Cytochrome P450 and glutathione in the liver of rats under exclusive sucrose ingestion.
1. The objective of the present investigation was to study some of the possible mechanisms involved in the protective effect of sucrose ingestion against liver necrosis induced by acetaminophen. Three groups of male Wistar rats (220-260 g) were submitted to the following experimental conditions for a period of 42 h: free access to a balanced commercial diet (Group I), an exclusive sucrose diet (Group II) and fasting (Group III). At the end of the experiment, hepatic cytochrome P450 levels were measured in 11 rats from each group, plasma antipyrine half-life (t1/2) was determined in 40 rats from each group, and hepatic glutathione (GSH) concentration in 10 rats from each group. GSH consumption elicited by a high dose of acetaminophen (ACP, 1.0 g/kg, by gavage) was also determined in 30 rats each from Groups II and III. 2. The liver of Group II rats presented a significant reduction of cytochrome P450 levels in the microsome fraction (range 0.31-0.46, median, 0.37 nmol/mg vs range 0.60-0.93, median 0.74 for group I, and range 0.63-1.22, median 0.91 for group III, reported as nmol/mg microsome protein; range 23.8-48.4, median 40.4 vs 66.6-130, median 81.8 for group I and range 59.0-117.1, median 77.1 for group III, reported as nmol/100 g body weight), and a prolongation of antipyrine half-life (146.4 vs 83.4 min for group I and 93.6 for group III) when compared with the rats of the two other groups. 3. Since the toxicity of acetaminophen depends on the production of a reactive metabolite by the cytochrome P450 system in the liver, we conclude that changes in this system brought about by exclusive sucrose ingestion for 42 h may explain the liver protection against the toxicity of a high dose of the drug even in the presence of a significant concomitant reduction in liver GSH levels.
Martinelli
A L
AL
Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil.
Meneghelli
U G
UG
Zucoloto
S
S
D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D000983:Antipyrine / Q000097:blood; D001835:Body Weight; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D005215:Fasting; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000008:administration & dosage*; D013997:Time Factors
D000082:Acetaminophen; D013395:Sucrose; D002786:Cholesterol Side-Chain Cleavage Enzyme; D005978:Glutathione; D000983:Antipyrine