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 pro-inflammatory 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 renal 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 carboplatindose 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.

Amelioration of Carboplatin-Induced Changes in Rat Renal Cortical Tubulesby Alpha-Tocopherol

“…Statistical difference was significant when it was compared with Group A. These findings were comparable to other studies, [19][20][21] which showed tubular degenerative changes, including desquamation and necrosis on histological sections. It was mentioned that oxidative stress plays an important role in causing the nephrotoxicity of carboplatin by generating free radicals and reactive oxygen species.…”

Efek Samping Kemoterapi Berbasis Karboplatin Terhadap Fungsi Ginjal Pada Pasien Kanker Ginekologi

“…Hal ini karena poliuria yang disebabkan oleh kerusakan tubular yang mengarah pada dehidrasi, salah satu penyebab kenaikan BUN. 12,38,39 Karboplatin merupakan generasi kedua dari agen kemoterapi platinum yang dibuat lebih rendah efek nefrotoksisitas dan neuropati perifernya dibanding cisplatin, sehingga karboplatin menjadi alternatif pilihan lain dari cisplatin pada beberapa kanker dengan kondisi fungsi ginjal pasien yang menurun. 33,[40][41][42] Hasil penelitian oleh Chen et al (2017) menunjukkan bahwa histologi ginjal dengan pengecatan HE menggambarkan tidak adanya efek nefrotoksisitas karboplatin dan hasil qPCR yang menunjukkan bahwa karboplatin tidak memberikan efek pada kadar Organic Cation Transporter-2 (rOCT2) mRNA yang merupakan salah satu marker dari terjadinya nefrotoksisitas.…”