Erythropoietin Attenuation Of Early Upregulation Of Kidney Injury Parameters Levels In Cisplatin-Treated Rats..

Abstract

Background: cisplatin chemotherapy can cause acute kidney injury (AKI) in about 30% of patients that act as a major dose-limiting problem complicating chemotherapy by cisplatin that still commonly indicated as first line treatment of cancer management without relatively less toxic and equally effective substitutes. Cisplatin induced-DNA damage and oxidative- inflammatory hyper-reactivity with apoptosis are the bases for cisplatin-induced AKI. Erythropoietin has approved antioxidant, anti-inflammatory and to some extent antiapoptotic effects that may have ameliorative effect on early cisplatin-induced AKI. Kidney injury molecules-1 (KIM-1) and interleukin-18 (IL-18) were assumed to be more sensitive for detecting AKI than the traditional kidney function tests (serum creatinine and urea). Objective: assess the effect of erythropoietin on early upregulation of kidney injury parameters after cisplatin treatment. Methods: 27 adult male rats were randomized into three groups containing nine rats for each as follow: Sham group: rats received daily intraperitoneal injection of placebo for 4 days. Cisplatin group: rats received single intraperitoneal injection of 6 mg kg cisplatin. Cisplatin+Erythropoietin group: rats received single intraperitoneal injection of 6 mg kg cisplatin and daily intraperitoneal injection of 100 IU kg erythropoietin for 4 days. After scarification, blood samples are collected for serum creatinine measurement, kidneys are processed for measurement of renal MDA, KIM-1 and IL-18 and histopathlogical evaluation. Results: cisplatin produced significant (P<0.05) change in serum creatinine level, kidney MDA, KIM-1, IL-18 and score of histopathological damage severity when compared to that of other groups. In Cisplatin + Erythropoietin group, Serum creatinine, and kidney MDA, KIM-1, IL-18 and total severity score were significantly (P<0.05) less than that in cisplatin group. Conclusion: erythropoietin ameliorated early cisplatin–induced AKI evidenced by improving early injury parameters that give rise for early involvement of erythropoietin as early preventive measure for protection from nephrotoxicity.