The Role of Erythropoietin , Vitamin C and L-NAME in Carboplatin- Induced Hematological and Renal Dysfunctions

Abstract

Carboplatin is a neoplastic agent causing hematotoxicity, erythropoietin (EPO) resistance, increase oxidative stress and proinflammatory cytokines. Our study investigated the role of erythropoietin , vitamin C and L-NAME in carboplatin- induced hematological and renal dysfunctions.Seventy rats divided into seven groups; control, Carboplatin (100 mg/kg.), Carboplatin (250 mg/kg), Carboplatin (100 mg/kg.) pretreated by EPO , Carboplatin (250 mg/kg) pretreated by EPO, Carboplatin ( 250 mg/kg ) pretreated by EPO & Vitamin C and Carboplatin (250 mg/kg) pretreated by EPO & L-NAME. Hematological, plasma inflammatory cytokines, renal functions , oxidant, antioxidant parameters , serum EPO and vitamin C were measured with histopathology of liver tissue. Carboplatin decreased RBC count, hemoglobin concentration, packed cells volume, platelets count , superoxide dismutase , catalase and glutathione peroxidase, serum erythropoietin and vitamin C while WBCs count, interleukin 1, interleukin 6, tumor necrosis factor alpha, high-sensitivity C-reactive protein, serum blood urea nitrogen, serum creatinine, malondialdehyde and nitric oxide were increased. Vitamin C and L-NAME improved hematological derangement, EPO resistance, antioxidant parameters and histopathological findings while worsen plasma inflammatory markers, renal functions parameters and oxidative parameters. There was insignificant change in blood indices in all groups. We concluded that carboplatin had a hematological toxicity and oxidant stress effect in addition to increase proinflammatory cytokines and consequent renal insult. The development of EPO resistance was carboplatin – dose dependent . Vitamin C and L-NAME alleviate the hematological toxicity, oxidative stress, EPO resistance and decrease proinflammatory cytokines and in turn recovery of renal structure and functions.