Hypothesis paperRenal damage mediated by oxidative stress: a hypothesis of protective effects of red wine
Introduction
Considerable experimental evidence supports the view that reactive oxygen species (ROS) play a key role in the pathophysiologic processes of renal diseases. The cellular damage is mediated by an alteration in the antioxidant status, which increases the concentration of ROS in the stationary state (oxidative stress). The abundance of polyunsaturated fatty acids (PUFA) makes the kidney an organ particularly vulnerable to ROS attack [1]. The involvement of ROS is supported by two lines of experimental evidence; namely, (i) detection of products of oxidant injury in renal tissue or urine, and (ii) experimental demonstration of a protective effect of metabolic inhibitors of ROS [2].
Oxidative stress mediates a wide range of renal impairments, from acute renal failure [3], [4], [5], [6], [7], rhabdomyolysis [6], [8], obstructive nephropathy [9], [10], hyperlipidemia [11], [12], [13], [14], and glomerular damage [15], [16], [17] to chronic renal failure and hemodialysis [18], [19], [20], [21], as summarized in Table 1. Therefore, interventions favoring the scavenging and/or depuration of ROS (dietary and pharmacological antioxidants), should attenuate or prevent the oxidative stress, thereby mitigating against the subsequent renal damage. Polyphenols are a group of naturally occurring antioxidant substances found in vegetables, fruits or tea, and are particularly abundant in red wine [22].
In recent years, the benefits of moderate consumption of alcoholic beverages, particularly red wine, in the prevention of heart diseases has received increasing attention in the popular media as well as in the scientific community [23]. The health benefits of wine in human health are well documented [24], and it has been associated with increased longevity and diminished risk of coronary heart diseases [25]. The antioxidant protection by wine might be due to the combined effects of ethanol and nonalcoholic components with antioxidant properties. Also, moderate prandial wine consumption had no adverse effects on the glycemic control of diabetic patients [26], and it did not improve or impair insulin sensitivity in overweight women or change any of the known correlates of insulin sensitivity, including body weight and composition, blood lipids, and blood pressure [27].
We present a hypothesis of a protective effect of red wine against renal injuries mediated by oxidative stress, based on recent biochemical, morphologic, and functional data supporting this view. The mechanisms of renal damage mediated by oxidative stress, and their possible attenuation by wine, will be analyzed focusing on the cellular effects of free radicals on the kidney.
Section snippets
Wine components and their antioxidant properties
Antioxidant effects of wine can be attributed either to ethanol and nonalcoholic components. The beneficial effects of low to moderate intake of alcohol are shown by epidemiological studies reporting its association with lower mortality from cardiovascular diseases [25]. Also, a role of phytochemicals, such as those contained in red wine, has been recently suggested to improve age-related neurological dysfunctions [28]. Therefore, the possibility exists that these effects also occur in the
Renal alterations associated with oxidative stress
Oxidative stress constitutes the mechanism of production and progression of numerous renal diseases. Thus, increased levels of malondialdehyde and F2-isoprostanes, both products of lipid peroxidation, have been reported in various situations associated with renal damage [65]. Clinical and experimental evidences of renal damage mediated by oxidative stress will be grouped in glomerular, tubulointerstitial, and endothelial alterations.
Cellular redox signalling and its intervention by antioxidants
Cellular redox state is a component of stress-induced response in disease. The prototypic mediator of this response is NF-κB, a transcription factor that exists in a latent form in the cytoplasm of unstimulated cells. NF-κB is a dimer that has long been recognized as being activated by ROS, and behaving as a second messenger. The activation of NF-κB is controlled by a family of repressor proteins called IκB, that release NF-κB. The translocation of NF-κB into the nucleus, results in its binding
Conclusions
Cumulative data indicate that oxidative stress represents a step common to the mechanism of a wide range of seemingly unrelated renal diseases. The involvement of ROS has been reported in glomerular and tubulointerstitial alterations. Naturally occurring antioxidants (e.g., polyphenols), in beverages or pharmacological agents (e.g., N-acetylcysteine, or α-tocopherol), show renoprotective effects against oxidative challenges. Isolated wine poliphenols, such as quercetin, G-rutin, curcumin, or
Acknowledgements
This research was supported by the Fondo Nacional de Ciencia y Tecnologı́a (FONDECYT, grant 1990784). The authors would like to thank Dr. Eduardo Lissi for his valuable comments during the editing of the manuscript.
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