Hepatic lesions microsomes

In sheep pretreated with DDT, a dose of 63.2 mg carbon disulfide/kg/day was reported to cause hepatic lesions accompanied by microsomal enzyme suppression and increases in total liver water and electrolytes (Wilkie et al. 1985). This study is of limited value because of its lack of controls to eliminate or account for possible synergistic effects of carbon disulfide and DDT. 

Liver contained 156 (68-563) pg PCB 126/kg FW pronounced liver enlargement lymphoid depletion of spleen 10-fold increase in hepatic microsomal EROD and benzyoxyresorufin-O-dealkylase 5-fold increase in methoxyresorufin-O-dealkylase Liver had 380 pg PCB 126/kg FW with increasing necrosis above effects plus decreased bone growth, decreased spleen weight, and degenerative lesions of thyroid Liver had 1.1 (0.6-4.5) mg PCB 126/kg FW above effects plus decreased body weight, decreased hepatic thiol concentrations, and increased plasma enzyme activities... 

Hepatic Effects. The hepatotoxic potential of PCB mixtures is well-documented in animals by oral and other routes of exposure. The spectrum of possible hepatic effects in animals is broad and includes microsomal enzyme induction, liver enlargement, increased serum levels of liver enzymes and lipids, and histopathologic alterations that progress to fatty and necrotic lesions and tumors. The findings of human studies, however, are not as obvious. Many of the human studies involving worker and other populations with high body burdens of PCBs report associations between PCBs and hepatic indices such as liver... 

Other significant experiments have corroborated the metabolic pyrrole hypothesis. When cells other than those capable of microsomal oxidation (i.e., cells other than liver) were incubated with pyrrolizidine alkaloids toxicity was not observed. However when these cells were exposed to synthetically prepared necine pyrroles, severe mitotic inhibition was observed. The chemical stability of the pyrrolic alkaloids is much less than that of the corresponding necine pyrroles and the former have not been detected Ija vivo. However when synthetic monocrotaline pyrrole was injected into the mesenteric vein of rats it produced the lesions typical of pyrrolizidine alkaloid poisoning portal vascular degeneration, hepatic necrosis, and inhibition of hepatocyte mitosis (63,64). Injected into the jugular veins of rats and dogs... 

Centrilobular hepatic necrosis by single doses of coumarin (1,2-benzopyrone, ds-o-coumarinic acid lactone) have been reported in the rat (Lake 1984, Lake et al. 1989, Fentem et al. 1992), whereas chronic administration resulted in bile duct lesions (Hagan etal. 1967, Cohen 1979, Evans etal. 1989). The mechanism of acute coumarin-induced hepatotoxicity in the rat has been investigated by comparing the effects of coumarin with those of a number of methyl-substituted coumarin derivatives (Lake etal. 1994). Coumarin administration produced dose-related hepatic necrosis and a marked elevation of plasma alanine aminotransferase and aspartate aminotransferase activities. In contrast, non of the coumarin derivatives examined produced either hepatic necrosis or elevated plasma transaminase activities. Coumarin reduced hepatic microsomal ethylmorphine N-demethylase and 7-ethoxycoumarin 0-deethylase activities, whereas one or both mixed function oxidases appeared to be induced by treatment with 3,4-dimethylcoumarin, 4-methylcoumarin, 3-methyloctahydrocoumarin and 4-methyloctahydrocoumarin. These results provides an evidence that acute coumarin-induced hepatotoxicity in the rat is due to the formation of a coumarin 3,4-epoxide intermediate. 

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