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)

Liver damage induced in rats by carbon tetrachloride (CCL4) was obvious macroscopically as well as microscopically in stained sections. Levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transpeptidase (gamma-GT) were also significantly raised. Adenosine and inosine effectively countered the damage when these were given before and during the period during which CCl4 produces the typical damage. The beneficial effect was seen in biochemical as well as pathological studies.
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PMID:Effect of adenosine and inosine on carbon tetrachloride-induced liver damage in rats. 135 Jul 72

To assess whether potential toxic interactions occur between ethanol and allyl alcohol or carbon tetrachloride following subacute, concurrent chemical exposure, male Fischer 344 rats, approximately 70 d of age, were given ethanol at 0, 0.05, 0.1, 0.2, or 0.5 ml/kg in corn oil daily by gavage for 14 d (ETOH group), or the same levels of ethanol with 21 mg allyl alcohol/kg (ALAC group), or the same levels of ethanol with 20 mg carbon tetrachloride/kg (CCL4 group). Hepatic response was assessed 24 h after the last dose. Interactions were evaluated by comparing the ETOH group with either the ALAC group or the CCL4 group using multivariate analysis of variance procedures. No statistically significant interaction was seen between the ETOH group and the ALAC group at the dosages used. Although an interaction between ethanol and carbon tetrachloride given simultaneously was not statistically significant, a small interactive effect on weight gain from d 0 to termination was apparent (p = .057). Exposure to ethanol alone resulted in a concentration-dependent decrease in absolute and relative liver weight, with a threshold between 0.05 and 0.1 ml/kg. There was no histopathological evidence of hepatic damage with ethanol alone, and no effect on hepatic cytochrome P-450 and glutathione levels or on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALK). Exposure to allyl alcohol alone resulted in significant increases in absolute and relative liver weights, liver glutathione, and periportal hepatocellular vacuolar degeneration. Exposure to carbon tetrachloride alone resulted in significant increases in absolute and relative liver weight, serum levels of ALT, AST, and ALK, and centrilobular hepatocellular vacuolar degeneration and necrosis. These observations indicate that subacute, concurrent exposure of ethanol with carbon tetrachloride or allyl alcohol at ethanol levels comparable to those reported in gavage vehicles did not result in interactive toxicity.
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PMID:Hepatotoxic interactions of ethanol with allyl alcohol or carbon tetrachloride in rats. 152 9

Potentiation of haloalkane hepatotoxicity by ketones and ketogenic agents is a well-known phenomenon. The importance of the CCl4 dosage in these combinations, however, has not been explored. Its influence was investigated in male Sprague-Dawley rats. Dose-effect curves for potentiation were generated using 1,3-butanediol, methyl n-butyl ketone or methyl isobutyl ketone as potentiation agents. Animals were orally treated with these compounds prior to a challenge of CCl4 (0 to 0.5 ml/kg, ip). Liver injury was assessed by monitoring plasma ALT activity and bilirubin concentrations after CCl4 treatment. The minimal effective dosage (MED) for each potentiator was used as the criterion of comparison for each combination. The MED values were determined from the plasma ALT data. Results showed that when the CCl4 dosage was increased from 0.01 to 0.10 ml/kg, the MED of each potentiator decreased 10-fold. For a given potentiator, the product of the CCl4 dosage (H, "hepatotoxicant") by the corresponding MED value (P, "potentiator") remained the same in this range of CCL4 dosages. The severity of the liver injury was similar. These findings suggest that a given level of liver injury induced by a ketone/haloalkane combination could be evaluated on the basis of the [P X H] product.
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PMID:Potentiation of CCl4-induced liver injury by ketonic and ketogenic compounds: role of the CCl4 dose. 338 17

Treatment of male and female rats with carbon tetrachloride (CCl4, twice weekly, 0.2 ml/kg p.o.) and a 5% alcohol solution during four weeks evoked strong increments of the serum enzyme activities of the aminotransferases (GOT, GPT) and the sorbitol dehydrogenase (SDH). These occurred earlier and were more pronounced in male compared to female rats. Hepatic triglyceride contents as a measure of fatty infiltration was augmented three-fold both in males and females at the end of the experiment. Hepatic hydroxyproline contents were enhanced seven-fold in males, but only two-fold in females. It is concluded that female rats are less susceptible to CCl4--alcohol-induced liver damage, especially hydroxyproline accumulation, which is explained by the known fact that females are more resistant against CCL4-hepatotoxicity as a consequence of a minor role of bioactivation in the metabolic degradation of CCL4 by females.
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PMID:Sex differences in the susceptibility of rats to carbon tetrachloride--alcohol-induced liver injury. 670 9

