

  4. 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

  5. Fenitrothion induced oxidative stress and morphological alterations of sperm and testes in male sprague-dawley rats

    PubMed Central

    Taib, Izatus Shima; Budin, Siti Balkis; Ghazali, Ahmad Rohi; Jayusman, Putri Ayu; Louis, Santhana Raj; Mohamed, Jamaludin

    2013-01-01

    OBJECTIVE: Fenitrothion residue is found primarily in soil, water and food products and can lead to a variety of toxic effects on the immune, hepatobiliary and hematological systems. However, the effects of fenitrothion on the male reproductive system remain unclear. This study aimed to evaluate the effects of fenitrothion on the sperm and testes of male Sprague-Dawley rats. METHODS: A 20 mg/kg dose of fenitrothion was administered orally by gavages for 28 consecutive days. Blood sample was obtained by cardiac puncture and dissection of the testes and cauda epididymis was performed to obtain sperm. The effects of fenitrothion on the body and organ weight, biochemical and oxidative stress, sperm characteristics, histology and ultrastructural changes in the testes were evaluated. RESULTS: Fenitrothion significantly decreased the body weight gain and weight of the epididymis compared with the control group. Fenitrothion also decreased plasma cholinesterase activity compared with the control group. Fenitrothion altered the sperm characteristics, such as sperm concentration, sperm viability and normal sperm morphology, compared with the control group. Oxidative stress markers, such as malondialdehyde, protein carbonyl, total glutathione and glutathione S-transferase, were significantly increased and superoxide dismutase activity was significantly decreased in the fenitrothion-treated group compared with the control group. The histopathological and ultrastructural examination of the testes of the fenitrothion-treated group revealed alterations corresponding with the biochemical changes compared with the control group. CONCLUSION: A 20 mg/kg dose of fenitrothion caused deleterious effects on the sperm and testes of Sprague-Dawley rats. PMID:23420164

  6. Effect of Norbinaltorphimine on Δ9-Tetrahydrocannabinol (THC)-Induced Taste Avoidance in Adolescent and Adult Sprague-Dawley Rats

    PubMed Central

    Flax, Shaun M.; Wakeford, Alison G.P.; Cheng, Kejun; Rice, Kenner C.; Riley, Anthony L.

    2017-01-01

    Rationale The aversive effects of Δ9-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the aversive effects induced by KOR agonists, a different mechanism might mediate the aversive effects of THC in this age group. Objectives The present study was designed to assess the impact of KOR antagonism on the aversive effects of THC in adolescent and adult rats using the conditioned taste avoidance (CTA) procedure. Methods Following a single pretreatment injection of norbinaltorphimine (norBNI; 15 mg/kg), CTAs induced by THC (0, 0.56, 1.0, 1.8 and 3.2 mg/kg) were assessed in adolescent (n = 84) and adult (n = 83) Sprague Dawley rats. Results The KOR antagonist, norBNI, had weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that norBNI both attenuated and strengthened taste avoidance dependent on dose and trial. norBNI had limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, norBNI had no effect on THC-induced taste avoidance in adult rats as well. Conclusions That norBNI had no significant effect on THC-induced avoidance in adults and a minor and inconsistent effect in adolescents demonstrates that the aversive effects of THC are not mediated by KOR activity as assessed by the CTA design in Sprague Dawley rats. PMID:26025420

  7. 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.

  8. The effect of ethanol on spermatogenesis and fertility in male Sprague-Dawley rats pretreated with acetylsalicylic acid.

    PubMed

    Dare, W N; Noronha, C C; Kusemiju, O T; Okanlawon, O A

    2002-12-01

    Prenatal alcohol is associated with a variety of developmental abnormalies, including neuroanatomical, physical and behavioural features. This study was designed to determine the effects of administration of alcohol, exemplified mostly by ethanol (15 ml/kg, 25%, v/v) and acetylsalicylic acid (ASA, 15 mg/kg) as a representative of nonsteroidal anti-inflammatory drugs, individually and their combination (ethanol 15 ml/kg, 25%, v/v ASA 15 mg/kg) on semen quality and fertility after paternal intraperitoneal administration in Sprague-Dawley rats. In the combination study, the rats received ASA about 1 hour before ethanol administration. The combination experiments were conducted to determine if the effects of ethanol can be prevented by pre-treatment with acetyl salicylic acid (ASA) which has been reported to antagonise the rate-depressant effects of ethanol. All animals received this treatment for ten weeks. Semen parameters were determined and compared with controls. The result showed that when given alone, ethanol significantly reduced the sperm density and percentage of motile spermatozoa relative to controls. Pre-treatment with ASA failed to stop the decrease in sperm density and percentage motility caused by ethanol. Moreover none of the experimental male rats was able to fertilize the females exposed to them despite successful mating demonstrated by the presence of sperm plug. The present study demonstrates that chronic consumption of ethanol or ingestion of ASA has toxic effect on spermatozoa and impairs fertility in male Sprague-Dawley rats. Moreover, pre-treatment with ASA has no effect on the deleterious effects caused by ethanol.

  9. Hypobaric Hypoxia Induces Depression-like Behavior in Female Sprague-Dawley Rats, but not in Males

    PubMed Central

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

    2015-01-01

    Abstract Kanekar, Shami, Olena V. Bogdanova, Paul R. Olson, Young-Hoon Sung, Kristen E. D'Anci, and Perry F. Renshaw. Hypobaric hypoxia induces depression-like behavior in female Sprague-Dawley rats, but not males. High Alt Med Biol 16:52–60, 2015—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. PMID:25803141

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

    USGS Publications Warehouse

    Patlolla, Anita K.; Todorov, Todor; 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.

  11. 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

  12. Prenatal low protein and postnatal high fat diets induce rapid adipose tissue growth by inducing Igf2 expression in Sprague Dawley rat offspring

    USDA-ARS?s Scientific Manuscript database

    Maternal low protein diets during prenatal development contribute to the development of obesity and insulin resistance in offspring. In this study, obese-prone Sprague -Dawley rats were fed diets having either 8% (low protein, LP) or 20% (normal protein, NP) protein for 3-wk prior to conception and...

  13. 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...

  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. 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...

  17. 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 ...

  18. 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....

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  1. 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...

  2. 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....

  3. 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 ...

  4. 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...

  5. 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...

  6. 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...

  7. Continuous exposure to dizocilpine facilitates escalation of cocaine consumption in male Sprague-Dawley rats

    PubMed Central

    Allen, Richard M.

    2013-01-01

    Background Although the escalation of cocaine consumption is a hallmark of cocaine dependence, the neurobiological mechanisms that underlie this change in behavior are not well understood. Methods This study used an extended access version of the drug self-administration procedure to explore how N-methyl-D-aspartate (NMDA) receptors are involved in escalation of cocaine consumption. Male Sprague–Dawley rats (n = 59) were first trained to self-administer cocaine (0.33 mg/infusion, i.v.) under a fixed-ratio 1 (FR1) schedule of reinforcement. After training, rats were implanted with subcutaneous osmotic minipumps filled with vehicle or the non-competitive NMDAR antagonist, dizocilpine (0.2 or 0.4 mg/kg/d), and subsequently allowed to self-administer cocaine in 2 h or 6 h self-administration sessions. Results In the 6 h groups, vehicle-treated rats escalated cocaine self-administration across 15 self-administration sessions; rats treated with dizocilpine escalated cocaine self-administration at a greater rate and to a greater degree. Rats that self-administered cocaine during 2 h sessions did not escalate consumption of cocaine under any treatment condition. Discontinuation of dizocilpine treatment in the 6 h access condition led to a substantial decrease in cocaine consumption, down to pre-escalation levels, and then control rates of escalation thereafter. Despite large differences in intake under the FR1 schedule, post-escalation break point under a progressive ratio schedule of reinforcement did not differ between groups. Conclusion These data suggest that glutamate tone through NMDA receptors can play a dynamic role in regulating cocaine intake and escalation of consumption. PMID:24103127

  8. 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.

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

    PubMed Central

    Walsh, Kathryn R.; Kuwabara, Jill T.; Shim, Joon W.

    2015-01-01

    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

  10. Effect of aqueous extract of the bark of Carica papaya on testicular histology in Sprague-Dawley rats.

    PubMed

    Kusemiju, T O; Osinubi, A A; Noronha, C C; Okanlawon, A O

    2010-01-01

    Males generally have few options for controlling their fertility and these options are far from being satisfactory. There is a great need for research to develop more contraceptive modalities for males. The overall aim of this research was to determine the histological responses of the testes of Sprague-Dawley rats to aqueous extract of bark of Carica papaya using a single daily dose of 100 mg/kg and also to investigate if these responses are reversible or not. Sixty mature (6-8 weeks old) male Sprague-Dawley rats, divided into 2 equal groups, were used for this experiment. Group 1 rats were fed with 100 mg/kg/day of the extract for 4 and 8 weeks, while group 2 rats served as the control subjects. Each cauda epididymis of the rats was exteriorized, incised and sperm motility and count conducted on expressed fluid. The testes were harvested and processed for histological examination under light microscope. Phytochemical analysis was done to ascertain the main constituents in the extract, while the LD50 was conducted to guide in the dose of administration of the extract. A subgroup of the animals was allowed a recovery period of 8 weeks before sacrifice. The results showed that 500 mg/kg (LD50) of the extract of bark of Carica papaya produced signs of toxicity with mortality of 50% of the rats. The extract at a dose of 100 mg/kg caused histological changes ranging from seminiferous tubular distortion to outright destruction/ degeneration of the seminiferous tubules. In addition, the testicular interstitia of extract-treated rats showed disorganization and hypocellularity. The extract also caused a significant (p < 0.05) reduction in both sperm count and motility. There was no significant reversal of these antispermatogenic effects following a recovery period of 8 weeks. Aqueous extract of the bark of Carica papaya has deleterious effects on both the seminiferous tubules and testicular interstitium and deserves to be further investigated as a potential male

  11. 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.

  12. 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.

  13. 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.

  14. Effect of Nigella sativa L. seed extract on cisplatin-induced delay in gastric emptying in Sprague-Dawley rats.

    PubMed

    Riyaz, Ambreena; Nazir, Shahid; Khushtar, Mohammad; Mishra, Anuradha; Jahan, Yasmeen; Ahmad, Asad

    2017-03-01

    The aim of this study was focused on investigating the possible protective effect of Nigella sativa L. seed extract against cisplatin-induced delay in gastric emptying, in a rat model. Twenty-five male Sprague-Dawley rats were divided into five equal groups as follows: Group I or control group, Group II (cisplatin 10 mg/kg, i.p at day 5), Group III (N. sativa L. 250 mg/kg for 5 days + cisplatin 10 mg/kg, i.p on day 5), Group IV (N. sativa L. 500 mg/kg for 5 days + cisplatin 10 mg/kg, i.p on day 5) and Group V (ondansetron 3 mg/kg/day, per os + cisplatin 10 mg/kg, i.p on day 5). Phenol red meal was adopted to estimate gastric emptying in different groups of the rats. Gastric emptying was significantly increased (p < 0.01) in N. sativa L. seed extract-pretreated rats (Group III and Group IV) when compared to cisplatin treatment alone (Group II). However, ondansetron produced significantly (p < 0.01) better reversal than N. sativa L. seed extract.

  15. 4-Vinylcyclohexene diepoxide (VCD) inhibits mammary epithelial differentiation and induces fibroadenoma formation in female Sprague Dawley rats.

    PubMed

    Wright, Laura E; Frye, Jennifer B; Lukefahr, Ashley L; Marion, Samuel L; Hoyer, Patricia B; Besselsen, David G; Funk, Janet L

    2011-07-01

    4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that targets ovarian follicles and accelerates ovarian failure in rodents, was used to test the effect of early-onset reproductive senescence on mammary fibroadenoma formation. One-month female Sprague Dawley rats were dosed with VCD (80 mg/kg or 160 mg/kg) and monitored for 22 months for persistent estrus and tumor development. Only high-dose VCD treatment accelerated the onset of persistent estrus relative to controls. However, both doses of VCD accelerated mammary tumor onset by 5 months, increasing incidence to 84% (vs. 38% in controls). Tumor development was independent of time in persistent estrus, 17 β-estradiol, androstenedione and prolactin. Delay in VCD administration until after completion of mammary epithelial differentiation (3 months) did not alter tumor formation despite acceleration of ovarian senescence. VCD administration to 1-month rats acutely decreased mammary alveolar bud number and expression of β-casein, suggesting that VCD's tumorigenic effect requires exposure during mammary epithelial differentiation.

  16. Long-Term Supplementation with Chromium Malate Improves Short Chain Fatty Acid Content in Sprague-Dawley Rats.

    PubMed

    Wu, Huiyu; Feng, Weiwei; Mao, Guanghua; Zhao, Ting; Wu, Xiangyang; Wang, Songmei; Zou, Yanmin; Yang, Liuqing; Wang, Liang

    2016-11-01

    Our previous study showed that chromium malate improved the composition of intestinal flora, glycometabolism, glycometabolism-related enzymes, and lipid metabolism in type 2 diabetes mellitus (T2DM) rats. The present study was designed to evaluate the effect of chromium malate with long-term supplementation on short chain fatty acid (SCFA) content in Sprague-Dawley rats. The samples were analyzed by gas chromatography with high linearity (R (2) ≥ 0.9995), low quantification limit (0.011-0.070 mM), and satisfactory recoveries. The method was simple and environmentally friendly. The acetic content in cecum of 3-month control group was significantly higher than that of 1-year control group. When compared with 1-year control group, chromium malate (at a dose of 20.0 μg Cr/kg bw) could significantly increase acetic, propionic, i-butyric butyric, butyric, i-valeric, valeric, and n-caproic levels. The acetic, propionic, i-butyric, valeric, and n-caproic contents of 1-year chromium malate group (at a dose of 20.0 μg Cr/kg bw) had a significant improvement when compared with 1-year chromium picolinate group. Acetic, propionic, and butyric contained approximately 91.65 % of the total SCFAs in 1-year group. The results indicated that the improvement of chromium malate on short chain fatty acid content change was better than that of chromium picolinate.

  17. 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.

  18. Possible mechanisms of action of the hypotensive effect of Annona muricata (soursop) in normotensive Sprague-Dawley rats.

    PubMed

    Nwokocha, Chukwuemeka R; Owu, Daniel U; Gordon, Angeline; Thaxter, Karen; McCalla, Garsha; Ozolua, Raymond I; Young, Lauriann

    2012-11-01

    Annona muricata Linn (Annonaceae) (soursop) is a food plant reported to have antihypertensive properties. We investigated the blood pressure reducing effect of its aqueous leaf extract and the possible mechanisms that may be responsible. Intravenous administration of an aqueous leaf extract (9.17-48.5 mg/kg) of A. muricata on the mean arterial pressure and heart rate were recorded invasively on anaesthetized, normotensive Sprague-Dawley rats. Contractile responses of rat aortic rings to the extract (0.5-4.0 mg/mL) were studied using standard organ bath techniques. A. muricata (9.17-48.5 mg/kg) caused significant (p < 0.05) dose-dependent reduction in blood pressure without affecting the heart rates. The hypotensive effects were unaffected by atropine (2 mg/kg), mepyramine (5 mg/kg), propranolol (1 mg/kg) and L-NAME (5 mg/kg). A. muricata leaf aqueous extract significantly (p < 0.05) relaxed phenylephrine (10(-9)-10(-4) M) and 80 mM KCl induced contractions in endothelium intact and denuded aortic rings; and caused a significant (p < 0.05) rightward shift of the Ca(2+) dose response curves in Ca(2+)-free Kreb's solution containing 0.1 mM EGTA. The hypotensive effects of A. muricata are not mediated through muscarinic, histaminergic, adrenergic and nitric oxide pathways, but through peripheral mechanisms involving antagonism of Ca(2+).

  19. Effect of ascorbic acid on fatigue of skeletal muscle fibres in long-term cold exposed Sprague Dawley rats.

    PubMed

    Rashid, Aneeqa; Khan, Umar Ali; Ayub, Muhammad

    2011-01-01

    On exposure to prolonged cold temperature, the body responds for effective heat production both by shivering and non-shivering thermogenesis. Cold exposure increases the production of reactive oxygen species which influence the sarcoplasmic reticulum Ca++ release from the skeletal muscles and affect their contractile properties. The role of ascorbic acid supplementation on force of contraction during fatigue of cold exposed skeletal muscles was evaluated in this study. Ninety healthy, male Sprague Dawley rats were randomly divided into three groups of control (I), cold exposed (II), and cold exposed with ascorbic acid 500 mg/L supplementation mixed in drinking water (III). Group II and III were given cold exposure by keeping their cages in ice-filled tubs for 1 hr/day for one month. After one month, the extensor digitorum longus muscle was dissected out and force of contraction during fatigue in the skeletal muscle fibres was analysed on a computerised data acquisition system. The cold exposed group showed a significant delay in the force of contraction during fatigue of skeletal muscle fibres compared to control group. Group III showed easy fatigability and a better force of contraction than the cold exposed group. Ascorbic acid increases the force of contraction and decreases resistance to fatigue in the muscles exposed to chronic cold.

  20. 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

  1. 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.

  2. 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.

  3. Effect of dietary fiber on the lipid metabolism and immune function of aged Sprague-Dawley rats.

    PubMed

    Yamada, Koji; Tokunaga, Yoko; Ikeda, Atsushi; Ohkura, Ken-ichi; Kaku-Ohkura, Shihoko; Mamiya, Soichi; Lim, Beong Ou; Tachibana, Hirofumi

    2003-02-01

    Eight-month-old Sprague-Dawley rats were fed on diets containing dietary fiber at the 5% level for 3 weeks to examine the effect on the lipid metabolism and immune function. Among cellulose, guar gum, partially hydrolyzed guar gum (PHGG), glucomannan and highly methoxylated pectin, guar gum induced a significant decrease in the food intake and weight gain, as well as a significant increase in the liver weight. In addition, the epidydimal adipose tissue weight of the rats fed on PHGG was significantly higher than that of the rats fed on cellulose. There was no significant effect on the serum lipid levels, but the serum IgG level of the rats fed on guar gum was significantly lower than that of the rats fed on cellulose. The IgA and IgG productivity in mesenteric lymph node (MLN) lymphocytes was significantly higher in the rats fed on guar gum, glucomannan and pectin than in those fed on cellulose, while the effect on Ig productivity in spleen lymphocytes was not as marked. In addition, only guar gum induced a significant increase of IgM productivity in MLN lymphocytes when compared to the cellulose group. These results suggest that enhancement of the immune function by dietary fiber is mainly expressed in the gut immune system.

  4. Effects of sex, age, and fasting conditions on plasma lipidomic profiles of fasted Sprague-Dawley rats.

    PubMed

    Saito, Kosuke; Ishikawa, Masaki; Murayama, Mayumi; Urata, Masayo; Senoo, Yuya; Toyoshima, Katsuko; Kumagai, Yuji; Maekawa, Keiko; Saito, Yoshiro

    2014-01-01

    Circulating lipid molecules reflect biological processes in the body and, thus, are useful tools for preclinical estimation of the efficacy and safety of newly developed drugs. However, background information on profiles of circulating lipid molecules in preclinical animal models is limited. Therefore, we examined the effects of multiple factors such as sex (fasted male vs. female), age (fasted 10 vs. 30 weeks old), and feeding conditions (feeding vs. fasting, 16 vs. 22 hr fasting, 10 AM vs. 4 PM blood collection), on the global profiles of lipid molecules in plasma from Sprague-Dawley rats by using a lipidomic approach. Our assay platform determined 262 lipid molecules (68 phospholipids, 20 sphingolipids, 138 neutral lipids, and 36 polyunsaturated fatty acids and their metabolites) in rat plasma. Multivariate discriminant analysis (orthogonal partial least squares discriminant analysis) and heat maps of statistically significant lipid molecules revealed that the plasma lipid profiles in rats are predominantly influenced by feeding conditions, followed by sex and age. In addition, the fasting duration (16 vs. 22 hr fasting) or the time of blood collection (10 AM vs. 4 PM blood collection) has limited or no contribution on the profiles of lipid molecules in rat plasma. Our results provide useful, fundamental information for exploring and validating biomarkers in future preclinical studies and may help to establish regulatory standards for such studies.

  5. Pharmacokinetic studies and LC-MS/MS method development of ganciclovir and dipeptide monoester prodrugs in Sprague Dawley rats.

    PubMed

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

    2015-09-01

    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 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 exhibit higher systemic availability of regenerated GCV upon oral administration and thus seem to be promising drug candidate in the treatment of systemic herpes infections.

  6. 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

  7. Effectiveness of anchovy substrate application on decreasing acid solubility of Sprague Dawley rats’ tooth enamel (in vivo)

    NASA Astrophysics Data System (ADS)

    Triputra, F.; Puspitawati, R.; Gunawan, H. A.

    2017-08-01

    Anchovies (Stolephorus insularis), a natural resource of Indonesia, contain fluoride in the form of CaF2 and can function as a fluoridation material to prevent dental caries. The aim of this study is to study the effectiveness of anchovy substrate, through food or topical application, in decreasing the acid solubility of tooth enamel. This research used 14 Sprague Dawley rats as subjects divided into the following 5 groups: baseline, experimental feeding, experimental smearing, and their negative controls. After 15 days of anchovy substrate application, lower incisors were extracted and the acid solubility of enamel was analyzed qualitatively and quantitatively using a stereo microscope and a Micro-Vickers Hardness Tester. Analysis of enamel surface destruction and enamel surface microscopic hardness shifting after a 60 sec application of H2PO4 (50% concentration) resulted in a decrease in acid solubility of enamel treated with anchovy substrate. This result can be seen with both the chewing and smearing method. S. insularis can be used as an alternative material for fluoridation.

  8. Effects of applying anchovy (Stolephorus insularis) substrates on the microhardness of tooth enamel in Sprague-Dawley rats

    NASA Astrophysics Data System (ADS)

    Hendrik, Y. C.; Puspitawati, R.; Gunawan, H. A.

    2017-08-01

    Anchovies (Stolephorus insularis) contain high levels of fluor in the form of CaF2. The aim of this study is to analyze changes in tooth enamel microhardness after application of anchovy substrates by feeding or as a topical fluoridation material. An in vivo study of the lower left incisors of nine Sprague-Dawley rats was conducted. The sample was comprised of baseline and treatment groups, including feeding application, topical application, negative control feeding, and negative control topical groups. The treatment groups were given 5% anchovy substrates through feeding and topical applications. After treatment, tooth samples were extracted from each of the rats for examination, and statistical analyses were performed after determining hardness numbers for enamel surfaces using Vickers microhardness tester. Vickers hardness numbers (VHNs) for anchovy substrate application and consumption by feeding (440.3 ± 24.72) were higher than for the negative control (315.80 ± 17.51). VHNs for the topical application group were higher than for the negative control (347.28 ± 28.56) and for the feeding group. The use of anchovy as a fluoridation material in form of topical application is potentially an effective method for increasing the microhardness of the tooth enamel surface

  9. The effect of anchovy substrate application to fluor retention rate on Sprague Dawley rat tooth email (in vivo)

    NASA Astrophysics Data System (ADS)

    Zabrina, S.; Puspitawati, R.; Gunawan, H. A.

    2017-08-01

    Usage of anchovies (Stolephorus insularis), which contain a high fluoride concentration in a CaF2 compound, needs to be examined as a topical fluoridative agent. Aim: To study the effects of an anchovy substrate application, either by chewing or smearing, in increasing fluoride retention of enamel. Fourteen Sprague Dawley rats were divided into five groups: baseline, experimental (feeding and smearing), and negative controls. After 15 days, lower incisor teeth were extracted and fluoride retention on the enamel surface was measured using EDX. Data were analyzed by the independent samples t-test, the Mann-Whitney U test, and the Kruskal-Wallis test. There was a significant increase in fluoride retention on enamel from the experimental groups compared to the negative control group (p < 0.05). Fluoride retention levels of the experimental feeding group (6.823%) were slightly higher than those of the experimental smearing group (6.783%), though the difference was not statistically significant (p < 0.05). Anchovy substrate application, either by chewing or smearing, increases fluoride retention on tooth enamel.

