Gestational vinclozolin exposure suppresses fetal Leydig cell development in rats

Abstract Background: Vinclozolin is not only a common dicarboximide fungicide used to protect crops against diseases but also an endocrine disruptor. This study aimed to investigate the effects of gestational vinclozolin exposure on the development of rat fetal Leydig cells.Methods: Female pregnant Sprague-Dawley rats were exposed to vinclozolin (0, 25, 50, and 100 mg/kg body weight/day) by oral gavage from gestational day 14 to 21.Results: Vinclozolin dose-dependently depressed serum testosterone levels at doses of 50 and 100 mg/kg and anogenital distance at 100 mg/kg. RNA-seq, qPCR, and Western blot showed that vinclozolin down-regulated the expression of Nr5a1 , Sox9 , Lhcgr , Cyp11a1 , Hsd3b1 , Hsd17b3 , Amh , Pdgfa , and Dhh and their encoded proteins. Vinclozolin depressed NR2F2-positive stem Leydig cell number at a dose of 100 mg/kg and also enhanced autophagy in the testis.Conclusion: Vinclozolin disrupts fetal Leydig cell development via several pathways.

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Faculty Opinions recommendation of Prenatal testosterone exposure permanently masculinizes anogenital distance, nipple development, and reproductive tract morphology in female Sprague-Dawley rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1067093.520083 ◽

2007 ◽

Author(s):

Paul Foster

Keyword(s):

Reproductive Tract ◽

Sprague Dawley ◽

Anogenital Distance ◽

Prenatal Testosterone ◽

Sprague Dawley Rats

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Toxicokinetic and Genotoxicity Study of NNK in Male Sprague-Dawley Rats Following Nose-Only Inhalation Exposure, Intraperitoneal Injection, and Oral Gavage

Toxicological Sciences ◽

10.1093/toxsci/kfab049 ◽

2021 ◽

Author(s):

Shu-Chieh Hu ◽

Matthew S Bryant ◽

Estatira Sepehr ◽

Hyun-Ki Kang ◽

Raul Trbojevich ◽

...

Keyword(s):

Human Lung ◽

Inhalation Exposure ◽

Systemic Exposure ◽

Sprague Dawley ◽

Oral Gavage ◽

Sd Rats ◽

New Information ◽

Sprague Dawley Rats ◽

Tissue Specimens

Abstract The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5x10−5, 5x10−3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 hour. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal (IP) injection and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated timepoints and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 hours post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the toxicokinetics and genotoxicity of NNK.

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NIFEDIPINEON;

The Professional Medical Journal ◽

10.29309/tpmj/2019.26.02.3084 ◽

2019 ◽

Vol 26 (02) ◽

Author(s):

Sidra Hamid ◽

Qaiser Aziz ◽

Aneela Jamil ◽

Lubna Meraj ◽

Shazia Muazam ◽

...

Keyword(s):

Blood Pressure ◽

Luteinizing Hormone ◽

Serum Testosterone ◽

Serum Testosterone Level ◽

Control Group ◽

Channel Blockers ◽

Sprague Dawley ◽

Study Objective ◽

Serum Luteinizing Hormone ◽

Sprague Dawley Rats

Background: The most potent and effective drugs used for the management of blood pressure in hypertensive patients are Calcium channel blockers (CCBs). Nifedipine, a CCB, acts by blocking entry of calcium ions all the way through the voltage gated calcium channels (VGCCs) of L-type present in the smooth muscle cells of blood vesselsand reducing the blood pressure by decreasing the peripheral vascular resistance. Objectives: The study objective was to determine the effect of nifedipine on serum luteinizing hormone (LH) and serum testosterone in male Sprague Dawley rats. Study Design: Animal experimental study. Setting: All experiments were conducted at the Research laboratory of Shifa College of Medicine, Islamabad along with National Institute of Health (NIH), Islamabad. Period: October, 2012 to April, 2014. Methods: The study was done on adult male Sprague-Dawley rats (N= 60) aged 90-120 days old and their body weights varied between 200 + 50 grams. Rats were divided intotwo groups (n=30). Group A was administered0.5 ml distilled water/rat daily orally, group B was administered orally with nifedipine 50 mg/kg/rat dissolved in 1ml of DMSO. All the doses were given to rats for 8 weeks. After 8 weeks, serum luteinizing hormone and serum testosterone were measured in both groups. Results: In Nifedipine treated group, serum testosterone was significantly decreasedand serum LH was unaffected as compared to the control group. Conclusion: Nifedipine has adverse effects on male fertility as it decreases serum testosterone level.

