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

Abstract

BACKGROUND: The therapeutic value of pregabalin in managing various pathological states, such as sleep, anxiety, and bipolar disorders, fibromyalgia, epilepsy, and others, cannot be overstated. Nevertheless, the gonadotoxicity of this drug remains a concern. In contrast, melatonin, an endogenous hormone, is known for its beneficial effects on reproductive tissues following various 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 and 140 g, were randomly assigned to six groups, with each group consisting of ten rats. The control group was given 0.5 ml of normal saline orally, whereas melatonin was administered alone at 10 mg/kg/BW, and pregabalin was delivered at low and high doses of 150 and 300 mg/kg/BW orally, respectively. At the specified dosages, rats were also treated simultaneously with low and high doses of pregabalin in combination with melatonin. All treatments lasted for 56 days. Biomarkers were assayed in the testicular and epididymal tissues, while hormones were assayed in the serum. RESULTS: Pregabalin treatment resulted in notable decreases in the percentage body weight change, 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 administered melatonin in conjunction with pregabalin. Pregabalin treatment also caused significant elevations in lactate, pyruvate, LDH, GGT, MDA, caspase, IL-1β, NF-κB, and TNF-α, and distorted testicular histoarchitecture, but these effects were blunted in the group co-administered with pregabalin and melatonin. The histological findings paralleled the biochemical assays. CONCLUSION: Conclusively, melatonin has a protective effect against pregabalin-induced gonadotoxicity through anti-oxidative, anti-inflammatory, anti-apoptotic, enzymatic, and hormonal regulatory mechanisms. CLINICAL TRIAL NUMBER: Not applicable.