Journal Article

Testicular toxicity following chronic codeine administration is via oxidative DNA damage and up-regulation of NO/TNF-α and caspase 3 activities

Ajayi, Ayodeji, Akhigbe, Roland

2020

Overview

Codeine, a 3-methylmorphine, and other related opioids have been implicated in androgen suppression, although the associated mechanisms remain unclear. Therefore, the objective of the current study was to elucidate the in vivo molecular mechanisms underlying codeine-induced androgen suppression. This study made use of twenty-one healthy male rabbits, distributed into three groups randomly, control and codeine-treated groups. The control had 1ml of normal saline daily p.o. The codeine-treated groups received either 4mg/kg b.w of codeine or 10mg/kg b.w of codeine p.o. for six weeks. Reproductive hormonal profile, testicular weight, testicular enzymes, oxidative and inflammatory parameters, testicular DNA fragmentation, histological examination and apoptosis marker were evaluated to examine the effects of codeine use. Oral administration of codeine resulted in testicular atrophy and alterations in testicular histomorphology, elevated testicular enzymes, and suppression of circulatory and intra-testicular testosterone. These changes were associated with a marked rise in oxidative markers and decline in the activities of testicular enzymatic antioxidants, as well as oxidative DNA damage, inflammatory response, testicular DNA fragmentation, and caspase-dependent apoptosis (p<0.05). In conclusion, chronic codeine use resulted in testicular degeneration and testosterone suppression, which is attributable to TNF-α/nitric oxide-/oxidative stress-mediated caspase-dependent apoptotic testicular cell death and loss of testicular function.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Administration, Oral / Androgens / Animals / Antioxidants / Antioxidants - metabolism / Apoptosis / Apoptosis - drug effects / Atrophy / Biocompatibility / Biology and Life Sciences / Biosynthesis / Body Weight - drug effects / Caspase 3 - metabolism / Caspase-3 / Cell death / Codeine / Codeine - administration & dosage / Codeine - toxicity / Damage / Degeneration / Deoxyribonucleic acid / DNA / DNA damage / DNA fragmentation / DNA Fragmentation - drug effects / Drug dosages / Enzymes / Fertility / Fragmentation / In vivo methods and tests / Infertility / Inflammation / Inflammatory response / Laboratory animals / Male / Markers / Medicine and Health Sciences / Molecular modelling / Narcotics / Nitric oxide / Nitric Oxide - metabolism / Opioids / Oral administration / Oxidative stress / Oxidative Stress - drug effects / Peptides / Phosphatase / Physiology / Rabbits / Random Allocation / Research and Analysis Methods / Signal Transduction - drug effects / Spermatogenesis / Testes / Testis - drug effects / Testis - metabolism / Testosterone / Testosterone - metabolism / Toxicity / Tumor Necrosis Factor-alpha - metabolism / Tumor necrosis factor-α / Up-Regulation - drug effects