Liver nuclear activation of carbon tetrachloride or trichlorobromomethane to trichloromethyl and trichloromethyl peroxyl free radicals. Their reactions with lipids and proteins.

SL FANELLI,; GD CASTRO; M GALELLI; JA CASTRO.

Biomedical and Environmental Sciences

CAPM. Ca Academic Press

Lugar: San Diego; Año: 1998 vol. 11 p. 101 - 114

0895-3988

The formation of · CCl3 radicals on liiver nuclei was suggested by spin trapping of them with N-t-butyl-a-phenylnitrone followed by GC/MS detection of the resulting adduct. Comparison of its formation in microsomal biotransformation of CCl4 was made. In aerobic nuclear activation mixtures containing NADPH and CCl4, significant decrease in the arachidonic acid content of nuclear lipids was observed (27.8 %, compared to control), the intensity of this decrease was lower than that occurring in the corresponding microsomal incubation mixtures (29.1 %). Significant decreases in arachidonic acid content of nuclear and endoplamic reticulum lipids were also observed in animals at 6 hours of poisoning with the haloalkane. During aerobic nuclear metabolism of CCl4 or CBrCl3, cholesterol oxidation products were detected: a ketocholesterol, an epoxide like structure and 7-ketocholesterol. Nuclear protein carbonyl formation was not promoted during nuclear CCl4 biotransformation. NADPH by itself may lead to protein carbonyl formation during prolonged periods of   incubation. CBrCl3 in contrast, led to decreased protein carbonyl   formation. No increase in nuclear protein carbonyl formation was observed in CCl4 intoxicated animals during periods of time between 1 to 6 hours after treatment. The results indicate that during nuclear biotransformation of CCl4 or CBrCl3 reactive free radicals, PUFA degradation, reactive aldehydes and cholesterol oxidation products are formed, nearly DNA and regulatory proteins.