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Effects of Xuesaitong on the Pharmacokinetics of Losartan: An In Vivo UPLC-MS/MS Study

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/8373476 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Weina Ma ◽

Lei Lv ◽

Jungang Guo ◽

Yongjun Meng ◽

Yinghua Wang ◽

...

Keyword(s):

Apparent Volume ◽

Volume Of Distribution ◽

Sprague Dawley ◽

Oral Gavage ◽

Sprague Dawley Rats ◽

Liquid Chromatography Tandem Mass ◽

Multiple Blood ◽

Apparent Volume Of Distribution ◽

Noncompartmental Model

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P<0.05). The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; P<0.05). The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P<0.05). Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; P<0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.

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Oral (gavage), in utero and postnatal exposure of Sprague–Dawley rats to low doses of tributyltin chloride. Part 1: Toxicology, histopathology and clinical chemistry

Food and Chemical Toxicology ◽

10.1016/j.fct.2003.09.003 ◽

2004 ◽

Vol 42 (2) ◽

pp. 211-220 ◽

Cited By ~ 50

Author(s):

G.M Cooke ◽

H Tryphonas ◽

O Pulido ◽

D Caldwell ◽

G.S Bondy ◽

...

Keyword(s):

Clinical Chemistry ◽

In Utero ◽

Low Doses ◽

Postnatal Exposure ◽

Sprague Dawley ◽

Oral Gavage ◽

Sprague Dawley Rats ◽

Tributyltin Chloride

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Regression of white adipose tissue in diabetic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.4.e547 ◽

1989 ◽

Vol 257 (4) ◽

pp. E547-E553 ◽

Cited By ~ 4

Author(s):

A. Geloen ◽

P. E. Roy ◽

L. J. Bukowiecki

Keyword(s):

Endothelial Cells ◽

Adipose Tissue ◽

Protein Content ◽

Cell Number ◽

Diabetic Rats ◽

Total Protein Content ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Wet Weight

The effects of long-term diabetes (4 wk) on the development of parametrial (PWAT) and retroperitoneal (RWAT) white adipose tissues were studied in young Sprague-Dawley rats (170-200 g) injected with a single dose of streptozotocin (75 mg/kg). Diabetes stopped animal growth and totally abolished the normal increases in the wet weight, total protein content, and cellularity (estimated by DNA content) of PWAT and RWAT. Remarkably, the prolonged lack of insulin induced a progressive decrease of the cellularity of RWAT to levels that were lower than those of the initial controls. It also resulted in a marked reduction of adipocyte size. The tiny adipocytes seen in diabetic animals were characterized by the presence of multilocular triglyceride droplets. In general, the decreases in cell number, cell size, and protein content were more pronounced in RWAT than in PWAT. Quantitative cellular frequency studies revealed that adipocytes, and possibly also endothelial cells, contribute to the decrease in RWAT cellularity. The results demonstrate that 1) diabetes inhibits proliferative activity in adipose tissue, 2) total cell number reduction may occur in adipose depot of young growing rats, 3) this effect is depot dependent, and 4) the turnover of adipocytes and endothelial cells is relatively slow (several weeks).

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Early Occurrence of Spontaneous Tumors in CD-1 Mice and Sprague—Dawley Rats

Toxicologic Pathology ◽

10.1080/01926230490440871 ◽

2004 ◽

Vol 32 (4) ◽

pp. 371-374 ◽

Cited By ~ 60

Author(s):

Woo-Chan Son ◽

Chirukandath Gopinath

Keyword(s):

Life Sciences ◽

Male Rats ◽

Sprague Dawley ◽

Control Groups ◽

Oral Gavage ◽

Short Term ◽

Young Control ◽

Sprague Dawley Rats ◽

Early Occurrence ◽

General Profile

It is sometimes difficult to assess the relevance of tumors that occur in treated animals in short-term studies. This report is intended to establish a general profile of tumor occurrence in young control CD-1 mice and Sprague—Dawley rats. Data from 20 rat and 20 mouse carcinogenicity studies conducted between 1990 and 2002 at Huntingdon Life Sciences, UK, were collected and evaluated. The route of administration was either dietary or oral gavage, and the analysis was confined to sporadic deaths (decedents) in control groups occurring during the first 50 weeks of study. In addition, tumor occurrence between 50—80 weeks were compared. In mice, the most common tumor was lymphoma, followed by bronchiolo-alveolar adenoma. In rats, the most common tumor was adenoma of the pituitary gland, followed by mammary fibroadenoma, and adenocarcinoma. When studies of up to 50 weeks, between 50 and 80 weeks, and at 2-year termination were compared, there was no great difference in tumor occurrence except in male rats, in which the most common tumor up to 50 weeks on study was lymphoma, whereas the most common tumor between 50—80 weeks and at 2 years was pituitary adenoma.

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