Oxidative stress and protective effects of polyphenols: Comparative studies in human and rodent kidney. A review

Abstract

Reactive oxygen species (ROS) play a key role in the pathophysiological processes of a wide range of renal diseases. Thus, antioxidants are expected to decrease the vulnerability of the kidney to oxidative challenges. Polyphenols, particularly abundant in red wine, could act as ROS scavengers, iron chelators and enzyme modulators. In addition, chronic exposure to moderate amounts of ethanol results in increased activity of the renal antioxidant enzymes, further supporting a renoprotective effect of red wine based on its antioxidant properties. An enhancement of plasma antioxidant capacity following red wine consumption has been reported both in man and rodents, thereby providing a contributory factor to its renoprotective effect because the kidney is a highly perfused organ. Although phenol concentration of red wine does not influence the activity of antioxidant enzymes of the kidney, the concentration of these compounds is negatively correlated with tissue lipid peroxidation, assessed by thiobarbituric acid reactive substances, and positively correlated with the antioxidant capacity of plasma. Moreover, amelioration of myoglobinuric renal damage was found in rats following chronic exposure to flavonol-rich red wine. Also, pretreatment with resveratrol, or other red wine polyphenols, decreased kidney damage caused by ischaemia–reperfusion. The aim of the present review is to examine the pathophysiological basis of the renoprotective effect of red wine in man and rodents, based on functional, biochemical and ultrastructural evidence.

Introduction

Considerable experimental evidence has contributed to support a key role of reactive oxygen species (ROS) in the numerous mechanisms of seemingly unrelated nephropathies (Rodrigo and Rivera, 2002). While enzymatic and non-enzymatic systems preserve the antioxidant/oxidant status, these defense systems become overwhelmed during oxidative stress, a metabolic derangement due to an imbalance caused by excessive generation of ROS or a diminished antioxidant capacity. It has long been recognized that ROS are harmful for cells, mainly because they injure lipids, proteins, and nucleic acids, which leads to structural and functional impairments (Freeman and Crapo, 1982, Mantle and Preedy, 1999). Numerous interventions have been put forward to counteract the effects of ROS, by reinforcing the antioxidant defense systems. Dietary supplementation with the antioxidant vitamin E slowed the rate of progression of renal deterioration (Fryer, 1997), attenuated the nephrotoxicity caused by ferric nitrilotriacetate (Fe-NTA) (Iqbal and Athar, 1998) and ameliorated the glomerulosclerosis occurring in the nephrectomy remnant kidney model in the rat (Hahn et al., 1999). Also, gentamicin-induced nephrotoxicity was ameliorated with garlic, known to be rich in polyphenols (Pedraza-Chaverri et al., 2000). Recently, the possible advantage of a moderate wine consumption in patients with chronic renal failure was hypothesized (Caimi et al., 2004). Therefore, it is expected that the naturally occurring nutritional sources of antioxidants, such as fruits, vegetables, tea or wine, would also attenuate the renal damage caused by oxidative challenges. Polyphenolic compounds, abundant in these nutritional sources, could play a major role in enhancing the antioxidant system, since they behave as ROS scavengers, metal chelators and enzyme modulators (Pietta et al., 1998). In agreement with this view, it was demonstrated that resveratrol, a stilbene polyphenol found in grapes and red wine, suppresses the proteinuria, hypoalbuminemia and hyperlipidemia induced by anti-rat kidney antiserum (Nihei et al., 2001). Also, renoprotective effects have been reported for other polyphenols such as quercetin (Ishikawa and Kitamura, 2000) and alpha-G-rutin (Shimoi et al., 1997). Although these studies have been performed in rodents, it was suggested that this protection may be useful to prevent or treat myoglobinuric acute renal failure in humans (Stefanovic et al., 2000), two species with great similarity on the mechanism of renal injury in this setting. Although dietary supplements containing polyphenols have been used in humans, a safety assessment of the applied dose has been recommended due to the possibility of some adverse effect of this mode of consumption (Mennen et al., 2005). The aim of the present review is to examine the pathophysiological basis of the renoprotective effect of red wine polyphenols in humans and rodents, based on functional, biochemical and ultrastructural evidences.