  10. 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.

  11. Metabonomic studies on the physiological effects of acute and chronic psychological stress in Sprague-Dawley rats.

    PubMed

    Teague, Claire R; Dhabhar, Firdaus S; Barton, Richard H; Beckwith-Hall, Bridgette; Powell, Jonathan; Cobain, Mark; Singer, Burton; McEwen, Bruce S; Lindon, John C; Nicholson, Jeremy K; Holmes, Elaine

    2007-06-01

    The biochemical effects of acute and chronic psychological stress have been investigated in male Sprague-Dawley rats using a combination of 1H NMR spectral analysis of plasma and conventional hematological analyses. Animals were subjected to 35 consecutive days of 6-h sessions of stress, and following a 9 day break, were stressed for a further 6-h period. Plasma samples were collected at 0, 1, 3, and 6 h on days 1, 9, 21, 35, and 44, measured using 600 MHz 1H NMR spectroscopy, and analyzed by Principal Components Analysis. Time-dependent biochemical effects of psychological stress on a range of endogenous metabolites were evident and were correlated with the intensity of the stress response as defined by corticosterone and hematological parameters. Following acute stress, increases in the levels of glucose and ketone bodies, and decreases in the levels of acetate, alanine, isoleucine, lactate, leucine, valine, and lipoproteins, were observed. Chronic stress-induced increases in plasma levels of alanine, lactate (day 9), and leucine, valine, and choline (day 44) and decreases in acetate (day 9) and lipoprotein concentrations were observed. Positive correlations between plasma corticosterone level and glucose and glycerol, and between plasma lipoprotein concentrations and hemoglobin levels, were established using Projection to Latent Structures (PLS) analysis. This study indicates the potential of using NMR-based metabonomic strategies for the characterization of endogenous metabolic perturbations induced by psychological stressors and lifestyle choices.

  12. 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.

  13. MSG intake suppresses weight gain, fat deposition, and plasma leptin levels in male Sprague-Dawley rats.

    PubMed

    Kondoh, Takashi; Torii, Kunio

    2008-09-03

    Monosodium l-glutamate (MSG), an umami taste substance, may be a key molecule coupled to a food intake signaling pathway, possibly mediated through a specific l-glutamate (GLU) sensing mechanism in the gastrointestinal tract. Here we investigated the effect of the spontaneous ingestion of a 1% MSG solution and water on food intake and body weight in male Sprague-Dawley rats fed diets of varying caloric density, fat and carbohydrate contents. Fat mass and lean mass in the abdomen, blood pressure, and several blood metabolic markers were also measured. Rats given free access to MSG and water showed a high preference (93-97%) for the MSG solution, regardless of the diet they consumed. Rats ingesting MSG had a significantly smaller weight gain, reduced abdominal fat mass, and lower plasma leptin levels, compared to rats ingesting water alone. Naso-anal length, lean mass, food and energy intakes, blood pressure, blood glucose, and plasma levels of insulin, triglyceride, total cholesterol, albumin, and GLU were not influenced by the ingestion of the MSG solution. These same effects were observed in a study of adult rats. Together, these results suggest that MSG ingestion reduces weight gain, body fat mass, and plasma leptin levels. Moreover, these changes are likely to be mediated by increased energy expenditure, not reduced energy intake or delayed development. Conceivably, these effects of MSG might be mediated via gut GLU receptors functionally linked to afferent branches of the vagus nerve in the gut, or the afferent sensory nerves in the oral cavity.

  14. Assessment of the short-term toxicity of TiO2 nanofiber in Sprague Dawley rats.

    PubMed

    Gato, Worlanyo E; Hunter, Daniel A; Byrd, Ian C; Mays, Christopher A; Yau, Wilson; Wu, Ji

    2017-02-09

    Synthetic nanomaterials have many unique chemical and physical properties, mainly due to their high specific surface area and quantum confinement effect. Specifically, titanium dioxide (TiO2 ) nanomaterial has high stability, anticorrosive, and photocatalytic properties. However, there are concerns over adverse biological effects resulting from bioeffects. This study was to investigate adverse effects associated with acute ingestion of TiO2 nanofiber (TDNF). TDNF was fabricated via electrospinning method, followed by dissolution in water. Six- to seven-week-old male Sprague Dawley rats were exposed to a total of 0, 40, and 60 ppm of TDNF for 2 weeks via oral gavage. Serum total protein and weight gain during the course of this study displayed marginal concentration-dependent alterations. These findings were followed by a global gene expression analysis to identify which transcripts might be responsive to TNDF toxicity. Differentially expressed mRNA levels were dose-dependently higher in animals exposed to TNDF. The majority of the affected genes were biochemically involved in immune response and inflammation. We believe this is due to the fact that TNDF is unable to penetrate the cell and forms phagocytosis sites that trigger inflammatory and immune response. All results taken together, short-term ingestion of TNDF produced marginal effects indicative of inflammation. Finally, the broad gene expression data were validated through quantification of immunoglobulin heavy chain alpha (Igha). Igha gene was upregulated in treated groups, showing similar expression patterns to the global gene expression data.

  15. Salvinorin A fails to substitute for the discriminative stimulus effects of LSD or ketamine in Sprague-Dawley rats.

    PubMed

    Killinger, Bryan A; Peet, Mary M; Baker, Lisa E

    2010-09-01

    Salvia divinorum is a small perennial shrub that has gained recent popularity among the drug-using subculture as a legal alternative to hallucinogens. Salvinorin A, the main active compound found in the S.divinorum plant, is an atypical hallucinogen with pharmacological selectivity at kappa opioid (KOP) receptor sites and is a unique non-nitrogenous neoclerodane diterpene which is structurally distinct from other opioid compounds. The novel structure of salvinorin A and its specific binding affinity to KOP receptors provide a unique opportunity to investigate neurochemical mechanisms of hallucination and hallucinogenic compounds. The current investigation assessed the substitution of salvinorin A in 16 male Sprague-Dawley rats trained to discriminate either the prototypical serotonergic hallucinogen, LSD (0.08mg/kg, S.C., n=8) or the dissociative anesthetic and glutamatergic hallucinogen, ketamine (8.0mg/kg, I.P., n=8) from vehicle under a FR 20 schedule of food-reinforced responding. Results indicated that neither LSD nor ketamine discrimination generalized to salvinorin A. These findings are consistent with the growing body of evidence that salvinorin A is pharmacologically distinct from other traditional hallucinogenic compounds.

  16. Anticarcinogenic Effect of Corn Tortilla Against 1,2-Dimethylhydrazine (DMH)-Induced Colon Carcinogenesis in Sprague-Dawley Rats.

    PubMed

    Reynoso-Camacho, Rosalía; Guerrero-Villanueva, Guadalupe; Figueroa, Juan de Dios; Gallegos-Corona, Marco A; Mendoza, Sandra; Loarca-Piña, Guadalupe; Ramos-Gomez, Minerva

    2015-06-01

    Mexico has the highest per capita consumption of corn in the world, which is consumed mainly as tortilla. However, only a few in vivo studies have demonstrated the anticarcinogenic potential of some maize components against colon cancer, but not as a whole food product. Therefore, our objective was to evaluate the protective effect of corn tortillas against the development of colon cancer. First, blue, red, yellow and white corn grains were lime-cooked and processed to elaborate tortillas. Then, tortillas were administered into the diet (27% w/w) to male Sprague-Dawley rats induced with the colon carcinogen 1,2-dimethylhydrazine (DMH). Our results indicated that consumption of tortillas, particularly from white and blue corns, significantly decreased adenocarcinoma incidence (up to 77.5%) and mean number compared to DMH-treated animals. In addition, an inhibition of β-glucuronidase activity, and induction of detoxifying enzymes in liver and colon, as well as a decrease in the expression of the two most important proliferative proteins (K-ras and β-catenin) involved in colon carcinogenesis, were also observed. These results highlight some of the molecular mechanisms related to the chemopreventive effect of tortillas, thus indicating that corn products retain their biological properties even after nixtamalization and tortilla processing.

  17. 20-HETE contributes to myogenic activation of skeletal muscle resistance arteries in Brown Norway and Sprague-Dawley rats.

    PubMed

    Frisbee, J C; Roman, R J; Falck, J R; Krishna, U M; Lombard, J H

    2001-02-01

    To evaluate the role of 20-hydroxyeicosatetraenoic acid (20-HETE), a product of arachidonic acid omega-hydroxylation via cytochrome P450 (CP450) 4A enzymes, in regulating myogenic activation of skeletal muscle resistance arteries from normotensive Brown Norway (BN) and Sprague-Dawley (SD) rats. Gracilis arteries (GA) were isolated from each animal, viewed via television microscopy, and vessel diameter responses to elevated transmural pressure were measured with a video micrometer under control conditions and following pharmacological inhibition of the CP450 4A enzyme system. Under control conditions, GA from both rat groups exhibited strong, endothelium-independent myogenic activation, which was impaired following treatment with either 17-octadecynoic acid (17-ODYA) or dibromo-dodecenylmethylsulfimide (DDMS), two mechanistically different inhibitors of 20-HETE production. The addition of tetraethylammonium (KCa channel inhibitor) to 17-ODYA-treated GA restored myogenic reactivity to levels comparable to those under control conditions. Treatment of GA from BN and SD rats with 6(Z),15(Z)-20-HEDE, a selective antagonist for 20-HETE receptors, mimicked the effects of 17-ODYA and DDMS treatment on myogenic reactivity. These results suggest that the production of 20-HETE via CP450 4A enzymes contributes to the myogenic activation of skeletal muscle resistance arteries from normotensive BN and SD rats. 20-HETE may act through a receptor-mediated process to block vascular smooth muscle KCa channels in response to the elevated transmural pressure.

  18. Brain, Liver, and Serum Salusin-alpha and -beta Alterations in Sprague-Dawley Rats with or without Metabolic Syndrome

    PubMed Central

    Citil, Cihan; Konar, Vahit; Aydin, Suleyman; Yilmaz, Musa; Albayrak, Serdal; Ozercan, Ibrahim Hanifi; Ozkan, Yusuf

    2014-01-01

    Background This metabolic syndrome (MetS) study was designed to investigate changes in expression of the neuropeptides salusin-α (Sal-α) and salusin-β (Sal-β) in brain and liver tissue in response to obesity and related changes induced by high-fructose diet and explored how these changes were reflected in the circulating levels of Sal-α and Sal-β, as well as revealing how the lipid profile and concentrations of glucose and uric acid were altered. Material/Methods The study included 14 Sprague-Dawley rats. The control group was fed ad libitum on standard rat pellets, while the intervention group was given water with 10% fructose in addition to the standard rat pellet for 3 months. Sal-α and Sal-β concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to demonstrate expression of the hormones in brain and liver. Results Sal-α and Sal-β levels in both the serum and the brain and liver tissue supernatants were lower in the MetS group than the control group. Sal-α and Sal-β were shown by immunohistochemistry to be produced in the brain epithelium, the supraoptic nucleus of the hypothalamus, and the liver hepatocytes. Conclusions The decrease in Sal-α and Sal-β might be involved in the etiopathology of the metabolic syndrome induced by fructose. PMID:25070707

  19. 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.

  20. 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

  1. 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

  2. An evaluation of the effects of nonselective and cardioselective β-blockers on wound healing in Sprague Dawley rats

    PubMed Central

    Raut, Sanket B.; Nerlekar, Sharmada R.; Pawar, Sudhir; Patil, Amol N.

    2012-01-01

    Objectives: To investigate the effect of a nonselective β-blocker (propranolol) and cardioselective β-blocker (metoprolol) on wound healing in rats using incision and excision wound models and to compare the effect of these drugs on wound healing. Materials and Methods: Propranolol and metoprolol were given orally. Sprague Dawley rats of either sex were used. Incision and excision wound models were used to evaluate the wound-healing activity. Effects of metoprolol and propranolol on tensile strength, period of epithelialization, and hydroxyproline content were observed. Histological analysis was done to see collagen deposition and inflammatory infiltrate. Statistical Analysis Used: The data was subjected to analysis of variance (ANOVA) followed by Scheffe's test. P < 0.05 was considered to be statistically significant. Statistical analysis was done using SPSS software version 15.0. Results: Administration of propranolol or metoprolol was shown to decrease tensile strength, delay wound contraction and re-epithelialization, increase inflammatory infiltrate, and reduce collagen density and hydroxyproline levels. Conclusions: The results suggest that nonselective and cardioselective β-blockers delay wound healing and these effects are mediated by β1-receptors. PMID:23112427

  3. Morinda citrifolia L. leaf extract prevent weight gain in Sprague-Dawley rats fed a high fat diet.

    PubMed

    Jambocus, Najla Gooda Sahib; Ismail, Amin; Khatib, Alfi; Mahomoodally, Fawzi; Saari, Nazamid; Mumtaz, Muhammad Waseem; Hamid, Azizah Abdul

    2017-01-01

    Background: Morinda citrifolia L. is widely used as a folk medicinal food plant to manage a panoply of diseases, though no concrete reports on its potential anti-obesity activity. This study aimed to evaluate the potential of M. citrifolia leaf extracts (MLE60) in the prevention of weight gain in vivo and establish its phytochemical profile. Design: Male Sprague-Dawley rats were divided into groups based on a normal diet (ND) or high fat diet (HFD), with or without MLE60 supplementation (150 and 350 mg/kg body weight) and assessed for any reduction in weight gain. Plasma leptin, insulin, adiponectin, and ghrelin of all groups were determined. (1)H NMR and LCMS methods were employed for phytochemical profiling of MLE60. Results: The supplementation of MLE60 did not affect food intake indicating that appetite suppression might not be the main anti-obesity mechanism involved. In the treated groups, MLE60 prevented weight gain, most likely through an inhibition of pancreatic and lipoprotein activity with a positive influence on the lipid profiles and a reduction in LDL levels . MLE60 also attenuated visceral fat deposition in treated subjects with improvement in the plasma levels of obesity-linked factors . (1)Spectral analysis showed the presence of several bioactive compounds with rutin being more predominant. Conclusion: MLE60 shows promise as an anti-obesity agents and warrants further research.

  4. An organotin mixture found in polyvinyl chloride (PVC) pipe is not immunotoxic to adult Sprague-Dawley rats.

    PubMed

    DeWitt, Jamie C; Copeland, Carey B; Luebke, Robert W

    2008-01-01

    Organotin compounds used in polyvinyl chloride (PVC) pipe production are of concern to the U.S. Environmental Protection Agency (EPA) because they leach from supply pipes into drinking water and are reported multisystem toxicants. Immune function was assessed in male Sprague-Dawley rats exposed to the mixture of organotins used in PVC pipe production. Although several of these organotins are reported immunotoxicants, their immunotoxicity as a mixture when given by drinking water has not been evaluated. Adult male rats were given drinking water for 28 d containing a mixture of dibutyltin dichloride (DBTC), dimethyltin dichloride (DMTC), monobutyltin trichloride (MBT), and monomethyltin trichloride (MMT) in a 2:2:1:1 ratio, respectively, at 3 different concentrations (5:5:2.5:2.5, 10:10:5:5, or 20:20:10:10 mg organotin/L), MMT alone (20 or 40 mg MMT/L), or plain water as a control. Delayed-type hypersensitivity, antibody synthesis, and natural killer cell cytotoxicity were evaluated in separate endpoint groups (n = 8/dose; 24/endpoint) immediately after exposure ended. The evaluated immune functions were not affected by the mixture or by MMT alone. Our data suggest that immunotoxicity is unlikely to result from the concentration of organotins present in drinking water delivered via PVC pipes, as the concentrations used were several orders of magnitude higher than those expected to leach from PVC pipes.

  5. 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.

  6. 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.

  7. Pulmonary Lesions in Female Harlan Sprague-Dawley Rats Following Two-Year Oral Treatment with Dioxin-Like Compounds

    PubMed Central

    Walker, Nigel J.; Yoshizawa, Katsuhiko; Miller, Rodney A.; Brix, Amy E.; Sells, Donald M.; Jokinen, Micheal P.; Wyde, Michael E.; Easterling, Michael; Nyska, Abraham

    2009-01-01

    Dioxin and dioxin-related compounds have been associated with high incidences of pulmonary dysfunctions and/or cancers in humans. To evaluate the relative potencies of effects of these compounds, the National Toxicology Program completed a series of two-year bioassays which were conducted using female Harlan Sprague-Dawley rats. The rats were treated orally for up to 2 years with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3′,4,4′,5-pentachlorobiphenyl (PCB126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), and a ternary mixture of TCDD, PCB126 and PeCDF. In addition to treatment-related effects reported in other organs, a variety of pulmonary lesions were observed that were related to exposure. Pulmonary CYP1A1-associated 7-ethoxyresorufin-O-deethylase (EROD) activity was increased in all dosed groups. The most common non-neoplastic lesions, which occurred in all studies, were bronchiolar metaplasia and squamous metaplasia of the alveolar epithelium. Cystic keratinizing epithelioma was the most commonly observed neoplasm which occurred in all studies. A low incidence of squamous cell carcinoma was associated only with PCB126 treatment. Potential mechanisms leading to altered differentiation and/or proliferation of bronchiolar and alveolar epithelia may be through CYP1A1 induction or disruption of retinoid metabolism. PMID:18098034

  8. Protective effects of thymoquinone and avenanthramides on titanium dioxide nanoparticles induced toxicity in Sprague-Dawley rats.

    PubMed

    Hassanein, Khaled M A; El-Amir, Yasmin O

    2017-01-01

    The protective effect of thymoquinone (TQ), the major active ingredient of Nigella sativa seeds, and avenanthramides (AVA) enriched extract of oats on titanium dioxide naonparticles (TiO2 NPs) induced toxicity and oxidative stress in Sprague-Dawley (SD) rats was investigated. Sixty rats were divided into 6 equal groups. The first, second, third, fourth and fifth groups received TiO2 NPs, TiO2 NPs and TQ, TiO2 NPs and AVA, TQ only, or AVA only for 6 weeks. The sixth group served as the control. Exposure to TiO2 NPs resulted in increased liver enzyme markers, oxidative stress indices, tumor necrosis factor alpha (TNF-α) and DNA damage. Histopathological alterations were also observed in the liver, brain, lung, kidney, heart and testes. Co-administration of TQ and AVA with TiO2 NPs decreased the level of liver enzymes, oxidative stress, TNF-α and DNA damage. Furthermore, TQ and AVA increased the total antioxidant and glutathione (GSH) levels. In conclusion, TiO2 NPs induce hazardous effects in different organs and are closely related to oxidative stress. TQ and AVA have antioxidative and anti-inflammatory effect against the detrimental effect of TiO2 NPs.

  9. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Sex Differences in (+)-Amphetamine- and (+)-Methamphetamine-induced Behavioral Response in Male and Female Sprague-Dawley Rats

    PubMed Central

    Milesi-Hallé, Alessandra; McMillan, Donald E.; Laurenzana, Elizabeth M.; Byrnes-Blake, Kelly A.; Owens, S. Michael

    2007-01-01

    (+)-Methamphetamine (METH) and (+)-amphetamine (AMP) are structurally similar drugs that are reported to induce similar pharmacological effects in rats of the same sex. Because pharmacokinetic data suggest female rats should be more affected than males, the current studies sought to test the hypothesis that the behavioral and temporal actions of METH and AMP should be greater in female Sprague-Dawley rats than in males. Using a dosing regimen designed to reduce the possibility of tolerance and sensitization, rats were administered 1.0 and 3.0 mg/kg intravenous drug doses. Distance traveled, rearing events and focal stereotypies (e.g., head weaving, sniffing) were measured. Female rats traveled significantly greater distances and displayed a greater number of rearing events than males after both doses. Analysis of stereotypy ratings after 3.0 mg/kg revealed that focal stereotypies were more pronounced and lasted longer in females. The second study compared the potencies of METH and AMP in inducing locomotor activity and focal stereotypies in each sex. No differences in potency were found when METH and AMP effects were compared within males or females. In summary, these studies showed female rats displayed greater and longer-lasting locomotor activity and more stereotypic behaviors, supporting earlier evidence of significant sexual dimorphism in pharmacokinetics. PMID:17275894

  11. 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.

  12. Comparison of the potency of lidocaine and chloroprocaine in sciatic nerve block in Sprague-Dawley rats.

    PubMed

    Yung, Elliot; Yarmush, Joel M; Weinberg, Jonathan; SchianodiCola, Joseph J; Ray, Sidhartha D

    2009-01-01

    This study investigates the relative potencies and ED(50) of the local anesthetics lidocaine and chloroprocaine in a sciatic block in Sprague-Dawley rats. The study involved 80 rats (chloroprocaine n = 40, lidocaine n = 40). Each rat was injected close to the sciatic nerve with 0.1 ml of the concentration of local anesthetic being tested. Using the up-and-down allocation technique, the next concentration was determined by the response of the previous subject to a higher or lower concentration. A successful block was assessed by pinching the fifth metatarsal. Absent vocalization and a very weak withdrawal response were defined as the onset of block. Using the up-and-down methodology, the estimates of ED(50) for chloroprocaine was 0.1 ml of 1.2% (with 95% CI of 1.1-1.6), and that for lidocaine was 0.1 ml of 0.65% (with 95% CI of 0.65-0.88), giving a lidocaine/chloroprocaine potency ratio of 1.85 (with 95% CI of 1.66-2.61). Using the results of this study, the effects of the two drugs can be compared using the commercially available concentrations of chloroprocaine and lidocaine in a peripheral nerve block. Copyright 2009 S. Karger AG, Basel.

  13. 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.

  14. Social interactions in adolescent and adult Sprague-Dawley rats: impact of social deprivation and test context familiarity.

    PubMed

    Varlinskaya, Elena I; Spear, Linda P

    2008-04-09

    Interactions with peers become particularly important during adolescence, and age differences in social interactions have been successfully modeled in rats. To determine the impact of social deprivation on social interactions under anxiogenic (unfamiliar) or non-anxiogenic (familiar) test circumstances during ontogeny, the present study used a modified social interaction test to assess the effects of 5 days of social isolation or group housing on different components of social behavior in early [postnatal day (P) 28], mid (P35), or late (P42) adolescent and adult (P70) male and female Sprague-Dawley rats. As expected, testing in an unfamiliar environment suppressed social interactions regardless of age, housing, and sex. Social deprivation drastically enhanced all forms of social behavior in P28 animals regardless of test situation, whereas depriving older animals of social interactions had more modest effects and was restricted predominantly to play fighting -- an adolescent-characteristic form of social interactions. Social investigation -- more adult-typical form of social behavior was relatively resistant to isolation-induced enhancement and was elevated in early adolescent isolates only. These findings confirm that different forms of social behavior are differentially sensitive to social deprivation across ontogeny.

  15. Investigation of the anxiolytic effects of xanthohumol, a component of humulus lupulus (Hops), in the male Sprague-Dawley rat.

    PubMed

    Ceremuga, Thomas E; Johnson, Lori A; Adams-Henderson, Jamilia M; McCall, Suzanne; Johnson, Don

    2013-06-01

    The purpose of this study was to investigate the anxiolytic effects of xanthohumol, a component of Humulus lupulus (hops), and its potential interaction with the benzodiazepine binding site on the y-aminobutyric acid (GABAA) receptor in the male Sprague-Dawley rat. This was a prospective, randomized, between-subjects experimental study. Fifty-five rats were assigned to 1 Sof 5 groups with 11 rats per group: control (vehicle), xanthohumol, midazolam, midazolam with xanthohumol, and flumazenil with xanthohumol. In this study the elevated plus maze measured the behavioral components of anxiety and motor movements. A 2-tailed multivariate analysis of variance and least significant difference post hoc test was used to determine if a significant difference existed. Our data suggest that xanthohumol does not produce anxiolysis by modulation of the GABAA receptor; however, there may be a possible interaction between xanthohumol and midazolam, or xanthohumol may influence the modulation of another neurotransmitter site in the central nervous system. Alone, xanthohumol does not show significant modulation of the benzodiazepine receptor. Additional research should investigate if xanthohumol acts as a benzodiazepine GABAA partial agonist or antagonist or if it modulates another neurotransmitter system in the central nervous system.

