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

Abstract

AbstractBackgroundCodeine, a 3-methylmorphine, and other related opioids have been implicated in androgen suppression, although the associated mechanisms remain unclear.AimTherefore, the objective of the current study was to elucidate the in vivo molecular mechanisms underlying codeine-induced androgen suppression.MethodsThis 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 dailyp.o. The codeine-treated groups received either 4mg/kg b.w of codeine or 10mg/kg b.w of codeinep.o. for six weeks. Reproductive hormonal profile, testicular weight, enzymes, oxidative and inflammatory parameters, histological examination and apoptosis marker were evaluated to examine the effects of codeine use.Key findingsOral 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, including oxidative DNA damage, inflammatory response, and caspase-dependent apoptosis.SignificanceIn conclusion, chronic codeine use resulted in testicular degeneration and testosterone suppression, which may be attributable to nitric oxide-/oxidativestress-mediated caspase-dependent apoptotic testicular cell death.