Free Radical Mediated Toxicity of Drugs of Abuse

Abstract

1. Isolated purified rat serosal mast cells were incubated with given concentrations of drugs of abuse (morphine, cocaine, methadone), with oxidative enzymes (prostaglandin-H-synthetase, PHS; rat liver homogenate fraction - S-10 mix), and with the drugs of abuse in the presence of oxidative enzymes. 2. The release of mast cell histamine and the generation of malonyl-dialdehyde (MDA) is present only when mast cells were incubated with the drugs of abuse in the presence of oxidative enzymes. 3. The release of histamine and the generation of MDA were abated by the free radical scavengers, reduced glutathione (GSH) and α-tocopherol. 4. It is suggested that morphine, cocaine and methadone are activated into free radicals producing membrane lipid perturbation and histamine release. 5. The metabolic activation of morphine, cocaine and methadone into free radicals could entail pathophysiological relevance in the organic injuries of drug addiction.