Abstract

Nordihydroguaiaretic acid (NDGA) is a lignan with antioxidant properties present in high concentration in the leaves of Larrea tridentata. In the present study the potential protective effect of NDGA on ischemia-reperfusion (I/R) induced renal damage, oxidant stress and mitochondrial alterations was examined. Four groups of male Wistar rats were used: 1. Control; 2. NDGA; 3. I/R, and 4. I/R+NDGA. NDGA was injected i.p. (10 mg/Kg/day) starting 48 h before I/R. NDGA was able to prevent the following alterations induced by I/R: (a) renal dysfunction (evaluated by measuring blood urea nitrogen and plasma creatinine), (b) renal histological damage (quantified by automated morphometry), (c) oxidant stress (evaluated by immunohistochemical analyses of 3-nitrotyrosine, 4-hydroxynonenal and malondialdehyde), (d) decrease in the activity of the renal antioxidant enzymes glutathione peroxidase, glutathione reductase, glutathione-S-transferase and catalase, (e) decrease in state 3 mitochondrial oxygen consumption, (f) decrease in the activity of mitochondrial complex I and (g) increase in the mitochondrial content of 4-hydroxynonenal and malondialdehyde. It is concluded that the renoprotective effect of NDGA pretreatment on I/R-induced renal damage was associated to the preservation of antioxidant enzymes and to the prevention of oxidant stress and mitochondrial alterations.

Key words: Ischemia and reperfusion injury, antioxidant, oxidant stress, mitochondrial oxygen consumption, mitochondrial complex I activity.