  16. Effects of Sex, Age, and Fasting Conditions on Plasma Lipidomic Profiles of Fasted Sprague-Dawley Rats

    PubMed Central

    Saito, Kosuke; Ishikawa, Masaki; Murayama, Mayumi; Urata, Masayo; Senoo, Yuya; Toyoshima, Katsuko; Kumagai, Yuji; Maekawa, Keiko; Saito, Yoshiro

    2014-01-01

    Circulating lipid molecules reflect biological processes in the body and, thus, are useful tools for preclinical estimation of the efficacy and safety of newly developed drugs. However, background information on profiles of circulating lipid molecules in preclinical animal models is limited. Therefore, we examined the effects of multiple factors such as sex (fasted male vs. female), age (fasted 10 vs. 30 weeks old), and feeding conditions (feeding vs. fasting, 16 vs. 22 hr fasting, 10 AM vs. 4 PM blood collection), on the global profiles of lipid molecules in plasma from Sprague-Dawley rats by using a lipidomic approach. Our assay platform determined 262 lipid molecules (68 phospholipids, 20 sphingolipids, 138 neutral lipids, and 36 polyunsaturated fatty acids and their metabolites) in rat plasma. Multivariate discriminant analysis (orthogonal partial least squares discriminant analysis) and heat maps of statistically significant lipid molecules revealed that the plasma lipid profiles in rats are predominantly influenced by feeding conditions, followed by sex and age. In addition, the fasting duration (16 vs. 22 hr fasting) or the time of blood collection (10 AM vs. 4 PM blood collection) has limited or no contribution on the profiles of lipid molecules in rat plasma. Our results provide useful, fundamental information for exploring and validating biomarkers in future preclinical studies and may help to establish regulatory standards for such studies. PMID:25375860

  17. Differential resolution of inflammation and recovery after renal ischemia-reperfusion injury in Brown Norway compared with Sprague Dawley rats.

    PubMed

    Sáenz-Morales, David; Conde, Elisa; Blanco-Sánchez, Ignacio; Ponte, Belen; Aguado-Fraile, Elia; de Las Casas, Gonzalo; García-Martos, Maria; Alegre, Laura; Escribese, Maria M; Molina, Ana; Santiuste, Carmen; Liaño, Fernando; García-Bermejo, Maria-Laura

    2010-05-01

    To investigate mechanisms conferring susceptibility or resistance to renal ischemia, we used two rat strains known to exhibit different responses to ischemia-reperfusion. We exposed proximal tubule cells isolated from Sprague Dawley or Brown Norway rats, to a protocol of hypoxia, followed by reoxygenation in vitro. The cells isolated from both rat strains exhibited comparable responses in the disruption of intercellular adhesions and cytoskeletal damage. In vivo, after 24 h of reperfusion, both strains showed similar degrees of injury. However, after 7 days of reperfusion, renal function and tubular structure almost completely recovered and inflammation resolved, but only in Brown Norway rats. Hypoxia-inducible factor-dependent gene expression, ERK1/2, and Akt activation were different in the two strains. Inflammatory mediators MCP-1, IL-10, INF-gamma, IL-1beta, and TNF-alpha were similarly induced at 24 h in both strains but were downregulated earlier in Brown Norway rats, which correlated with shorter NFkappaB activation in the kidney. Moreover, VLA-4 expression in peripheral blood lymphocytes and VCAM-1 expression in kidney tissues were initially similar at 24 h but reached basal levels earlier in Brown Norway rats. The faster resolution of inflammation in Brown Norway rats suggests that this strain might be a useful experimental model to determine the mechanisms that promote repair of renal ischemia-reperfusion injury.

  18. Reference control data obtained from an in vivo comet-micronucleus combination assay using Sprague Dawley rats.

    PubMed

    Kasamoto, Sawako; Masumori, Shoji; Tanaka, Jin; Ueda, Maya; Fukumuro, Masahito; Nagai, Miho; Yamate, Jyoji; Hayashi, Makoto

    2017-04-04

    According to the International Conference on Harmonization Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use (ICH S2(R1)), a positive response in any in vitro assay necessitates additional in vivo test(s) (other tissue/endpoint) in addition to the erythrocyte micronucleus test when Option 1 of the test battery is selected. When Option 2 of the test battery is selected, a bacterial gene mutation test and two in vivo tests with different tissues/endpoint are required. The in vivo alkaline comet assay is recommended as the second in vivo test because it can detect a broad spectrum of DNA damage in any tissue and can be combined with the erythrocyte micronucleus test. Considering animal welfare, a combination assay is preferable to an individual assay. Thus, we validated the protocol for the in vivo comet-micronucleus combination assay in rats with three daily administrations and determined the dose of the positive control (ethyl methanesulfonate; EMS, 200mg/kg/day). We also collected the negative control (vehicle) and positive control (EMS) data from the comet (liver, stomach, and kidney) and micronucleus (bone marrow) combination assay using male Sprague Dawley (SD) rats. The negative control data were comparable to our historical control data obtained from stand-alone assays. The positive control data showed clear and consistent positive responses in both endpoints.

  19. 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.

  20. [Contraction responses of isolated aortic rings of pika (Ochotona curzoniae) and Sprague-Dawley rat to hypoxia].

    PubMed

    Ma, Shuang; Ma, Yan; Ge, Ri-Li

    2013-04-25

    The aim of the present study was to observe the effects of hypoxia on tensions of aortic rings of pika (Ochotona curzoniae) and Sprague-Dawley (SD) rat. The aortic rings were prepared, and in vitro vascular ring perfusion was used to assay the effects of hypoxia or different drugs on contraction responses of the rings with or without endothelium. The results showed that, there was no difference of the contractions to KCl (80 mmol/L) between the aortic rings of the pikas and SD rats. After pre-contraction with NE (1 μmol/L), the aortic rings with endothelium of the SD rats showed obvious relaxation to ACh (1 μmol/L), whereas the aortic rings of the pikas, no matter with or without endothelium, showed significant and unusual contraction to ACh. The aortic rings of pikas, no matter with or without endothelium, exhibited greater contraction when treated by 1 h of hypoxia, compared with those in SD rats; The similar result was showed under hypoxia in combination with Ca(2+) removal. These results suggest that the contraction response to hypoxia in pika is more sensitive compared to that in SD rat, which is dependent on the release of calcium from intracellular calcium store.

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

    PubMed

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

    1993-02-01

    Circadian rhythmicities are oscillations of physiological cycles designed to create temporal organization. Circadian rhythms ensure that physiological mechanisms are expressed in proper relationship to each other and the 24 hour day. Light is the main zeitgeber ("time giver") for biological clocks. The daily variations in light intensity from dawn to dusk, and seasonally due to the rotation of the earth, act upon organisms to give them photoperiodic information. This entrainment allows them to vary biologically to prepare for reproduction, hibernation, migration and the daily adaptations necessary for survival. In most mammals, the suprachiasmatic nucleus of the anterior hypothalamus has been implicated as the central diving 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.

  2. 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

  3. [Impact of diet on the induction of infection with Giardia lamblia cysts in Sprague-Dawley rats].

    PubMed

    Díaz-Cinco, Martha Elvia; Ballesteros-Vázquez, Martha Nydia; Pérez-Morales, Rosalba; Mata-Haro, Verónica

    2002-01-01

    To assess the effect of malnutrition on the development of giardiasis in Sprague-Dawley rats, using different inoculum sizes of Giardia lamblia cysts. An experimental study was conducted between 1995 and 1999 at Centro de Investigación, Alimentación y Desarrollo (Center for Research, Food, and Development), in Hermosillo, Sonora, Mexico. The study population consisted of two groups of six to eight experimental units that were fed two different diets and inoculated five different concentrations of Giardia lamblia cysts. Data were collected on excretion of cysts, weight gain, food intake, bowel contents, and macro and microscopic lesions in the intestinal mucosa. Statistical analysis consisted of analysis of variance and residuals. Animals fed with a diet meeting nutritional requirements required an infecting inoculum of 60 cysts, while malnourished rats required only six cysts to develop mucosal lesions. Weight gain monitored during ten days was not a good indicator of Giardia lamblia infection. Infection depended on cyst inoculum size as well as on the nutritional status of the tested animals. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

  4. Protective effects of Cuscutae semen against dimethylnitrosamine-induced acute liver injury in Sprague-Dawley rats.

    PubMed

    Kim, Eun-Young; Kim, Eun Kyoung; Lee, Hyun-Sam; Sohn, Youngjoo; Soh, Yunjo; Jung, Hyuk-Sang; Sohn, Nak-Won

    2007-08-01

    We investigated the protective effect of Cuscutae semen (CS) on acute liver injury induced by dimethylnitrosamine (DMN) in Sprague-Dawley rats. CS is an important traditional herbal medicine widely used as a tonic and aphrodisiac to nourish the liver and kidney and to treat impotence and seminal emission. Rats were given a single intraperitoneal injection of DMN (40 mg/kg), and were then treated with CS daily by oral gavage for 4 d. Immunohistochemical studies for alpha-smooth muscle actin (alpha-SMA) and proliferating cell nuclear antigen (PCNA) were performed, along with hydroxyproline and biological assay. Liver injury caused by DMN-injection was significantly inhibited in the CS-treated group compared to the silymarin-treated group. The results of blood biological assay were significantly protected by CS in serum total protein (T-protein), T-bilirubin (T-bili), D-bilirubin (D-bili), GOT, GPT, and ALP. The hydroxyproline content and amount of active alpha-SMA and PCNA were significantly decreased in the CS-treated group than in the silymarin-treated group. CS exhibited an in vivo hepatoprotective effect and anti-fibrogenic effects against DMN-induced acute liver injury and inhibited the formation of hydroxyproline, which suggests that CS may be useful in preventing fibrogenesis after liver injury.

  5. Safety assessment of So-cheong-ryong-tang: subchronic toxicity study in Crl:CD Sprague Dawley rats.

    PubMed

    Lee, Mee-Young; Seo, Chang-Seob; Cha, Shin-Woo; Shin, Hyeun-Kyoo

    2014-06-01

    So-cheong-ryong-tang, an oriental herbal formula, is used in Korea for treating pulmonary disorders, including asthma, bronchitis and allergic diseases. The objective of the present study was to investigate the potential adverse effects, if any, of subchronic administration of So-cheong-ryong-tang aqueous extract (SCRT) in male and female rats. In the present study, 0, 1,000, 2,000 and 5,000 mg/kg/day of SCRT was administered to Crl:CD Sprague Dawley rats (10/gender/group) for 13 weeks via oral gavage. Administration of the SCRT did not result in any mortality. There were no clinical or ophthalmological signs, changes in urinalysis, body weight, food consumption, gross findings, hematology, serum biochemistry, organ weight or histopathology attributable to the administration of SCRT. Any alterations noted were incidental and consistent with those historically observed in the age and strain of rats used in the present study. Based on the results of the present study, the no observed adverse effect level for SCRT under the present experimental conditions was determined to be 5,000 mg/kg/day, the highest dose assessed, for both genders.

  6. Dietary taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in streptozotocin-induced Sprague-Dawley rats.

    PubMed

    Yu, Xiaoping; Xu, Zhaoxia; Mi, Mantian; Xu, Hongxia; Zhu, Jundong; Wei, Na; Chen, Ka; Zhang, Qianyong; Zeng, Kaihong; Wang, Jian; Chen, Fang; Tang, Yong

    2008-03-01

    The purpose of this study was to investigate whether taurine ameliorate the diabetic retinopathy, and to further explore the underlying mechanisms. The Sprague-Dawley rats were injected with streptozotocin to establish experimental diabetic model, then fed without or with 1.2% taurine for additional 4-12 weeks. After that, the protective effects of dietary taurine supplementation on diabetic retinopathy were estimated. Our results showed that chronic taurine supplement effectively improved diabetic retinopathy as changes of histopathology and ultrastructure. The supplementation could not lower plasma glucose concentration (P > 0.05), but caused an elevation in taurine content and a decline in levels of glutamate and gamma-aminobutyric acid (GABA) in diabetic retina (P < 0.05). Moreover, chronic taurine supplementation increased glutamate transporter (GLAST) expression (P < 0.05), decreased intermediate filament glial fibrillary acidic protein (GFAP) and N-methyl-D: -aspartate receptor subunit 1 (NR1) expression in diabetic retina (P < 0.05). These results demonstrated that chronic taurine supplementation ameliorates diabetic retinopathy via anti-excitotoxicity of glutamate in rats.

  7. 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

  8. 4-Vinylcyclohexene Diepoxide (VCD) Inhibits Mammary Epithelial Differentiation and Induces Fibroadenoma Formation in Female Sprague Dawley Rats

    PubMed Central

    Wright, Laura E.; Frye, Jennifer B.; Lukefahr, Ashley L.; Marion, Samuel L.; Hoyer, Patricia B.; Besselsen, David G.; Funk, Janet L.

    2011-01-01

    4-Vinylcyclohexene diepoxide (VCD), an occupational chemical that targets ovarian follicles and accelerates ovarian failure in rodents, was used to test the effect of early-onset reproductive senescence on mammary fibroadenoma formation. One-month female Sprague Dawley rats were dosed with VCD (80 mg/kg or 160 mg/kg) and monitored for 22 months for persistent estrus and tumor development. Only high-dose VCD treatment accelerated the onset of persistent estrus relative to controls. However, both doses of VCD accelerated mammary tumor onset by 5 months, increasing incidence to 84% (vs. 38% in controls). Tumor development was independent of time in persistent estrus, 17β-estradiol, androstenedione and prolactin. Delay in VCD administration until after completion of mammary epithelial differentiation (3 months) did not alter tumor formation despite acceleration of ovarian senescence. VCD administration to 1-month rats acutely decreased mammary alveolar bud number and expression of β-casein, suggesting that VCD’s tumorigenic effect requires exposure during mammary epithelial differentiation. PMID:21621605

  9. Electromagnetic fields from mobile phones do not affect the inner auditory system of Sprague-Dawley rats.

    PubMed

    Galloni, Paolo; Parazzini, Marta; Piscitelli, Marta; Pinto, Rosanna; Lovisolo, Giorgio A; Tognola, Gabriella; Marino, Carmela; Ravazzani, Paolo

    2005-12-01

    The auditory system is the first biological structure facing the electromagnetic fields emitted by mobile phones. The aim of this study was to evaluate the cochlear functionality of Sprague-Dawley rats exposed to electromagnetic fields at the typical frequencies of GSM mobile phones (900 and 1800 MHz) by distortion product otoacoustic emissions, which are a well-known indicator of the status of the cochlea's outer hair cells. A population of 48 rats was divided into exposed and sham-exposed groups. Three sets of four loop antennas, one for sham-exposed animals and two for exposed animals, were used for the local exposures. Rats were exposed 2 h/day, 5 days/week for 4 weeks at a local SAR of 2 W/kg in the ear. Distortion product otoacoustic emissions tests were carried out before, during and after the exposure. The analysis of the data shows no statistically significant differences between the audiological signals recorded for the different groups.

  10. Role of astrocyte activation in fine particulate matter-enhancement of existing ischemic stroke in Sprague-Dawley male rats.

    PubMed

    Zhang, Chengcheng; Meng, Qingtao; Zhang, Xin; Wu, Shenshen; Wang, Shizhi; Chen, Rui; Li, Xiaobo

    2016-01-01

    Exposure to particulate matter (PM) with an aerodynamic diameter of less than 2.5 μm (PM2.5) is associated with increased risk of ischemic stroke, but potential neurotoxic mechanisms remain to be determined. In this study, adult male Sprague- Dawley (SD) rats were divided into four groups as follows: control (CON), PM2.5 exposure (PM alone), ischemic stroke (IS), and ischemic stroke and PM2.5 (IS-PM). Ischemic stroke groups were prepared by middle cerebral artery occlusion (MCAO), and neurobehavior was assessed daily for 7 consecutive days. The control group was administered intranasally 20 μl PBS, while PM2.5 alone was given as 20 μl of PM2.5 (10 mg/ml) intranasal daily for 7 consecutive days. The spontaneous locomotion and exploratory behavior of rats were assessed by the open field test. Cells positive for glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS) were determined for astrocyte activation and inflammatory reactions. Neuronal edema and pyknosis in the cerebral cortex, hippocampus, and midbrain were observed in IS groups with or without PM2.5 treatment. Astrocyte activity was enhanced, whereas spontaneous locomotion and exploratory movements decreased in the IS-PM group. Data demonstrated that astrocytes activation and inflammatory reactions may play a role in IS and that exposure to PM2.5 may aggravate the neurobehavioral alterations observed in rats suffering from IS.

  11. 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.

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

    PubMed Central

    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.; Hayes Bouknight, Schantel A.; Fenton, Suzanne E.

    2016-01-01

    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 interpretation of 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 which 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

  13. 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.

  14. Short-term toxicity study of ST-20 (NSC-741804) by oral gavage in Sprague-Dawley rats.

    PubMed

    Terse, Pramod S; Johnson, Jerry D; Hawk, Michael A; Ritchie, Glenn D; Ryan, Michael J; Vasconcelos, Daphne Y; Contos, Denise A; Perrine, Susan P; Peggins, James O; Tomaszewski, Joseph E

    2011-06-01

    ST-20 (sodium 2,2-dimethylbutyrate) is a potential therapeutic agent for treatment of β-thalassemia and sickle cell disease. A subchronic oral toxicity study was conducted in Sprague-Dawley rats (10/sex/dose) at gavage dosages of 0 (vehicle control), 200, 600, or 1,000 mg/kg, once daily for up to 15 days followed by a 14-day recovery. Ataxia (females), rough coat/thin appearance (males), and decreased body weights were observed at 1,000 mg/kg. Functional observational battery (FOB) deficits were observed more frequently in females and included decreased body tone, rectal temperature, emotional reactivity, neuromotor-neuromuscular activity (as exhibited by a deficit in visual/tactile placing accuracy, ataxia, hind limb dragging, and decreased grip strength), and rearing. ST-20 caused a decrease in WBC/RBC counts and RBC parameters; increase in reticulocytes and red cell inclusion bodies; decrease in total protein, globulin, and glucose; and increase in AG ratio. Micronucleated polychromatic erythrocytes of the bone marrow increased significantly in males at 1,000 mg/kg. Mean liver and kidney weights increased, and hepatocellular hypertrophy was observed in males at 1,000 mg/kg. Toxicologic findings were fully recovered during the 14-day recovery period. In conclusion, the no-observed adverse effect level for FOB and general toxicity was 200 mg/kg following gavage administration of ST-20 for up to 15 consecutive days.

  15. Morinda citrifolia L. leaf extract prevent weight gain in Sprague-Dawley rats fed a high fat diet

    PubMed Central

    Jambocus, Najla Gooda Sahib; Ismail, Amin; Khatib, Alfi; Mahomoodally, Fawzi; Saari, Nazamid; Mumtaz, Muhammad Waseem; Hamid, Azizah Abdul

    2017-01-01

    ABSTRACT Background: Morinda citrifolia L. is widely used as a folk medicinal food plant to manage a panoply of diseases, though no concrete reports on its potential anti-obesity activity. This study aimed to evaluate the potential of M. citrifolia leaf extracts (MLE60) in the prevention of weight gain in vivo and establish its phytochemical profile. Design: Male Sprague-Dawley rats were divided into groups based on a normal diet (ND) or high fat diet (HFD), with or without MLE60 supplementation (150 and 350 mg/kg body weight) and assessed for any reduction in weight gain. Plasma leptin, insulin, adiponectin, and ghrelin of all groups were determined. 1H NMR and LCMS methods were employed for phytochemical profiling of MLE60. Results: The supplementation of MLE60 did not affect food intake indicating that appetite suppression might not be the main anti-obesity mechanism involved. In the treated groups, MLE60 prevented weight gain, most likely through an inhibition of pancreatic and lipoprotein activity with a positive influence on the lipid profiles and a reduction in LDL levels . MLE60 also attenuated visceral fat deposition in treated subjects with improvement in the plasma levels of obesity-linked factors . 1Spectral analysis showed the presence of several bioactive compounds with rutin being more predominant. Conclusion: MLE60 shows promise as an anti-obesity agents and warrants further research. PMID:28814950

  16. Characterization of the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone in male Sprague-Dawley rats.

    PubMed

    Berquist, Michael D; Baker, Lisa E

    2017-08-01

    Recreational use of 3,4-methylenedioxypyrovalerone (MDPV) in the early 2000s prompted numerous scientific investigations of its behavioral and neurochemical effects. The purpose of this study was to further characterize the interoceptive stimulus effects of MDPV using a validated in-vivo drug-detection assay. Male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg MDPV from saline under a fixed ratio 20 (FR 20) schedule of food reinforcement. After stimulus control was established with MDPV (∼35 training sessions), substitution tests were commenced with drugs from several chemical classes, including drugs with predominantly dopaminergic actions [MDPV, D-amphetamine, (+)-methamphetamine, (-)-cocaine], drugs with predominantly serotonergic actions [(+)-lysergic acid diethylamide, (+)-fenfluramine], and drugs with both serotonergic and dopaminergic actions (3,4-methylenedioxymethamphetamine, 4-methylmethcathinone). Full substitution for the 0.3 mg/kg MDPV cue was observed with D-amphetamine, (+)-methamphetamine, and (-)-cocaine. Surprisingly, the 5-HT releaser (+)-fenfluramine fully substituted in half the subjects, but completely suppressed responding in the remaining subjects. 3,4-Methylenedioxymethamphetamine, 4-methylmethcathinone, and (+)-lysergic acid diethylamide failed to fully substitute for MDPV. These results indicate that the MDPV cue is similar to cues produced by drugs with predominantly dopamine-increasing effects and perhaps serotonin-releasing effects among individual subjects. Given these findings, further research is warranted to directly assess the contributions of dopamine and serotonin receptor isoforms to the discriminative stimulus functions of MDPV.

  17. 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

  18. Studies on the Toxicity and Distribution of Indium Compounds According to Particle Size in Sprague-Dawley Rats

    PubMed Central

    Han, Jeong-Hee; Cho, Hae-Won; Kang, Mingu

    2014-01-01

    Objectives: The use of indium compounds, especially those of small size, for the production of semiconductors, liquid-crystal panels, etc., has increased recently. However, the role of particle size or the chemical composition of indium compounds in their toxicity and distribution in the body has not been sufficiently investigated. Therefore, the aim of this study was to examine the effects of particle size and the chemical composition of indium compounds on their toxicity and distribution. Methods: Male Sprague-Dawley rats were exposed to two different-sized indium oxides (average particle sizes under 4,000 nm [IO_4000] and 100 nm [IO_100]) and one nano-sized indium-tin oxide (ITO; average particle size less than 50 nm) by inhalation for 6 hr daily, 5 days per week, for 4 weeks at approximately 1 mg/m3 of indium by mass concentration. Results: We observed differences in lung weights and histopathological findings, differential cell counts, and cell damage indicators in the bronchoalveolar lavage fluid between the normal control group and IO- or ITO-exposed groups. However, only ITO affected respiratory functions in exposed rats. Overall, the toxicity of ITO was much higher than that of IOs; the toxicity of IO_4000 was higher than that of IO_100. A 4-week recovery period was not sufficient to alleviate the toxic effects of IO and ITO exposure. Inhaled indium was mainly deposited in the lungs. ITO in the lungs was removed more slowly than IOs; IO_4000 was removed faster than IO_100. IOs were not distributed to other organs (i.e., the brain, liver, and spleen), whereas ITO was. Concentrations of indium in the blood and organ tissues were higher at 4 weeks after exposure. Conclusions: The effect of particle size on the toxicity of indium compounds was not clear, whereas chemical composition clearly affected toxicity; ITO showed much higher toxicity than that of IO. PMID:24795801

  19. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Inhibition of colon carcinogenesis by post-initiation induction of NQO1 in Sprague-Dawley rats.

