Background: Cisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has\nbeen a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin\nagainst nephrotoxicity induced by cisplatin in rats.\nMethods: Forty male Wistar albino rats were randomly divided into 4 groups. Rats of group 1 control group\nintraperitoneal (i.p.) received 2.5 ml/kg, group 2 CP group received single dose 5 mg/kg cisplatin i.p. group 3 rutin\ngroup orally received 30 mg/kg rutin group 4 (CP plus rutin) received CP and rutin as in group 2 and 3. Kidneys\nwere harvested for histopathology and for the study the gene expression of c-Jun N-terminal kinases (JNK),\nMitogen-activated protein kinase 4 (MKK4), MKK7, P38 mitogen-activated protein kinases (P38), tumor necrosis\nfactors alpha (TNF-�±), TNF Receptor-Associated Factor 2 (TRAF2), and interleukin-1 alpha (IL-1-�±).\nResults: The cisplatin single dose administration to rats induced nephrotoxicity associated with a significant\nincrease in blood urea nitrogen (BUN) and serum creatinine and significantly increase Malondialdehyde (MDA) in\nkidney tissues by 230 �± 5.5 nmol/g compared to control group. The animal treated with cisplatin showed a\nsignificant increase in the expression levels of the IL-1�± (260%), TRFA2 (491%), P38 (410%), MKK4 (263%), MKK7 (412%)\n, JNK (680%) and TNF-�± (300%) genes compared to control group. Additionally, histopathological examination\nshowed that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, cell infiltrate, acute\ntubular injury with reactive atypia and apoptotic cells. Rutin administration attenuated cisplatin-induced alteration in\ngene expression and structural and functional changes in the kidney. Additionally, histopathological examination of\nkidney tissues confirmed gene expression data.\nConclusion: The present study suggested that the anti-oxidant and anti-inflammatory effect of rutin may prevent\nCP-induced nephrotoxicity via decreasing the oxidative stress, inhibiting the interconnected ROS/JNK/TNF/P38 MAPK\nsignaling pathways, and repairing the histopathological changes against cisplatin administration.
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