Melatonin protect against pregabalin-induced gonadotoxicity via anti-oxidative, anti- inflammatory, anti-apoptotic, enzymatic and hormonal regulatory mechanisms

Background: The therapeutic value of pregabalin in the management of different pathological states like sleep, anxiety and bipolar disorders, fibromyalgia, epilepsy, among others, cannot be overemphasized. Nevertheless, the gonadotoxicity of this drug remains a point of concern. Contrarily, melatonin, an endogenous hormone is known for its favourable effects on the reproductive tissues following different insults. Thus, this study aimed to examine the impact of melatonin on male Wistar rats exposed to pregabalin. Methods: A total of sixty male Wistar rats weighing between 120-140g were assigned randomly to six groups, with each group consisting of ten rats. The control group was given 0.5ml of normal saline orally, whereas melatonin alone and increasing dosages of pregabalin were delivered at 10, 150, and 300 mg/kg/BW orally, respectively. At the specified dosages, two groups were simultaneously treated with melatonin and low and high doses of pregabalin. All treatments lasted for 56 days. With the excepton of the hormones, biomarkers were assayed in the testicular and epididymal tissues. Results: Pregabalin resulted in notable decreases in the percentage body weight, testicular weight, relative testicular weight, FSH, LH, testosterone, 3β-HSD, 17β-HSD, SOD, catalase, and GSH, as compared to the control group. However, these effects were mitigated in the groups who received melatonin in conjunction with pregabalin. Overall, the administration of melatonin had no negative impact on the levels and activities of the biomarkers. Pregabalin caused significant elevations in lactate, pyruvate, LDH, GGT, MDA, caspase, IL-1β, NFk, TNF-a, and distorted testicular histoarchitecture, but this effects was blunted in the group that were co-administered with melatonin. The impact of the two doses of pregabalin on all the biomarkers exhibited an irregular combination. The histological findings were parallel to the biochemical assays. Conclusion: Conclusively, melatonin has a protective effect against pregabalin-induced gonadotoxicity via anti-oxidative, anti-inflammatory, anti-apoptotic, and enzymatic and hormonal regulatory mechanisms. Clinical trial number : not applicable