    PubMed

    Begleiter, Asher; Sivananthan, Kosala; Lefas, Georgia M; Maksymiuk, Andrew W; Bird, Ranjana P

    2009-06-01

    Inducers of phase II detoxifying enzymes have been studied as chemopreventive agents for a variety of cancers. Phase II detoxifying enzymes may play a significant role in preventing carcinogen-induced colon cancer at the initiation and post-initiation stage, but the contribution of NAD(P) H:quinone oxidoreductase 1 (NQO1) to this effect remains unclear. Using the carcinogen-induced colon cancer Sprague-Dawley rat model, we previously showed that oltipraz selectively induces NQO1 in the colons of these rats without inducing other phase II detoxifying enzymes. We demonstrated that selective induction of NQO1 in the rat colon prior to treatment with a carcinogen significantly inhibited the formation of aberrant crypt foci (ACF). Using the same rat model, we found that rats fed oltipraz containing diet following treatment with the colon carcinogen, azoxymethane (AOM), had 60% fewer ACF after 12 weeks compared with rats fed a control diet. In addition, rats fed oltipraz containing diet after AOM treatment developed 40% fewer colon adenomas and fewer colon tumors than rats fed a control diet. There was also a 60% increase in the percentage of apoptotic cells in ACF from oltipraz fed rats compared with ACF from control fed rats. Together, these results suggest that NQO1 can contribute to inhibition of colon carcinogenesis at the post-initiation stage. A possible mechanism for this effect may be that induction of NQO1 increases apoptosis in carcinogen initiated colonic epithelial cells that prevents these cells from progressing to a neoplastic state. Thus, NQO1 may be an important target for chemoprevention of colon cancer.

  1. Dietary effects of mead acid on N-methyl-N-nitrosourea-induced mammary cancers in female Sprague-Dawley rats.

    PubMed

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Hamazaki, Kei; Emoto, Yuko; Yuri, Takashi; Yuki, Michiko; Kawashima, Hiroshi; Shikata, Nobuaki; Tsubura, Airo

    2016-01-01

    The effect of mead acid (MA; 5,8,11-eicosatrienoic acid) on the suppression of the development and growth of N-methyl-N-nitrosourea (MNU)-induced mammary cancer in female Sprague-Dawley rats was examined. The MA diet (2.4% MA) or control (CTR) diet (0% MA) was started at 6 weeks of age, MNU was injected intraperitoneally at 7 weeks of age, and the rats were maintained on the respective diets for the whole experimental period (until 19 weeks of age). All induced mammary tumors were luminal A subtype carcinomas (estrogen and progesterone receptor positive and HER2/neu negative). The MA diet significantly suppressed the initiation and promotion phases of mammary carcinogenesis; MA suppressed the development (incidence, 61.5 vs. 100%; multiplicity, 2.1 vs. 4.5) and the growth (final tumor weight, 427.1 vs. 1,796.3 mg) of mammary cancers by suppressing cell proliferation, but not by accelerating cell death. There were evident changes in the major fatty acid composition of n-3, n-6, and n-9 fatty acids in the serum of the MA diet group; there was a significant increase in MA and significant decreases in oleic acid (OA), linoleic acid, arachidonic acid and docosahexaenoic acid. In non-tumorous mammary tissue, there was a significant increase in MA and a significant decrease in OA in the MA diet group. The n-6/n-3 ratios in serum and mammary tissue of the MA diet group were significantly decreased. The MA diet suppressed MNU-induced luminal A mammary cancer by lowering cancer cell proliferation. Therefore, MA may be a chemopreventive and chemotherapeutic agent. In addition to hormone therapy, MA supplementation may be a beneficial chemotherapeutic agent for the luminal A subtype of breast cancer.

  2. 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

    2014-06-05

    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.

  3. 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.

  4. 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.

  5. Effect and mechanism of SHED on ulcer wound healing in Sprague-Dawley rat models with diabetic ulcer

    PubMed Central

    Lv, Yue; Ge, Lihong; Zhao, Yuming

    2017-01-01

    To evaluate the effect of stem cells from human exfoliated deciduous teeth (SHED) upon the ulcer wound healing and evaluate the mechanism underlying the role of SHED in Sprague-Dawley rat models with diabetic foot ulcer. The rats with diabetic ulcer were established and treated with SHED, mesenchymal stem cell (MSC) and PBS, respectively. The expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-2 (MMP-2) and MMP9 at both protein and RNA levels was quantitatively measured. The serum levels of VEGF, IL-1β, TNF-1α and IL-10 were detected by ELISA. The remaining tissues were fixed in 4% chloral hydrate for hematoxylin and eosin (H.E) staining and immunohistochemical staining. MSC and SHED administration could reduce ulceration area and accelerate wound healing at 7 and 14 d after treatment as compared with the control group (all P<0.05), which were validated by H.E and immunohistochemical staining. Western blot results revealed that the expression levels of VEGF, eNOS, MMP2 and MMP9 proteins in the MSC and SHED groups were considerably up-regulated compared with those in the control group at different time points (all P<0.05). The same trend was also observed in the mRNA expression of these cytokines detected by RT-PCR. At 3-d after treatment, no statistical significance was noted in the IL-10 level among three groups, but the IL-10 concentration in the SHED and MSC groups was significantly down-regulated at 7- and 14-d post-treatment (all P<0.05). SHED administration, similar to MSCs, could accelerate wound healing, promote angiogenesis and suppress inflammatory responses in rat models with diabetic ulceration. PMID:28337277

  6. Plasma Intermedin Level Indicates Severity and Treatment Efficacy of Septic Shock in Sprague-Dawley (SD) Rats

    PubMed Central

    Yang, Su-Xian; Chen, Yun-Xiu; Xu, Jing; Yang, Zhao-Hui

    2016-01-01

    Background The aim of this study was to investigate the value of plasma intermedin (IMD) in assessing severity and treatment efficacy of septic shock. Material/Methods Healthy male Sprague-Dawley (SD) rats were chosen and divided into a normal control group (n=15) and a shock model group (n=27) that received intravenous injection of lipopolysaccharide (LPS). Then, 3 specimens were taken from each group. The shock model group rats were divided into an LPS group and a treatment group with 12 rats each. The treatment group received intravenous injection of compound sodium lactate solution. Plasma IMD and IMD1-47 mRNA expressions were compared and analyzed. Results Mean arterial pressure (MAP) was lower while white blood cell count and TNF-α were higher in the shock model group than in the normal control group (P<0.05). After 10 h and 20 h, the treatment group had lower plasma IMD and IMD1-47 mRNA expressions compared with the LPS group (P<0.05). Plasma IMD and IMD1-47 mRNA expressions in the LPS group after 20 h were significantly higher than after 10 h (P<0.05). IMD was positively correlated with interleukins (IL-3, IL-6, and IL-8), white blood cell count, and body temperature (all P<0.05), but were negatively correlated with systolic pressure (r=−0.8474, P=0.0040). Conclusions Plasma IMD level can effectively reflect the severity of septic shock and can be used as an important indicator of septic shock treatment effectiveness. PMID:27999422

  7. Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury.

    PubMed

    Schober, Michelle E; Requena, Daniela F; Davis, Lizeth J; Metzger, Ryan R; Bennett, Kimberly S; Morita, Denise; Niedzwecki, Christian; Yang, Zhihui; Wang, Kevin K W

    2014-07-29

    After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 Spectrin breakdown products (SBDPs) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Alpha II Spectrin Breakdown Products in Immature Sprague Dawley Rat Hippocampus and Cortex after Traumatic Brain Injury

    PubMed Central

    Schober, Michelle E; Requena, Daniela F; Davis, Lizeth J; Metzger, Ryan; Bennett, Kim; Morita, Denise; Niedzwecki, Christian; Yang, Zhihui; Wang, Kevin K W

    2014-01-01

    After traumatic brain injury (TBI), proteolysis of Alpha II Spectrin by Calpain 1 produces 145 SBDPs (Spectrin Breakdown Products) while proteolysis by Caspase 3 produces 120 SBDPs. 145 and 120 SBDP immunoblotting reflects the relative importance of caspase-dependent apoptosis or calpain-dependent excitotoxic/necrotoxic cell death in brain regions over time. In the adult rat, controlled cortical impact (CCI) increased 120 SBDPs in the first hours, lasting a few days, and increased 145 SBDPs within the first few days lasting up to 14 days after injury. Little is known about SBDPs in the immature brain after TBI. Since development affects susceptibility to apoptosis after TBI, we hypothesized that CCI would increase 145 and 120 SBDPs in the immature rat brain relative to SHAM during the first 3 and 5 days, respectively. SBDPs were measured in hippocampi and cortices at post injury days (PID) 1, 2, 3, 5, 7 and 14 after CCI or SHAM surgery in the 17 day old Sprague Dawley rat. 145 SBDPs increased in both brain tissues ipsilateral to injury during the first 3 days, while changes in contralateral tissues were limited to PID2 cortex. 145 SBDPs elevations were more marked and enduring in hippocampus than in cortex. Against expectations, 120 SBDPs only increased in PID1 hippocampus and PID2 cortex. 145 SBDPs elevations occurred early after CCI, similar to previous studies in the adult rat, but resolved more quickly. The minimal changes in 120 SBDPs suggest that calpain-dependent, but not caspase-dependent, cell death predominates in the 17 day old rat after CCI. PMID:24929209

  9. 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

  10. Pharmacokinetic Interaction of astragaloside IV with atractylenolide I and prim-O-glucosylcimifugin in male Sprague Dawley rats.

    PubMed

    Song, Jue; Zheng, Shi-rui; Jin, Yong; Li, Jun

    2014-02-01

    Astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin are main medicinal components of the traditional Chinese medicine prescription Yu-ping-feng which is composed of three herbs: Astragalus membranaceus, Atractylodes macrocephala, and Saposhnikovia divaricata. This study is aimed to assess the influence of atractylenolide I and prim-O-glucosylcimifugin on the pharmacokinetic profile of astragaloside IV so as to investigate the pharmacokinetic mechanisms of the Yu-ping-feng prescription. Fifteen Sprague Dawley rats were randomized to three groups; astragaloside IV, astragaloside IV plus atractylenolide I, and a combination of astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin were respectively administered to rats of these three groups via intragastric gavage. Serum samples were collected at different times after drug administration, and serum concentrations of astragaloside IV and atractylenolide I were simultaneously detected using HPLC-electrospray ionization-MS. Compared with administration of astragaloside IV alone, concentrations of astragaloside IV in the serum were significantly increased when it was given in combination with atractylenolide I or atractylenolide I+prim-O-glucosylcimifugin, with higher values for Cmax (p = 0.019 and p = 0.033 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively) and AUC (p = 0.0052 and p = 0.0047 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively). Improvement in mean oral Cmax and mean systemic serum exposure because of the pharmacokinetic interaction between astragaloside IV and atractylenolide I might explain the rationale for the use of multiple herbs in Yu-ping-feng and of combinations of A.membranaceus and A. macrocephala.

  11. Comparison of the antinociceptive response to morphine and morphine-like compounds in male and female Sprague-Dawley rats.

    PubMed

    Peckham, Elizabeth M; Traynor, John R

    2006-03-01

    Male rats are more sensitive to the antinociceptive effects of morphine than female rats. This difference is seen across several rat strains using a variety of nociceptive stimuli. However, the literature in regard to sex differences in antinociceptive responses to mu-opioids other than morphine is less consistent. The present study was designed to examine whether there is a structure-activity rationale that determines which mu-opioids will show a differential antinociceptive response between male and female rats. A series of morphinans closely related in structure to morphine, namely, codeine, heroin, hydrocodone, hydromorphone, oxymorphone, and oxycodone, were examined for their antinociceptive activity in male and female Sprague-Dawley rats and compared with the structurally unrelated mu-opioid agonists methadone and fentanyl. Antinociception was measured by the warm-water tail-withdrawal assay. The results show that morphine is more potent in males compared with females > hydromorphone = hydrocodone = oxymorphone, but there was no observable sex difference in the antinociceptive potency of codeine, heroin, oxycodone, methadone, or fentanyl. The potency to stimulate guanosine 5'-O-(3-[35 S]thio)triphosphate ([35S]GTPgammaS) binding and binding affinity of the various morphinans was compared in rat glioma C6 cells expressing the rat mu-opioid receptor; relative efficacy was also compared by stimulation of [35S]GTPgammaS binding in slices of rat brain thalamus. The presence of a sex difference in antinociceptive responsiveness was not related to drug potency, efficacy, or affinity. Consequently, it is likely that differential metabolism of the opioid, possibly by glucuronidation, determines the presence or absence of a sex difference.

  12. Pituitary Adenylate Cyclase-Activating Polypeptide Disrupts Motivation, Social Interaction, and Attention in Male Sprague Dawley Rats.

    PubMed

    Donahue, Rachel J; Venkataraman, Archana; Carroll, F Ivy; Meloni, Edward G; Carlezon, William A

    2016-12-15

    Severe or prolonged stress can trigger psychiatric illnesses including mood and anxiety disorders. Recent work indicates that pituitary adenylate cyclase-activating polypeptide (PACAP) plays an important role in regulating stress effects. In rodents, exogenous PACAP administration can produce persistent elevations in the acoustic startle response, which may reflect anxiety-like signs including hypervigilance. We investigated whether PACAP causes acute or persistent alterations in behaviors that reflect other core features of mood and anxiety disorders (motivation, social interaction, and attention). Using male Sprague Dawley rats, we examined if PACAP (.25-1.0 µg, intracerebroventricular infusion) affects motivation as measured in the intracranial self-stimulation test. We also examined if PACAP alters interactions with a conspecific in the social interaction test. Finally, we examined if PACAP affects performance in the 5-choice serial reaction time task, which quantifies attention and error processing. Dose-dependent disruptions in motivation, social interaction, and attention were produced by PACAP, as reflected by increases in reward thresholds, decreases in social behaviors, and decreases in correct responses and alterations in posterror accuracy. Behavior normalized quickly in the intracranial self-stimulation and 5-choice serial reaction time task tests but remained dysregulated in the social interaction test. Effects on attention were attenuated by the corticotropin-releasing factor receptor-1 antagonist antalarmin but not the κ opioid receptor antagonist JDTic. Our findings suggest that PACAP affects numerous domains often dysregulated in mood and anxiety disorders, but that individual signs depend on brain substrates that are at least partially independent. This work may help to devise therapeutics that mitigate specific signs of these disorders. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Antibiotics Suppress Activation of Intestinal Mucosal Mast Cells and Reduce Dietary Lipid Absorption in Sprague-Dawley Rats.

    PubMed

    Sato, Hirokazu; Zhang, Linda S; Martinez, Kristina; Chang, Eugene B; Yang, Qing; Wang, Fei; Howles, Philip N; Hokari, Ryota; Miura, Soichiro; Tso, Patrick

    2016-11-01

    The gut microbiota affects intestinal permeability and mucosal mast cells (MMCs) responses. Activation of MMCs has been associated with absorption of dietary fat. We investigated whether the gut microbiota contributes to the fat-induced activation of MMCs in rats, and how antibiotics might affect this process. Adult male Sprague-Dawley rats were given streptomycin and penicillin for 4 days (n = 6-8) to reduce the abundance of their gut flora, or normal drinking water (controls, n = 6-8). They underwent lymph fistula surgery and after an overnight recovery were given an intraduodenal bolus of intralipid. We collected intestinal tissues and lymph fluid and assessed activation of MMCs, intestinal permeability, and fat transport parameters. Compared with controls, intestinal lymph from rats given antibiotics had reduced levels of mucosal mast cell protease II (produced by MMCs) and decreased activity of diamine oxidase (produced by enterocytes) (P < .05). Rats given antibiotics had reduced intestinal permeability in response to dietary lipid compared with controls (P < .01). Unexpectedly, antibiotics also reduced lymphatic transport of triacylglycerol and phospholipid (P < .01), concomitant with decreased levels of mucosal apolipoproteins B, A-I, and A-IV (P < .01). No differences were found in intestinal motility or luminal pancreatic lipase activity between rats given antibiotics and controls. These effects were not seen with an acute dose of antibiotics or 4 weeks after the antibiotic regimen ended. The intestinal microbiota appears to activate MMCs after the ingestion of fat in rats; this contributes to fat-induced intestinal permeability. We found that the gut microbiome promotes absorption of lipid, probably by intestinal production of apolipoproteins and secretion of chylomicrons. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  14. Effects of a mixture of pesticides on the adult female reproductive system of Sprague-Dawley, Wistar, and Lewis rats.

    PubMed

    Pascotto, Viviane M; Guerra, Marina T; Franci, Janete Aparecida Anselmo; de Camargo, João Lauro V; Kempinas, Wilma G; Franchi, Carla A S

    2015-01-01

    The Brazilian federal government Agency for Health Surveillance detected pesticide residues in fresh food available for consumers all over the country. The current study investigated the effects of a mixture of some of those pesticides (dichlorvos, dicofol, dieldrin, endosulfan, and permethrin) on the reproductive system of Sprague-Dawley (SD), Wistar (WT), and Lewis (LEW) rats. Female rats from each strain were randomized into three experimental groups and were fed a control diet or diets added with pesticides mixture at their respective no-observed-effect level (NOEL)/no-observed-adverse-effect level (NOAEL) (low dose) (mg/kg/d): dichlorvos (0.23), dicofol (0.5), dieldrin (0.025), endosulfan (0.7), permethrin (5), or lowest-observed-effect level (LOEL)/lowest-effect level (LEL)/ lowest-observed-adverse-effect level (LOAEL) (toxically effective dose) (mg/kg/d): dichlorvos (2.3), dicofol (2.1), dieldrin (0.05), endosulfan (3.8), and permethrin (25) as reported in the literature. Euthanasia was performed between wk 10 and 12, during the estrous stage. Decreased body weights gain (SD and WT) and increased liver weights (SD, WT, and LEW) were observed in each strain fed the pesticides mixture at the higher levels. At that dose level, rat strains also varied in their responses regarding the estrous cycle, hormonal levels, and number of developing ovarian follicles. The studied mixture of pesticides was found to interfere with the female reproductive system when individual pesticides were mixed above a certain level, indicating a threshold exists for each of the strains studied.

  15. Gender-modulated endogenous baseline neuropeptide Y Y1-receptor activation in the hindlimb of Sprague-Dawley rats

    PubMed Central

    Jackson, Dwayne N; Milne, Kevin J; Noble, Earl G; Shoemaker, J Kevin

    2005-01-01

    This study examined the effect of neuropeptide Y Y1-receptor blockade both alone, and in interaction with α1-adrenoceptor antagonism, on basal hindlimb vascular conductance in male and female Sprague-Dawley rats. Hindlimb vascular conductance was measured during infusion of BIBP3226 (Y1-receptor antagonist; 100 μg kg−1), prazosin (α1-receptor antagonist; 20 μg kg−1), and combined blockade. In males, vascular conductance increased 1.1 ± 0.3 μl min−1 mmHg−1 above baseline with BIBP3226, and 2.4 ± 0.4 μl min−1 mmHg−1 above baseline with prazosin (both P < 0.05). The increase in vascular conductance during combined blockade (5.1 ± 0.7 μl min−1 mmHg−1) was greater than the sum of the independent BIBP3226 and prazosin responses (P < 0.05). In females, basal hindlimb vascular conductance was unaffected by Y1-receptor blockade. However, α1-receptor blockade resulted in a 3.5 ± 0.6 μl min−1 mmHg−1 increase in vascular conductance above baseline, which was not different than the combined blockade condition. Males had greater skeletal muscle neuropeptide Y concentration (P < 0.05; ELISA) than females. Furthermore, compared with females, male skeletal muscle contained greater Y1-receptor expression (P < 0.05; Western blot). It was concluded that, under baseline conditions, agonist and receptor-based mechanisms for Y1-receptor dependent control of vascular conductance in skeletal muscle was greater in male versus female rats. PMID:15513938

  16. Wild blueberry (Vaccinium angustifolium) consumption affects the composition and structure of glycosaminoglycans in Sprague-Dawley rat aorta.

    PubMed

    Kalea, Anastasia Z; Lamari, Fotini N; Theocharis, Achilleas D; Cordopatis, Paul; Schuschke, Dale A; Karamanos, Nikos K; Klimis-Zacas, Dorothy J

    2006-02-01

    It has been documented that increased intake of polyphenols may provide protection against coronary heart disease and stroke. Blueberries (Vaccinium angustifolium) are one of the richest sources of antioxidants among fruits and vegetables. Phenolic compounds from berry extracts inhibit human low density lipoprotein and liposome oxidation. Glycosaminoglycans (GAGs) and proteoglycans (PGs) are structural components of aortas with great structural diversity. Their interaction with compounds such as enzymes, cytokines, growth factors, proteins and lipoproteins and their subsequent role in degenerative diseases has been documented. We investigated the effects of a diet rich in blueberries on the content and structure of GAGs. Sprague-Dawley rats were fed either a control (C) or a blueberry (B) diet for 13 weeks. Aortic tissue GAGs were isolated with papain digestion, alkaline borohydride treatment and anion-exchange chromatography. Cellulose acetate electrophoresis and treatment of the fractions with specific lyases revealed the presence of three GAG populations, i.e. hyaluronan (HA), heparan sulfate (HS) and galactosaminoglycans (GalAGs). Disaccharide composition was determined by high-performance capillary electrophoresis following enzymatic degradation. A 13% higher amount of total GAGs in aortas of B-fed rats was attributed to a higher content of GalAGs (67%). Determination of the sulfated disaccharides showed an overall lower concentration of oversulfated disaccharides in both HS and GalAG populations in the aortas of the B group. Our results demonstrate for the first time that a diet rich in blueberries results in structural alterations in rat aortic tissue GAGs. These changes may affect cellular signal transduction pathways and could have major consequences for the biological function of GAG molecules within the vascular environment.

  17. High Fructose Feeding Induces Copper Deficiency in Sprague-Dawley rats: A Novel Mechanism for Obesity Related Fatty Liver

    PubMed Central

    Song, Ming; Schuschke, Dale A; Zhou, Zhanxiang; Chen, Theresa; Pierce, William M.; Wang, Renwei; Johnson, W. Thomas; McClain, Craig J.

