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)

Mice ingesting a standard rodent diet supplemented with polybrominated biphenyls (PBBs) were more susceptible to chlorinated hydrocarbon solvent-induced renal and hepatic damage, as well as the lethal effects of CHCl3 and CCl4, than were mice consuming control diet. As little as 0.025 ml/kg CHCl3 caused a significant increase in serum glutamic oxaloacetic transaminase (SGOT) and blood urea nitrogen (BUN) and a significant decrease in renal cortical slices accumulation of p-aminohippurate (PAH) in PBB-pretreated but not control mice. SGOT and serum glutamic pyruvate transaminase (SGPT) were greater in PBB-pretreated mice than in control mice after 0.125 and 0.005 ml/kg CCl4, respectively. Renal cortical PAH accumulation was greatly reduced in PBB-pretreated but not control mice aftter 0.125 ml/kg CCl4. The solvent-induced decrease in PAH accumulation was also greater in PBB-pretreated mice than in control mice following administration of 1.0 ml/kg trichloroethylene (TRI) and 0.15 ml/kg 1,1,2-trichloroethane (TCE).
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PMID:Potentiation of hepatic and renal toxicity of various compounds by prior exposure to polybrominated biphenyls. 20 82

Male mice treated with nicotine hydrochloride either acutely (5 mg/kg i.p.) or subchronically (5 mg/kg i.p. daily for 3 weeks; 25 mg/liter in drinking water for 2-3 months) showed no evidence of hepatic dysfunction, as measured by serum glutamic-pyruvic transaminase or serum alkaline phosphatase activities. Neither acute nor subchronic administration modified the hepatotoxic response to a potent hepatotoxin (carbon tetrachloride), nor that of less potent hepatotoxins chloroform or 1, 1, 1-trichloroethane, nor was the cholestatic effect of alpha-naphthylisothiocyanate modified.
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PMID:Hepatic function after acute of subchronic nicotine administration in untreated mice and mice treated with hepatotoxic chemicals. 99 92

After a chloroform intraperitoneal injection, lactate dehydrogenase, alanine aminotransferase and particularly aspartate aminotransferase serum activities are much more raised in deficient animals. Liver ornithine decarboxylase (ODC) activity normally decreases in rats between the 4th. and the 7th. month after the weaning. In vitamin A deficient animals, basal values of the enzyme activity are lower and the decrease is deeper. But even at month 7, liver sustains a partial capacity of ODC recovery if retinol is fed during 15 days. Chloroform administration strongly enhances liver ODC activity in normal rats. In the deficiency, stimulation is lower in absolute value but relatively higher if referred to basal level. After retinol refeeding, chloroform stimulates enzyme activity to nearly normal values. Vitamin A deficiency impairs obviously liver ODC activity and its response to chloroform stimulation in rats, but the stroke is at least partially reversible in our conditions. Moreover, deficient animals maintain a non negligible capacity of ODC response under chloroform stimulation.
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PMID:[Toxicity of chloroform and vitamin A status in the rat]. 145 50

Individual serum bile acids (SBA) are emerging as potentially useful early indicators of liver injury. This study was undertaken to compare the usefulness of individual SBA with the routinely used assays for detecting the effects of the hepatotoxicants carbon tetrachloride (CCl4) and chloroform (CHCl3). Serum samples were assayed for liver injury by determination of alanine aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP), bilirubin and total bile acid (by enzymatic kit). These results were compared with levels of individual SBA measured by high performance liquid chromatography (HPLC). Liver samples from CCl4-treated rats were taken for light and electron microscopic examination. The highest dose for each chemical caused increases in serum ALT and AST but not ALP. Chloroform at the highest dose increased bilirubin. Total SBA levels as assayed by the kit were elevated in response to CCl4 and CHCl3 at doses below which serum enzymes and bilirubin were increased. Some individual SBA were increased at a still lower dose for each of these two chlorinated solvents. At the lowest dose of CCl4 tested no consistent light microscopic or ultrastructural changes were found. At all the higher doses periacinar cells displayed typical accumulation of lipid droplets and degranulation and dilation of rough endoplasmic reticulum. The extent of the ultrastructural changes were dose-dependent. Thus individual SBA assayed by HPLC may be considered as a very sensitive indicator of liver injury induced by the classical hepatotoxicants carbon tetrachloride and chloroform.
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PMID:Individual serum bile acids as early indicators of carbon tetrachloride- and chloroform-induced liver injury. 145 31

