Protective Effects of Vitamin C Concomitant Treatment on Deferasirox-induced Renal Toxicity in Rats

Abstract

Background and Aim: Deferasirox (Exjade) is an iron-chelating drug used in patients with beta-thalassemia major. Oxidative stress is among f the major causes of nephrotoxicity and its progression. Deferasirox, due to oxidative stress and increased cell apoptosis causes the dysfunction of renal tubules and renal toxicity. According to its antioxidant and anti-inflammatory properties, the present study explored the effect of vitamin C on deferasirox-induced kidney damage. Methods & Materials: This study was performed on 30 Wistar rats in 3 groups of control, deferasirox, and deferasirox plus vitamin C. To induce the nephrotoxicity, the intra-peritoneum injection of deferasirox (75 mg/kg/day) was used. After taking plasma from the blood samples of the explored rats, we determined the values of Cr, Na+, K+, Mg+, osmolality, and BUN in the obtained plasma and urine samples. The creatinine clearance, as well as the relative and absolute excretion of sodium and potassium, were also calculated. After separating the two kidneys, they were used for the histologic study with Hematoxylin and Eosin (H&E) staining, as well as Malondialdehyde (MDA) and Ferric Reducing Antioxidant Power (FRAP) biochemical studies. Ethical Considerations This study was approved by the Research Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1396.309). Results: Cotreatment with deferasirox and vitamin C reduced renal tissue MDA and relative and absolute Na and K excretion and urine osmolarity; this method also increased creatinine clearance and renal tissue FRAP. Conclusion: The co-administration of vitamin C presented a significant protective effect on the renal toxicity induced by deferasirox. The protective property of deferasirox is because of the antioxidant impacts of vitamin C in reducing oxidative stress and lipid peroxidation.

Keywords

• renal toxicity
• vitamin c
• deferasirox
• exjade
• rat