Amelioration of myoglobinuric renal damage in rats by chronic exposure to flavonol-rich red wine.

Abstract

Myoglobinuric acute renal failure causes increased oxidative stress. Since ethanol upregulates renal antioxidant enzymes and wine polyphenols behave as antioxidants, we tested the hypothesis that red wine components would ameliorate the renal damage caused by rhabdomyolysis. Adult rats received water (control), alcohol-free red wine, ethanol 12.5% (v/v) or red wine for 10 weeks. Rhabdomyolysis was induced by glycerol injection (50%, 10 ml/kg, i.m.), and urine and blood samples were collected 6 h later to measure renal function parameters, creatine kinase (CK) activity, free F(2)-isoprostanes and total antioxidant capacity. Kidneys were then harvested for morphological studies and determinations of lipid peroxidation, protein carbonylation, (Na + K)-ATPase and antioxidant enzyme activities. In the control group, myoglobinuria was associated with a 68% decrease in creatinine clearance and increases in plasma creatinine and blood urea nitrogen of 3.2 and 1.8 times above baseline, respectively. Controls also showed increases in plasma free F(2)-isoprostanes levels and CK activity, together with enhanced renal expression of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase, as well as increased production of malondialdehyde and carbonyls. Rhabdomolysis reduced renal (Na + K)-ATPase activity and this reduction was associated with a 5-fold increase in fractional sodium excretion as well as morphological damage to the kidney. These changes were significantly attenuated by pretreatment with chronic red wine exposure prior to glycerol injection. A less marked degree of functional and biochemical protection was also observed in response to the administration of alcohol-free red wine and ethanol. The present data suggest that red wine protects against functional, biochemical and morphological damage caused by rhabdomyolysis in the rat, and this protection may be due to the synergistic effects of ethanol and non-alcoholic red wine components.