Kidney Tubular Cell Protection; Recent Findings

Hamid Nasri1, MD; Mahmoud Rafieian-Kopaei2*, MD 1Department of Nephrology, Division of Nephro pathology, Isfahan University of Medical Sciences, Isfahan, 2Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran Received: Aug 22, 2013; Accepted: Sep 30, 2013; First Online Available: Dec 12, 2014 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[1-3]. Acute renal failure may lead to numerous complications including metabolic acidosis, uremia 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[4-8]. Recently, attentions are mostly on protection or prevention as well as accelerating the regeneration of tubular cells against injurious insults to the kidney. To study acute kidney injury, various models have been defined for each specific condition. Gentamicin (GM) which is an aminoglycoside antibiotic and is derived from gram-positive bacteria, has a potential for the treatment of aerobic gramnegative infections. Gentamicin is extensively used for induction of ARF in preclinical studies and evaluation of renal protective agents. Gentamicin is usually accumulated in kidney proximal tubular cells which may trigger renal injury, leading to brush border network damage[9,11]. The kidney toxicity is usually caused by increased free radical production, suppression of antioxidant defense mechanisms as well as acute renal tubular cells necrosis[9-12], which lead to kidney dysfunction and diminished glomerular filtration rate (GFR). 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 necrosis[10-15]. 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[9,10]. Therefore, scientists usually focus on the use of various antioxidants for the treatment of gentamicin renal toxicity[9,10]. 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 reactive oxygen species (ROS) and reactive nitrogen species (RNS) and/or decrease in body antioxidants. 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. Therefore, in gentamicin administration in should be noted that it might induce severe renal toxicity. The renal toxicity of gentamicin is high enough to be used in the study of drug-induced acute kidney damage. In fact, 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[8-11]. Renal toxicity may also be induced by other complications like diabetes, chronic renal failure or vascular complications, all of which induce oxidative stress and hence put the patients at higher risk of acute renal failure due to ischemic and nephrotoxic insults[11-15]. Medicinal plants which mostly possess a lot of phytochemicals with antioxidant properties have been recently in the focus of researchers and scientists for treatment and prevention of various oxidative stress-related complications[8,16,17]. These plants have antioxidant activities due to phytochemicals including phenolic and carotenoid compounds[16-19]. Phenolic compounds are abundantly presented in herbal medicines and food products and mainly consist of flavonoids, anthocyanins, phenolic acids and tannins with antioxidant activities[16-21]. These Letters to Editor Iran J Pediatr Dec 2014; Vol 24 (No 6), Pp: 781-789