The effect of coadministration of CHCl3 on CCl4-induced hepatic damage was investigated at low dose inhalation. Coexposure of CHCl3 did not influence CCl4-induced changes in any index of hepatic damage in control rats. Coadministration of CHCl3, however, enhanced CCl4 (10 ppm)-induced hepatic damage of ethanol treated rats in a dose- and duration-dependent manner: simultaneous exposure of 50 ppm CHCl3 potentiated CCl4-induced increase in plasma GPT activity and number of necrotic hepatocytes; the enhancement of CCl4-induced hepatic damage by 50 ppm CHCl3 was found over the 4 h exposure; simultaneous exposure of 10 and 25 ppm CHCl3 potentiated the CCl4-induced increase in liver malondialdehyde (MDA) content. In contrast, coadministration of 50 ppm trichloroethylene and 200 ppm 1,1,1-trichloroethane decreased CCl4-induced increase in plasma GPT activity, though these exposures did not influence the liver MDA content. These results suggest that the concentration of 10 ppm CCl4 may be significant for CHCl3 to potentiate the hepatic damage caused by CCl4 in ethanol-treated rats. Heavy drinkers may have a higher hepatotoxic risk for a mixture of CCl4 and CHCl3 than for a single exposure to CCl4 or CHCl3, and a particular attention should be therefore given to the joint exposure to CCl4 and CHCl3.
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PMID:Hepatotoxic interaction between carbon tetrachloride and chloroform in ethanol treated rats. 146 93

Dichloro- and trichloroacetic acids (DCA and TCA) and chloroform are formed during chlorination disinfection of drinking water. The effects of DCA and TCA treatment on CHCl3 toxicity were assessed in these studies. Male and female rats were gavaged with DCA or TCA (0.92 and 2.45 mmol/kg administered 3 times over 24 h). Three hours after the last dose CHCl3 was injected ip (0.75 mg/kg). Male rats experienced some weight loss (15%) and slight increases of ALT and BUN, but there were no effects of either DCA or TCA on any of these responses. In females, CHCl3 increased plasma ALT and this response was greater (up to threefold) in the DCA group, compared to saline controls. Similarly, BUN was increased by CHCl3 and this was more severe (up to threefold) in both the DCA and TCA pretreated groups. These results show that CHCl3 toxicity is increased by DCA and TCA, and this effect is gender-specific, occurring only in females. DCA increases both liver and kidney toxicity, whereas TCA affects only kidney toxicity.
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PMID:Dichloroacetic acid and trichloroacetic acid increase chloroform toxicity. 152 7

Previous studies have shown that dichloroacetate and trichloroacetate increase the toxicity of CHCl3. The present experiments were designed to determine if monochloroacetate (MCA) similarly affects CHCl3 toxicity. There were occasional differences, but overall kidney function indices (urine volume, osmolality and electrolyte concentration, glucosuria, retention of urea nitrogen in plasma) were not affected differently at either 24 or 48 hr after CHCl3 in saline and MCA pretreated Sprague-Dawley rats of either sex. Males pretreated with MCA had 45-fold greater plasma alanine aminotransferase (ALT) compared to the saline pretreated group similarly dosed with CHCl3. ALT was increased threefold in female rats, a modest change that suggests hepatic damage, and BUN was nonsignificantly increased. Therefore hepatic and renal functions were assessed in females. MCA pretreatment did not alter the effects of CHCl3 on hepatic excretory function or glomerular or tubular function. Bile production and glomerular filtration were both decreased in the MCA group treated with peanut oil, suggesting that MCA impairs both liver and kidney function in female rats. MCA pretreatment increases CHCl3 hepatoxicity markedly in male rats and only slightly in female rats. This difference is likely due to the different effects, in males and females, of MCA on the cytochrome P450 isoforms that activate CHCl3. The effects of MCA on renal function in females would decrease CHCl3 delivery to kidney cells, suggesting that MCA may alter the distribution of CHCl3.
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PMID:Sex differences in monochloroacetate pretreatment effects on chloroform toxicity in rats. 160 Dec 11

