Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbon tetrachloride (CCl4)-induced hepatotoxicity was potentiated by pretreatment with beta-phenethyl alcohol, abundantly present in sake. The injury was determined by serum GPT levels and histological examination. Similar results were observed in ethanol- and phenobarbital-pretreated rats. Acetaminophen-induced hepatotoxicity was not accentuated by beta-phenethyl alcohol or ethanol pretreatment. The activities of liver microsomal enzymes, such as cytochrome P-450, cytochrome b5 reductase, aniline hydroxylase and aminopyrine demethylase, were not altered in beta-phenethyl alcohol-pretreated rats. Thus, CCl4-induced hepatotoxicity potentiation by beta-phenethyl alcohol administration is postulated to be due to a mechanism other than increased free radical generation.
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PMID:Potentiation of carbon tetrachloride hepatotoxicity by beta-phenethyl alcohol. 608 1

Previous work has established the marked potentiation of CCl4 hepatoxicity by prior exposure to chlordecone (CD). This study was conducted to determine if prior exposure to CD results in enhancement of CCl4-induced destruction of the hepatic microsomal mixed-function oxygenase (MFO) system. Male Sprague-Dawley rats received a single oral dose of CD (10 mg/kg) or corn oil vehicle alone (1 ml/kg) 24 hr prior to a single ip injection of CCl4 (0-100 microliter/kg). Mirex (M; 10 mg/kg) and phenobarbital (PB; 80 mg/kg/day for two days) were used as negative and positive controls respectively for the potentiation of CCl4 hepatotoxicity. Hepatotoxicity was evaluated 24 hrs after CCl4 administration by elevations of three serum enzymes (GPT, GOT, and ICD). The key hepatic microsomal MFO parameters measured were microsomal protein, cytochrome P-450 content, glucose-6-phosphatase (G-6-Pase), and aminopyrine demethylase (APD). As previously demonstrated using a subchronic dietary pretreatment protocol, CD potentiated CCl4 hepatotoxicity over a range of CCl4 doses to a greater extent than PB or M, as judged by elevations in serum enzymes. PB caused the greatest increase in total P-450 content and the greatest increase in CCl4-mediated destruction of microsomal protein and APD activity. M caused the least destruction of total hepatic cytochrome P-450, despite the same level of cytochrome P-450 as in the PB group. CD treatment caused the greatest decrease in G-6-Pase activity in comparison to PB or M pretreatments and a similar degree of P-450 destruction as observed with the PB group. These findings suggest that in general, CCl4-induced destruction of hepatic MFO parameters measured in this study is disproportional to the known degree of potentiated hepatotoxicity by the pretreatments and does not accurately reflect the potentiation of CCl4 hepatotoxicity by CD.
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PMID:Destruction of hepatic mixed-function oxygenase parameters by CCl4 in rats following acute treatment with chlordecone, Mirex, and phenobarbital. 619 92

The possible protective effect of cysteine on chemical-induced liver injury was studied in rats in vivo and in vitro. There was no increase in the activity of serum glutamic oxaloacetic transaminase (GOT) of rats pretreated with cysteine (1.2 g/kg, p,o.) followed by 0.25 ml/kg carbon tetrachloride (CCl4), d-galactosamine (GalN) or alpha-naphthylisothiocyanate (ANIT). However, rats pretreated with cysteine followed by 0.5 ml/kg CCl4 were not protected. The content of cytochrome P-450, activity of aminopyrine N-demethylase or serum ratio of 5,5-dimethyl-2,4-oxazolidinedione (DMO) to trimethadione (TMO) (DMO/TMO ratio) after CCl4, GalN or ANIT were not altered by pretreatment with cysteine. However, pretreatment with cysteine prevented changes in the content of cytochrome P-450, activity of aminopyrine N-demethylase and DMO/TMO ratio in serum as well as the activities of serum GOT and GPT when the rats were treated with bromobenzene (BZ). The degree of lipid peroxidation from CCl4 was markedly reduced by the presence of 10(-4)M cysteine. These results suggest that cysteine has a protective effect on chemical-induced liver injury produced via epoxide metabolites.
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PMID:The protective effect of cysteine on chemical-induced liver injury in rats. 650 63

