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

---

Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, it was investigated whether the prostacyclin derivative Iloprost would protect hepatocytes against CCl4-induced liver injury and which mechanism(s) of hepatocellular pathogenesis might be affected by it. Rats were treated with a single oral dose of CCl4 (2 ml per kg); Iloprost was infused continuously from 2 to 4 hr before intoxication until killing. The following results were obtained. The CCl4-induced release of AST, lactate dehydrogenase and alkaline phosphatase into the serum was reduced by 50 to 70% in rats treated with doses of 0.1 and 0.5 micrograms Iloprost per kg per min. Infusion of 0.02 and 0.004 micrograms Iloprost per kg per min did not affect the CCl4-induced enzyme release into the blood. CCl4 induced the occurrence of aldehydes (products of lipid peroxidation), which were detected by histochemical and biochemical means. At 12, 48 and 72 hr after CCl4, the aldehyde-positive liver section area was about 58, 69 and 16% in rats treated with CCl4 alone, but only about 18, 13 and less than 1% in rats treated additionally with Iloprost. The aldehyde-positive hepatocytes were located predominantly in the centrilobular zone of the liver. At 24 hr the extent of the aldehyde-positive section area was the same in rats with or without Iloprost treatment (about 90%). Biochemical determination, however, revealed that at this time point the malondialdehyde content after Iloprost in rats was about 70% lower than without Iloprost treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Histochemical and biochemical studies on the effect of the prostacyclin derivative iloprost on CCl4-induced lipid peroxidation in rat liver and its significance for hepatoprotection. 246 34

Chlordecone greatly potentiates carbon tetrachloride (CCl4) hepatotoxicity. In order to quantitate the degree of this potentiation, the effects of a range of doses of CCl4 on two microsomal enzymatic functions and liver enzyme release were examined in chlordecone-treated and control rats. Male Sprague-Dawley rats were pretreated with 15 mg chlordecone per kilogram body weight (BW) intragastrically or with vehicle. After 48 hours, 0 to 250 microliters CCl4 per 100 g body weight were given intraperitoneally (IP), and the rats were killed 24 hours later. Chlordecone treatment produced approximately a 17-fold potentiation of the CCl4-dependent loss of cytochrome P-450 and glucose-6-phosphatase activity, so that a dose of 6 microliters CCl4 per 100 g body weight in the chlordecone-treated animals resulted in a similar amount of damage as observed with 100 microliters CCl4 per 100 g body weight in controls. A similar potentiation by chlordecone was seen with CCl4 induced increases in serum glutamic-oxaloacetic transaminase (SGOT) levels. Chlordecone treatment also increased hepatic cytochrome P-450 levels by 67% and resulted in an increase in the covalent binding of [14-C]-CCl4-derived metabolites to microsomal protein and lipid in vivo.
...
PMID:Potentiation of carbon tetrachloride hepatotoxicity by chlordecone: dose-response relationships and increased covalent binding in vivo. 246 94

Previous histomorphometric studies led us to hypothesize that suppression of hepatocellular regeneration and the repair of the hepatolobular architecture was involved besides bioactivation phenomenon in the progressive and irreversible phase of toxicity resulting from CD + CCl4 interaction. We have recently observed significant protection from CD potentiated CCl4 toxicity in animals which are stimulated for active hepatocellular regeneration. The present work is an extension of our earlier histomorphometric investigation, taking 3H-thymidine (3H-T) incorporation as a biochemical parameter to assess hepatocellular regeneration followed by autoradiographic analysis of liver sections in normal (N) or chlordecone (CD) treated (10 ppm in diet for 15 days) male rats undergoing sham (SH) or partial hepatectomies (PH). Initial experiments established that in normal (N) rats, greatest 3H-T incorporation into hepatocellular nuclear DNA occurs at 2 days post-PH which returns to basal levels by 7 days. CD treatment alone did not change this phenomenon. 3H-T incorporation into nuclear DNA and the percentage of labelled cells as evidenced by autoradiography of liver sections were significantly elevated in N rats at 1-2 h after CCl4 (100 microliters/kg) administration and returned to basal level by 6 h. Serum enzymes (AST and ALT) in N rats undergoing SH and PH were not altered, but were significantly elevated in CD rats following CCl4 (100 microliters/kg) administration. CCl4-induced serum enzyme elevations were significantly lower in 2 days post-PH (PH2) rats when compared to SH rats or 7 days post-PH (PH7) rats maintained on CD diet, indicating that CD potentiated CCl4 hepatotoxicity is significantly reduced in livers stimulated for regenerative activity by PH.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Role of hepatocellular regeneration in chlordecone potentiated hepatotoxicity of carbon tetrachloride. 247 60

