Potentiation of CCl4-induced hepatotoxicity in the dog by chronic exposure to phenobarbital
| Autor: | E.J. Van Loon, C.L. Litterst, T.M. Farber |
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| Rok vydání: | 1973 |
| Předmět: |
Time Factors
CCL4 In Vitro Techniques Pharmacology Toxicology digestive system Beagle chemistry.chemical_compound Dogs medicine Animals Fluorometry Carbon Tetrachloride Triglycerides chemistry.chemical_classification Lipid peroxide Carbon Tetrachloride Poisoning digestive oral and skin physiology Alanine Transaminase Drug Synergism digestive system diseases Peroxides Enzyme Liver chemistry Phenobarbital Toxicity Microsomes Liver Carbon tetrachloride Microsome Chemical and Drug Induced Liver Injury medicine.drug |
| Zdroj: | Toxicology and Applied Pharmacology. 25:354-362 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/0041-008x(73)90309-8 |
| Popis: | Carbon tetrachloride (CCl 4 ) hepatotoxicity was studied in normal and in phenobarbital-pretreated beagle dogs. The liver content of triglycerides (TG) and lipid peroxides, and activities of microsomal enzymes as well as serum glutamicoxaloacetic (SGOT) and glutamic-pyruvic (SGPT) transaminases were monitored for periods up to 24 hr after CCl 4 administration. CCl 4 alone produced no consistent changes in the parameters studied. Phenobarbital pretreatment produced significant increases in liver TG content, microsomal enzyme activities and SGPT activity. Phenobarbital pretreatment had no effect on CCl 4 -induced changes in glucose-6-phosphatase activity, but produced an immediate increase in lipid peroxide content, which declined to normal by 24 hr after treatment. The TG content of livers from phenobarbital-pretreated dogs began to increase by 3 hr after CCl 4 administration and continued to increase as the time after administration increased. Activities of SGOT and SGPT were strikingly increased 3 hr after administration of CCl 4 and were still apparently increasing 24 hr after treatment. CCl 4 administration to phenobarbital-treated dogs eliminated the increase in activities of all microsomal drug-metabolizing enzymes that were seen with phenobarbital pretreatment alone. It was concluded that phenobarbital produced a true potentiation of the toxicity of CCl 4 by apparently decreasing the threshold at which the hydrocarbon becomes toxic. The results produced no definitive evidence to explain the mechanism by which phenobarbital produces the increase in CCl 4 toxicity. |
| Databáze: | OpenAIRE |
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