Central Sympathoplegic and Norepinephrine-Depleting Effects of Antioxidants

Abstract

Carbon disulfide (CS₂), tetraethyl lead (TEL), tetraethyl tin (TeET), dithiothreitol (DTT), and gossypol acetic acid (GAA) significantly decreased brain norepinephrine (NE) in rats. The central dopamine (DA) increased after ip administration of CS₂, TEL, and DTT, but decreased after TeET and GAA. The brain serotonin decreased only after TeET. Two doses of DTT decreased the NE longer than one dose (24 vs 2 hr) but did not increase DA. L-DOPA, given SC with DTT, delayed the decrease in NE by 24 hr. The similar behavioral and autonomic effects of each of these compounds suggest a central sympatholytic effect and an antipsychotic type of sedation and rigidity. A possible mechanism is reversible inhibition of dopamine β-hydroxylase through the reduction of the copper ion of the enzyme. Each of these reducing agents, together with the boranes previously studied, has similar behavioral and autonomic effects and a common effect on NE concentration, suggesting that the agents act through a physicochemical property rather than by combination with a cellular component. These data have applications to the toxicity of the single agents. They also provide an index of activity, previously lacking, of systemic antoxidant effect.