Clomiphene Citrate-Induced Nephrotoxicity and the Renoprotective Role of Metformin in Adult Female Wistar Rats

This study investigated the micromorphological effects of clomiphene citrate on renal tissue in adult female Wistar rats pretreated with metformin. A total of 28 rats, with an average weight of 122.90g, were divided into seven groups. The control group received only food and water for 28 days. The remaining groups were treated as follows: Group 1 (1 mg/kg clomiphene citrate), Group 2 (2 mg/kg clomiphene citrate), Group 3 (10 mg/kg clomiphene citrate), Group 4 (1 mg/kg clomiphene citrate + 5 mg/kg metformin), Group 5 (2mg/kg clomiphene citrate + 5 mg/kg metformin), and Group 6 (10 mg/kg clomiphene citrate + 5 mg/kg metformin). At the end of the experiment, the kidneys were harvested and subjected to histological analysis. The results showed a significant increase (P<0.05) in body weight among the rats treated with clomiphene citrate alone (Groups 1, 2, and 3), but no significant changes in relative kidney weight across all groups compared to the control. Histological examination revealed that clomiphene citrate alone caused nephrotoxicity, characterized by an enlarged glomerulus and the absence of urinary space between the glomerulus and Bowman’s capsule. However, co-administration of metformin with clomiphene citrate mitigated these harmful effects, as normal renal structures were observed in the metformin-pretreated groups. The study concluded that clomiphene citrate induces body weight gain and nephrotoxicity in rats,but these adverse effects can be alleviated with metformin co-administration. Despite these findings, the use of these medications should be strictly under a physician's guidance to avoid potential risks.