The Effect of Pregabalin and Aceclofenac on Testicular Tissue of Adult Albino Rats: Evaluation of Toxicity and Potential Reversibility of Toxic Effects

Abstract

Male reproductive function is highly susceptible to drug-induced toxicity, particularly following prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antiepileptic agents. Despite the frequent co-prescription of aceclofenac and pregabalin for chronic pain management, their combined effects on testicular function remain poorly understood. This study aimed to evaluate the testicular toxicity induced by aceclofenac and pregabalin, administered individually and concurrently, and to assess the potential reversibility of these effects following drug withdrawal. Thirty-five adult male albino rats were divided into control, aceclofenac-treated, pregabalin-treated, combined-treatment, and corresponding recovery groups evaluated 8 weeks after drug cessation. Serum testosterone levels, oxidative stress markers (SOD, GSH, and MDA), inflammatory markers (TNF-α and ALP), histopathological changes, immunohistochemical expression of PCNA and c-Kit, and sperm ultrastructure using transmission electron microscopy (TEM) were assessed. Both drugs induced significant testicular toxicity, evidenced by reduced testosterone levels, increased oxidative stress, and elevated inflammatory markers. Histopathological examination demonstrated degeneration of seminiferous tubules, with the most severe damage observed in the combined-treatment group. Expression of PCNA and c-Kit was markedly reduced, whereas TEM analysis confirmed extensive ultrastructural abnormalities in sperm flagella. Following drug withdrawal, pregabalin-treated rats showed near-complete recovery, whereas aceclofenac-treated rats demonstrated only partial improvement. The combined-treatment group exhibited the least degree of recovery. In conclusion, aceclofenac and pregabalin significantly impair testicular function, with combined administration exacerbating damage through synergistic oxidative and inflammatory mechanisms. Although pregabalin-induced effects appear largely reversible, aceclofenac causes more persistent structural and ultrastructural damage to testicular tissue and sperm cells.