Time-of-day–dependent variation in gentamicin–artesunate nephrotoxicity across distinct seasonal cohorts in male Wistar rats

Abstract

Circadian rhythms regulate renal physiology, drug disposition, and oxidative stress, influencing susceptibility to nephrotoxicity. Seasonal (circannual) variations may also affect renal vulnerability to drug-induced injury. This study evaluated the combined effects of dosing time and seasonal conditions on gentamicin-induced renal injury and its interaction with artesunate in male Wistar rats. A total of 128 rats were divided into sixteen groups (n=8). Animals were grouped by season (rainy and dry) and dosing time (12:00 h, light phase; 00:00 h, dark phase). Gentamicin, artesunate, their combination, or normal saline was administered for one week. Renal injury was assessed using renal function markers, electrolyte balance, oxidative stress indices, and histopathology. Gentamicin induced significant renal injury, evidenced by elevated urea and creatinine, electrolyte imbalance, increased oxidative stress, and histopathological damage. Injury was time-dependent, with greater effects at 12:00 h than at 00:00 h, and season-dependent, with more severe damage during the dry season. Artesunate showed protective effects during the rainy season, but this protection was reduced during the dry season at 00:00 h. Gentamicin-induced renal injury and its interaction with artesunate are influenced by both dosing time and circannual variation.