Tubular Kidney Protection by Antioxidants

Acute renal failure (ARF) or acute kidney injury (AKI) may develop due to numerous factors including obstruction of the urinary tract, toxic substances to kidney and low blood volume (1). Acute renal failure may lead to numerous complications including metabolic acidosis, ure-mia and changes in body fluid balance. The diagnosis of acute kidney injury is based mainly on the laboratory findings, such as blood creatinine and urea nitrogen. Management includes treatment of the underlying disorder and supportive care. Recently, attentions are mostly on protection or prevention as well as accelerating the regenera-tion of tubular cells against injurious insults to the kidney (1,2). Gentamicin is usually accumulated in kidney proximal tubular cells which may trigger renal injury , leading to brush border network damage (2,3). The kidney toxicity is usually caused by increased free radical production, suppression of antioxidant defense mechanisms as well as acute renal tubular cells necrosis which leads to kidney dysfunction and diminished glomerular filtration rate (GFR) (2,3). The pathological mechanisms include increase in endothelin-1, augmentation of oxidative stress, upregulation of transforming growth factor-beta (TGF-β), apoptosis, significant increase in monocyte/macrophage infiltration into the renal cortex or medulla and eventually necro-sis (2,4). Gentamicin has also been shown to increase the generation of reactive oxygen species (ROS), hydrogen peroxide, superoxide anions and hydroxyl radicals in proximal tubular cells, leading to kidney damage (3,4). Therefore, scientists usually focus on the use of various antioxidants for the treatment of gentamicin renal toxicity (2-4). In this regards, the role of antioxidants in mitigating the gentamicin renal toxicity protection, tubular effects and integrative glomerular and possible interplay have been described. Oxidative stress is induced by an increase in reac-tive oxygen species (ROS) and reactive nitrogen species (RNS) and/or decrease in body antioxi-dants. Indeed it is usually described as an imbalance between the level of production and removal of cell oxidants. This imbalance causes a decline in the ability of biological systems in detoxification of the reactive intermediates or repair of the resulting damage (3-5). Gentamicin induced acute renal toxicity is a common clinical entity with high mortality and morbidity rates which has been attributed to induction of oxidative stress in the kidney (4,5). Renal toxicity may also be induced by other complications like diabetes, chronic renal failure or vascular complications which all attributed to oxidative stress and hence put the patients at higher risk of acute renal failure due to ischemic and nephrotoxic insults …