Acute or chronic treatment of rats with isopropanol caused a significant increase in hepatic cytochrome P-450 content and a two- to threefold increase in aniline hydroxylase and 7-ethoxycoumarin O-deethylase activities, but no significant change in ethylmorphine N-demethylase or benzo(a)pyrene hydroxylase activity. In rats treated with isopropanol and challenged with CCl4, liver toxicity of CCl4 was characteristically potentiated, as assessed by elevation of serum glutamic-pyruvic transaminase (SGPT) levels. Isopropanol pretreatment also potentiated CCl4-induced damage to the hepatic monooxygenase system. In addition to a decrease in cytochrome P-450, rats treated with isopropanol and challenged with CCl4 showed a nonspecific decrease not only in aniline hydroxylase and 7-ethoxycoumarin O-deethylase activities, but also in ethylmorphine N-demethylase, benzo(a)pyrene hydroxylase, and NADPH-cytochrome c reductase activities. These results were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized microsomes. The electrophoretic results showed that isopropanol pretreatment markedly potentiated the CCl4-caused destruction of cytochrome P-450 hemeproteins. The data strongly suggest that isopropanol increases one or more forms of cytochrome P-450 which selectively enhance the metabolism of CCl4 to an active metabolite. This active metabolite then causes a nonselective damage to the microsomal mixed-function oxidase system.
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PMID:Isopropanol enhancement of cytochrome P-450-dependent monooxygenase activities and its effects on carbon tetrachloride intoxication. 663 85

Concurrent treatments of cobalt chloride (CoCl2) and phenobarbital (PB), alone or in combination with lithocholic acid (LCA), were administered to rats for 7 days to assess whether or not a hypoactive hypertrophic smooth endoplasmic reticulum (HHSER) could be induced, as well as investigating the potential role of HHSER in the pathogenesis of cholestasis. LCA given alone slightly reduced hepatic triglycerides, significantly elevated plasma triglycerides and decreased microsomal glucose-6-phosphatase (G6P-ase) activity. PB administered alone significantly increased hepatic phospholipids and microsomal protein, phospholipid and cytochrome P-450 contents, as well as microsomal aminopyrine-N-demethylase (APDM-ase) activity. Functional indicators of liver impairment were associated primarily with CoCl2 treatment, whether given alone or in combination with PB + LCA. These signs included significantly reduced hepatic triglycerides, and increased plasma triglycerides associated with enhanced release of hepatic VLDL-triglycerides, as well as significantly decreased microsomal G6P-ase activity and/or reduced APDM-ase activity and cytochrome P-450 content. Elevated plasma bilirubin levels, and aspartate and alanine aminotransferase activities were also evident with concurrent CoCl2 + PB + LCA treatments. Combined CoCl2 + PB treatments, with or without LCA, caused significant increases in microsomal protein and phospholipid, and decreased activity of the rough endoplasmic reticulum (RER) marker G6P-ase, but no changes in cytochrome P-450 levels and no marked alterations in the activity of the SER marker APDM-ase. The data indicated that simultaneous CoCl2 and PB treatments, whether given alone or in combination with LCA, caused a functional impairment of the RER, and did not induce HHSER membranes.
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PMID:Functional responses of the rat hepatic endoplasmic reticulum to treatment proposed as a model for cholestasis. 668 66

Previous studies indicate that pretreatment with acetone or isopropanol, fasting, and streptozotocin-induced diabetes enhance hepatic microsomal nitroso-dimethylamine (NDMA) demethylase in rats. This study demonstrates that these same treatments also potentiate the hepatotoxicity of NDMA as indicated by plasma glutamic pyruvate transaminase (GPT) levels and histologic data. Pretreatment with acetone or isopropanol (2.5 ml/kg) and 2 days of fasting caused a 2-fold potentiation of NDMA-induced plasma GPT elevation, whereas streptozotocin-induced diabetes caused a 4.6-fold potentiation. The centrilobular necrosis produced by NDMA was more severe after pretreatment with the inducers. NDMA treatment also decreased hepatic microsomal demethylase activity. These results lend support to the concept that a NDMA demethylase is responsible for the activation of NDMA in vivo to a toxic intermediate, and induction of this enzyme activity potentiates NDMA hepatotoxicity.
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PMID:Potentiation of the hepatotoxicity of N-nitrosodimethylamine by fasting, diabetes, acetone, and isopropanol. 671 61