Carbonyl compounds released during the NADPH-Fe dependent lipid peroxidation and identified as 4-hydroxyalkenals (almost entirely as 4-hydroxynonenal), when incubated with isolated hepatocytes, produce loss of viability in 95% of the cells, as measured by the trypan blue exclusion test. They also produce an almost complete permeabilization of the plasma-membrane, as measured by the test of the permeability to NADH. concomitantly with the permeabilization of the plasma-membrane, a marked release of enzymes (lactate dehydrogenase and glutamate-pyruvate transaminase) from the hepatocytes occurs. These and other activities of the above mentioned carbonyl compounds suggest the possibility that these products represent some of the effective mediators of the liver injury produced by those toxins, such as CCL4, which promote the peroxidation of membrane lipids.
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PMID:[Cytotoxic effects of carbonyl compounds (4-hydroxyalkenals) derived from peroxidation of hepatic microsomal lipids on isolated hepatocytes]. 689 79

A number of biochemical events accompany the development of chronic liver disease and its evolution into hepatic cancer. Low plasma zinc and high plasma copper levels have been observed in individuals with advanced hepatocellular liver disease. Moreover, many investigators have demonstrated an increase in serum estradiol levels in individuals with chronic liver disease and hepatocellular carcinoma (HCC). In the present study, the relationship between these biochemical events and HCC was investigated in an animal model. Specifically, carbon tetrachloride (CCL4) was administered intragastrically to 20 female Sprague Dawley rats for 30 weeks. All 20 animals developed cirrhosis. Six (30%) developed HCC. Significantly higher serum estradiol, zinc and copper levels were observed in the rats developing HCC as compared with those with cirrhosis alone (P < or = 0.05, 0.01 and 0.001, respectively). A trend toward increased serum levels of progesterone, ALT and total bilirubin (0.1 > or = P < or = 0.05) was found in the animals developing HCC. No differences in serum testosterone and alkaline phosphatase levels were noted between animals with and without HCC. These studies demonstrate that in animals with experimental CCL4-induced cirrhosis and HCC serum levels of estradiol, zinc and copper are increased, as is the case in man.
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PMID:CCL4-induced liver cirrhosis and hepatocellular carcinoma in rats: relationship to plasma zinc, copper and estradiol levels. 795 73

The modulation of CCl4-induced hepatotoxicity in response to alkyl sulfides and alkyl ethers including allyl disulfide (ADS), allyl sulfide (AS), allyl ether (AE), propyl disulfide (PDS), propyl sulfide (PS), propyl ether (PE) and butyl sulfide (BS) was studied. Whereas pretreatment of rats with either ADS or AS (50 mg/kg, 7 days) blocked a CCl4-induced increase in plasma alanine aminotransferase (ALT) activity by 91 and 56%, respectively, AE, PDS, PS, PE or BS treatment enhanced CCl4-induced ALT activity by 52, 55, 238, 25 or 86%, respectively. Histochemical examinations supported the results of plasma ALT activity. Injection of GdCl3 to PS-pretreated rats failed to block the potentiated ALT increase, whereas GdCl3 completely prevented vitamin A-enhanced elevation of ALT activity. AS treatment completely blocked PS-potentiated CCl4 intoxication. Concomitant treatment of animals with both PS and vitamin A followed by a CCl4 insult resulted in super-potentiation of CCl4-induced hepatotoxicity, suggesting that the mechanism of PS-enhanced hepatotoxicity differs from that caused by vitamin A. Pyridine or phenobarbital potentiation of CCl4-induced increases in ALT activity implys that cytochrome P450 2E1 (P450 2E1) and P450 2B expression may be associated with the increased toxicity. P450 2E1 expression appeared to be associated with the alkyl sulfide-modulated hepatotoxicity, as evidenced by both immunoblot analyses and metabolic activity. P450 2B immunoblot analysis revealed that either AS or PS substantially induced hepatic P450 2B1/2 levels. Thus, PS-enhanced CCL4 hepatotoxicity may be related in part with P450 2B induction. ADS, AS or PS treatment caused increases in the glutathione S-transferase (GST) conjugating activity toward 1-chloro-2,4-dinitro-benzene. ADS, AS or PS induced Ya and Yb1 subunits by 2- to 3-fold. ADS or AS treatment also significantly elevated the levels of Yc subunits. PS failed to induce Yc expression, although this agent effectively increased Yb2 expression. Northern blot analyses revealed that ADS and AS concomitantly stimulated GST Ya, Yb1 and Yc2 gene expression, whereas PS increased the levels of Ya, Yb1, and Yb2 mRNA, but not Yc2 mRNA levels. The expression of GST subunit Yc2 in response to these compounds might be associated with hepatoprotective effects. These results demonstrate that ADS and AS have distinct capability of blocking CCl4-induced hepatotoxicity, whereas certain saturated alkyl sulfides rather potentiate CCl4-induced hepatotoxicity and that the underlying mechanism is associated with P450 2E1 and P450 2B expression, and possibly with certain GST expression.
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PMID:Molecular mechanism for alkyl sulfide-modulated carbon tetrachloride-induced hepatotoxicity: the role of cytochrome P450 2E1, P450 2B and glutathione S-transferase expression. 862 17

