MECHANISM OF THE NEUROTOXIC AND HEPATOTOXIC EFFECTS OF CARBON DISULFIDE

Abstract

The mechanisms of carbon disulfide toxicity can be divided into two categories; nonmicrosomal and microsomal. The nonmicrosomal pathway involves nonenzymatic spontaneous reaction of carbon disulfide with amino or thiol groups that leads to formation of dithiocarbamates or GSH conjugates as well as inhibition of certain enzymes such as dopamine beta-hydroxylase. These reactions primarily lead to neurotoxic effects. The second mechanism of carbon disulfide toxicity involves its metabolism by hepatic microsomal enzymes to two reactive sulfur atoms that bind covalently to cell macromolecules causing hepatotoxicity. This oxidative metabolism of carbon disulfide has been suggested to be responsible for much of the liver pathology and impairment of liver metabolism of other endogenous substrates as well as exogenous compounds entering the body.