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‐dihydroxy‐phenylalanine (DOPA), and 3,4‐dihydroxyphenylacetic 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‐cysteinyl 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 scorbutogenic 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.