Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although butylated hydroxytoluene (BHT) is non-mutagenic, at high doses it has recently been associated with an increased incidence of liver tumours in laboratory rodents. To establish whether chronic liver cell injury may be involved in the genesis of these tumours, BHT was administered to rats by orogastric gavage at doses of 0, 25, 250 or 500 mg/kg/day for up to 28 days and also at daily doses of 1000 and 1250 mg BHT/kg for up to 4 days (sublethal doses). The sublethal doses induced centrilobular necrosis within 48 hr, whereas administration of BHT for 7 or 28 days caused dose-related hepatomegaly and at the highest dose level induced progressive periportal hepatocyte necrosis. The periportal lesions were associated with proliferation of bile ducts, persistent fibrous and inflammatory cell reactions, hepatocyte hyperplasia and hepatocellular and nuclear hypertrophy. Biochemical changes consisted of dose-related induction of epoxide hydrolase, dose-related changes in the ratio of cytochrome P-450 isoenzymes and depression of glucose-6-phosphatase. Measurement of BHT demonstrated a dose-related accumulation in fat but not in the liver. Changes in hepatic activating and detoxifying enzyme profiles are implicated both in the mechanism of periportal hepatocyte damage and in the change of site of damage according to the dose and duration of the treatment. The persistent and active nature of the lesions in rats dosed with 500 mg BHT/kg for 28 days, combined with evidence of cell damage at doses equivalent to those associated with hepatic tumours (250 mg BHT/kg), suggests that chronic liver cell damage may be involved in their aetiology. In this and several other studies, there was no evidence that BHT causes liver damage at a dose level of 25 mg/kg/day. As this is several hundred times higher than the normal human intake, it is considered unlikely that BHT poses a threat to human health.
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PMID:Hepatic responses to the administration of high doses of BHT to the rat: their relevance to hepatocarcinogenicity. 302 37

Studies have been made of the morphology, enzyme activity and protein composition of liver endoplasmic reticulum in rats exposed to acute doses of the carcinogen, 2-acetylaminofluorene (2-AAF). Electron microscopic examination revealed numerous ultrastructural changes in the hepatocyte; most consistent alterations were the disorganisation of endoplasmic reticulum system with apparent increase of smooth endoplasmic reticulum. Administration of 2-AAF to rats immediately depressed microsomal glucose-6-phosphatase activity and eventually induced epoxide hydratase activity 6--7-fold over control activity. The induction was time-dependent and maximal rates of induction were observed at dosages greater than 40 mg/kg body wt. The treatment also induced cytochrome b5 content, NADH and NADPH cytochrome c reductase activities (1.0--1.5-fold). Only very small changes in the total content of cytochrome P-45- were noted. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of microsomal proteins from 2-AAF pretreated animals showed time-dependent induction of two polypeptides which differed slightly in migration, in the region of Mr = 48000; the fast-migrating induced polypeptide has been identified as epoxide hydratase. Two-dimensional PAGE analysis of microsomal proteins from 2-AAF exposed rats showed a reproducible deletion of a protein with molecular weight in the region of 67000. The basis for the alterations in the protein composition of endoplasmic reticulum in response to 2-AAF treatment is discussed.
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PMID:Alterations in the enzyme activity and polypeptide composition of rat hepatic endoplasmic reticulum during acute exposure to 2-acetylaminofluorene. 707 8