Chloroform hepatotoxicity was investigated in precision-cut liver slices from male Sprague-Dawley rats pretreated with phenobarbital to predispose animals to CHCl3 intoxication. Liver slices were exposed to 0.2, 0.5 and 1.0 mM chloroform for a total of 9 h in a roller culture system. Intracellular K+ loss was found to be concentration- and time-dependent over the duration of the experiment. Histopathological changes were also evident. Glucose 6-phosphate dehydrogenase and beta-glucuronidase were significantly decreased at 3 h relative to controls where a loss of 61% and 36% occurred, respectively. Enzyme levels of alanine aminotransferase and lactate dehydrogenase, both found predominantly in periportal hepatocytes, remained identical to controls over the duration of the experiment. A significant time-dependent depletion of glutathione occurred as early as 3 h following the administration of 0.5 mM chloroform. Mitochondrial viability, measured by the reduction of a specific dye, was significantly lower than controls in treated slices at 6 h following chloroform administration. Precision-cut liver slices appear to be especially useful for the biochemical and histopathological examination of site-specific hepatotoxicants such as CHCl3.
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PMID:The hepatotoxicity of chloroform in precision-cut rat liver slices. 163 1

Acetone potentiation of haloalkane-induced liver injury is a well-known phenomenon. Acetone-treated rats challenged with a trichloroethylene-CCl4 mixture exhibit a more sever liver injury than that predicted by the addition of the single potentiating effects of each. The purpose of the present study was to determine if acetone exerted similar interactions with other haloalkane mixtures. The testing protocol used was designed and performed to allow categorization of interactions occurring among two or three agents. Rats were treated (p.o.) with corn oil or acetone (10.2 mmol/kg) and were administered (i.p.) 18 h later 1,1-dichloroethylene (0.6 mmol/kg), trichloroethylene (5.6 mmol/kg), tetrachloroethylene (19.6 mmol/kg), 1,1,1-trichloroethane (10.0 mmol/kg), 1,1,2-trichloroethane (1.1 mmol/kg), 1,1,2,2-tetrachloroethane (1.0 mmol/kg), CHCl3 (6.2 mmol/kg), CCl4 (1.0 mmol/kg), or a mixture of two haloalkanes (all 28 combinations were tested). Liver injury was assessed 24 h later using plasma alanine aminotransferase activity and a quantitative histological evaluation. In corn oil pretreated rats, the hepatotoxic responses observed for the 28 mixtures were additive for 26 of 28 mixtures and supra-additive for 2 of 28, whereas in acetone-pretreated rats the responses observed were additive for 17 of 28, infra-additive for 10 of 28, and supra-additive for 1 of 28. Mixtures containing 1,1,1-trichloroethane or tetrachloroethylene resulted only in no change in toxicity or infra-additivity. Increased toxic responses (additivity and supra-additivity) were observed with certain binary mixtures containing CCl4, CHCl3, 1,1,2-trichloroethane, or 1,1-dichloroethylene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of acetone on the severity of the liver injury induced by haloalkane mixtures. 180 61

Chloroform was administered ip to Balb/c mice as a single dose ranging from 1/8 to 1 of the approximate lethal dose. At different time periods after administration, mice were sacrificed. Serum glutamate-pyruvate transaminase (SGPT) and sorbitol dehydrogenase (SDH) as well as glutathione (GSH) and malondialdehyde (MDA) levels in the liver were determined. Increased SGPT and SDH levels were found for all doses exceeding 1/8 of the approximate lethal dose. The depletion of GSH level was kept within 40% for all doses. A 2-4 fold increase of hepatic MDA level was found. The depletion of hepatic GSH and, to some extent the increase of serum SGPT and SDH, occurred in biphasic fashion. Dose-effect functions for these biochemical alterations could only be constructed for the second, delayed phase of action. It is postulated that the hepatotoxicity of chloroform is mainly dependent on radical formation in the course of biotransformation.
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PMID:The hepatotoxic action of chloroform: short-time dynamics of biochemical alterations and dose-effect relationships. 181 48


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