Hepatotoxicity of aflatoxin B1 (2.0 and 4.0 mg/kg i.p.) as determined by plasma enzyme activities (GPT and GOT), liver triglycerides and histopathologic changes was enhanced in rats pretreated with four oral doses of ethanol (4.0 g/kg each) at 48, 45, 24 and 21 hrs prior to aflatoxin B1 administration. Pretreatment with ethanol (4.0 g/kg) slightly increased liver weight without changing hepatic microsomal protein contents. Also it caused an increase in microsomal aniline hydroxylase but a decrease in p-nitroanisole-o-demethylase, 48 hrs after the first ethanol dose. In the rats pretreated with ethanol, aflatoxin B1 was metabolized at a higher extent to aflatoxins M1 and Q1. These results suggest that an increased hepatotoxicity of aflatoxin B1 after pretreatment with ethanol may presumably due to an increase in microsomal formation of active aflatoxin B1 metabolite.
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PMID:Enhanced hepatotoxicity of aflatoxin B1 by pretreatment of rats with ethanol. 681 83

The influence of Zn on the acute hepatotoxicity of pyrrolizidine alkaloids (PAs) was determined in male rats. Zinc, 72 mumol/kg as ZnCl2, was administered ip for 3 consecutive days, followed 16 h after the last dose by a single ip injection of purified mixed PAs (80, 120, or 160 mg/kg) obtained from tansy ragwort (Senecio jacobaea). Hepatotoxicity of the PAs was assessed by measuring the activities of plasma glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) and by histological examination of the liver. There was a dose-dependent increase in plasma GOT and GTP 24 h after PA administration, whereas no significant increase of these enzymes was seen after administering Zn alone. The 7-fold increase in plasma GOT and 12-fold increase in GPT after PA (120 mg/kg) were reduced to 2.4- and 2.1-fold, respectively, by Zn pretreatment. The PA-induced liver necrosis was either reduced in severity or abolished by Zn when the PA dose was 80 or 120 mg/kg. These results suggest a protective effect of Zn against PA hepatotoxicity. The protective effect was associated with a marked increase in liver metallothionein and a significant decrease in hepatic cytochrome P-450 content, aminopyrine N-demethylase activity, and in vitro microsomal conversion of the PAs to pyrroles. Liver nonprotein sulfhydryls were unchanged. The possible role of metallothionein in the sequestration of pyrrole metabolites merits further investigation.
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PMID:Protective action of zinc against pyrrolizidine alkaloid-induced hepatotoxicity in rats. 709 90

In rats, i.v. administration of praseodymium, cerium and lanthanum (3 to 14 mg/kg) produced a dose-dependent increase in the serum activities of GOT, GPT and SDH. These dose-response curves of serum enzyme activities were shifted to the right by simultaneous treatment with silybin (75 mg/kg i.p.). Silybin also attenuated the increase of bromosulphthaleine retention and prevented the accumulation of liver triglycerides induced by praseodymium (7 mg/kg i.v.). Furthermore, silybin reduced the mortality rate of rats treated with high doses of the lanthanides. Rats treated with praseodymium (7 mg/kg i.v.) developed a pronounced hypoglycemia. On the 3rd day after praseodymium injection liver glycogen decreased to 4%, liver glutathione (GSH) to 82%, hepatic microsomal cytochrome P-450 content to 53%, aniline hydroxylase activity to 58% and aminophenazone demethylase activity to 40% of the control values. Silybin prevented praseodymium-induced hypoglycemia completely and the changes in the biochemical parameters of liver function partially but did not influence the decrease of liver GSH.
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PMID:The influence of silybin on the hepatotoxic and hypoglycemic effects of praseodymium and other lanthanides. 719 8

Groups of CFY rats were exposed to toluene inhalation as follows: both males and females to 1000 mg/m3 6 h daily five times a week for 6 months; only males to 3500 mg/h3 8 h daily every day for 6 months; and only males to 1500, 3000 and 6000 mg/m3 8 h daily for 4 weeks. Control groups were exposed to air inhalation under identical conditions. Toluene was found to inhibit growth but to cause no abnormal light-microscopical changes. Hepatic changes were: (i) Signs of compensation such as increased relative liver weight, SER proliferation; increased succinate dehydrogenase activity; a decrease in glycogen content; increased cytochrome P-450 and b5 concentration; increased hepatic aniline hydroxylase and aminopyrine N-demethylase activity. (ii) Non-specific subcellular effect was observed in a small number of hepatocytes, namely RER dilatation, separation of ribosomes, mitochondria of variable shapes, an increased number of autophagous bodies. As regards indicators of the hepatic function, BSP retention decreased, GOT and GPT activity did not change. The changes were observed in both sexes, were dose-dependent and reversible, and showed no--or only a slight--dependence on exposure time. Chronic toluene exposure has no specific hepatotoxic effect leading to chronic liver disease.
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PMID:Effect of toluene inhalation on the liver of rats--dependence on sex dose and exposure time. 744 Sep 61


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