    2011-01-01

    Background/Aims Dietary copper deficiency is associated with a variety of manifestations of the metabolic syndrome, including hyperlipidemia and fatty liver. Fructose feeding has been reported to exacerbate complications of copper deficiency. In this study, we investigated whether copper deficiency plays a role in fructose-induced fatty liver and explored the potential underlying mechanism(s). Methods Male weanling Sprague-Dawley rats were fed either an adequate copper or a marginally copper deficient diet for 4 weeks. Deionized water or deionized water containing 30% fructose (w/v) was also given ad lib. Copper and iron status, hepatic injury and steatosis, duodenum copper transporter-1(Ctr-1) were assessed. Results Fructose feeding further impaired copper status and led to iron overload. Liver injury and fat accumulation were significantly induced in marginal copper deficient rats exposed to fructose as evidenced by robust increased plasma aspartate aminotransferase (AST) and hepatic triglyceride. Hepatic carnitine palmitoyl-CoA transferase I (CPT I) expression was significantly inhibited, whereas hepatic fatty acid synthase (FAS) was markedly up-regulated in marginal copper deficient rats fed with fructose. Hepatic antioxidant defense system was suppressed and lipid peroxidation was increased by marginal copper deficiency and fructose feeding. Moreover, duodenum Ctr-1 expression was significantly increased by marginal copper deficiency, whereas this increase was abrogated by fructose feeding. Conclusion Our data suggest that high fructose-induced nonalcoholic fatty liver disease (NAFLD) may be due, in part, to inadequate dietary copper. Impaired duodenum Ctr1 expression seen in fructose feeding may lead to decreased copper absorption, and subsequent copper deficiency. PMID:21781943

  18. 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

  19. High-fat diet-induced obesity Rat model: a comparison between Wistar and Sprague-Dawley Rat

    PubMed Central

    Marques, Cláudia; Meireles, Manuela; Norberto, Sónia; Leite, Joana; Freitas, Joana; Pestana, Diogo; Faria, Ana; Calhau, Conceição

    2016-01-01

    ABSTRACT In the past decades, obesity and associated metabolic complications have reached epidemic proportions. For the study of these pathologies, a number of animal models have been developed. However, a direct comparison between Wistar and Sprague-Dawley (SD) Rat as models of high-fat (HF) diet-induced obesity has not been adequately evaluated so far. Wistar and SD rats were assigned for 2 experimental groups for 17 weeks: standard (St) and high-fat (HF) diet groups. To assess some of the features of the metabolic syndrome, oral glucose tolerance tests, systolic blood pressure measurements and blood biochemical analysis were performed throughout the study. The gut microbiota composition of the animals of each group was evaluated at the end of the study by real-time PCR. HF diet increased weight gain, body fat mass, mesenteric adipocyte's size, adiponectin and leptin plasma levels and decreased oral glucose tolerance in both Wistar and SD rats. However, the majority of these effects were more pronounced or earlier detected in Wistar rats. The gut microbiota of SD rats was less abundant in Bacteroides and Prevotella but richer in Bifidobacterium and Lactobacillus comparatively to the gut microbiota of Wistar rats. Nevertheless, the modulation of the gut microbiota by HF diet was similar in both strains, except for Clostridium leptum that was only reduced in Wistar rats fed with HF diet. In conclusion, both Wistar and SD Rat can be used as models of HF diet-induced obesity although the metabolic effects caused by HF diet seemed to be more pronounced in Wistar Rat. Differences in the gut microbial ecology may account for the worsened metabolic scenario observed in Wistar Rat. PMID:27144092

  20. A 3D map of the hindlimb motor representation in the lumbar spinal cord in Sprague Dawley rats

    NASA Astrophysics Data System (ADS)

    Borrell, Jordan A.; Frost, Shawn B.; Peterson, Jeremy; Nudo, Randolph J.

    2017-02-01

    Objective. Spinal cord injury (SCI) is a devastating neurological trauma with a prevalence of about 282 000 people living with an SCI in the United States in 2016. Advances in neuromodulatory devices hold promise for restoring function by incorporating the delivery of electrical current directly into the spinal cord grey matter via intraspinal microstimulation (ISMS). In such designs, detailed topographic maps of spinal cord outputs are needed to determine ISMS locations for eliciting hindlimb movements. The primary goal of the present study was to derive a topographic map of functional motor outputs in the lumbar spinal cord to hindlimb skeletal muscles as defined by ISMS in a rat model. Approach. Experiments were carried out in nine healthy, adult, male, Sprague Dawley rats. After a laminectomy of the T13-L1 vertebrae and removal of the dura mater, a four-shank, 16-channel microelectrode array was inserted along a 3D (200 µm) stimulation grid. Trains of three biphasic current pulses were used to determine evoked movements and electromyographic (EMG) activity. Via fine wire EMG electrodes, stimulus-triggered averaging (StTA) was used on rectified EMG data to determine response latency. Main results. Hindlimb movements were elicited at a median current intensity of 6 µA, and thresholds were significantly lower in ventrolateral sites. Movements typically consisted of whole leg, hip, knee, ankle, toe, and trunk movements. Hip movements dominated rostral to the T13 vertebral segment, knee movements were evoked at the T13-L1 vertebral junction, while ankle and digit movements were found near the rostral L1 vertebra. Whole leg movements spanned the entire rostrocaudal region explored, while trunk movements dominated medially. StTAs of EMG activity demonstrated a latency of ~4 ms. Significance. The derived motor map provides insight into the parameters needed for future neuromodulatory devices.

  1. 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.

  2. 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

  3. Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats

    PubMed Central

    Zhang, Xiaofang; Zhang, Xiaodong; Yuan, Bojun; Ren, Lijun; Zhang, Tianbao; Lu, Guocai

    2016-01-01

    Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD) rats was identified. Dogs and rats received HZ1006 orally (0–80 and 0–120 mg/kg/day, respectively) on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006’s NOAEL (No Observed Adverse Effect Level) by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies. PMID:27916918

  4. 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

  5. Evaluation of N-butylbenzenesulfonamide (NBBS) neurotoxicity in Sprague-Dawley male rats following 27-day oral exposure.

    PubMed

    Rider, C V; Janardhan, K S; Rao, D; Morrison, J P; McPherson, C A; Harry, G J

    2012-12-01

    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 400mg/kg/d) via oral gavage (5 ml/kg bwt) daily/5d/week for 27 d. Deaths were observed in the 400mg/kg/d dose group in the first 5d 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. Published by Elsevier B.V.

  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. Immune function is not impaired in Sprague-Dawley rats exposed to dimethyltin dichloride (DMTC) during development or adulthood.

    PubMed

    DeWitt, Jamie C; Copeland, Carey B; Luebke, Robert W

    2007-04-11

    Organotins are used commercially as pesticides, antifouling agents and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted butyltins, used in PVC pipe production, are of concern to the US EPA because they leach from supply pipes into drinking water and are reported multisystem toxicants. We assessed several immune functions in Sprague-Dawley rats after adult or developmental dimethyltin dichloride (DMTC) exposure because various organotins have been reported to be immunotoxic. Adult male and female rats were given drinking water containing 0, 20 or 40 mg DMTC/L (0, 1.7, or 3.4 mg DMTC/kg body weight [BW]) for 28 days. Pregnant females were given the same DMTC drinking water concentrations for a total of 37 days, from gestational day (GD) six through weaning of pups (0, 2.4, or 4.6 mg DMTC/kg BW during gestational exposure; 0, 3.6, or 6.9 mg DMTC/kg BW during postnatal exposure). On postnatal day (PND) two, litters were sexed, weighed, and culled to four males and four females per dam. Delayed-type hypersensitivity (DTH), antibody synthesis, and natural killer (NK) cell activity were evaluated in adults (N=8/sex/group) and in immunologically mature offspring (N=6/sex/group). Although water consumption was decreased in all of the DMTC dose groups, the immune functions evaluated were not affected. Our data suggest that these immune functions are not sensitive to the levels of DMTC anticipated to occur in drinking water delivered via PVC pipe as the concentrations we used were several orders of magnitude higher than those expected to leach from PVC pipes.

  8. Single Intramuscular-dose Toxicity of Water soluble Carthmi-Flos herbal acupuncture (WCF) in Sprague-Dawley Rats

    PubMed Central

    Lee, Hyung-geol; Kim, Sungchul; Jung, Da-jung; Choi, Yoo-min; Sin, Min-seop; Choi, Seok-Woo; Song, Beom-yong; Kim, Jong-uk; Hong, Seung-won; Yook, Tae-han

    2014-01-01

    Objectives: This experiment was conducted to examine the toxicity of Water soluble Carthmi-Flos herbal acupuncture (WCF) by administering a single intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and to find the lethality dose for WCF. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices under a request by the Korean Pharmacopuncture Institute. This experiment was performed based on the testing standards of “Toxicity Test Standards for Drugs” by the Ministry of Food and Drug Safety. Subjects were divided into 4 groups: 1 control group in which normal saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was administered; a single intramuscular dose was injected into 5 males and 5 females in each group. General symptoms and body weights were observed/measured for 14 days after injection. At the end of the observation period, hematological and clinical chemistry tests were performed, followed by necropsy and histopathological examinations of the injected sections. Results: No mortalities were observed in any group. Also, symptoms, body weight, hematology, clinical chemistry and necropsy were not affected. However, histopathological examination of the injected part in one female in the 1.0-mL group showed infiltration of mononuclear cells and a multi-nucleated giant cell around eosinophilic material. Conclusion: Administration of single intramuscular doses of WCF in 3 groups of rats showed that the approximate lethal dose of WCF for all rats was in excess of 1.0 mL, as no mortalities were observed for injections up to and including 1.0 mL. PMID:25780687

  9. Association of elevated blood pressure and impaired vasorelaxation in experimental Sprague-Dawley rats fed with heated vegetable oil

    PubMed Central

    2010-01-01

    Background Poor control of blood pressure leads to hypertension which is a major risk factor for development of cardiovascular disease. The present study aimed to explore possible mechanisms of elevation in blood pressure following consumption of heated vegetable oil. Methods Forty-two male Sprague-Dawley rats were equally divided into six groups: Group I (control) - normal rat chow, Group II - fresh soy oil, Group III - soy oil heated once, Group IV - soy oil heated twice, Group V - soy oil heated five times, Group VI - soy oil heated ten times. Blood pressure was measured at the baseline level and at a monthly interval for six months. Plasma nitric oxide, heme oxygenase and angiotensin-converting enzyme levels were measured prior to treatment, at month-three and month-six later. At the end of treatment, the rats were sacrificed and thoracic aortas were taken for measurement of vascular reactivity. Results Blood pressure increased significantly (p < 0.01) in the repeatedly heated oil groups compared to the control and fresh soy oil groups. Consumption of diet containing repeatedly heated oil resulted higher plasma angiotensin-converting enzyme level and lower nitric oxide content and heme oxygenase concentration. Reheated soy oil groups exhibited attenuated relaxation in response to acetylcholine or sodium nitroprusside, and greater contraction to phenylephrine. Conclusion As a result of consumption of repeatedly heated soy oil, an elevation in blood pressure was observed which may be due to the quantitative changes in endothelium dependent and independent factors including enzymes directly involved in the regulation of blood pressure. PMID:20573259

  10. Alterations in endocrine responses in male Sprague-Dawley rats following oral administration of methyl tert-butyl ether.

    PubMed

    Williams, T M; Cattley, R C; Borghoff, S J

    2000-03-01

    Methyl tert-butyl ether (MTBE) is an oxygenated fuel additive used to decrease carbon monoxide emissions during combustion. MTBE is a nongenotoxic chemical that induces Leydig cell tumors (LCT) in male rats. The mechanism of MTBE-induced LCT is not known; however, LCT induced by other nongenotoxic chemicals have been associated with the disruption of the hypothalamus-pituitary-testicular (HPT) axis. The objective of this study was to determine whether MTBE functions as an endocrine-active compound by affecting levels of specific hormones involved in the maintenance of the HPT axis. Nine-week-old male Sprague-Dawley rats were administered MTBE by gavage at 0, 250, 500, 1000, or 1500 mg MTBE/kg/day for 15 or 28 consecutive days and sacrificed 1 h following the last dose. Relative testis weights were increased only in high-dose animals treated for 28 days, and no testicular lesions were observed at any dose level. Adrenal gland, liver, and kidney weights were also increased. Histologic changes included protein droplet nephropathy of the kidney and centrilobular hypertrophy of the liver. Interstitial fluid and serum testosterone levels as well as serum prolactin levels were decreased only in animals treated with 1500 mg MTBE/kg/day for 15 days. At 28 days, serum triiodothyronine (T3) was significantly decreased at 1000 and 1500 mg MTBE/kg/day compared to control animals, and a decrease in serum luteinizing hormone and dihydrotestosterone was observed at 1500 mg MTBE/kg/day. These results indicate that MTBE causes mild perturbations in T3 and prolactin; however, the changes in testosterone and LH levels did not fit the pattern caused by known Leydig cell tumorigens.

  11. Evaluation of the chronic toxicity and carcinogenicity of perfluorohexanoic acid (PFHxA) in Sprague-Dawley rats.

    PubMed

    Klaunig, James E; Shinohara, Motoki; Iwai, Hiroyuki; Chengelis, Christopher P; Kirkpatrick, Jeannie B; Wang, Zemin; Bruner, Richard H

    2015-02-01

    Perfluorohexanoic acid (PFHxA), a 6-carbon perfluoroalkyl (C6; CAS # 307-24-4), has been proposed as a replacement for the commonly used 8-carbon perfluoroalkyls: perfluorooctanoic acid and perfluorooctane sulfonate. PFHxA is not currently a commercial product but rather the ultimate degradation product of C6 fluorotelomer used to make C6 fluorotelomer acrylate polymers. It can be expected that, to a greater or lesser extent, the environmental loading of PFHxA will increase, as C6 fluorotelomer acrylate treatments are used and waste is generated. This article reports on a chronic study (duration 104 weeks) that was performed to evaluate the possible toxicologic and carcinogenic effects of PFHxA in gavage (daily gavage, 7 days per week) treated male and female Sprague-Dawley (SD) rats. In the current study, dosage levels of 0, 2.5, 15, and 100 mg/kg/day of PFHxA (males) and 5, 30, and 200 mg/kg/day of PFHxA (females) were selected based on a previous subchronic investigation. No effects on body weights, food consumption, a functional observational battery, or motor activity were observed after exposure to PFHxA. While no difference in survival rates in males was seen, a dose-dependent decrease in survival in PFHxA-treated female rats was observed. Hematology and serum chemistry were unaffected by PFHxA. PFHxA-related histologic changes were noted in the kidneys of the 200-mg/kg/day group females. Finally, there was no evidence that PFHxA was tumorigenic in male or female SD rats at any of the dosage levels examined.

  12. Metabolism of 5-(glutathion-S-yl)-alpha-methyldopamine following intracerebroventricular administration to male Sprague-Dawley rats.

    PubMed

    Miller, R T; Lau, S S; Monks, T J

    1995-01-01

    5-(Glutathion-S-yl)-alpha-methyldopamine [5-(GSyl)-alpha-MeDA] is a putative metabolite of the serotonergic neurotoxicants 3,4-(+/-)-(methylenedioxy)amphetamine and 3,4-(+/-)-(methylenedioxy)methamphetamine. Glutathione (GSH) conjugates of several polyphenols are biologically (re)active. Therefore, as part of our studies on the role of 5-(GSyl)-alpha-MeDA in MDA-mediated neurotoxicity, we determined the regional brain metabolism of 5-(GSyl)-alpha-MeDA (720 nmol) following intracerebroventricular administration to male Sprague-Dawley rats. 5-(GSyl)-alpha-MeDA was rapidly cleared from all brain regions examined, and regional differences in the distribution of gamma-glutamyl transpeptidase (gamma-GT) correlated with the formation of 5-(cystein-S-yl)-alpha-methyldopamine (5-[CYS]-alpha-MeDA). We also observed the formation of 5-(N-acetyl-L-cystein-S-yl)-alpha-MeDA (5-[NAC]-alpha-MeDA) in all brain regions, indicating that the brain has the ability to synthesize mercapturic acids. Peak concentrations of 5-(NAC)-alpha-MeDA were found in the order: hypothalamus > midbrain/diencephalon/telencephalon > pons/medulla > hippocampus > cortex > striatum. In contrast to 5-(GSyl)-alpha-MeDA and 5-(CYS)-alpha-MeDA, 5-(NAC)-alpha-MeDA was eliminated relatively slowly from the brain. Differences were also found in cystein conjugate N-acetyltransferase activity in microsomes prepared from the various brain regions, but little difference was observed in brain cytosolic N-acetyl-L-cysteine conjugate N-deacetylase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Effect of different spectral transmittances through tinted animal cages on circadian metabolism and physiology in Sprague-Dawley rats.

    PubMed

    Wren, Melissa A; Dauchy, Robert T; Hanifin, John P; Jablonski, Michael R; Warfield, Benjamin; Brainard, George C; Blask, David E; Hill, Steven M; Ooms, Tara G; Bohm, Rudolf P

    2014-01-01

    The suprachiasmatic nucleus is synchronized by the light:dark cycle and is the master biologic clock that serves as a pacemaker to regulate circadian rhythms. We explored the hypothesis that spectral transmittance (tint) of light through caging alters circadian rhythms of endocrine and metabolic plasma constituents in nonpigmented Sprague-Dawley rats. Rats (Crl:SD; n = 12 per group) were housed in a 12:12-h light:dark environment (300 lx; 123.0 μ W/cm(2); lights on, 0600) in either clear-, amber-, blue-, or red-tinted rodent cages. Blood was collected at 0400, 0800, 1200, 1600, 2000, and 2400 and measured for melatonin, total fatty acids, pH, glucose, lactic acid, corticosterone, insulin, and leptin. As expected, plasma melatonin levels were low during the light phase but higher during the dark phase in all groups; however, when compared with the clear-cage group, rats in amber-, blue-, and red-tinted cages had 29%, 74%, and 48%, respectively, greater total daily melatonin levels due to an increased duration and, in some cases, amplitude of the nocturnal melatonin signal. No differences were found in dietary and water intake, body growth rates, total fatty acids, pH, or glucose among groups. Disruptions in circadian rhythms, manifesting as alterations in phase timing, amplitude, or duration, occurred in the melatonin, lactic acid, corticosterone, insulin, and leptin levels of rats in tinted compared with clear cages. Therefore, the use of variously tinted animal cages significantly alters circadian rhythms in plasma measures of metabolism and physiology in laboratory rats, thus potentially altering the outcomes of scientific investigations.

  14. 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

  15. Fermented soybean product (Cheonggukjang) improved some attributes of protein and growth hormone measurements in Sprague-Dawley rats.

    PubMed

    Hwang, In Sik; Kim, Ji Eun; Lee, Young Ju; Kwak, Moon Hwa; Go, Jun; Son, Hong Joo; Kim, Dong Sup; Hwang, Dae Youn

    2014-04-01

    We hypothesized that the administration of Cheonggukjang (CKJ) would exert positive effects on factors implicated with growth in Sprague-Dawley (SD) rats. To test this hypothesis, we measured specific aspects of bone and organ growth in male SD rats that were treated for 6 weeks with 3 concentrations of CKJ. Although the CKJ extract contained high concentrations of flavonoids and phenolic compounds, no significant differences in body length, organ weights, or femur weight were detected between the CKJ- and vehicle-treated groups. However, thicknesses of the epiphyseal growth plate in the proximal femoral epiphysis and the compact bone in the linea aspera were broadest in the femur of the 2 CKJ-treated groups when compared with the vehicle-treated groups. Furthermore, the levels of growth hormone (GH) and calcium ion were higher in the sera of the high-concentration CKJ-treated groups, whereas the expression level of GH receptor was higher in muscle tissue of all CKJ-treated groups and in the liver tissue of the high-concentration CKJ-treated group. In the GH receptor downstream signaling pathway, the phosphorylation levels of Akt and Erk were expressed differently between liver and muscle tissues upon CKJ treatment. However, the phosphorylation level of STAT5 was very similar to the expression level of the GH receptor in all CKJ-treated groups. These results indicate that CKJ extract may increase the thickness of the epiphyseal growth plate and the compact bone of the femur, elevate GH secretion, and stimulate regulation of the GH receptor downstream signaling pathway in the liver and muscle tissues of SD rats.

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

    PubMed Central

    Hooper, J. S.; Hadley, S. H.; Morris, K. F.; Breslin, J. W.; Dean, J. B.

    2015-01-01

    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

  17. Safety evaluation of Astragalus extract mixture HT042 and its constituent herbs in Sprague-Dawley rats.

    PubMed

    Song, Jungbin; Lee, Donghun; Min, Byoungjae; Bae, Jin-Sook; Chang, Gyu Tae; Kim, Hocheol

    2017-08-15

    Astragalus extract mixture HT042 is a combination of three standardized extracts from Astragalus membranaceus root, Eleutherococcus senticosus stem, and Phlomis umbrosa root, which has proven to stimulate children's height growth. The aim of this study was to demonstrate the safety of HT042 and its three constituent herbs when administered orally. Acute and sub-chronic oral toxicity studies were conducted using male and female Sprague-Dawley rats. In the acute toxicity study, HT042 and each of the herbs was administered at single doses of up to 5000 mg/kg. In the 13-week sub-chronic toxicity study, HT042 was administered at repeated doses of up to 4000 mg/kg/day. In the acute toxicity study of HT042 and each of the herbs, no deaths occurred and there was no indication of toxicity, on the basis of clinical signs, body weight, and necropsy findings. In the sub-chronic toxicity study of HT042, there were no deaths and no changes in clinical signs or the findings of ophthalmic examinations. Although there were some treatment-related changes in other findings, these alterations were not considered toxicologically significant because they remained within normal ranges or recovered during the recovery period. The oral approximate lethal doses of HT042 and each of the herbs were > 5000 mg/kg, and the no-observed-adverse-effect level of HT042 was 4000 mg/kg/day in male and female rats. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Vascular endothelial growth factor receptor inhibitor enhances dietary salt-induced hypertension in Sprague-Dawley rats.

    PubMed

    Gu, Jian-Wei; Manning, R Davis; Young, Emily; Shparago, Megan; Sartin, Brandi; Bailey, Amelia Purser

    2009-07-01

    Clinical evidence links the inhibition of VEGF to hypertension. However, the mechanisms by which VEGF affects the pathogenesis of hypertension remain in question. We determined 1) whether administration of VEGF receptor inhibitor SU5416 enhances dietary salt-induced hypertension in Sprague-Dawley (SD) rats, and 2) whether VEGF or SU5416 directly affects proliferation of cultured human renal proximal tubular epithelial cells (HRPTEC) and endothelial nitric oxide synthase (eNOS) expression in cultured human glomerular microvessel endothelial cells (HGMEC). Ten 10-wk-old male SD rats received a high sodium diet (HS; 8%) and the other 10 SD rats received a normal sodium diet (NS; 0.5%) for 4 wks. After 2 wks of the dietary program, five rats were administered with SU5416 at 10 mg x kg(-1) x day(-1) ip or DMSO (vehicle) for 14 days in HS and NS groups. Mean arterial pressure was significantly higher in rats treated with SU5416, as opposed to those treated with DMSO and fed with HS for 4 wk (157.6 +/- 3.9 vs. 125.9 +/- 4.3 mmHg, P < 0.01). Increased proteinuria and albuminuria were associated with marked renal histological abnormalities in HS group with SU5416 administration, compared with those in the vehicle HS group. 3H-thymidine incorporation assay showed that SU5416 blocked the actions of both exogenous and endogenous VEGF on the proliferation of HRPTEC. VEGF (10 ng/ml) significantly increased eNOS protein levels by 29% in cultured HGMEC, but its action was completely abolished by SU5416. These results suggest that VEGF receptor inhibition enhances dietary salt-induced hypertension and kidney injury, possibly by direct damage on renal cells and decreasing NO production by eNOS.

  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. Impact of low dose prenatal ethanol exposure on glucose homeostasis in Sprague-Dawley rats aged up to eight months.

    PubMed

    Probyn, Megan E; Parsonson, Kylie R; Gårdebjer, Emelie M; Ward, Leigh C; Wlodek, Mary E; Anderson, Stephen T; Moritz, Karen M

    2013-01-01

    Excessive exposure to alcohol prenatally has a myriad of detrimental effects on the health and well-being of the offspring. It is unknown whether chronic low-moderate exposure of alcohol prenatally has similar and lasting effects on the adult offspring's health. Using our recently developed Sprague-Dawley rat model of 6% chronic prenatal ethanol exposure, this study aimed to determine if this modest level of exposure adversely affects glucose homeostasis in male and female offspring aged up to eight months. Plasma glucose concentrations were measured in late fetal and postnatal life. The pancreas of 30 day old offspring was analysed for β-cell mass. Glucose handling and insulin action was measured at four months using an intraperitoneal glucose tolerance test and insulin challenge, respectively. Body composition and metabolic gene expression were measured at eight months. Despite normoglycaemia in ethanol consuming dams, ethanol-exposed fetuses were hypoglycaemic at embryonic day 20. Ethanol-exposed offspring were normoglycaemic and normoinsulinaemic under basal fasting conditions and had normal pancreatic β-cell mass at postnatal day 30. However, during a glucose tolerance test, male ethanol-exposed offspring were hyperinsulinaemic with increased first phase insulin secretion. Female ethanol-exposed offspring displayed enhanced glucose clearance during an insulin challenge. Body composition and hepatic, muscle and adipose tissue metabolic gene expression levels at eight months were not altered by prenatal ethanol exposure. Low-moderate chronic prenatal ethanol exposure has subtle, sex specific effects on glucose homeostasis in the young adult rat. As aging is associated with glucose dysregulation, further studies will clarify the long lasting effects of prenatal ethanol exposure.

