Melatonin and alpha lipoic acid attenuate lopinavir/ritonavir - induced testicular toxicity in albino rats

Abstract

The use of lopinavir/ritonavir (LPV/r) could be associated with testicular toxicity as a limiting factor. The present study evaluated the effects of melatonin (MT) and alpha lipoic (ALA) acid on LPV/r–induced testicular toxicity in male albino rats. Eighty five male albino rats used for this study were randomized into 6 groups (A-F). Rats in groups A1 and A2 served as placebo and solvent control and were orally exposed to water and 1% ethanol, respectively. Rats in group B were exposed to oral doses of MT (10 mg kg-1/day), ALA (10 mg kg-1/day) and combined doses of MT and ALA, respectively. Rats in group C were exposed to oral doses of LPV/r (22.9/5.71 - 91.4/22.9 mg kg-1/ day), respectively. Rats in group D-F were exposed to oral doses of MT (10 mg kg-1/day), ALA (10 mg kg-1/day) and combined doses of MT and ALA prior to oral exposure to LPV/r (22.9/5.71 - 91.4/22.9 mg kg-1/day), respectively. At the end of 60 days of exposure to drugs, rats were sacrificed; blood was collected and serum extracted and evaluated for testosterone. Testes were collected and evaluated for sperm parameters. LPV/r-treated rats showed significant (P<0.05) and dose-dependent decreases in sperm count, sperm motility, sperm viability and serum testosterone levels with increases in abnormal sperm cells, debris, and primordial sperm cells when compared to placebo control. However, LPV/r-induced changes in sperm parameters and serum testosterone levels were attenuated in rats pretreated with MT and ALA. The best effects were observed in rats pretreated with combined doses of MT and ALA. Melatonin and alpha lipoic acid have potential to reduce testicular toxicity associated with lopinavir/ritonavir treatment.