Reactive oxygen species: production and role in the kidney

Abstract

Reactive oxygen species (ROS) are formed by incomplete reduction of molecular oxygen. They include superoxide anion (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (OH.), and singlet oxygen (1O2). ROS may induce different types of cell injury, particularly lipid peroxidation and membrane damage. ROS have been shown to play an essential role in the mechanisms of experimental models of several renal diseases: ischemic acute renal failure, renal graft rejection, acute glomerulonephritis, and toxic renal diseases. They are produced by the renal cells and also by the inflammatory bone marrow-derived cells invading the renal tissue. ROS, regardless of their origin, may degrade the glomerular basement membrane and alter the glomerular and tubular cell functions. Particularly, they produce an increase in cyclic AMP synthesis and prostaglandin production in the glomeruli. Recent studies have shown that the glomerular mesangial cells themselves generated ROS on stimulation by phagocytosis of foreign particles or exposure to the complement membrane attack complex or platelet-activating factor. Production of ROS is in narrow relationship with the metabolism of arachidonic acid. Conversion of this fatty acid via the lipoxygenase pathway is associated with an increase of ROS, whereas its transformation into prostaglandins via the cyclooxygenase pathway results in the opposite effect. Production of ROS in activated mesangial cells can be inhibited by glucocorticoids via a receptor-mediated mechanism. The fact that some of these characteristics are different in leukocytes suggests the possibility in the future of the more specific pharmacological control of the inflammatory process in the glomerular mesangium.

Identification of Renox, an NAD(P)H oxidase in kidney

“…The kidney is susceptible to oxidative damage induced by ischemia-reperfusion, inflammatory, and toxic drug reactions that can lead to renal diseases such as acute ischemic renal failure, acute glomerulonephritis, and chronic or acute tubular disease (9). Although circulating leukocytes are known to be important mediators of oxidative damage to renal tissues, particularly the glomerular basement membrane, several resident renal cell types are also recognized for their capacity for significant superoxide release.…”

“…Cell-free assays have also detected NADH and NADPH-dependent oxidase activities in tubular cell membrane preparations (25), although the identities of these enzymes have been unclear. The identification of Renox as a source of superoxide in proximal convoluted tubules could have important physiological and pathological implications, because ROS play significant roles in tubular hypertrophic responses to angiotensin II (26) and the nephrotoxicity of drugs such as cyclosporin and aminoglycosides (9).…”

“…Overproduction of ROS in the kidney is also thought to have other important pathophysiological consequences, because it is associated with tissue injury and inflammatory reactions affecting tubular and glomerular cell functions (9). Herein, we describe the identification and characterization of a previously uncharacterized source of superoxide in the kidney referred to as a renal oxidase or Renox, which is highly expressed in the proximal tubules of the renal cortex and may fulfill the function of the putative oxygen sensor in the kidney.…”

Effect of Antioxidants (Vitamin C) on Tissue Ceruloplasmin Following Renal Ischemia Reperfusion in Wistar Rats

“…Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure, [3][4][5][6] . Several in vivo animal studies document a role of reactive oxygen molecules in causing tissue injury [7][8][9][10] Ascorbic acid has been used to protect against corneal damage from free radicals in rabbits 11 . In addition, it has also been used to improve the renal hemodynamics and decrease oxidative stress, inflammation and fibrosis in the ischemic kidney of pigs 12 .…”

Impairment of Mineralocorticoid Receptor (MR)-dependent Biological Response by Oxidative Stress and Aging

“…A profound imbalance between oxidants and antioxidants has been related to renal disorders, from minimal change nephritic syndrome to obstructive nephropathy (16,18). Moreover, patients with end-stage renal failure on maintenance hemodialysis are chronically exposed to the oxidative stress generated by reactive oxygen species due to perdialytic neutrophil activation (19).…”