  1. 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

  2. The influence of red light exposure at night on circadian metabolism and physiology in Sprague-Dawley rats.

    PubMed

    Dauchy, Robert T; Wren, Melissa A; Dauchy, Erin M; Hoffman, Aaron E; Hanifin, John P; Warfield, Benjamin; Jablonski, Michael R; Brainard, George C; Hill, Steven M; Mao, Lulu; Dobek, Georgina L; Dupepe, Lynell M; Blask, David E

    2015-01-01

    Early studies on rodents showed that short-term exposure to high-intensity light (> 70 lx) above 600 nm (red-appearing) influences circadian neuroendocrine and metabolic physiology. Here we addressed the hypothesis that long-term, low-intensity red light exposure at night (rLEN) from a 'safelight' emitting no light below approximately 620 nm disrupts the nocturnal circadian melatonin signal as well as circadian rhythms in circulating metabolites, related regulatory hormones, and physi- ologic parameters. Male Sprague-Dawley rats (n = 12 per group) were maintained on control 12:12-h light:dark (300 lx; lights on, 0600) or experimental 12:12 rLEN (8.1 lx) lighting regimens. After 1 wk, rats underwent 6 low-volume blood draws via cardiocentesis (0400, 0800, 1200, 1600, 2000, and 2400) over a 4-wk period to assess arterial plasma melatonin, total fatty acid, glucose, lactic acid, pO2, pCO2, insulin, leptin and corticosterone concentrations. Results revealed plasma melatonin levels (mean ± 1 SD) were high in the dark phase (197.5 ± 4.6 pg/mL) and low in the light phase (2.6 ± 1.2 pg/mL) of control condi- tions and significantly lower than controls under experimental conditions throughout the 24-h period (P < 0.001). Prominent circadian rhythms of plasma levels of total fatty acid, glucose, lactic acid, pO2, pCO2, insulin, leptin, and corticosterone were significantly (P < 0.05) disrupted under experimental conditions as compared with the corresponding entrained rhythms under control conditions. Therefore, chronic use of low-intensity rLEN from a common safelight disrupts the circadian organization of neuroendocrine, metabolic, and physiologic parameters indicative of animal health and wellbeing.

  3. Endothelin-like action of Pausinystalia yohimbe aqueous extract on vascular and renal regional hemodynamics in Sprague Dawley rats.

    PubMed

    Ajayi, A A; Newaz, M; Hercule, H; Saleh, M; Bode, C O; Oyekan, A O

    2003-12-01

    The bark of the African tree Pausinystalia yohimbe has been used as a food additive with aphrodisiac and penile erection enhancing properties. The effect of an aqueous extract of P. yohimbe (CCD-X) on renal circulation was assessed in order to test the hypothesis that it possesses additional effects on nitric oxide production and/or endothelin-1 (ET-1)-like actions. In vivo studies with CCD-X in Sprague Dawley rats demonstrated a dose-dependent (1-1000 ng/kg) increase in mean blood pressure (p < 0.001) and an increase in medullary blood flow (MBF) (p < 0.001). Both the pressor action and renal medullary vasodilation were blocked by endothelinA (ETA) receptor antagonist BMS182874 and endothelinB (ETB) receptor antagonist BQ788 in combination. L-Nomega-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg) also inhibited the increase in MBF induced by CCD-X. In vitro studies in isolated perfused kidney and in pressurized renal microvessels confirmed the dose-dependent vasoconstrictor action of this extract. ETA receptor antagonist BQ610 and ETB receptor antagonist BQ788 separately and significantly attenuated the renal vasoconstrictor actions of the extract (p < 0.001 ANOVA). These preliminary observations indicate that, in addition to the alpha-adrenergic antagonist actions that characterize yohimbine, CCD-X possesses endothelin-like actions and affects nitric oxide (NO) production in renal circulation. These findings suggest a strong possibility of post-receptor cross-talk between alpha2-adrenoceptors and endothelin, as well as a direct effect of alpha2-adrenoceptors on renal NO production.

  4. Establishment of a highly metastatic buccal squamous cell carcinoma cell line from a Sprague-Dawley Rat.

    PubMed

    Qin, Xing; Yan, Ming; Zhang, Jianjun; Xu, Qin; Lv, Zhongjing; Chen, Wantao

    2016-02-01

    The incidence of buccal squamous cell carcinoma (buccal SCC) is considered to be the second highest out of all oral cancers, but the unsatisfactory in vivo tumorigenicity and metastatic potential of the widely used cell lines have greatly delayed studies on the mechanisms of tumor progression. This study aimed to establish a highly metastatic buccal SCC cell line, which may serve a useful tool in buccal SCC research. Buccal SCC was induced by 4-nitroquinoline-1-oxide (4NQO) in Sprague-Dawley rats. The cancer samples were collected, and the tumor cells were purified in vitro. A highly aggressive cell line termed "Rca-B" was established by an invasion assay. Its proliferative ability, cell cycle distribution, baseline level of apoptosis, carcinogenicity and metastatic behavior in nude mice were investigated. To date, Rca-B cells have been stably cultured in vitro for more than 180 passages. These cells were polygonal or spindle-shaped, grew adhesively, and exhibited a stable epithelial phenotype as characterized by positive expression of cytokeratin. The population doubling time was 25.09 h. Cells in S-phase of the cell cycle accounted for 31.17% of the total number of cells, and the baseline level of apoptosis was 8.52%. The in vitro migration and invasion assays revealed highly aggressive features of Rca-B cells. In addition, the rate of xenograft formation was 100%, and the incidence of experimental lung metastasis was 81.8% in immunodeficient nude mice. The Rca-B cell line was established as a highly metastatic rat buccal SCC cell line, and its in-depth characterization, which includes malignant behaviors, allows for a wealth of functional studies on the molecular mechanisms of buccal SCC progression and targeted therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. 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.

  6. A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

    PubMed Central

    Kim, Jinhee; Lee, Jongcheol; Kim, Sungchul

    2015-01-01

    Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur). Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP) regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD) rats. The 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 super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018). Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence. PMID:26392913

  7. Combining Sprague-Dawley rat uterus cell membrane chromatography with HPLC/MS to screen active components from Leonurus artemisia.

    PubMed

    Fan, Jiangbo; Wei, Fen; Zhang, Yu; Su, Hongli; Ji, Zongzheng; He, Jianyu; Han, Shengli

    2016-01-01

    Leonurus artemisia (Lour.) S.Y.Hu (Lamiaceae) (YiMuCao in Chinese) is a traditional Chinese medicine. Leonurus artemisia has been shown to have many pharmacological effects such as increasing uterine contraction amplitude, and tension, but the active components are still unknown. The objective of this study is to determine active components of L. Artemisia that are responsible for the biological activity using HPLC and cell membrane-based system. The whole L. artemisia ethanol extract and its eight fractions were screened using Sprague-Dawley rat uterus cell membrane chromatography (CMC) combined with the HPLC/MS system. Oxytocin was used to investigate the activity of CMC column. The effect of active components screened from L. artemisia was studied by tension measurement of isolated rat uterine strips in vitro at a dose of 10(-7)-10(-4 )mol/L with oxytocin as a control. The acetone extract showed obvious activity when compared with the eight extracts of L. artemisia. From the acetone extract, in the negative ionization mode, the active compound was identified as genkwanin, with a molecular weight of 283. In vitro pharmacological experiments proved that genkwanin promoted uterine contractions at a dose from 10(-7) to 10(-4 )mol/L. The EC50 value was 4.86 ± 4.21 μmol/L for genkwanin and 4.30 ± 3.65 μmol/L for oxytocin on the contractile amplitude of uterine strips isolated from rats. Genkwanin was identified as the active compound in L. artemisia by this method. In vitro pharmacological experiments proved that genkwanin promoted uterine contractions. Genkwanin may be used to uterine inertia and may have an effect on postpartum hemorrhage.

  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.

  9. Age-dependent regulation of GABA transmission by kappa opioid receptors in the basolateral amygdala of Sprague-Dawley rats.

    PubMed

    Przybysz, K R; Werner, D F; Diaz, M R

    2017-02-03

    Anxiety disorders are one of the most common and debilitating mental illnesses worldwide. Growing evidence indicates an age-dependent rise in the incidence of anxiety disorders from adolescence through adulthood, suggestive of underlying neurodevelopmental mechanisms. Kappa opioid receptors (KORs) are known to contribute to the development and expression of anxiety; however, the functional role of KORs in the basolateral amygdala (BLA), a brain structure critical in mediating anxiety, particularly across ontogeny, are unknown. Using whole-cell patch-clamp electrophysiology in acute brain slices from adolescent (postnatal day (P) 30-45) and adult (P60+) male Sprague-Dawley rats, we found that the KOR agonist, U69593, increased the frequency of GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in the adolescent BLA, without an effect in the adult BLA or on sIPSC amplitude at either age. The KOR effect was blocked by the KOR antagonist, nor-BNI, which alone did not alter GABA transmission at either age, and the effect of the KOR agonist was TTX-sensitive. Additionally, KOR activation did not alter glutamatergic transmission in the BLA at either age. In contrast, U69593 inhibited sIPSC frequency in the central amygdala (CeA) at both ages, without altering sIPSC amplitude. Western blot analysis of KOR expression indicated that KOR levels were not different between the two ages in either the BLA or CeA. This is the first study to provide compelling evidence for a novel and unique neuromodulatory switch in one of the primary brain regions involved in initiating and mediating anxiety that may contribute to the ontogenic rise in anxiety disorders.

  10. 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.

  11. 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

  12. Dietary Selenium as a Modulator of PCB 126–Induced Hepatotoxicity in Male Sprague-Dawley Rats

    PubMed Central

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

    2011-01-01

    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

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

    PubMed Central

    Broadwater, Margaret; Spear, Linda P.

    2013-01-01

    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 minutes 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 24 hours 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 Exp1, 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. PMID:23810415

  14. High fructose feeding induces copper deficiency in Sprague-Dawley rats: a novel mechanism for obesity related fatty liver.

    PubMed

    Song, Ming; Schuschke, Dale A; Zhou, Zhanxiang; Chen, Theresa; Pierce, William M; Wang, Renwei; Johnson, W Thomas; McClain, Craig J

    2012-02-01

    Dietary copper deficiency is associated with a variety of manifestations of the metabolic syndrome, including hyperlipidemia and fatty liver. Fructose feeding has been reported to exacerbate complications of copper deficiency. In this study, we investigated whether copper deficiency plays a role in fructose-induced fatty liver and explored the potential underlying mechanism(s). Male weanling Sprague-Dawley rats were fed either an adequate copper or a marginally copper deficient diet for 4 weeks. Deionized water or deionized water containing 30% fructose (w/v) was also given ad lib. Copper and iron status, hepatic injury and steatosis, and duodenum copper transporter-1 (Ctr-1) were assessed. Fructose feeding further impaired copper status and led to iron overload. Liver injury and fat accumulation were significantly induced in marginal copper deficient rats exposed to fructose as evidenced by robustly increased plasma aspartate aminotransferase (AST) and hepatic triglyceride. Hepatic carnitine palmitoyl-CoA transferase I (CPT I) expression was significantly inhibited, whereas hepatic fatty acid synthase (FAS) was markedly up-regulated in marginal copper deficient rats fed with fructose. Hepatic antioxidant defense system was suppressed and lipid peroxidation was increased by marginal copper deficiency and fructose feeding. Moreover, duodenum Ctr-1 expression was significantly increased by marginal copper deficiency, whereas this increase was abrogated by fructose feeding. Our data suggest that high fructose-induced nonalcoholic fatty liver disease (NAFLD) may be due, in part, to inadequate dietary copper. Impaired duodenum Ctr-1 expression seen in fructose feeding may lead to decreased copper absorption, and subsequent copper deficiency. Copyright © 2011 European Association for the Study of the Liver. All rights reserved.

  15. Effect of the juice of lime (Citrus aurantifolia) on estrous cycle and ovulation of Sprague-Dawley rats.

    PubMed

    Salawu, Adeola A; Osinubi, Abraham A A; Dosumu, Olufunke O; Kusemiju, Taiwo O; Noronha, Cressie C; Okanlawon, Abayomi O

    2010-01-01

    To determine the effect of lime juice on the estrous cycle and ovulation of cyclic female rats. Twenty-five adult female Sprague-Dawley rats were used. The study was divided into 2 experiments (I and II). In experiment I, 15 rats were randomly subclassified into 3 groups (Ia, Ib, and Ic) of 5 rats each. The estrous cycles of the rats were studied for the first 16 days to establish cyclicity, after which lime juice was administered by gastric gavage for the next 24 days. Rats in group Ia received 1 mL of undiluted lime juice, rats in group Ib received 1 mL of 50% diluted lime juice, and rats in group Ic (control animals) received only distilled water. In experiment II, 10 female rats were used and were categorized into 2 groups (IIa and IIb), with 5 rats in each group. Rats in group IIa received 1 mL of undiluted lime juice during the morning of proestrus, and those in group IIb received only distilled water on the day of proestrus. The rats were killed the next day with use of chloroform anesthesia. The upper parts of the oviducts were excised and examined under the light microscope for assessment of the number of ova shed. There was an irregular pattern in all phases of the estrous cycle of 100% of the rats given undiluted lime juice and in 80% of those given 50% diluted lime juice. There was a significant (P = .001) reduction in the number of ova shed in rats administered undiluted lime juice in comparison with the control animals. Ovulation was partially blocked, as shown by the reduced number of ova observed in the oviducts from the rats given undiluted lime juice (5.10 +/- 2.37) in comparison with the control rats (12.70 +/- 1.14). In rats, lime juice causes irregularity of the estrous cycle, partially blocks ovulation, and may possibly compromise fertility.

  16. 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

  17. Therapeutic Potential of Cerium Oxide Nanoparticles for the Treatment of Peritonitis Induced by Polymicrobial Insult in Sprague-Dawley Rats.

    PubMed

    Manne, Nandini D P K; Arvapalli, Ravikumar; Nepal, Niraj; Thulluri, Srinivasarao; Selvaraj, Vellaisamy; Shokuhfar, Tolou; He, Kun; Rice, Kevin M; Asano, Shinichi; Maheshwari, Mani; Blough, Eric R

    2015-11-01

    Peritonitis is a life-threatening disease that is associated with high mortality. The purpose of this study was to determine if cerium oxide nanoparticles can be used to diminish intra-abdominal infection-induced mortality and systemic inflammatory response syndrome in the laboratory rat. Randomized, controlled animal study and cell culture study. University research laboratory. Male Sprague-Dawley rats aged 12 weeks, RAW 246.7 macrophage cell line. Intra-abdominal infection or peritonitis was induced by intraperitoneal injection of cecal material (600 mg/kg in 5% sterile dextrose water at a dosage of 5 mL/kg) obtained from healthy donors. Rats in control and peritonitis groups received 200 μL of sterile deionized water IV via the tail vein, whereas rats in cerium oxide-only group and peritonitis+cerium oxide group received cerium oxide nanoparticles (0.5 mg/kg) IV at the time of polymicrobial injection. Survival rate was monitored for 14 days, while in other experiments, animals were killed at 3 and 18 hours after induction of peritonitis for biochemical analysis. Administration of a single dose (0.5 mg/kg) of cerium oxide nanoparticles IV to rats in the peritonitis group significantly improved survival rates and functioned to restore core body temperature toward baseline. Treatment-induced increases in animal survivability were associated with reduced systemic and hepatic oxidative stress, diminished serum cytokines, and chemokine levels. Changes in serum inflammatory markers with treatment were accompanied by decreased monocyte and lymphocyte extravasation into the peritoneal cavity along with decreased infiltration of macrophages into liver. In the heart, treatment diminished extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase-Stat-3 signaling and attenuated endothelial expression of P-selectin and vascular cell adhesion molecule-1. Cerium oxide nanoparticles attenuate the systemic inflammatory response associated with peritonitis

  18. Sex differences in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone in the Sprague-Dawley rat.

    PubMed

    Chan, Samuel; Edwards, Stephen R; Wyse, Bruce D; Smith, Maree T

    2008-03-01

    1. The pharmacokinetics and oxidative metabolism of oxycodone were investigated following intravenous and oral administration in male and female Sprague-Dawley (SD) rats. 2. High-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS-MS) was used to quantify plasma concentrations of oxycodone and its oxidative metabolites noroxycodone and oxymorphone following administration of single bolus intravenous (5 mg/kg) and oral (10 mg/kg) doses of oxycodone. 3. The mean (+/-SEM) clearance of intravenous oxycodone was significantly higher in male than female SD rats (4.9 +/- 0.3 vs 3.1 +/- 0.3 L/h per kg, respectively; P < 0.01). Mean areas under the plasma concentration versus time curves (AUC) for oxycodone were significantly higher in female than male SD rats following intravenous (approximately 1.6-fold; P < 0.01) and oral (approximately sevenfold; P < 0.005) administration. 4. The oral bioavailability of oxycodone was low (at 1.2 and 5.0%, respectively) in male and female SD rats, a finding consistent with high first-pass metabolism. Noroxycodone : oxycodone AUC ratios were significantly higher in male than female SD rats after intravenous (approximately 2.4-fold; P < 0.005) and oral (approximately 12-fold; P < 0.005) administration. 5. Circulating oxymorphone concentrations remained very low following both routes of administration. Noroxycodone : oxymorphone AUC ratios were greater in male than female SD rats after intravenous (approximately 13- and fivefold, respectively) and oral (approximately 90- and sixfold, respectively) administration. 6. Sex differences were apparent in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone. Systemic exposure to oxycodone was greater in female compared with male SD rats, whereas systemic exposure to metabolically derived noroxycodone was higher in male than female SD rats. 7. Oral administration of oxycodone to the SD rat is a poor model of the human for

  19. Gadolinium accumulation in organs of Sprague-Dawley® rats after implantation of a biodegradable magnesium-gadolinium alloy.

    PubMed

    Myrissa, Anastasia; Braeuer, Simone; Martinelli, Elisabeth; Willumeit-Römer, Regine; Goessler, Walter; Weinberg, Annelie Martina

    2017-01-15

    Biodegradable magnesium implants are under investigation because of their promising properties as medical devices. For enhancing the mechanical properties and the degradation resistance, rare earth elements are often used as alloying elements. In this study Mg10Gd pins were implanted into Sprague-Dawley® rats. The pin volume loss and a possible accumulation of magnesium and gadolinium in the rats' organs and blood were investigated in a long-term study over 36weeks. The results showed that Mg10Gd is a fast disintegrating material. Already 12weeks after implantation the alloy is fragmented to smaller particles, which can be found within the intramedullary cavity and the cortical bones. They disturbed the bone remodeling until the end of the study. The results concerning the elements' distribution in the animals' bodies were even more striking, since an accumulation of gadolinium could be observed in the investigated organs over the whole time span. The most affected tissue was the spleen, with up to 3240μgGd/kg wet mass, followed by the lung, liver and kidney (up to 1040, 685 and 207μgGd/kg). In the brain, muscle and heart, the gadolinium concentrations were much smaller (less than 20μg/kg), but an accumulation could still be detected. Interestingly, blood serum samples showed no accumulation of magnesium and gadolinium. This is the first time that an accumulation of gadolinium in animal organs was observed after the application of a gadolinium-containing degradable magnesium implant. These findings demonstrate the importance of future investigations concerning the distribution of the constituents of new biodegradable materials in the body, to ensure the patients' safety.

  20. Effect of dietary blueberry pomace on selected metabolic factors associated with high fructose feeding in growing Sprague-Dawley rats.

    PubMed

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

    2012-09-01

    An experiment was conducted to study the protective effect of feeding extruded and unextruded blueberry pomace (BBP) on selected metabolic parameters associated with metabolic syndrome in a model of high fructose (HF)-fed growing Sprague-Dawley rats. Treatments were as follows: (1) control (modified AIN-based diet); (2) HF diet (AIN diet with 58% fructose); (3) HF diet with 1.5% unextruded BBP; (4) HF diet with 1.5% extruded BBP; (5) HF diet with 3% unextruded BBP; and (6) HF diet with 3% extruded BBP. Compared with the control, HF feeding increased fasting plasma insulin and fasting and postprandial plasma triglycerides as well as homeostatic scores of insulin resistance and β-cell function, but not weight gain, diet intake and efficiency, abdominal fat, oral glucose tolerance, and fasting and postprandial plasma glucose, cholesterol, and leptin levels. Inclusion of unextruded or extruded BBP was effective in minimizing or ameliorating the fructose-induced metabolic anomalies, except postprandial plasma triglycerides, especially at 3% of the diet. In addition, unextruded or extruded BBP at 3% of the diet was also able to reduce plasma cholesterol and abdominal fat relative to the HF control, which may impart additional health benefits. Compared with the control, inclusion of unextruded or extruded BBP at both 1.5% and 3% resulted in lower total fat weight, and animals fed a diet supplemented with 3% unextruded BBP in fasting state or 3% unextruded BBP in fed state had lower leptin levels than the control. This is the first study demonstrating the beneficial effects of feeding blueberry pomace on health.

  1. 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.

  2. Effects of chromium nanoparticle dosage on growth, body composition, serum hormones and tissue chromium in Sprague-Dawley rats*

    PubMed Central

    Zha, Long-ying; Xu, Zi-rong; Wang, Min-qi; Gu, Liang-ying

    2007-01-01

    This 6-week study was conducted to evaluate the effects of seven different levels of dietary chromium (Cr) (0, 75, 150, 300, 450, 600, and 1 200 ppb Cr) in the form of Cr nanoparticle (CrNano) on growth, body composition, serum hormones and tissue Cr in Sprague-Dawley (SD) rats. Seventy male SD rats (average initial body weight of (83.2±4.4) g) were randomly assigned to seven dietary treatments (n=10). At the end of the trial, body composition was assessed via dual energy X-ray absorptiometry (DEXA). All rats were then sacrificed to collect samples of blood, organs and tissues for determination of serum hormones and tissue Cr contents. The results indicated that lean body mass was significantly increased (P<0.05) due to the addition of 300 and 450 ppb Cr from CrNano. Supplementation of 150, 300, 450, and 600 ppb Cr decreased (P<0.05) percent body fat significantly. Average daily gain was increased (P<0.05) by addition of 75, 150, and 300 ppb Cr and feed efficiency was increased (P<0.05) by supplementation of 75, 300, and 450 ppb Cr. Addition of 300 and 450 ppb Cr decreased (P<0.05) the insulin level in serum greatly. Cr contents in liver and kidney were greatly increased (P<0.05) by the addition of Cr as CrNano in the dosage of from 150 ppb to 1 200 ppb. In addition, Supplementation of 300, 450, and 600 ppb Cr significantly increased (P<0.05) Cr content in the hind leg muscle. These results suggest that supplemental CrNano has beneficial effects on growth performance and body composition, and increases tissue Cr concentration in selected muscles. PMID:17542060

  3. Combined effects of modafinil and d-amphetamine in male Sprague-Dawley rats trained to discriminate d-amphetamine.

    PubMed

    Quisenberry, Amanda J; Prisinzano, Thomas; Baker, Lisa E

    2013-09-01

    Modafinil is a novel wake-promoting drug with FDA approval for the treatment of sleep-related disorders that has recently been investigated as a potential agonist replacement therapy for psychostimulant dependence. Previous research in animals and humans indicates modafinil has a lower abuse liability than traditional psychostimulants, although few studies have carefully assessed modafinil's stimulus properties in combination with other psychostimulants. The current study trained male Sprague-Dawley rats to discriminate subcutaneous injections of 0.3 mg/kg (n=8) or 1.0 mg/kg d-amphetamine (n=8) from saline under an FR 20 schedule of food reinforcement and substitution tests were administered with d-amphetamine (0.03-1.0 mg/kg, s.c.), modafinil (32-256 mg/kg, i.g.), and a low modafinil dose (32 mg/kg, i.g.) in combination with d-amphetamine (0.03-1.0 mg/kg, s.c.) to determine if these drugs have additive effects. The selective D2 dopamine agonist, PNU-91356A, was also tested as a positive control and ethanol and morphine were tested as negative controls. Results indicate that modafinil produced dose-dependent and statistically significant d-amphetamine-lever responding in both groups and nearly complete substitution in animals trained to discriminate 1.0 mg/kg d-amphetamine. Modafinil pretreatment slightly increased the discrimination of low d-amphetamine doses in animals trained to discriminate 0.3 mg/kg d-amphetamine. These results support previous findings that modafinil and d-amphetamine may have additive effects. In consideration of recent interests in modafinil as an agonist treatment for psychostimulant dependence, additional preclinical investigations utilizing other methodologies to examine modafinil in combination with other stimulants, such as behavioral sensitization paradigms or drug self-administration, may be of interest.

