The hepatotoxicity of carbon disulphide in sheep.
Carbon Disulphide (CS2) caused liver injury when dosed orally (intraruminally) at 0.05 ml per kg body weight to overnight fasted sheep which had been given 200 mg kg-1 DDT intraruminally 1 week previously to enhance the hepatic mixed function oxygenases. The liver lesion was a periacinar hepatocellular vacuolar degeneration, fully developed at 24 h and lasting from 4 to 5 days after which the hepatic morphology returned to normal. At 24 h after dosing with CS2 there was an increase in total liver water, sodium and potassium ions but without an increase in the concentration of these cations in total liver water, and a 50% reduction in microsomal cytochrome P450 levels. Calcium concentration was either unchanged or only slightly increased. The cytoplasmic vacuoles were mainly distensions of the rough endoplasmic reticulum and contained fine amorphous or fibrillary material, probably originating from damaged smooth endoplasmic reticulum membranes. The transient influx of fluid into these organelles is thought to be due to osmotic action generated by molecules derived from the latter macromolecular membrane fragments. The lesion resembles that seen in the rat due to CS2 after pretreatment with phenobarbitone. In situations in which sheep are drenched with CS2 and CCl4 in combination, it is suggested that the development of hepatic periacinar hydropic change due to the CS2 in animals normally susceptible to CCl4 because of enhanced microsomal cytochrome P450 levels would provide a better chance of survival than if CCl4 alone was administered and extensive periacinar coagulative necrosis occurred.
D000818:Animals; D002246:Carbon Disulfide / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003634:DDT / Q000633:toxicity; D004573:Electrolytes / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D012756:Sheep
D004573:Electrolytes; D003577:Cytochrome P-450 Enzyme System; D003634:DDT; D002246:Carbon Disulfide