Effects of tramadol administration on male reproductive toxicity in Wistar rats The role of oxidative stress, mitochondrial dysfunction, apoptosis-related gene expression, and nuclear factor kappa B signalling

Bratislava Medical Journal

article

M. Koohsari¹  N. Ahangar³  E. Mohammadi⁴  F. Talebpour Amiri⁵  F. Shaki¹ 

[1] Pharmaceutical Sciences Research Centre, Haemoglobinopathy Institute, Mazandaran University of Medical Sciences;Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences;Department of Pharmacology, School of Medicine, Guilan University of Medical Sciences;Environmental Health Research Centre, Research Institute for Health Development, Kurdistan University of Medical Sciences;Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Centre, Mazandaran University of Medical Sciences

关键词: tramadol;    oxidative stress;    apoptosis;    inflammation;    mitochondria;    testis;   

DOI  :  10.4149/BLL_2020_065

学科分类：医学（综合）

来源: AEPress, s.r.o.

【 摘 要 】

AIM: The present study investigated the role of redox balance, inflammation, mitochondrial dysfunction, and apoptosis in Tramadol (Tra)-induced testicular toxicity. METHOD: Twenty-four male Wistar rats were randomly divided into either the control group or the groups receiving different doses of Tra (25, 50, and 75 mg/kg/day, i.p.) for 21 successive days. Testicular tissues were collected for oxidative stress, mitochondrial function, sperm assays and histopathological evaluation. Real-time polymerase chain reaction was performed to evaluate the markers of inflammation and apoptosis. RESULTS: Tra caused a significant reduction in the sperm count, motility and morphology, while it caused a marked increase in oxidative stress parameters. In addition, Tra induced testicular mitochondrial dysfunction due to the collapse of mitochondrial membrane potential and mitochondrial swelling. It also led to the significant inhibition of anti-apoptotic Bcl-2 expression, besides a significant increase in pro-apoptotic Bax expression. There was a significant increase in the level of tumour necrosis factor-α, interlukin-1β and nuclear factor kappa B. Histopathological degenerative changes were observed in the testis after Tra exposure. CONCLUSIONS: The present results suggest that Tra exposure may lead to reproductive toxicity due to the loss of the antioxidant defence system, mitochondrial dysfunction, and activation of inflammatory and apoptotic pathways (Tab. 4, Fig. 5, Ref. 63).

【 授权许可】

CC BY