Inhibition of tetrachloromethane-induced cross-linking of microsomal fatty acids by the spin-trap α-phenyl- N - t -butylnitrone

Abstract

The effect of the spin-trap α-phenyl-N-t-butylnitrone (PBN) on the formation of fatty acid dimers induced by the anoxic microsomal metabolism of tetrachloromethane was investigated in vitro, in particular, with respect to cross-linking of arachidonic acid with a second one (C20–C20) and of arachidonic acid with docosahexaenoic acid (C20–C22). PBN exerted no effect on anaerobic tetrachloromethane metabolism but inhibited dimer formation, half-maximally at a concentration of 0.1 mmol L−1. Trichloromethyl octadecenoic acid was also found, but at levels 10-fold lower than the fatty acid dimers. The data suggest that the hepato-protective effect of PBN against tetrachloromethane-toxicity may be due to its ability to scavenge fatty acid radicals, resulting in stable, non-reactive entities, which do not undergo secondary reactions such as cross-linking. The data confirm and extend previous findings that crosslinking plays an important role in tetrachloromethane toxicity and similar cases of metabolic radical-induced toxicity.