Introduction: Deferasirox, as an oral iron chelator, is presently the first-choice medication for iron overload caused by repeated blood transfusions due to its ease of use, efficacy, and high bioavailability, yet deferasirox has been also reported with the occurrence of acute kidney injury and tubular dysfunction. Vitamin E is a potent antioxidant and anti-inflammatory agent.
Aim of the Work: To study the effect of deferasirox on the oxidative status, histological structure, apoptosis, proliferation, and inflammation of the renal cortical tubules and examine the potential protective role of vitamin E against such effect in adult male albino rat.
Material and Methods: Twenty-four adult male albino rats were subdivided into four equal groups; control, vitamin E-treated (100 mg/kg/day vitamin E orally for 4weeks), deferasirox-treated group (100 mg/kg/day deferasirox orally for 4weeks), and vitamin E&deferasirox-treated group (concomitantly administered vitamin E and deferasirox). Kidney specimens were processed for different biochemical, histological, and immunohistochemical studies.
Results: Deferasirox-treated group revealed loss of the normal histological architecture of the renal cortex involving numerous nuclear and cytoplasmic alterations of renal cortical tubules with inflammatory signs. Tissue malonaldehyde level was significantly surged. A significant increase in caspase-3, Ki67, and iNOS immunohistochemical expression was recorded, whereas a significant drop in the histochemical expression of PAS was detected. Results from the group concomitantly administered with vitamin E and deferasirox exhibited an apparently normal histology of the renal cortex with a non-significant difference in all studied parameters compared to the control group.
Conclusion: Deferasirox administration led to histological alterations in the renal cortical tubules through inducing oxidative stress, apoptosis, proliferation, and inflammation. Concomitant supplementation with vitamin E exerted a protective action against deferasirox harmful effects most probably through its antioxidative, antiapoptotic, and anti-inflammatory properties.