Carbon disulphide induced activation of liver UDP glucuronosyltransferase in rats pretreated with phenobarbitone.
Carbon disulphide (CS2) exposure has been shown to activate the UDP glucuronosyltransferase of liver microsomes in rats pretreated with phenobarbitone. Now the nature of CS2 induced activation of the enzymes has been studied further. Phenobarbitone pretreated rats were exposed to 0.15% CS2 for 2 hrs on two successive days. The activity of UDP glucuronosyltransferase was measured from the liver microsomes after the enzymes was activated by incubation of the microsomes with various concentrations of the detergents Triton X-100, digitonin and cetylpyridinium chloride. The exposed animals showed an increased enzyme activity at all applied concentrations of the detergents; therefore in addition to membrane destruction by CS2 exposure, some other mechanism must also be involved in the CS2 induced activation of liver microsomal UDP glucuronosyltransferase. The changes in membrane lipid-protein interactions with l-anilino-8-naphthalene sulphonate (ANS) were also probed. The CS2 exposed animals had more high-affinity binding sites for ANS in their liver microsomal membranes, and in addition the quantum yield of ANS fluorescence was enhanced by CS2. The changes differed from those found after carbon tetrachloride exposure and suggest that, even if the two drugs have some common effects on microsomes, e.g. UDP glucuronosyltransferase activation, P-450 destruction and lipid peroxidation induction, the changes they cause in the microsomal micro-environment differ.
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D002246:Carbon Disulfide / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002594:Cetylpyridinium / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004072:Digitonin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D013451:Sulfonic Acids / Q000494:pharmacology
D013451:Sulfonic Acids; D011092:Polyethylene Glycols; D003577:Cytochrome P-450 Enzyme System; D002594:Cetylpyridinium; D014453:Glucuronosyltransferase; D004072:Digitonin; D002246:Carbon Disulfide; D010634:Phenobarbital