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

UÇAR, Bünyamin ; HUYUT, Zübeyir ; ALTINDAĞ, Fikret ; Keleş, Ömer Faruk; YILDIZHAN, Kenan

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. In this study, the relationship between ABE administration and nephrotoxicity and the protective effect of Curcumin (CMN) was investigated. Forty female rats were equally divided into the sham, dimethyl sulfoxide (DMSO), CMN, abemaciclib and ABE+CMN groups. Aquaporin (AQP) 1-7, TNF-α, IL-1β, 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 TNFα, IL-1β, MDA, caspase-3 and Bax/Bcl2 were high. In addition, kidney tissue was examined histopathologically. However, AQP1 and 7 levels in the ABE+CMN group were higher than in the ABE group, while TNF-α, IL-1β, MDA, Caspase-3 levels and Bax/Bcl2 ratio were low. In addition, the poor histopathological changes in the ABE group were largely 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

Keyword(s)

Abemaciclib; Apoptosis; Aquaporin; Curcumin; Nephrotoxicity

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