  4. Comprehensive Behavioural Analysis of Long Evans and Sprague-Dawley Rats Reveals Differential Effects of Housing Conditions on Tests Relevant to Neuropsychiatric Disorders

    PubMed Central

    Turner, Karly M.; Burne, Thomas H. J.

    2014-01-01

    Genetic (G) and environmental (E) manipulations are known to alter behavioural outcomes in rodents, however many animal models of neuropsychiatric disorders only use a restricted selection of strain and housing conditions. The aim of this study was to examine GxE interactions comparing two outbred rat strains, which were housed in either standard or enriched cages. The strains selected were the albino Sprague-Dawley rat, commonly used for animal models, and the other was the pigmented Long Evans rat, which is frequently used in cognitive studies. Rats were assessed using a comprehensive behavioural test battery and included well-established tests frequently employed to examine animal models of neuropsychiatric diseases, measuring aspects of anxiety, exploration, sensorimotor gating and cognition. Selective strain and housing effects were observed on a number of tests. These included increased locomotion and reduced pre-pulse inhibition in Long Evans rats compared to Sprague Dawley rats; and rats housed in enriched cages had reduced anxiety-like behaviour compared to standard housed rats. Long Evans rats required fewer sessions than Sprague Dawley rats to learn operant tasks, including a signal detection task and reversal learning. Furthermore, Long Evans rats housed in enriched cages acquired simple operant tasks faster than standard housed Long Evans rats. Cognitive phenotypes in animal models of neuropsychiatric disorders would benefit from using strain and housing conditions where there is greater potential for both enhancement and deficits in performance. PMID:24671152

  5. 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.

  6. 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

  7. Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments.

    PubMed

    Brownlow, Milene L; Jung, Seung H; Moore, Raquel J; Bechmann, Naomi; Jankord, Ryan

    2017-01-01

    Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a) augment cognitive outcomes in healthy subjects; and (b) prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD), ketone supplemented (KS), or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA) axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the control diet group

  8. Nutritional Ketosis Affects Metabolism and Behavior in Sprague-Dawley Rats in Both Control and Chronic Stress Environments

    PubMed Central

    Brownlow, Milene L.; Jung, Seung H.; Moore, Raquel J.; Bechmann, Naomi; Jankord, Ryan

    2017-01-01

    Nutritional ketosis may enhance cerebral energy metabolism and has received increased interest as a way to improve or preserve performance and resilience. Most studies to date have focused on metabolic or neurological disorders while anecdotal evidence suggests that ketosis may enhance performance in the absence of underlying dysfunction. Moreover, decreased availability of glucose in the brain following stressful events is associated with impaired cognition, suggesting the need for more efficient energy sources. We tested the hypotheses that ketosis induced by endogenous or exogenous ketones could: (a) augment cognitive outcomes in healthy subjects; and (b) prevent stress-induced detriments in cognitive parameters. Adult, male, Sprague Dawley rats were used to investigate metabolic and behavioral outcomes in 3 dietary conditions: ketogenic (KD), ketone supplemented (KS), or NIH-31 control diet in both control or chronic stress conditions. Acute administration of exogenous ketones resulted in reduction in blood glucose and sustained ketosis. Chronic experiments showed that in control conditions, only KD resulted in pronounced metabolic alterations and improved performance in the novel object recognition test. The hypothalamic-pituitary-adrenal (HPA) axis response revealed that KD-fed rats maintained peripheral ketosis despite increases in glucose whereas no diet effects were observed in ACTH or CORT levels. Both KD and KS-fed rats decreased escape latencies on the third day of water maze, whereas only KD prevented stress-induced deficits on the last testing day and improved probe test performance. Stress-induced decrease in hippocampal levels of β-hydroxybutyrate was attenuated in KD group while both KD and KS prevented stress effects on BDNF levels. Mitochondrial enzymes associated with ketogenesis were increased in both KD and KS hippocampal samples and both endothelial and neuronal glucose transporters were affected by stress but only in the control diet group

  9. 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

  10. The gastro protective effects of Cibotium barometz hair on ethanol-induced gastric ulcer in Sprague-Dawley rats.

    PubMed

    Al-Wajeeh, Nahla Saeed; Hajerezaie, Maryam; Noor, Suzita Mohd; Halabi, Mohammed Farouq; Al-Henhena, Nawal; Azizan, Ainnul Hamidah Syahadah; Kamran, Sareh; Hassandarvish, Pouya; Shwter, Abdrabuh N; Karimian, Hamed; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen

    2017-01-19

    Cibotium barometz is a medical herb used traditionally in the Malaysian peninsula for several ailments, including gastric ulcer. The aim of this study was assessment the anti-ulcer effects of C. barometz hair on ethanol-induced stomach hemorrhagic abrasions in animals. Seven groups of Sprague Dawley (SD) rats were administered 10% Tween 20 in the normal control and ulcer control groups, and omeprazole 20 mg/kg and 62.5, 125, 250, and 500 mg/kg of C. barometz hair extract in the experimental groups. After 60 min, the normal control group of rats was orally administered 10% Tween 20, while absolute ethanol was orally administered to the groups of ulcer control, omeprazole and experimental groups. Stomachs of the rats were examined macroscopically and histologically. Homogenates of stomachs were used to evaluate endogenous antioxidant enzyme activities. Rats pre-fed with plant extract presented a significant decrease in the sore area, increased pH of gastric contents and preserved stomach wall mucus compared to the ulcer group. Histologically, rats pre-fed with C. barometz hair extract showed mild to moderate disruptions of the surface epithelium while animals pre-fed with absolute ethanol showed severe disruptions of the stomach epithelium with edema and leucocyte penetration of the submucosal layer. A Periodic acid Schiff (PAS) staining revealed that each rat pre-treated with the plant extract displayed an intense uptake of stomach epithelial glycoprotein magenta color compared to the ulcer control group. Immunohistochemical analysis revealed that rats pre-fed with the plant extract showed an up-regulation of the heat shock protein 70 (HSP70) and down-regulation of Bax proteins compared to ulcer control rats. Homogenates of the stomach tissue demonstrated significant increases in the endogenous antioxidant enzymatic activity and decreased lipid peroxidation (MDA) in rats pre-treated with C. barometz hair extract compared with the ulcer control rats. In acute

  11. 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.

  12. 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

  13. 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

  14. 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

  15. Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats

    PubMed Central

    Ari, Csilla; Kovács, Zsolt; Juhasz, Gabor; Murdun, Cem; Goldhagen, Craig R.; Koutnik, Andrew P.; Poff, Angela M.; Kesl, Shannon L.; D’Agostino, Dominic P.

    2016-01-01

    Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE; 1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE; ~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S; ~25 g/kg/day, KS) and βHB-S + medium chain triglyceride (MCT; ~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance traveled in open arms (chronic KS and KSMCT: SPD rats) and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a

  16. The effect of losartan and carvedilol on renal haemodynamics and altered metabolism in fructose-fed Sprague-Dawley rats.

    PubMed

    Abdulla, Mohammed H; Sattar, Munavvar A; Abdullah, Nor A; Johns, Edward J

    2012-09-01

    The aim of this study is to assess the effects of losartan and carvedilol on metabolic parameters and renal haemodynamic responses to angiotensin II (Ang II) and adrenergic agonists in the model of fructose-fed rat. Thirty-six Sprague-Dawley rats were fed for 8 weeks either 20% fructose solution (F) or tap water (C) ad libitum. F or C group received either losartan or carvedilol (10 mg/kg p.o.) daily for the last 3 weeks of the study (FL and L) and (FCV and CV), respectively, then in acute studies the renal vasoconstrictor actions of Ang II, noradrenaline (NA), phenylephrine (PE) and methoxamine (ME) were determined. Data, mean±SEM were analysed using ANOVA with significance at P <0.05. Losartan and carvedilol decreased the area under the glucose tolerance curve of the fructose-fed group. The responses (%) to NA, PE, ME and Ang II in F were lower (P <0.05) than C (F vs. C, 17±2 vs. 38±3; 24±2 vs. 48±2; 12±2 vs. 34±2; 17±2 vs. 26±2), respectively. L had higher (P <0.05) responses to NA and PE while CV had blunted (P <0.05) responses to NA, PE and Ang II compared to C (L, CV vs. C, 47±3, 9±2 vs. 38±3; 61±3, 29±3 vs. 48±2; 16±3, 4±3 vs. 26±2), respectively. FL but not FCV group had enhanced (P <0.05) responses to NA, PE and ME compared to F (FL vs. F, 33±3 vs. 17±2; 45±3 vs. 24±2; 26±3 vs. 12±2), respectively. Losartan and carvedilol had an important ameliorating effect on fructose-induced insulin resistance. Losartan treatment could be an effective tool to restore normal vascular reactivity in the renal circulation of the fructose-fed rat.

  17. Evaluation of sub-chronic toxic effects of petroleum ether, a laboratory solvent in Sprague-Dawley rats

    PubMed Central

    Parasuraman, Subramani; Sujithra, Jeyabalan; Syamittra, Balakrishnan; Yeng, Wong Yeng; Ping, Wu Yet; Muralidharan, Selvadurai; Raj, Palanimuthu Vasanth; Dhanaraj, Sokkalingam Arumugam

    2014-01-01

    Background: In general, organic solvents are inhibiting many physiological enzymes and alter the behavioural functions, but the available scientific knowledge on laboratory solvent induced organ specific toxins are very limited. Hence, the present study was planned to determine the sub-chronic toxic effects of petroleum ether (boiling point 40–60°C), a laboratory solvent in Sprague-Dawley (SD) rats. Materials and Methods: The SD rats were divided into three different groups viz., control, low exposure petroleum ether (250 mg/kg; i.p.) and high exposure petroleum ether (500 mg/kg; i.p.) administered group. The animals were exposed with petroleum ether once daily for 2 weeks. Prior to the experiment and end of the experiment animals behaviour, locomotor and memory levels were monitored. Before initiating the study animals were trained for 2 weeks for its learning process and its memory levels were evaluated. Body weight (BW) analysis, locomotor activity, anxiogenic effect (elevated plus maze) and learning and memory (Morris water navigation task) were monitored at regular intervals. On 14th day of the experiment, few ml of blood sample was collected from all the experimental animals for estimation of biochemical parameters. At the end of the experiment, all the animals were sacrificed, and brain, liver, heart, and kidney were collected for biochemical and histopathological analysis. Results: In rats, petroleum ether significantly altered the behavioural functions; reduced the locomotor activity, grip strength, learning and memory process; inhibited the regular body weight growth and caused anxiogenic effects. Dose-dependent organ specific toxicity with petroleum ether treated group was observed in brain, heart, lung, liver, and kidney. Extrapyramidal effects that include piloerection and cannibalism were also observed with petroleum ether administered group. These results suggested that the petroleum ether showed a significant decrease in central nervous system

  18. Inhibition of NAD(P)H oxidase potentiates AT2 receptor agonist-induced natriuresis in Sprague-Dawley rats.

    PubMed

    Sabuhi, Rifat; Asghar, Mohammad; Hussain, Tahir

    2010-10-01

    A positive association between renin-angiotensin system, especially AT1 receptor, and oxidative stress in the pathogenesis of hypertension and cardiovascular/renal diseases has been suggested. However, the role of oxidative stress, especially superoxide radicals in renal sodium handling in response to AT1 and AT2 receptors, is not known. Therefore, the present study was designed to investigate the role of NAD(P)H oxidase (NOX), a major superoxide radical producing enzyme, in AT1 and AT2 receptor function on natriuresis/diuresis in Sprague-Dawley rats. The rats under anesthesia were intravenously infused with NOX inhibitor apocynin (3.5 μg·kg(-1)·min(-1)), the AT1 receptor antagonist candesartan (100 μg/kg; bolus), and the AT2 receptor agonist CGP-42112A (1 μg·kg(-1)·min(-1)) alone and in combinations. Candesartan alone significantly increased urinary flow (UF; μl/30 min) by 53 and urinary Na excretion (U(Na)V; μmol/min) by 0.4 over basal. Preinfusion of apocynin had no effect on the net increase in UF or U(Na)V in response to candesartan. On the other hand, apocynin preinfusion caused profound increases in CGP-42112A-induced UF by 72, U(Na)V by 1.14, and fractional excretion of Na by 7.8. Apocynin and CGP-42112A alone did not cause significant increase in UF or U(Na)V over the basal. CGP-42112A infusion in the presence of apocynin increased urinary nitrite/nitrates and cGMP over basal. The infusion of candesartan, apocynin, and CGP-42112A alone or in combinations had no effect on the blood pressure or the glomerular filtration rate, suggesting tubular effects on natriuresis/diuresis. The data suggest that NOX may have an antagonistic role in AT2 receptor-mediated natriuresis/diuresis possibly via neutralizing nitric oxide and thereby influence fluid-Na homeostasis.

  19. Exposure to welding fumes activates DNA damage response and redox-sensitive transcription factor signalling in Sprague-Dawley rats.

    PubMed

    Krishnaraj, Jayaraman; Kowshik, Jaganathan; Sebastian, Robin; Raghavan, Sathees C; Nagini, Siddavaram

    2017-05-15

    Occupational exposure to welding fumes containing a complex mixture of genotoxic heavy metals, radiation, gases and nanoparticles poses a serious health hazard to welders. Since their categorization as possible carcinogens, welding fumes have gained increasing attention as high priority agents for risk assessment. The present study was undertaken to investigate the effects of welding fume inhalation on oxidative stress, DNA damage response (DDR), and nuclear factor erythroid 2-related factor-2 (Nrf2) and nuclear factor kappa B (NFκB) signalling in the lung tissues of male Sprague-Dawley rats. METHODS: Animals were divided into five groups. Group 1 animals served as control. Rats in groups 2-5 were exposed to 50mg/m(3) stainless steel (SS) welding fumes for 1h for 1day, 1 week, 2 weeks, and 4 weeks respectively. Reactive oxygen species (ROS) generation, 8-oxo-2'-deoxyguanosine (8-oxodG), xenobiotic-metabolizing enzymes (XMEs) and antioxidants were analysed. DNA damage sensors, DNA repair enzymes, inflammatory mediators, cell cycle progression, apoptosis and key players in Nrf2 and NFκB signalling were assessed by flow cytometry, quantitative real-time reverse transcriptase PCR, immunoblotting, immunohistochemistry and immunofluorescence. Rats exposed to welding fumes showed increased levels of chromium and ROS in lung tissues associated with accumulation of 8-oxodG and enhanced expression of XMEs and antioxidants. This was accompanied by upregulation of DNA damage sensors, cell cycle arrest in G1/S phase, overexpression of a multitude of DNA repair enzymes and caspase-mediated apoptosis. In addition, exposure to welding fumes induced activation of Nrf2 and NFκB signalling with enhanced expression of inflammatory mediators. The results of the present study unequivocally demonstrate that exposure of rats to SS welding fumes alters the expression of 37 genes involved in oxidative stress, detoxification, inflammation, DNA repair, cell cycle progression, and apoptosis

  20. Twenty-Eight-Day Repeated Inhalation Toxicity Study of Nano-Sized Neodymium Oxide in Male Sprague-Dawley Rats.

    PubMed

    Kim, Yong-Soon; Lim, Cheol-Hong; Shin, Seo-Ho; Kim, Jong-Choon

    2017-07-01

    Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide (Nd2O3) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized Nd2O3-containing aerosols via a nose-only inhalation system at doses of 0 mg/m(3), 0.5 mg/m(3), 2.5 mg/m(3), and 10 mg/m(3) for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the 2.5 mg/m(3) and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the 0.5 mg/m(3) treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the 0.5 mg/m(3) group, but were exacerbated in the 10 mg/m(3) group. The lowest-observed-adverse-effect concentration of nano-sized Nd2O3 was determined to be 0.5 mg/m(3), and the target organ was determined to

  1. Twenty-Eight-Day Repeated Inhalation Toxicity Study of Nano-Sized Neodymium Oxide in Male Sprague-Dawley Rats

    PubMed Central

    Kim, Yong-Soon; Lim, Cheol-Hong; Shin, Seo-Ho; Kim, Jong-Choon

    2017-01-01

    Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide (Nd2O3) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized Nd2O3-containing aerosols via a nose-only inhalation system at doses of 0 mg/m3, 0.5 mg/m3, 2.5 mg/m3, and 10 mg/m3 for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the 2.5 mg/m3 and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the 0.5 mg/m3 treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the 0.5 mg/m3 group, but were exacerbated in the 10 mg/m3 group. The lowest-observed-adverse-effect concentration of nano-sized Nd2O3 was determined to be 0.5 mg/m3, and the target organ was determined to be the lung

  2. First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats

    PubMed Central

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

    2006-01-01

    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 ≤ 0.05) and in females (p ≤ 0.01), in particular those females treated at 50,000 ppm (p ≤ 0.01); b) an increase in lymphomas and leukemias with a positive significant trend in both males (p ≤ 0.05) and females (p ≤ 0.01), in particular in females treated at doses of 100,000 (p ≤ 0.01), 50,000 (p ≤ 0.01), 10,000 (p ≤ 0.05), 2,000 (p ≤ 0.05), or 400 ppm (p ≤ 0.01); c) a statistically significant increased incidence, with a positive significant trend (p ≤ 0.01), of transitional cell carcinomas of the renal pelvis and ureter and their precursors (dysplasias) in females treated at 100,000 (p ≤ 0.01), 50,000 (p ≤ 0.01), 10,000 (p ≤ 0.01), 2,000 (p ≤ 0.05), or 400 ppm (p ≤ 0.05); and d) an increased incidence of malignant schwannomas of peripheral nerves with a positive trend (p ≤ 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 cannot be delayed. PMID:16507461

  3. Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats.

    PubMed

    Ari, Csilla; Kovács, Zsolt; Juhasz, Gabor; Murdun, Cem; Goldhagen, Craig R; Koutnik, Andrew P; Poff, Angela M; Kesl, Shannon L; D'Agostino, Dominic P

    2016-01-01

    Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE; 1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE; ~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S; ~25 g/kg/day, KS) and βHB-S + medium chain triglyceride (MCT; ~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance traveled in open arms (chronic KS and KSMCT: SPD rats) and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a

  4. Assessment of bioaccumulation, neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate.

    PubMed

    Normandin, Louise; Carrier, Gaétan; Gardiner, Phillip F; Kennedy, Greg; Hazell, Alan S; Mergler, Donna; Butterworth, Roger F; Philippe, Suzanne; Zayed, Joseph

    2002-09-01

    Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P < 0.05) while for the caudate/putamen, Mn concentrations were 1.06 vs 0.73 vs 0.62 vs 0.47 ppm (P < 0.05). The Mn concentrations in lung were also dose-dependent (10.30 vs 1.40 vs 0.42 vs 0.17 ppm; P < 0.05). No statistical difference was observed for loss of neurons in caudate/putamen and globus pallidus. Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the

  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. Investigations on anti-inflammatory and analgesic activities of Alnus nitida Spach (Endl). stem bark in Sprague Dawley rats.

    PubMed

    Sajid, Moniba; Khan, Muhammad Rashid; Shah, Sayed Afzal; Majid, Muhammad; Ismail, Hammad; Maryam, Sonia; Batool, Riffat; Younis, Tahira

    2017-02-23

    Stem bark of Alnus nitida (Spach) Endl. (family Betulaceae) is used by local communities in northern areas of Pakistan as a remedy for swelling, injuries and pain. However no pharmacological study of this plant has been reported to confirm these activities. In this study anti-inflammatory and analgesic effect of A. nitida stem bark have been evaluated. Powder of the stem bark of A. nitida was extracted with methanol (ANBM) and partitioned in escalating polarity to get the n-hexane (ANBH), chloroform (ANBC), ethyl acetate (ANBE) and the residual soluble aqueous (ANBA) fractions. The methanol extract and derived fractions were evaluated for anti-inflammatory activity by using in vitro heat induced albumin denaturation assay and various in vivo assays; carrageenan-induced hind paw edema method, Freunds' complete adjuvant induced arthritis, histamine induced paw edema and xylene induced ear edema in Sprague Dawley rat. The extracts/fractions were also evaluated for analgesic effects by using hot plate analgesic test and acetic acid induced writhing test in rat. The ANBM composition was analyzed by HPLC-DAD and GC-MS analysis. Results of heat induced albumin denaturation activity indicated that among the extract/fractions ANBC at concentration range of 100-500µg/ml remarkably protected the heat induced albumin denaturation. The pretreatment with ANBC significantly reduced the carrageenan induced edema with 90.81±1.6% after 4h, comparing with 86.63±3.42% reduction produced by the reference drug diclofenac potassium. Histopathological alterations of the gastric and hind paw were decreased with the extract/fractions. Furthermore, anti-inflammatory effects of ANBC were evident in Freunds' complete adjuvant induced arthritis, histamine induced paw edema and xylene induced ear edema. The latency time in hot plate analgesic assay with ANBC (61.59±0.38%) after 90min was comparable to standard drug morphine (69.31±2.67%) and aspirin (67.24±2.08%). Similarly ANBC

  7. A 4-week repeated oral dose toxicity study of fucoidan from the Sporophyll of Undaria pinnatifida in Sprague-Dawley rats.

    PubMed

    Kim, Kui-Jin; Lee, Ok-Hwan; Lee, Hee-Hyun; Lee, Boo-Yong

    2010-01-12

    Fucoidan is extracted from brown seaweeds, which can have anti-coagulant, antithrombotic, antitumor, and antiviral activities. However, detailed studies on the toxicology of fucoidan have not been performed. Here we tested the toxicity of fucoidan in Sprague-Dawley rats. Fucoidan (1350mg/kg bw/day for 4 weeks) did not induce statistically significant differences in groups matched by gender with respect to body weight, ophthalmoscopy, urinalysis, hematology, and histopathology. Fucoidan did not change prothrombin time or activated partial thromboplastin time, indicating an inability to change blood clotting. This study demonstrated that fucoidan is not toxic under this administration paradigm.

  8. 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.

  9. Marine collagen peptides prepared from chum salmon (Oncorhynchus keta) skin extend the life span and inhibit spontaneous tumor incidence in Sprague-Dawley Rats.

    PubMed

    Liang, Jiang; Pei, Xin-Rong; Wang, Nan; Zhang, Zhao-Feng; Wang, Jun-Bo; Li, Yong

    2010-08-01

    To observe the effects of marine collagen peptides (MCPs) prepared from chum salmon (Oncorhynchus keta) skin on life span and spontaneous tumor incidence, Sprague-Dawley rats were fed diets supplemented with MCP at concentrations of 0%, 2.25%, 4.5%, and 9% (wt/wt) from the age of 4 weeks until natural death. There were 40 rats in each group (male:female ratio = 1:1). The results showed that the MCP did not significantly influence body weight or food consumption of rats of either sex throughout the life span; it did dose-dependently inhibit the age-related decrease in the activities of antioxidant enzymes and the age-related increase in the levels of lipid peroxidation product in both sexes. MCP notably increased the mean life span, the life span of the last 30% of the survivors, and the maximal life span; it decreased overall spontaneous tumor incidence of both sexes with significance in the 4.5% and 9% MCP-treated male groups and 9% MCP-treated female group. Compared to the control group, the incidence of death from tumors was decreased in MCP groups in comparison with the control group of both sexes. Therefore, we concluded that MCPs dose-dependently increase life span and decrease spontaneous tumor incidence in Sprague-Dawley rats. Moreover, the antioxidative property of MCPs may be responsible for the increased life span and protection against tumor development.

