Catecholamines free-radical intermediates

A considerable amount of evidence has accumulated recently for the transient existence of free-radical intermediates in systems containing oxidizing catecholamines. Walaas and Walaas and their co-workers have shown that the interaction of catecholamines with cupric ion (either bound, as in ceruloplasmin, or as the free ion, cf. ref. 80) results initially in reduction of the copper atom to the... 

I. Mechanism of toxicity. Carbon tetrachloride and chloroform are CNS depressants and potent hepatic and renal toxins. They may also increase the sensitivity of the myocardium to arrhythmogenic effects of catecholamines. The mechanism of hepatic and renal toxicity is thought to be a result of a toxic free-radical intermediate of cytochrome P-450 metabolism. (Bioactivation of CCI4 has become a model for chemical toxicity induced by free radicals.) Chronic use of metabolic enzyme inducers such as phenobarbital and ethanol increases the toxicity of carbon tetrachloride. Carbon tetrachloride is a known animal and suspected human carcinogen. Chloroform is embryotoxic and an animal carcincogen. 

Borg [79] studied (a) the ceric sulphate oxidation of adrenaline, noradrenaline and DOPA in add solution (b) the ferricyanide oxidation of adrenaline and DOPA in alkaline solution and (c) the permanganate oxidation of adrenaline at neutral pH. Free radical intermediates, which were thought to be semiquinones formed in the first step of the oxidation, were detected in the reaction mixtures by means of e.p.r. spectroscopy. They were shown to have arisen before the aminochrome stage as the e.p.r. spectrum of oxidised adrenochrome was different from that observed in the initial stages of the oxidation of adrenaline. Thus the first stage in the oxidation of catecholamines involves the formation of a semiquinone [79]. 

The chemical transformations that occur on ultraviolet irradiation of adrenaline and noradrenaline solutions have been investigated by Walaas, who showed that the initial photoactivation of the catecholamine molecule is a direct effect (i.e., it is not dependent on the presence of trace metals) and that the activated species, probably free radical in nature, are readily autoxidizable in air.61 Walaas suggests that the activation of catecholamines by ultraviolet radiation may involve electronic changes similar to those initially occurring during the metal-catalyzed oxidation of catecholamines at an intermediate pH.14,61... 

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