Biochemical effects of pretreatment with vitamins E and C in rats submitted to intrastriatal hypoxanthine administration.

We previously demonstrated that intrastriatal injection of hypoxanthine, the major metabolite accumulating in Lesch-Nyhan disease, inhibited Na+,K+-ATPase activity and induced oxidative stress in rat striatum. In the present study, we evaluated the action of vitamins E and C on the biochemical alteration induced by hypoxanthine administration on Na+,K+-ATPase, TBARS, TRAP, as well as on superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx) activities in striatum of adult rats. Animals received pretreatment with vitamins E and C or saline during 7 days. Twelve hours after the last injection of vitamins or saline, animals were divided into two groups: (1) vehicle-injected group and (2) hypoxanthine-injected group. For all parameters investigated in this research, animals were sacrificed 30 min after drug infusion. Results showed that pretreatment with vitamins E and C prevented hypoxanthine-mediated effects on Na+,K+-ATPase, TBARS and antioxidant enzymes (SOD, CAT and GPx) activities; however the reduction on TRAP was not prevented by these vitamins. Although extrapolation of findings from animal experiments to humans is difficult, it is conceivable that these vitamins might serve as an adjuvant therapy in order to avoid progression of striatal damage in patients affected by Lesch-Nyhan disease.

Dietary soy prevents brain Na+, K(+)-ATPase reduction in streptozotocin diabetic rats.

The aim of this study was to investigate Na+, K(+)-ATPase activity in cerebral cortex, hippocampus and hypothalamus of diabetic rats. The action of dietary soy protein on the effect produced by diabetes on this activity was also tested. Forty-nine-day-old Wistar were divided into two groups: diabetes streptozotocin (50 mg/kg body weight) and control (citrate solution). Rats were sacrificed 56 days later. In other set of experiments, rats received a dietary with casein (control) from day 21 to the 49 of postnatal-age and were subjected to diabetes or received citrate (control). One week later, rats received a special dietary with soy protein with isoflavones or casein (control) from day 56 to the 105 of postnatal-age. Results showed that diabetic rats presented a reduction ( approximately 40%) of Na+, K(+)-ATPase activity in all structures studied. Pretreatment with soy protein prevented the inhibitory effects of diabetes on the enzyme activity. Assuming the possibility that these effects might also occur in the human condition, our findings may be relevant to explain, at least in part, the neurologic dysfunction associated with diabetes and might support a novel therapeutic strategy (soy protein) to slow the progression of neurodegeneration in this disorder.

Protective effect of antioxidants on brain oxidative damage caused by proline administration.

We have previously demonstrated that acute and chronic hyperprolinemia induce oxidative stress in cerebral cortex of rats. In the present study, we investigated the action of Vitamins E and C on the oxidative damage elicited by acute and chronic administration of proline (Pro) in rat cerebral cortex. Results showed that treatment with Vitamins E and C prevented the alterations caused by acute and chronic administration of proline on chemiluminescence, total radical-trapping antioxidant potential (TRAP) and on the activities of catalase and glutathione peroxidase. If these effects also occur in the human condition, it is possible that antioxidant administration might serve as a potential adjuvant therapy to avoid the progression of the neuropsychiatric dysfunction observed in hyperprolinemic patients.