Protection by Antioxidants against Lethal Doses of Carbon Tetrachloride

Abstract

Rees, Spector and Sinha¹ have shown that ‘Phenergan’, 10-(2-dimethylamino-isopropyl) phenothiazine hydrochloride, protects against necrosis of liver cells in rats dosed with carbon tetrachloride. Afterwards, Gallagher and Rees² found that ‘Phenergan’ maintained normal concentrations of oxidized pyridine nucleotides in the liver despite the administration of carbon tetrachloride. These findings, together with those of McLean^3,4 and Gallagher, Gupta, Judah and Rees⁵ that ‘Phenergan’ protects rats against liver necrosis due either to vitamin E deficiency or to administration of thioacetamide, suggested that ‘Phenergan’ operates on a general metabolic mechanism involved in the maintenance of cellular and mitochondrial integrity. The value of ‘Phenergan’ as an alternative to vitamin E indicated that its action might be associated with antioxidant properties. Therefore, the antioxidants^6,7 α-tocopherol, sodium selenite and NN¹-diphenyl-p-phenylenediamine were investigated as possible protective agents in carbon tetrachloride poisoning.