Homogenates of perfused rat brain generated oxidized glutathione from reduced glutathione during incubation with dopamine or serotonin. This activity was blocked by pargyline, a monoamine oxidase inhibitor, or by catalase, a scavenger of hydrogen peroxide. These results demonstrate formation of hydrogen peroxide by monoamine oxidase and the coupling of the peroxide to glutathione peroxidase activity. Oxidized glutathione was measured fluorometrically via the oxidation of NADPH by glutathione reductase. In the absence of added dopamine or serotonin, a much smaller amount of reduced glutathione was oxidized; this activity was blocked by catalase, but not by pargyline. Therefore, endogenous production of hydrogen peroxide, not linked to monoamine oxidase activity, was present. These results indicate that glutathione peroxidase (linked to hexose monophosphate shunt activity) can function to eliminate hydrogen peroxide generated by monoamine oxidase and other endogenous sources in aminergic neurons.
Catalase activity was measured in 11 areas of perfused adult rat brain. The hypothalamus and substantia nigra contained the highest activities. The corpus callosum, a white-matter structure, contained intermediate activity. The caudate-putamen and frontal cortex contained the lowest activities. Regional catalase bears some relationship to the reported distribution of microperoxisomes, but considerable activity is present in areas with few microperoxisomes. Catalase may function as one of the systems detoxifying H2O2 formed in CNS amine metabolism.
Seizures are a recognized complication of human immunodeficiency virus (HIV)-type-1 infection. CNS disease processes in these patients include encephalitis, focal brain lesions, and meningitis. Metabolic causes of seizures have received little attention. In a retrospective study, we selected 68 HIV-seropositive patients with new-onset seizures and information available for specified metabolic factors on the day of the first seizure. We sought an association of metabolic abnormalities with convulsive status epilepticus (CSE), which was the initial seizure in 12 patients, predominantly intravenous (i.v.) drug users. HIV-seropositive patients with new-onset seizures and hypomagnesemia or renal failure appeared to be at increased risk for CSE. All HIV-seropositive patients with new-onset seizures should undergo metabolic screening including renal function and serum magnesium levels.
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