The potentiation of CCl4 toxicity by pre-exposure to chlordecone (CD) is well established. Chlordecone-induced metabolism of CCl4 and suppressed hepatocellular repair have been offered as possible mechanisms for this potentiation. Recent work using the partially hepatectomized (PH) rat as a model for an actively regenerating liver has provided supportive evidence for the latter hypothesis. The present study was initiated to determine if metabolism and disposition of 14CC14 is altered in the PH rat, and if this is a contributing factor to the reported protective effect afforded by the PH procedure. Male Sprague-Dawley rats (150-175 g) maintained on dietary CD (10 ppm) for 15 days were partially hepatectomized or sham-operated (SH) on day 15. Another group of CD-pretreated rats received 0.9% CoCl2 (60 mg/kg, sc, qd for 2 days) in lieu of the surgical procedure. On day 16 the rats were challenged with a single dose of CCl4 (100 microL/kg, ip) containing 20 muCi 14CCl4. A radiolabel inventory consisting of exhaled 14CCl4, 14CO2 production, total hepatic 14C, free 14CCl4 and covalently bound 14C was taken over a 6-hr time period. Lipid peroxidation and serum enzyme activities [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] were measured in indices of toxicity. Neither CD pretreatment alone nor CoCl2 treatment alone produced significant alterations in metabolism of low dose (100 microliters/kg) CCl4. No significant difference in 14CCl4 recovery or 14CO2 production was detected for PH versus SH rats. Hepatic 14CCl4-derived 14C (per gram tissue) was greater in PH rats. Values for free 14CCl4, covalently bound 14C, and lipid peroxidation were similar for SH and PH rats.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Carbon tetrachloride metabolism in partially hepatectomized and sham-operated rats pre-exposed to chlordecone (Kepone). 248 48

The authors studied the pharmacotherapeutic efficacy of antioxidants vitamin E, sodium selenite, and their combination in damage to rat liver by CCl4 and the anthelmintic agent chloxyl. Changes of the intensity of peroxidation of biological membrane lipids, the activity of enzymes-markers of hepatocyte cytolysis--alanine aminotransferase and aspartate aminotransferase--in blood serum, and changes in the structure of the liver were studied. Antioxidants and their combination blocked lipid peroxidation, reduced the activity of alanine aminotransferase and aspartate aminotransferase in blood serum considerably, and caused a protective effect on the structure of rat liver in its damage by CCl4 and chloxyl.
...
PMID:[Experimental antioxidant therapy in toxic liver damage from CCl4 and chloxyl]. 255 82

The effect of vitamin A on experimental hepatic fibrosis in rats induced by administration of carbon tetrachloride (CCl4) and pig serum was studied. Vitamin A content in the CCl4-induced cirrhotic liver decreased significantly. Administration of pig serum caused hepatic fibrosis without hepatocytic damage. Vitamin A suppressed induction of experimental hepatic fibrosis by CCl4 and pig serum. Neither hepatocytic injury nor increased activities of serum aspartate aminotransferase and glutamic pyruvic transaminase induced by CCl4 was diminished by vitamin A. These data provide evidence that vitamin A inhibits hepatic fibrogenesis and that this effect may be mediated by an action on stellate cells rather than hepatocytes.
...
PMID:Suppression of experimental hepatic fibrosis by administration of vitamin A. 257 84

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.
...
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.
...
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.
...
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.
...
PMID:[Pathogenetic mechanisms of liver damage by the anthelmintic preparation chloxyl]. 274 47


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---