Protective effect of resveratrol on citrullinemia type I-induced brain oxidative damage in male rats.

Abstract

Citrullinemia Type I is an inborn error, which leads to accumulation of citrulline and ammonia in blood and body tissues. We evaluated the in vitro effects of citrulline, ammonia and the influence of resveratrol on oxidative stress parameters in the cerebrum of 30- and 60-day-old male Wistar rats. Citrulline (0.1, 2.5, 5.0mM), ammonia (0.01, 0.1, 1.0mM) and resveratrol (0.01, 0.1, 0.5mM) were added to the assays to measure thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl content and the activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Citrulline (2.5 and 5.0mM) increased TBA-RS in the cerebellum of 30-day-old and in the cerebral cortex and cerebellum of 60-day-old. Citrulline (5.0mM) increased SOD and reduced GSH-Px in the hippocampus of 30-day-old, whereas in the cerebellum it increased GSH-Px. In the cerebral cortex, 2.5 and 5.0mM citrulline reduced GSH-Px. In 60-day-old, 2.5 and 5.0mM citrulline increased SOD in the cerebellum, increased GSH-Px in the cerebral cortex and 5.0mM citrulline reduced CAT and increased SOD in the cerebral cortex. Ammonia (0.1 and 1.0mM) reduced the sulfhydryl content in the cerebral cortex of 30- and 60-day-old, 1.0mM ammonia increased SOD and reduced GSH-Px in the cerebellum of 30-day-old and increased SOD in the hippocampus and cerebellum of 60-day-old. Resveratrol was able to prevent the majority of these alterations. Thus, citrulline and ammonia induce oxidative stress in the cerebrum of rats; however, resveratrol was able to exert antioxidant effects against these substances.