Effects of oral cimetidine on the reproductive system of male rats

Liu,Xu; Jia,Yuling; Chong,Liming; Jiang,Juan; Yang,Yang; Li,Lei; Ma,Aicui; Sun,Zuyue; Zhou,Li

doi:10.3892/etm.2018.6065

Effects of oral cimetidine on the reproductive system of male rats

Authors:
- Xu Liu
- Yuling Jia
- Liming Chong
- Juan Jiang
- Yang Yang
- Lei Li
- Aicui Ma
- Zuyue Sun
- Li Zhou
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Affiliations: Pharmacology and Toxicology Research Laboratory, School of Pharmacy, Fudan University, Shanghai 201203, P.R. China, Pharmacology and Toxicology Research Laboratory, Shanghai Institute of Planned Parenthood Research, National Evaluation Centre for The Toxicology of Fertility Regulating Drugs, Shanghai 200032, P.R. China
Published online on: April 13, 2018 https://doi.org/10.3892/etm.2018.6065
Pages: 4643-4650
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cimetidine is widely used for the treatment of digestive tract ulcers, but it induces testis injury. To explore the mechanisms underlying cimetidine‑induced toxicity towards the testis, the effects of oral cimetidine on the reproductive system of male rats were assessed. Cimetidine was orally administered to male rats at 20, 40 or 120 mg/kg/day for 9 weeks. The rats were then euthanized, and serum, testis, epididymis, prostate gland, seminal vesicle, preputial gland, levator ani muscle and sphincter ani samples were collected. Sperm parameters were obtained by computer‑assisted sperm analysis. Serum hormone levels were measured by ELISA. Protein expression levels were detected by immunohistochemistry. Apoptosis was assessed with the DeadEnd™ Colorimetric Apoptosis Detection System. The results indicated that the sperm average path velocity, straight line velocity and curvilinear velocity were significantly decreased in the 120 mg/kg cimetidine group compared with the control group, while luteinizing hormone and testosterone levels were significantly higher compared with the control group. Testicular lesions were observed by histopathology in the 120 mg/kg cimetidine group. The amounts of cells positive for cyclooxygenase‑2 (COX‑2) and nuclear factor κB (NF‑κB) were increased in the 120 mg/kg cimetidine group compared with the control group. The amounts of cells positive for iNOS were increased in all cimetidine treatment groups. In addition, apoptotic cells were significantly more abundant in the 120 mg/kg cimetidine group compared with the control group, as indicated by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling. Overall, 9 weeks of oral cimetidine induced pathological changes in the testicles and hormone secretion disorder in rats. COX‑2, iNOS and NF‑κB upregulation and induction of apoptosis may be associated with the reproductive toxicity caused by cimetidine.

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