Research Overview

Prevention of renal injury after induction of ozone tolerance in rats submitted to warm ischaemia

Abstract

Introduction

Tissue ischaemia followed by reperfusion with oxy­genated blood occurs in a number of clinical situa­tions. In order to improve the success rate of renal transplantation, the timing of warm and cold ischae­mia is a major determinant for the kidney’s viability.1,2 After reimplantation, owing to reperfusion with oxygenated blood, the ischaemic kidney may develop tubular necrosis and the recipient needs to undergo dialysis. Furthermore, in order to avoid rejection, treatment with immunosuppressor drugs may, on one side worsen the renal damage, or become overtly toxic.1 Thus any prophylactic approach aiming at preserving the kidney is of a crucial importance. Recent advances in understanding the fundamental mechanisms of post-ischaemic injury have suggested that tissue injury is associated with higher oxygen (O2) tension in the tissue at the time of reperfusion.2i3 The reoxygenation leads to a massive production of reactive oxygen species (ROS), generated through several cytoplasmatic or mitochondrial mechanisms, inducing an unbalance between oxidants and anti-oxidants, i.e. an oxidant stress, which contributes to tissue injury.2,4-6 ROS among which superoxide anion (02-.) hydrogen peroxide (H2O2), hydroxyl radical (OH.), not only can damage cells by oxidizing nucleic acids, proteins and polyunsaturated lipids,7 but may ultimately lead to cell death. There is no doubt that ROS, if unquenched, can compromise renal function by impairing glomerular filtration and tubular reabsorption.8 In normal conditions, cells contain a powerful and articulate endogenous defense against ROS9 such as

antioxidant enzymes, namely superoxide dismutase (SOD), catalase, glutathione peroxidase, thioredoxin reductase, or nonenzymatic components such as ascorbic and uric acid, reduced glutathione, [3-car-otene, lycopene, vitamin E, bilirubin, etc.2‘8‘9 In several pathologic situations and after ischaemia, these defence mechanisms can be overwhelmed allowing the ROS to exert their deleterious effect.2

Taking into account that ischaemia-reperfusion is a process largely mediated by ROS generation2-6 and that a prolonged and judicious administration of 0} is able to stimulate the endogenous antioxidant sys­tems,11-14 and thereby to oppose the oxidative stress, we thought it worthwhile assessing renal morphology and function and a few biochemical parameters in rats undergoing a controlled, warm renal ischaemia.