Modulation of Oxygen Toxicity by Select Anti-Melanogenic Compounds

Abstract

Hyperbaric oxygen (HBO) is employed to treat various clinical disorders, however, its use has been limited in view of the associated toxicity to the central nervous system, lungs and circulating erythrocytes. In the present study, we assessed the efficacy of select anti-melanogenic agents to modulate the toxicity of 100percent HBO in malaria infected mice since malarial parasites generate oxidants which diminish the ability of host erythrocytes to prevent and repair oxidant damage. Accordingly, it was anticipated that HBO would cause selective lysis of parasitized erythrocytes and hence result in a depression in parasitemia. Furthermore, any benefit derived from an effective agent would be noted by the drug's ability to diminish the severity of parasitemia decline following HBO exposure. Female CD-1 mice (26-30 gm.) were given an intraperitioneal inoculum of 5.0 x 10 to the 4th power P. berghei- infected erythrocytes. The data clearly indicate that HBO is an effective maneuver to selectively lyse parasitized erythrocytes. In this regard, HBO effected a 20-40percent depression in circulating parasitemia relative to non-exposed controls, when monitored 24 hours (on day 11) after exposure. The drug 2- thiouracil in doses of 20 to 100 mg/kg body weight (but not 10 mg/kg) were effective in combating the HBO-induced decline in parasitemia. NOTE: Drugs tested include Disulfiram, D-Penicillamine, 2-Thiouracil, Isoascorbic Acid, Glutathione, Ascorbic Acid