In vivo and in vitro effects of proline on some parameters of oxidative stress in rat brain

Hyperprolinemia type II is an autosomal recessive disorder caused by the severe deficiency of Delta(1)-pyrroline-5-carboxylate dehydrogenase activity leading to tissue accumulation of proline (Pro). Most patients detected so far show neurological manifestations including epilepsy and mental retardation, whose pathophysiology is not yet fully established. In the present study, we determined the in vivo and in vitro effects of Pro on some parameters of oxidative stress, namely chemiluminescence, total radical-trapping antioxidant potential (TRAP) and the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) from cerebral cortex of 29-day-old Wistar rats. Results showed that acute administration of Pro provoked a significant increase of chemiluminescence and a decrease of TRAP, whereas chronic administration of the metabolite did not alter these parameters. Furthermore, in vitro brain exposure to Pro resulted in increased chemiluminescence and decreased TRAP at Pro concentrations similar to those observed in tissues of hyperprolinemic patients (0.5-1.0 mM). As regards to the antioxidant enzymes, acute injection of Pro significantly decreased CAT activity and did not alter SOD and GSH-Px activities, whereas chronic Pro administration provoked a significant increase of CAT activity, a decrease of GSH-Px activity and did not modify SOD activity. Furthermore, CAT, GSH-Px and SOD activities were not affected by the presence of Pro in the incubation medium. The data indicate that Pro induces oxidative stress in vivo and in vitro, which may be involved in the brain dysfunction observed in hyperprolinemic patients. (C) 2003 Elsevier B.V. All rights reserved.