Elevated reproductive toxicity effects of diclofenac after withdrawal: Investigation of the therapeutic role of melatonin.

Abstract

Although there are several reports on the toxic actions of sodium diclofenac (DF), there is dearth information on its effect on the male reproductive system. Therefore, the study investigated the effects of DF and melatonin in male rats. Twenty rats were used in this study, which lasted for 6 weeks. The control group (vehicle treated) received normal saline (0.1 ml/day, p.o.). In the experimental groups, DF was administered during the first (group 2) and last (group 3) three weeks of the study. However, in group 4, melatonin was administered for 3 weeks, after 3 weeks of treatment with DF. DF and melatonin were administered at 1 and 10 mg/kg b.w./day (p.o.) respectively. The results showed that unlike melatonin, DF had no effect on gonadotrophins; however, it caused significant decreases in GNRH and testosterone, but a significant increase in prolactin. Melatonin attenuated the pro-antioxidant and pro-inflammatory effects of DF, which caused significant decreases in SOD, TAC, CAT, but significant elevations in LDH, MDA, uric acid and CRP. Moreover, the hormone reversed the adverse effect of DF on sperm count, sperm motility and sperm morphology. There were slight evidence of the precipitation of imbalance in lipid metabolism by DF and the antidyslipidaemic action of melatonin. Compared to DF, DF recovery showed more adverse effects on prolactin, testosterone, LDH, MDA, UA, CRP, semen parameters (except sperm motility), TC, LDL-c, HDL-c and phospholipid. The histological results agreed with the biochemical assays. In conclusion, the reproductive toxicity effects of DF seem to escalate after withdrawal; however, these effects could be attenuated by treatment with melatonin.