Oxidative stress and protective effects of polyphenols: Comparative studies in human and rodent kidney. A review ☆ Ramón Rodrigo a, ⁎ , Cleofina Bosco b a Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile b Morphology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile 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. Keywords: Antioxidants; Oxidative stress; Antioxidant enzymes; Red wine; Ethanol; Renoprotection; Polyphenols; Lipid peroxidation Contents 1. Introduction .............................................................. 318 2. Protective effects of wine polyphenols in man ............................................ 318 3. Renal alterations associated with oxidative stress........................................... 319 3.1. Glomerular alterations ..................................................... 319 3.2. Tubulointerstitial alterations .................................................. 320 4. Integrated renoprotective effects of wine polyphenols ........................................ 321 4.1. Functional studies ....................................................... 321 4.2. Biochemical effects ...................................................... 323 4.3. Morphological studies ..................................................... 323 ☆ This paper is part of a special issue of CBP dedicated to “The Face of Latin American Comparative Biochemistry and Physiology” organized by Marcelo Hermes- Lima (Brazil) and co-edited by Carlos Navas (Brazil), Tania Zenteno-Savín (Mexico) and the editors of CBP. This issue is in honour of Cicero Lima and the late Peter W. Hochachka, teacher, friend and devoted supporter of Latin American science. ⁎ Corresponding author. Programa de Farmacología Molecular y Clínica, Facultad de Medicina, Universidad de Chile, Independencia 1027, Casilla 70058, Santiago 7, Chile. Fax: +56 2 7372783. E-mail address: rrodrigo@med.uchile.cl (R. Rodrigo).