Pathophysiology of iron overload-induced renal injury and dysfunction: Roles of renal oxidative stress and systemic inflammatory mediators.

Iron-overload has been recognized as a risk factor for organ dysfunction and damage resulting in diseases such as liver and heart disease, diabetes mellitus, and neurodegenerative diseases. This study investigated renal function and some systemic inflammatory indices in iron-overloaded male Wistar rats. Thirty animals were equally distributed into 3groups and treated daily i.p. with either normal saline (0.2 ml; control), iron (as ferrous sulphate) (15 mg/kg) or iron (30 mg/kg) for 21days respectively. Post-treatment, blood samples were obtained from each animal by cardiac puncture after light anaesthesia into plain sample bottles. Iron, ferritin, transferrin, creatinine, urea, albumin, total protein, interleukin-6 (IL-6), prostaglandins-E2 and tumor necrosis factor-α (TNF-α) were analysed in serum. Kidney homogenates were obtained per group and analysed for superoxide dismutase (SOD), total antioxidant capacity (TAC), reduced glutathione (GSH), lipid peroxidation (MDA) and nitric oxide (NO). Kidney histology was evaluated per group using both Haematoxylin and Eosin and periodic acid Schiff stains. Iron-overload caused a graded increase (p < 0.05) in serum iron, ferritin, transferrin, creatinine, urea, IL-6, TNF-α, TAC, MDA and NO levels as well as a reduction in albumin levels, renal SOD and GSH in groups 2 (iron 15 mg/kg) and 3 (iron 30 mg/kg) respectively compared to control. Histological evaluation of the kidney showed structural and tubular aberrations consistent with renal damage via inflammatory processes in iron overloaded rats. Our present study suggests that iron-overloading causes renal dysfunction by triggering the evolution of several inflammatory mediators which lead to a cascade of systemic and renal inflammatory processes that alter renal structure and function.