The ability of anthocyanin obtained from the petals of H. rosasinensis to prevent carbon tetrachloride-induced acute liver damage in the rat was examined. Treatment of separate groups of rats with 2.5 ml of 1, 5 and 10% anthocyanin extract in 5% aqueous ethanol/kg body weight, 5 days/week for 4 weeks before 0.5 ml/kg carbon tetrachloride (CCL4) resulted in significantly (P < 0.05) less hepatotoxicity than with CCL4 alone, as measured by serum aspartate and alanine aminotransferase activities 18 h after CCL4. These data suggest that H. rosasinensis anthocyanin may be protective against carbon tetrachloride-induced liver injury.
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PMID:Prevention of carbon tetrachloride-induced hepatotoxicity in the rat by H. rosasinensis anthocyanin extract administered in ethanol. 992 24

In order to study the contribution of eicosanoids to the regulation of the functions of normal and carbon tetrachloride (CCl4)-injured liver cells, primary cultures of hepatocytes (HC) either alone or in coculture with Kupffer cells (KC) were exposed for 4 and 24 h to lipoxygenase inhibitor (nordihydroguaiaretic acid-NDGA) or cyclooxygenase inhibitor (indomethacin-IND) in the presence and in the absence of CCl4. Treatment with CCl4 resulted in increased ALT release and a decreased mitochondrial respiration (MR) in HC and their cocultures with KC. The addition of NDGA decreased ALT levels and increased MR in control and CCL4-injured cells. Urea production (UP) was not significantly affected by NDGA. In contrast, addition of IND) decreased UP by HC (4 h), and did not alter ALT release and MR in control and CCl4-treated cells. These results indicate that arachidonic acid metabolites are involved in the regulation of HC flinctions. There is also evidence that a protective action of lipoxygenase inhibitors on CCl4-injured liver is mediated, at least partly, by their direct effects on HC and KC, in particular by increasing the mitochondrial respiration.
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PMID:Effects of nordihydroguaiaretic acid and indomethacin on the viability and functional activities of normal and carbon tetrachioride-injured rat hepatocytes cultured alone and with Kupffer cells. 1034 18

It has been reported that Nigella sativa oil possesses hepatoprotective effects in some models of liver toxicity. However, it is N. sativa seeds that are used in the treatment of liver ailments in folk medicine rather than its oil. Therefore, the aim of this study was to investigate the effect of the aqueous suspension of N. sativa on carbon tetrachloride (CCL4)-induced liver damage. Aqueous suspension of the seeds was given orally at two dose levels (250 mg/kg and 500 mg/kg) for five days. CCL4 (250 microl/kg intraperitoneally / day in olive oil) was given to the experimental group on days 4 and 5, while the control group was only treated with the vehicles. Animals treated with CCL4 showed remarkable centrilobular fatty changes and moderate inflammatory infiltrate in the form of neutrophil and mononuclear cells when compared to the controls. This effect was significantly decreased in animals pretreated with N. sativa. Histopathological or biochemical changes were not evident following administration of N. sativa alone. Serum levels of aspartic transaminase (AST), and L-alanine aminotransferase (ALT) were slightly decreased while lactate dehydrogenase (LDH) was significantly increased in animals treated with CCL4 when compared to the control group. LDH was restored to normal but ALT and AST levels were increased in animals pretreated with N. sativa. In conclusion, N. sativa seeds appeared to be safe and possibly protective against CCL4-induced hepatotoxicity. However, further studies may still be needed prior to supporting its use in folk medicine for hepatic diseases.
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PMID:Protective effect of Nigella sativa seeds against carbon tetrachloride-induced liver damage. 1469 75


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