Alpha-lipoic acid alleviates testicular dysfunction induced by olanzapine in male rats, involvement of adiposity, oxidative stress, inflammation, and male hormonal factors

Olanzapine, classified as an atypical antipsychotic pharmacological agent, has been linked with the onset of metabolic syndrome and reproductive dysfunction. The objective of this investigation was to examine the protective properties of alpha-lipoic acid (ALA) in counteracting the metabolic and reproductive disturbances induced by olanzapine in a rat model. Adult Wistar rats were allocated into four distinct groups: a control group, an olanzapine-treated group (10 mg/kg), and two groups receiving olanzapine in conjunction with alpha-lipoic acid (50 or 100 mg/kg). The treatment regimen was administered over a duration of 8 weeks. The group exposed to olanzapine exhibited statistically significant reductions in luteinizing hormone, testosterone levels, sperm motility, sperm count, and relative weights of reproductive organs, alongside an elevation in inflammatory markers (TNF-α and IL-6), oxidative stress (MDA, SOD and GSH), sperm abnormalities, body weight gain, and fat deposition when contrasted with control subjects. Notably, the concomitant administration of alpha-lipoic acid (at doses of 50 or 100 mg/kg) resulted in a partial, dose-dependent amelioration of the adverse effects induced by olanzapine. Specifically, alpha-lipoic acid (100 mg/kg) alleviated the harmful consequences of olanzapine on reproductive hormones, sperm quality metrics, organ weights, oxidative stress levels, and inflammatory markers. Furthermore, alpha-lipoic acid exhibited advantageous effects on body weight and fat accumulation. These observations indicate that alpha-lipoic acid may serve as a viable adjunctive therapeutic strategy to mitigate the metabolic and reproductive side effects associated with olanzapine administration. Additional investigations are necessary to clarify the underlying mechanisms of these protective effects and their potential clinical ramifications.