Membrane Stabilization as a Fundamental Event in the Mechanism of Chemoprotection Against Chemical Intoxication

Abstract

Elucidation of the mechanisms involved in chemical intoxication is difficult due to the concurrence of multiple cellular events. The major physiological consequences of toxicant-induced injury are organellar dysfunctions, including plasma membrane leakiness, loss of mitochondrial energy homeostasis, limited or pervasive autolysis due to release of lysozomal proteolytic enzymes, nucleic acid damage, and impairment of endoplasmic reticular functions including protein turnover, biotransformation, subcellular packaging and calcium homeostasis (Kaplowitz et al., 1986; Popper & Keppler, 1986). Often organellar associated events are correlated with biochemical events, such as alterations in thiol status, ion homeostasis, ATP levels or lipid peroxidation (Jones et al., 1986; Mitchell et al., 1982; Brattin et al., 1985; Comporti, 1989). In this report we have examined the physicochemical properties of 10 hydrophobic antioxidants that protect against chemical toxicity in isolated rat hepatocytes. Protection is shown to be correlated with both radical quenching and membrane stabilization properties of these compounds.