  10. 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.

  11. 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

  12. 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.

  13. Comparison of chronic toxicity and carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in two-year bioassays in female Sprague-Dawley rats

    PubMed Central

    Walker, Nigel J.; Wyde, Michael E.; Fischer, Lawrence J.; Nyska, Abraham; Bucher, John R.

    2007-01-01

    The cancer bioassay for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) conducted by the Dow Chemical company in the mid 70s been used extensively for conducting quantitative cancer risk assessments for human exposure to TCDD. More recently the National Toxicology Program (NTP) conducted a cancer bioassay of similar design as part of its evaluation of the dioxin TEF methodology. This report compares the design and the results of these two cancer bioassays. This comparison confirms, in most cases, previously published and widely used carcinogenic response characteristics with respect to dose, time course, organ selectivity, tumor type and maximum intensity of TCDD-induced carcinogenicity and toxicity in the Sprague-Dawley rat. Specifically increased in the incidences of neoplasms were seen in both studies in the liver, lung and oral mucosa. The most notable difference was the significant increase in the incidence of cholangiocarcinoma of the liver seen in the NTP study but not in the Dow study. The experimental designs for the two studies are similar but some protocol parameters differed such as vehicle, dosing schedule, diet and rat sub-strain utilized. Differences in the shapes of the dose response curves for several neoplasms were noted between the studies, with the NTP study showing non-linearity for all neoplasms. This may result from differences in the experimental protocols as well as divergence in the biological behavior of the different stocks of Sprague-Dawley rat strains used. PMID:16977594

  14. Joint feedback analysis modeling of nonesterified fatty acids in obese Zucker rats and normal Sprague-Dawley rats after different routes of administration of nicotinic acid.

    PubMed

    Tapani, Sofia; Almquist, Joachim; Leander, Jacob; Ahlström, Christine; Peletier, Lambertus A; Jirstrand, Mats; Gabrielsson, Johan

    2014-08-01

    Data were pooled from several studies on nicotinic acid (NiAc) intervention of fatty acid turnover in normal Sprague-Dawley and obese Zucker rats in order to perform a joint PKPD of data from more than 100 normal Sprague-Dawley and obese Zucker rats, exposed to several administration routes and rates. To describe the difference in pharmacodynamic parameters between obese and normal rats, we modified a previously published nonlinear mixed effects model describing tolerance and oscillatory rebound effects of NiAc on nonesterified fatty acids plasma concentrations. An important conclusion is that planning of experiments and dose scheduling cannot rely on pilot studies on normal animals alone. The obese rats have a less-pronounced concentration-response relationship and need higher doses to exhibit desired response. The relative level of fatty acid rebound after cessation of NiAc administration was also quantified in the two rat populations. Building joint normal-disease models with scaling parameter(s) to characterize the "degree of disease" can be a useful tool when designing informative experiments on diseased animals, particularly in the preclinical screen. Data were analyzed using nonlinear mixed effects modeling, for the optimization, we used an improved method for calculating the gradient than the usually adopted finite difference approximation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  15. Study of the variability in upper and lower airway morphology in Sprague-Dawley rats using modern micro-CT scan-based segmentation techniques.

    PubMed

    De Backer, Jan W; Vos, Wim G; Burnell, Patricia; Verhulst, Stijn L; Salmon, Phil; De Clerck, Nora; De Backer, Wilfried

    2009-05-01

    Animal models are being used extensively in pre-clinical and safety assessment studies to assess the effectiveness and safety of new chemical entities and delivery systems. Although never entirely replacing the need for animal testing, the use of computer simulations could eventually reduce the amount of animals needed for research purposes and refine the data acquired from the animal studies. Computational fluid dynamics is a powerful tool that makes it possible to simulate flow and particle behavior in animal or patient-specific respiratory models, for purposes of inhaled delivery. This tool requires an accurate representation of the respiratory system, respiration and dose delivery attributes. The aim of this study is to develop a representative airway model of the Sprague-Dawley rat using static and dynamic micro-CT scans. The entire respiratory tract was modeled, from the snout and nares down to the central airways at the point where no distinction could be made between intraluminal air and the surrounding tissue. For the selection of the representative model, variables such as upper airway movement, segmentation length, airway volume and size are taken into account. Dynamic scans of the nostril region were used to illustrate the characteristic morphology of this region in anaesthetized animals. It could be concluded from this study that it was possible to construct a highly detailed representative model of a Sprague-Dawley rat based on imaging modalities such as micro-CT scans.

  16. 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.

  17. 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.

  18. 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.

  19. Effects of oral administration of berberine on distribution and metabolism of 2-aminofluorene in Sprague-Dawley rats.

    PubMed

    Lin, Chin-Chung; Kao, Shung-Te; Ho, Chin-Chin; Ho, Heng-Chien; Hsia, Te-Chun; Yang, Mei-Due; Yeh, Chin-Chung; Liu, Po-Erh; Chung, Jing-Gung

    2007-01-01

    The effects of berberine on the in vivo N-acetylation and metabolism of 2-aminofluorene (2-AF) in bladder, blood, colon, kidney, liver, feces and urine samples and brain tissues (cerebrum, cerebellum and pineal gland) of male Sprague-Dawley rats were investigated. Major metabolites, such as 1-OH-2-AAF, 3-OH-2-AAF, 8-OH-2-AAF and 9-OH-2-AAF were found in bladder tissues, 1-OH-2-AAF, 5-OH-2-AAF and 8-OH-2-AAF were found in blood samples, 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF, 8-OH-2-AAF and 9-OH-2-AAF were found in colon tissues, 1-OH-2-AAF, 3-OH-2-AAF and 9-OH-2-AAF were found in kidney tissues, 1-OH-2-AAF, 3-OH-2-AAF and 8-OH-2-AAF were found in liver tissues, 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF, 7-OH-2-AAF, 8-OH-2-AA and 9-OH-2-AAF were found in feces samples and 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF, 7-OH-2-AAF, 8-OH-2-AA and 9-OH-2-AAF were also found in urine samples, 1-OH-2-AAF, 3-OH-2-AAF and 8-OH-2-AAF were found in cerebrum tissues, 1-OH-2-AAF, 3-OH-2-AAF and 7-OH-2-AAF were found in cerebellum tissues. In the control group, however, only 2-AF and 2-AAF were found in pineal gland after rats had been orally treated with 2-AF (50 mg/kg) for 24 h. Pre-treatment of male rats with berberine (40 mg/kg) 24 h prior to the administration of 2-AF (50 mg/kg), as well as the co-administration of berberine and 2-AF led to a decrease in the amounts of 3-OH-2-AAF and an increase in the amounts of 8-OH-2-AAF in bladder tissues. In blood samples, there were significant decreases of 2-AF, 2-AAF, 1-OH-2-AAF and 8-OH-2-AAF, after rats were pre-treated with berberine for 24 h before the addition of 2-AF. However, co-administration of berberine and 2-AF led to an increase in the amounts of 5-OH-2-AAF. In colon tissues, there were significant decreases of 2-AF, 2-AAF, 1-OH-2-AAF and 8-OH-2-AAF in colon samples after rats were treated with berberine for 24 h before the addition of 2-AF. 2-AF, 1-OH-2-AAF, 3-OH-2-AAF and 9-OH-2-AAF levels were significantly different between control and

  20. Comparative chronic toxicity and carcinogenicity of acrylonitrile by drinking water and oral intubation to Spartan Sprague-Dawley rats.

    PubMed

    Johannsen, Frederick R; Levinskas, George J

    2002-06-24

    Groups of 100 male and 100 female Spartan Sprague-Dawley rats were administered lifetime oral doses of Acrylonitrile (AN) by one of two routes of dosing, either at 0.1 or 10 mg/kg per day, 7 day per week by intubation or continually at 1 or 100 ppm AN in their drinking water. The doses selected were designed to approximate the same daily intake of AN in each of two separate studies, whether by a single bolus dose (intubation) or a more continuous dosing regimen in drinking water. Each study had its own untreated control group of 100 rats per sex. In the drinking water study, the equivalent mean dosage of AN administered to males and females were 0, 0.09, and 0.15 mg/kg per day, respectively, at the 1 ppm level, and 0, 8.0 and 10.7 mg/kg per day, respectively, for 100 ppm dose groups. In both studies, groups of ten rats per sex were sacrificed at 6, 12 and 18 months and at study term. Ophthalmoscopic, hematological, clinical biochemistry, urinalysis and full histopathological exams were performed on control and high dose groups of rats in each study. Similar tests were done in lower dose groups, as required, to define dose-responses of observed effects. All animals were necropsied and underwent microscopic examination of target tissues, including brain, ear canal, stomach, spinal cord and any observable tissue masses. High dose male and female rats in both studies exhibited statistically decreased body weights. Food consumption and water intake were reduced only in the drinking water study. Due to increased deaths in groups of high dose rats of both studies receiving AN, all intubation test groups were terminated after 20 months of treatment. Surviving males and females in the drinking water study were terminated after 22 and 19 months, respectively. Small, sometimes statistically significant, reductions in hemoglobin, hematocrit and erythrocyte count were observed in male and female rats in both high dose (10 mg/kg per day intubation and 100 ppm drinking water

  1. 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

  2. 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

  3. A longitudinal study of short- and long-term activity levels in male and female spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats.

    PubMed

    Ferguson, Sherry A; Cada, Amy M

    2003-04-01

    The pattern of locomotor activity across development was assessed in male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats. Open field activity did not indicate hyperactivity in the SHR. Instead, the SD strain was generally more active. Strains and sexes did not differ in open-field locomotor response to drug challenges. When short-term (10-12 min) activity in different apparatuses was compared, the SD were most active in the open field, the SHR in the residential figure-eight maze, and the WKY in the running wheel. Long-term tests indicated hyperactivity in the SHR in the residential figure-eight maze and hypoactivity in the SD in the running wheels. Until such strain differences in activity are thoroughly defined, the use of the SHR as a model of attention-deficit/ hyperactivity disorder is limited.

  4. Overlapping but distinct effects of genistein and ethinyl estradiol (EE(2)) in female Sprague-Dawley rats in multigenerational reproductive and chronic toxicity studies.

    PubMed

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

    2009-04-01

    Genistein and ethinyl estradiol (EE(2)) 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 EE(2) (0, 2, 10, or 50 ppb) in a low phytoestrogen diet. Nonneoplastic effects in females are summarized here. Genistein at 500 ppm and EE(2) 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. EE(2) 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.

  5. 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.

  6. Dietary daidzein, but not genistein, has a hypocholesterolemic effect in non-ovariectomized and ovariectomized female Sprague-Dawley rats on a cholesterol-free diet.

    PubMed

    Bhattarai, Keshab; Adhikari, Sudhashree; Fujitani, Mina; Kishida, Taro

    2017-09-01

    We compared the effects of two major isoflavones, daidzein and genistein, on lipid metabolism in rats. Daidzein (150 mg/kg diet), genistein (150 mg/kg diet), daidzein and genistein (1:1, 300 mg/kg diet), or control diets were fed to 4 groups of 6-week-old ovariectomized (Ovx) and non-Ovx Sprague Dawley rats for 4 weeks. Dietary daidzein, but not genistein, reduced serum and hepatic total cholesterol levels significantly relative to that by the control group, regardless of whether the rats had undergone ovariectomy. Genistein did not exhibit any physiological effects on lipid levels, but did affect genes involved in cholesterol metabolism. These results indicate that daidzein and genistein may influence lipid regulation via differing modes of action.

  7. Differential performance of Wistar Han and Sprague Dawley rats in behavioral tests: differences in baseline behavior and reactivity to positive control agents.

    PubMed

    Zmarowski, Amy; Beekhuijzen, Manon; Lensen, Joost; Emmen, Harry

    2012-09-01

    Developmental neurotoxicity (DNT) testing assesses potentially adverse effects on the developing nervous system. The present DNT study was conducted to generate historical data with the Wistar Han (WH) and Sprague Dawley (SD) rat strains, commonly used in Europe and the US, respectively. Potential differences between these strains in DNT endpoints have not been extensively investigated. Motor activity, startle response, learning and memory testing, and neurological (quantitative and qualitative) examinations were conducted using three groups of control, prenatally exposed (to Methylazoxymethanol [MAM] on gestation Day 15) and acutely treated (with IDPN, MK-801 or Chlorpromazine) animals for each strain. The positive controls produced clear effects in most endpoints investigated, with limited functional differences in baseline behavior and positive control sensitivity. However, SD rats were considerably more susceptible to MAM-induced learning and memory impairments and neurological damage. These data highlight differential sensitivity between the strains, which may require risk assessment consideration for developmental neurotoxicants.

  8. 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

  9. Long-term continuous administration of a hydro-ethanolic extract of Synedrella nodiflora (L) Gaertn in male Sprague-Dawley rats: biochemical, haematological and histopathological changes.

    PubMed

    Amoateng, Patrick; Adjei, Samuel; Osei-Safo, Dorcas; Ahedor, Believe; Mahmood, Seidu A; N'guessan, Benoit B; Asiedu-Gyekye, Isaac J; Nyarko, Alexander K

    2016-09-01

    Conflicting reports about the toxicity of Synedrella nodiflora (L) Gaertn (family Asteraceae), a plant traditionally used in Ghana for the management of epilepsy, abound in literature. The present study evaluates the effect of a 90-day continuous oral administration of a hydro-ethanolic whole plant extract of Synedrella nodiflora (SNE) in male Sprague-Dawley rats. The toxicological evaluation of the extract (100, 300 and 1000 mgkg(-1)) was focused on haematological, serum biochemical parameters and histopathological changes of some isolated organs. The extract produced no mortality in the rats treated during the study period. Only SNE 100 mgkg(-1) produced significant decrease in white blood cell and neutrophil counts and an increase in albumin, globulin, total bilirubin, total protein and potassium levels. The higher doses (SNE 300 and 1000 mgkg(-1)) had no significant effect on all the haematological and biochemical parameters measured. Histopathological assessment of the liver, kidney and heart revealed no abnormalities in rats treated with the extracts. Only the SNE 1000 mgkg(-1) produced distortions of the branching arrangements of the myocardial fibres and a congested vessel which indicates a healed infarction. The findings suggest hydro-ethanolic extract of Synedrella nodiflora (L) Gaertn generally has a low toxicity profile following a 90-day continuous oral administration in male Sprague-Dawley rats under the present laboratory conditions. However patients with renal or cardiac problems should use the plant with caution. Jointly supported by the International Foundation for Science, Stockholm, Sweden, through a grant (# F/5191-1) to Dr. Patrick Amoateng and the Office of Research, Innovation and Development (ORID), University of Ghana, Accra, Ghana, grant awarded to Dr. Patrick Amoateng (reference number: URF/6/ILG-002/2012-2013).

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

    PubMed

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

    2016-04-23

    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. 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). 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. Ovariectomy exacerbates the effect of chronic stress by preventing gonadal receptor-specific stress response reflected in the up-regulation 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.

  11. 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.

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

    PubMed Central

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

    2016-01-01

    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

  13. Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats.

    PubMed

    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

    2016-05-30

    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. 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. 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. hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity.

  14. Bicarbonate plus epinephrine shortens the onset and prolongs the duration of sciatic block using chloroprocaine followed by bupivacaine in sprague-dawley rats.

    PubMed

    Yung, Elliot; Lahoti, Tejas; Jafari, Soheila; Weinberg, Jonathan D; Schianodicola, Joseph J; Yarmush, Joel M; Ray, Sidhartha D

    2009-01-01

    Chloroprocaine is a fast-acting local anesthetic, whereas bupivacaine is a long-acting one. They have been coadministered with limited success. The objective of this study was to determine the effect of additives on the efficacy of regional blockade using chloroprocaine followed by bupivacaine. Four groups of Sprague-Dawley rats, 20 each, were administered chloroprocaine followed by bupivacaine to induce sciatic nerve blockade. Group 1 received chloroprocaine with isotonic sodium chloride solution followed by bupivacaine and was used as a control. Group 2 received chloroprocaine with isotonic sodium chloride solution and epinephrine followed by bupivacaine with epinephrine. Group 3 received chloroprocaine with sodium bicarbonate followed by bupivacaine, and group 4 received chloroprocaine with sodium bicarbonate and epinephrine followed by bupivacaine with epinephrine. The time to onset and duration of anesthesia were measured for all 4 groups. The block using chloroprocaine followed by bupivacaine in group 1 had an onset of 2.5 mins (SD, 0.4 mins) and duration of 104 mins (SD, 16 mins). Adding epinephrine to both chloroprocaine and bupivacaine (group 2) did not significantly change the onset (2.8 mins [SD, 1.3 mins]; P = 0.35) or duration (110 mins [SD, 25 mins]; P = 0.23). With group 3, adding bicarbonate to chloroprocaine hastened the onset (1.2 mins [SD, 0.4 mins]; P < 0.0001) and shortened the duration (87 mins [SD, 13 mins]; P = 0.008). In group 4, adding bicarbonate and epinephrine to chloroprocaine and epinephrine to bupivacaine hastened the onset (1.4 mins [SD, 0.4 mins]; P < 0.0001) and increased the duration (130 mins [SD, 23 mins]; P < 0.0001). Sodium bicarbonate plus epinephrine shortens the onset and prolongs the duration of a chloroprocaine-bupivacaine sciatic block in Sprague-Dawley rats.

  15. Chemopreventive Effects of Germinated Rough Rice Crude Extract in Inhibiting Azoxymethane-Induced Aberrant Crypt Foci Formation in Sprague-Dawley Rats.

    PubMed

    Saki, Elnaz; Saiful Yazan, Latifah; Mohd Ali, Razana; Ahmad, Zalinah

    2017-01-01

    Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR) crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age) were randomly divided into 5 groups which were (G1) induced with azoxymethane (AOM) and not given GRR (positive control), (G2) induced with AOM and given 2000 mg/kg GRR, (G3) induced with AOM and given 1000 mg/kg GRR, (G4) induced with AOM and given 500 mg/kg GRR, and (G5) not induced with AOM and not given GRR crude extract (negative control). To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg) for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF) were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC.

  16. Short-term administration of an aqueous extract of kalanchoe integra var. crenata (Andr.) Cuf leaves produces no major organ damage in Sprague-Dawley rats.

    PubMed

    Asiedu-Gyekye, Isaac J; Antwi, Daniel A; Awortwe, Charles; N'guessan, Benoit Banga; Nyarko, Alexander K

    2014-02-03

    Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Ghana and other parts of the world for the treatment of ulcers, pain and adenoma of the prostate gland. There is paucity of information concerning its short-term usage. The present study is aimed at conducting histopathological and biochemical studies in a 14-day sub-acute toxicity studies using female Sprague-Dawley rats. Crude extract of Ki leaves was prepared and freeze-dried. A 14-day sub-acute toxicity studies was conducted using 2 week old nulliparous and non-pregnant female Sprague-Dawley rats (120-150g). Reconstituted Ki was administered at a dosage of 900mgkg(-1) (high dose), 300mgkg(-1) with a control group receiving an equivalent volume of distilled water (as vehicle) by gastric lavage. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture into EDTA tubes after euthanisation. There was a significant decrease in urea (p<0.016) and creatinine levels (p<0.001) in both the high and low dose groups. There was an increase in ALP levels (P=0.01) in both the high and low dose groups. ALT and AST rather decreased significantly in both the high and low dose groups (p<0.0001). Histopathological results did not show any abnormalities in all the H&E stained paraffin sections. Thus the photomicrographs of the liver, kidney and heart were within histopathological limits. Ki leaf extract is non-toxic when administered by the oral route over a time period of 14 days at the above doses. © 2013 The Authors. Published by Elsevier Ireland Ltd All rights reserved.

  17. Chemopreventive Effects of Germinated Rough Rice Crude Extract in Inhibiting Azoxymethane-Induced Aberrant Crypt Foci Formation in Sprague-Dawley Rats

    PubMed Central

    Mohd Ali, Razana

    2017-01-01

    Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR) crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age) were randomly divided into 5 groups which were (G1) induced with azoxymethane (AOM) and not given GRR (positive control), (G2) induced with AOM and given 2000 mg/kg GRR, (G3) induced with AOM and given 1000 mg/kg GRR, (G4) induced with AOM and given 500 mg/kg GRR, and (G5) not induced with AOM and not given GRR crude extract (negative control). To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg) for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF) were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC. PMID:28116312

  18. Evaluation of White Sesame Seed Oil on Glucose Control and Biomarkers of Hepatic, Cardiac, and Renal Functions in Male Sprague-Dawley Rats with Chemically Induced Diabetes.

    PubMed

    Aslam, Farhan; Iqbal, Sanaullah; Nasir, Muhammad; Anjum, Aftab Ahmad; Swan, Pamela; Sweazea, Karen

    2017-05-01

    White sesame seed oil (WSSO) has been used in cooking and food preparations for centuries. It has many purported health benefits and may be a promising nutraceutical. The primary purpose of this study was to examine the effects of WSSO on fasting blood glucose (GLU) and insulin (INS) in male Sprague-Dawley rats with chemically induced diabetes. A secondary aim was to explore other hematological biomarkers of hepatic, cardiac, and renal function. Sixty-three male Sprague-Dawley rats were randomized into standard diet groups, normal control (NCON) (n = 21) and diabetic control (DCON) (n = 21), and a diabetic sesame oil (DSO) (n = 21) group, which were fed a diet containing 12% WSSO. Blood samples were analyzed at 0, 30, and 60 days. Differences between groups and across days were assessed with two-way repeated measures analysis of variance. At baseline, GLU and INS were similar in both diabetic groups, mean 248.4 ± 2.8 mg/dL and mean 23.4 ± 0.4 μU/mL, respectively. At 60 days, GLU was significantly (P < .05) higher in DCON (298.0 ± 2.3 mg/dL) compared with DSO (202.1 ± 1.0 mg/dL). INS showed similar favorable trends after WSSO supplementation. Consumption of WSSO significantly improved glucose control and other biomarkers of hepatic stress, as well as cardiac and renal health. WSSO may be a viable functional food to help reduce the detrimental effects of diabetes.

  19. 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.

  20. Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats.

    PubMed

    Wang, Zhenyu; Zhang, Xingyi

    2017-01-01

    Breast cancer is a predominant cause of death in women across the globe. Chemoprevention by using natural, dietary or synthetic products has been appearing to be a fascinating approach to combat the growing burden of breast cancer. In the current study, we intended to explore the mechanisms of chemopreventive action of honokiol against 7, 12 - dimethylbenz[a]anthracene (DMBA)-induced mammary cancer in female Sprague Dawlely (SD) rats. We induced mammary cancer in SD rats by administering single dose of DMBA (80 mg/kg) through intra gastric route. Chemopreventive effects of honokiol (80 mg/kg, i.p.) were confirmed from its ameliorating effect on the DMBA-induced anomalies such as liver marker enzymes, Phases I and II metabolizing enzymes and oxidative stress markers. Further, honokiol reversed the DMBA-induced abnormalities in inflammatory cytokines levels and serum tumor markers. Additionally, histopathological examination of mammary tissue and protein expression analysis of NF-κB revealed that honokiol is effective against DMBA-induced mammary cancer. In summary, the results of our study support the chemopreventive feature of honokiol in mammary cancer.

  1. 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

    USDA-ARS?s Scientific Manuscript database

    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...

  2. 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

  3. 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

  4. 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. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  5. 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

  6. Subchronic feeding study of stacked trait genetically-modified soybean (3Ø5423 × 40-3-2) in