Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats were injected intraperitoneally with CCl4 (2.5 ml/kg body wt.) and the hepatotoxicity was compared with that of rats receiving the same dose of CCl4 and an intraperitoneal injection of fructose 1,6-bisphosphate (2 g/kg body wt.). A 50-70% decrease in plasma aspartate aminotransferase and alanine aminotransferase activities was observed in the latter treatment, indicating a protective role of the sugar bisphosphate in CCl4 hepatotoxicity. The protection was accompanied by elevated hepatic activities of ornithine decarboxylase at 2, 6 and 24 h, S-adenosylmethionine decarboxylase at 6 h, and spermidine N1-acetyltransferase at 2 h. The increase in the enzymes involved in polyamine metabolism was shown in our previous work [Rao, Young & Mehendale (1989) J. Biochem. Toxicol. 4, 55-63] to correlate with increased polyamine synthesis or interconversion, which was related to the extent of hepatocellular regeneration. The hepatic contents of fructose 1,6-bisphosphate and ATP significantly decreased after CCl4 treatment, and administration of the sugar bisphosphate increased hepatic ATP. Fructose 1,6-bisphosphate, an intermediary metabolite of the glycolytic pathway, may decrease CCl4 toxicity by increasing the ATP in the hepatocytes. The ATP generated is useful for hepatocellular regeneration and tissue repair, events which enable the liver to overcome CCl4 injury.
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PMID:Protective role of fructose 1,6-bisphosphate during CCl4 hepatotoxicity in rats. 259 Jan 62

Water purification generates a variety of chlorinated contaminants, one of which is dichloromaleic acid (DCMA). Exposure to this compound is likely to occur in combination with other drinking water pollutants, some of which are hepatotoxic. This study was designed to examine the interactive effects of carbon tetrachloride (CCl4), a known hepatotoxin, with DCMA on liver and kidney function in the Sprague-Dawley rat. Administration of a single dose of DCMA (200-400 mg/kg, ip) caused modest dose-dependent increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and plasma urea nitrogen, as well as a marked depletion of nonprotein sulfhydryls (NPSH) in the liver, but not the kidney, by 24 hr. Pretreatment with inducers (phenobarbital or 3-methylcholanthrene) or an inhibitor (SKF 525A) of cytochrome P-450 activity failed to alter the response observed with DCMA alone. Alterations in 24-hr urine volume, osmolality, and water consumption also were observed. DCMA-mediated changes in plasma urea nitrogen and NPSH were reduced in magnitude with coadministration of CCl4 (1 ml/kg, ip), while anticipated CCl4-induced increases in ALT and AST were reduced with coexposure to DCMA. Renal slice experiments indicated that DCMA-treated rats were less able to accumulate the organic anion p-aminohippurate (PAH), whereas DCMA had no effect on accumulation of the organic cation tetraethylammonium (TEA). The combination of CCl4 and DCMA produced only additive effects on organic ion accumulation. These results suggest hepatic interaction possibly related to the metabolism of CCl4 and DCMA, resulting in renal and hepatic toxicity diminished from that observed with exposure to either agent alone.
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PMID:Effect in the rat of the interaction of dichloromaleic acid and carbon tetrachloride on renal and hepatic function. 261 81

The toxicity of carbon tetrachloride (CCl4) in monolayer cultures of primary hepatocytes was investigated at oxygen concentrations that prevail in the liver under conditions that range from normoxia to hypoxia: 0.5, 1, 2, and 20% O2. CCl4 was administered in the vapor phase at concentrations that produce aqueous concentrations at 37 degrees C of 0.4, 2.0, and 4.0 mM. Damage was assayed by leakage of aspartate transaminase and the inclusion of Trypan Blue immediately after the 2-hr incubation and after an additional 6-hr incubation in 20% O2. Only in the case of 0.5% O2 and 4 mM CCl4 were the monolayers damaged (18%) immediately after the 2-hr exposure; all other exposed cells were undamaged at that time point and the dose response of cell death as a function of CCl4 and oxygen concentration was not evident until the 6-hr time point. The monolayers exposed to 4 mM CCl4 and 1, 2, or 20% O2 exhibited little immediate damage but were all 100% dead 6 hr later. The monolayers exposed to 2 mM CCl4 and 0.5, 1, 2, or 20% O2 were 53, 48, 40, and 22 +/- 2% dead after 6 hr, respectively. These results suggest that effects of CCl4 exposure, for example alterations in the function or synthesis of essential proteins, require several hours to affect cell viability.
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PMID:Interaction of hypoxia and carbon tetrachloride toxicity in hepatocyte monolayers. 270 81

The pathogenetic mechanisms of hepatotoxicity of an anthelminthic drug chloxyl as compared with the mechanisms of CCl4 hepatotoxicity were studied on the basis of the change of the liver content of the primary (conjugated dienes) and secondary (malondialdehyde) products of lipid peroxidation. the activity of alanine aminotransferase and aspartate aminotransferase in the blood serum of rats and on the basis of the change of the liver structure. The pathogenetic mechanisms of chloxyl hepatotoxicity are close to those of CCl4 and consist in the activation of membrane lipid peroxidation, that is, an increase of the liver contents of the primary and secondary products of lipid peroxidation, an impairment of permeability of membranes of hepatocytes and their destruction with the release in the blood of cytoplasmic enzymes of alanine aminotransferase and aspartate aminotransferase.
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PMID:[Pathogenetic mechanisms of liver damage by the anthelmintic preparation chloxyl]. 274 47

