VITAMIN-C-DEFICIENCY FACILITATES 5-S-CYSTEINYLDOPAMINE FORMATION IN GUINEA-PIG STRIATUM

Being a catechol, dopamine (DA) is easily autoxidized in solution to a semiquinone and then further to a quinone. These quinones and by-products, as reduced forms of oxygen, are all cytotoxic. By quantifying quinone metabolites, such as 5-S-cysteinyl adducts of DA, 3,4-dihydroxyphenylalanine (DOPA), and 3,4-dihydroxphenylacetic acid (DOPAC), an indirect measure of catechol autoxidation is available. Ascorbic acid (AA) has an important role as an antioxidant in the organism. A group of guinea pigs (Dunkin-Hartley) received an AA-free diet for 37 days, whereas a control group was fed an AA-containing diet (1,400 mg/kg of pellets). To one group of AA-deprived animals a single dose of AA (500 mg/kg, i.p.) was administered 2 h before death, whereas another group received two doses 9 and 24 h before death. The striatal levels of 5-S-cysteinly adducts, DA, noradrenaline, and DOPAC and the cerebellar and the limbic levels of AA were determined. A significant increase in 5-S-cysteinyl-DA content was found in the striatum of AA-deficient animals (143 +/- 12% of control values). A further increase was found 2 h after an AA injection (177 +/- 16% of control values), which was significant compared with both controls and AA-deficient animals. An elevation in 5-S-cysteinyl-DA content was still observed following two AA injections during a 24-h period (153 +/- 7% of control values). The 5-S-cysteinyl-DOPAC content increased significantly (134 +/- 14% of control values) in the AA-deficient animals given AA acutely (2 h), both compared with controls and with the AA-deficient group. DA levels increased nonsignificantly to 113% 2 h following an AA injection and significantly to 117% following two doses of AA within 24 h of AA injection. No other changes compared with normal animals were detected for any catechol examined. In guinea pigs given a scrobutogenic diet the AA levels decreased to 11-12% in the cerebellum and in the limbic system. Following a single dose of AA the brain levels increased to 19-23%, and in animals given AA 9 and 24 h before death AA levels reached 61-72% of control values in the cerebellum and in the limbic system. Thus, the present study indicates an increased autoxidation rate of DA in the striatum of AA-depleted guinea pigs and a prooxidant acute effect of AA administration to these animals.