Relationship With Nephrotoxicity of Abemaciclib in Rats: Protective Effect of Curcumin

Abstract

Abemaciclib (ABE) has been reported to cause gastrointestinal toxicity. Therefore, it is important to investigate the question of whether abemaciclib administration causes nephrotoxicity in the gastrointestinal tract and if so, what pathophysiological pathways it follows. This study investigated the relationship between ABE administration, nephrotoxicity, and Curcumin's protective effect (CMN). Forty albino female rats were equally divided into five groups. The sham group was fed with standard pellet food. Dimethyl sulfoxide (DMSO) group: 150 mu L of DMSO was administered to each rat once a day for 28 days.CMN group: 30 mg/kg/day of CMN was administered to each rat for 28 days. ABE group:26 mg/kg/day of ABE was administered to each rat at a dose once a day for 28 days. ABE+CMN group: 26 mg/kg/day ABE and 30 mg/kg/day CMN were administered to each rat dose for 28 days. Aquaporin (AQP) 1-7, TNF-alpha, IL -113, intercellular adhesion molecule (ICAM)-1, IL-10 and IL-37 levels in serum and kidney tissue homogenates were measured by ELISA. In addition, Urea and Creatinine were measured in serum samples. Furthermore, histopathological examination was performed in kidney tissues and Bax, Caspase-3 and Bcl-2 expression levels were determined immunohistochemically. The levels of AQP1-7 and IL-10 in the ABE group were partially lower than in the other groups, while the ratio of TNF-alpha, IL -113, MDA, caspase-3 and Bax/Bcl2 were high. In addition, kidney tissue was examined histopathologically. However, AQP1 and AQP7 levels in the ABE+CMN group were higher than in the ABE group, while TNF-alpha, IL -113, MDA, Caspase-3 levels and Bax/Bcl2 ratio were low. In addition, the poor histopathological changes in the ABE group were mainly restored in the ABE+CMN. The data presented that ABE in rats can adversely affect functions and histology of kidneys through the increase in oxidative stress, pro-inflammatory cytokines and apoptosis, but CMN therapy may be protective against the nephrotoxic effects of ABE.