Aqueous extracts of the aerial parts of Melothria maderasptana and the leaves of Osbeckia octandra have been compared with (+)-3-cyanidanol with regard to their abilities to alleviate carbon tetrachloride (CCl4)-induced liver dysfunction in albino rats by comparing the abilities of these drugs to protect the liver against CCl4-mediated alterations in the liver histopathology and serum levels of aspartate aminotransferase (GOT), alkaline amino-transferase (GPT), and alkaline phosphatase. In both pretreatment and post-treatment (administration of drugs before or after CCl4 treatment) experiments, the most marked rate of recovery of the liver was exhibited by the group of rats treated with Melothria maderaspatana extract. Although the protection offered by (+)-3-cyanidanol and Osbeckia octandra appears to be comparable in post-treatment, Osbeckia was significantly more effective in pre-treatment. From the overall results obtained it appears that the aqueous extracts of Melothria maderaspatana and Osbeckia octandra are both as potent or in some instances (in pretreatment experiments) more potent than (+)-3-cyanidanol. Of the two plants tested under the present experimental conditions used, Melothria maderaspatana appears to be marginally more effective than Osbeckia octandra in protecting the liver against CCl4-induced alterations.
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PMID:An evaluation of the potency of Osbeckia octandra and Melothria maderaspantana as antihepatotoxic agents. 274 29

Two methods of inducing liver cirrhosis in the rat were studied. Intragastric administration of CCl4 for 16 weeks according to Proctor and Chatamra was compared to the administration of thioacetamide in the drinking water (0.3 g/l) for the same period. CCl4 administration induced micronodular cirrhosis in 6/8 animals with a 27% mortality. Thioacetamide induced cirrhosis in 6/8 animals without mortality. The histologic pictures differed somewhat in that the CCl4 group exhibited more necrosis and cellular swelling while the thioacetamide group had more nuclear atypias and proliferation. Biochemically both groups had elevated plasma levels of aspartate aminotransferase. The lysosomal enzyme beta-hexosaminidase (beta-NAG) showed a transient increase in the thioacetamide animals, while beta-glucuronidase decreased. CCl4-induced cirrhosis led to an increase in beta-NAG. Plasma zinc decreased in both groups as well as liver zinc content in the CCl4 group, while there was a continuous elevation of liver zinc in the thioacetamide group. We conclude that oral administration of thioacetamide is a simple and reliable method of inducing experimental liver cirrhosis. The differences in histological appearances and some biochemical parameters may be caused by the different mechanisms of action of thioacetamide and CCl4.
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PMID:Thioacetamide- and carbon tetrachloride-induced liver cirrhosis. 276 88

An investigation was carried out to evaluate the ability of Melothria maderaspatana to protect the livers of albino rats from carbon tetrachloride-mediated alterations in liver histopathology and serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Treatment with an aqueous extract of Melothria aerial parts (either before or after CCl4 administration) markedly decreased CCl4-mediated alterations in liver histopathology as well as serum enzyme levels. Results provide supportive evidence for the folklore view that this plant is a good hepatotonic.
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PMID:Evaluation of the efficacy of Melothria maderaspatana in the alleviation of carbon tetrachloride-induced liver dysfunction. 319 93

The toxicity of several halogenated and non-halogenated hydrocarbons (CH2Cl2, CHCl3, CCl4, C6H14, C8H10) in isolated rat hepatocytes were compared. Release of aspartate aminotransferase (AST) activity was rapid and concentration-dependent. Fractional AST release plateaued at 10-60 min following hydrocarbon exposure. Enzyme leakage at 60 min correlated with the oil/water partition coefficient (pi) of the compounds. All compounds, except n-hexane, also caused an immediate inhibition of the rate of cellular respiration. Inhibition of cell respiration also correlated with pi and was reversible. The recovery of cellular oxygen consumption was examined in detail for CCl4 and correlated with evaporation of the compound. These data suggest that acute hydrocarbon-induced injury in isolated hepatocytes is mediated by concentration-dependent direct solvent effects. Since halogenated hydrocarbons are widely used to induce general anesthesia, the clinical implications of possible direct effects by halocarbons on liver function in vivo and the potential relationship to liver injury are discussed.
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PMID:Rapid halogenated hydrocarbon toxicity in isolated hepatocytes is mediated by direct solvent effects. 362 14

'Arogyavardhini'-an indigenous formulation was evaluated for its hepatoprotective activity in rats, using two models of carbon tetrachloride (CCl4) hepatic damage, one simulating vital hepatitis and the other simulating fatty change. The protective effect was assessed from serum aspartate transaminase (AST) and alkaline phosphatase levels and from histopathological changes in liver. The results revealed that 'Arogyavardhini' (5 mg/100g, PO daily) was effective in minimizing the changes in serum levels of AST and alkaline phosphatase induced by CCI. The protective effect was also evident on histopathological examination.
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PMID:Effect of 'Arogyavardhini' against carbon tetrachloride induced hepatic damage in albino rats. 366 71

Carbon tetrachloride (CCl4) injection, but not partial hepatectomy, significantly increased gastric acid secretion and ulceration in rats. Both procedures did not influence serum IgG levels, but markedly elevated serum alanine and aspartate aminotransferase activities. It appears that short-term liver injury produced by CCl4, but not hepatectomy, adversely affects rat stomachs.
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PMID:The influence of partial hepatectomy and carbon tetrachloride on rat stomachs. 374 6


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