Effects of ochratoxin a on oxidative damage in rat kidney: protective role of melatonin

Abstract

Epidemiological studies indicate that ochratoxin A (OTA) may be involved in the pathogenesis of different forms of human nephropathies. Melatonin (MEL) displays antioxidant and free radical scavenger properties. In the present study, the effect of MEL on the oxidative stress induced by OTA administration in rats was investigated. Three groups of eight rats each were used: control, OTA (289 micro g kg(-1) day(-1)) and OTA + MEL (OTA, 289 micro g kg(-1) day(-1); MEL, 10 mg kg(-1) day(-1)), with treatment at two different time periods during the same day. After 4 weeks of treatment, the levels of lipid peroxidation (LPO) and the activities of catalase, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) were measured in homogenates of kidney. In OTA-treated rats, the levels of LPO and the activities of GSHPx and SOD were significantly decreased compared with controls. In OTA + MEL-treated rats, SOD, GSHPx and catalase activities and LPO levels were not changed significantly in comparison with controls.

Early cytotoxic effects of ochratoxin A in rat liver: A morphological, biochemical and molecular study

“…Low GSH concentrations in vitro (Schaaf et al, 2002;Kamp et al, 2005b) and in vivo have been reported after exposure to OTA (Gautier et al, 2001;Meki and Hussein, 2001;Ozcelik et al, 2004), as well as decreases in the activities of CAT, GPx, GR, and SOD in both liver and kidney (Meki and Hussein, 2001;Ozcelik et al, 2004). Here, we found that chronic treatment with OTA tended to reduce SOD mRNA levels, suggesting that OTA affects SOD at the transcriptional level too.…”

“…An increase in malondialdehyde (MDA), a biomarker of lipid peroxidation, was reported in serum and in the liver and kidney of OTA-treated rats (Meki and Hussein, 2001;Ozcelik et al, 2004). MDA levels were measured as thiobarbituric acid reactivity (TBARS) by spectrophotometric assay.…”

“…Although OTA seems to induce mild oxidative stress and it was suggested that the antioxidant melatonin might protect against OTA toxicity in rat liver and kidney (Meki and Hussein, 2001;Ozcelik et al, 2004;Abdel-Wahhab et al, 2005), the absence of significant alterations in a number of late biomarkers of severe oxidative stress (e.g. protein carbonyls) after exposure to OTA (Kamp et al, 2005a;Mally et al, 2005a,b) seems to indicate that severe oxidative stress is not a major contributor to OTA cytotoxicity.…”

Papaya fruits extracts enhance the antioxidant capacity and modulate the genotoxicity and oxidative stress in the kidney of rats fed ochratoxin A-contaminated diet

“…Taken together, the decreased in food intake reported herein and the interference of OTA with selenium absorption may be two reasons for the decreased activity of GSH-Px. On the other hand, SOD is a copper/ zinc-containing enzyme and is responsible for the catalytic dismutation of the highly reactive or potentially toxic superoxide radicals to hydrogen peroxide (Ozçelik et al, 2004;Sutken et al, 2007). In this concern, Meki and Hussein (2001) suggested that OTA interact with zinc and copper in SOD molecules and inhibits its activity and produces inhibition of the enzyme activity.…”

“…In addition, OTA produces various changes in the cells such as the enhancement of the cell permeability to Ca 2+ . The increase in Ca 2+ concentration in the cell beside the presence of OTA as prooxidant lead to uncouple the oxidative phosphorylation consequently increase the electrons leakage from respiratory chain, generate O 2-and hence H 2 O 2 (Abdel-Wahhab et al, 2005;Ozçelik et al, 2004). This lack in the adequate supply of GSH and NAD(P)H permits the consumption of H 2 O 2 by the NAD(P)H dependent GSR and GSH dependent GPx (Abdel-Wahhab et al, 2008;Hohler et al, 1997).…”