Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coccinia indica (Family: Cucurbitaceae, locally known as telakucha) leaves were extracted with 95% ethanol. Following evaporation of the solvents, the residue was suspended in distilled water. When this suspension was fed orally to male normal-fed and 48-hr starved rats, the blood glucose was lowered 21% (P less than 0.01) in normal-fed and 24% (P less than 0.001) in 48-hr starved animals respectively. Starvation had induced a 3-fold increase in the activity of glucose-6-phosphatase and this activity was depressed 19% (P less than 0.05) by extract feeding while basal activity of the enzyme in normal-fed rats remained unaffected. Consistent with the depression of glucose-6-phosphatase, urea cycle enzyme arginase was also depressed 21% (P less than 0.001) and 12% (P less than 0.01) in the liver of 48 hr-starved and normal-fed animals respectively. Unlike glucose-6-phosphatase, starvation induced levels of gluconeogenic enzymes alanine aminotransferase and aspartate aminotransferase were not affected by Coccinia extract. These results suggest that the hypoglycemic effect of C. indica is partly due to the repression of the key gluconeogenic enzyme glucose-6-phosphatase.
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PMID:Hypoglycemic effects of Coccinia indica: inhibition of key gluconeogenic enzyme, glucose-6-phosphatase. 133 43

Five healthy male adults were deprived of food for a short period (40 hr) and biochemical studies and urinalyses were done before and after fasting to determine the effects on liver and renal functions. Acceleration in lipid metabolism was seen with an increase of about 90% in NEFA and about 20% in TG. GOT, GPT and LDH showed elevations of about 40 to 100% indicating a slight effect of 40 hr fasting on liver functions. BUN, HDL-C and ALP showed increases of about 30% while, CPK and TC showed decreases of about 20%. In the other parameters changes of about 10% were seen. After a fasting with water intake of about 1,000 ml/day, a body weight loss of 1.2 kg was observed at 40 hr. During the short-term fasting (40 hr) as done in our study, changes were seen in glucose and lipid metabolism. However, since no abnormalities were seen in general biochemical parameters, we consider that a fasting of this duration is valuable for use as one of the fastings.
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PMID:Effect of short-term fasting treatment on liver and renal function. 134 10

While the clinical results of orthotopic liver transplantation have greatly improved, the viability of liver grafts and extension of the safe time for preservation are necessary factors in need of improvement. The liver is one of the organs most sensitive to anoxia. The addition of an oxygen carrying agent to the preservation solution was evaluated. Pyridoxalated hemoglobin-polyoxyethylene conjugate (PHP) is used as an oxygen carrier. Viaspan (UW) served as a control solution. Test solution (PHP+UW) composition was composed of a 1:1 mixture of PHP and UW solutions with hemoglobin 4.0g%, hydroxyethyl starch 2.5g%, osmolality 320 mOsm/kg H2O, and colloidal osmotic pressure 33 mmHg. The oxygen carrying capacity of PHP+UW solution is about 10 times higher than UW solution at 4 degrees C. Male Lewis rats (BW: 250-300 g) were divided into five groups. After flushing the solution via the portal vein, rat livers were harvested. Two preservation methods, simple storage and perfusion (0.1 ml/min/g liver), were studied at 4 degrees C for 24 or 48 hours. OxyHb, MetHb, pO2, pH, Na, K, GOT, and GPT of perfusate, hepatic mitochondrial functions after preservation, and tissue adenine nucleotides by HPLC were measured. Light microscopy on the tissue was also performed. No significant differences were noted in perfusate biochemical parameters. Oxygen consumption during the perfusion was significantly higher in the PHP+UW than in the UW group. Hepatic mitochondrial functions and tissue ATP levels were better preserved in perfusion than in simple storage, and in PHP+UW than in UW at 48 hours. The oxygen carrying agent, PHP, can provide significantly higher levels of oxygen to liver grafts and improve graft viability.
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PMID:Does oxygen supply improve graft viability in liver preservation? 139 76

Male and female Sprague-Dawley rats were administered drinking water containing 300, 600, 1200, or 2400 mg/L chloral hydrate for 90 days. A control group received distilled water only. No animals died during the study and no differences were observed in body weight gain or food and water consumption, except for males at the highest-dose level. Minor treatment-related effects were observed for organ weights and hematological parameters and these did not appear to be of toxicological significance. Some indications of toxicity were evident in the 2400 mg/L male group (equivalent to 168 mg/kg-day) including a significant decrease in food and water consumption and in weight gain. In addition, histopathological examination of these animals revealed an apparent increase in the incidence of focal hepatocellular necrosis. Increases in AST, ALT, and LDH, which occurred at several dose levels in males, but particularly at 200 mg/L, are consistent with the hepatocellular necrosis of minimal to mild severity diagnosed by microscopic examination. These liver changes, except for sporadic enzyme changes, were not seen in the female rats which actually consumed higher doses of chloral hydrate (e.g., 288 mg/kg-day at 2400 mg/L). On the basis of the mild liver toxicity (histopathological and clinical) observed in males at the highest doses (168 mg/kg-day), the no observed adverse effect level (NOAEL) for oral exposure of rats to chloral hydrate for 90 days is considered to be 96 mg/kg-day (600 mg/L).
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PMID:Ninety-day toxicity study of chloral hydrate in the Sprague-Dawley rat. 142 61

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

Endotoxin administration causes liver injury. Patients with alcoholic liver disease frequently have portal vein and systemic endotoxemia, and some investigators have suggested that endotoxin plays an etiologic role in alcoholic liver injury. Many of the metabolic effects of endotoxin are mediated by the cytokine tumor necrosis factor (TNF). It was the purpose of this study to determine whether TNF plays a role in ethanol-enhanced endotoxin liver injury. Rats were fed either a diet in which 36% of the calories were from ethanol or an isocaloric control diet. After 6 weeks, groups of 10 rats were intravenously injected with either saline, 1 mg/kg endotoxin, or 30 micrograms/kg of a prostaglandin E1 (PGE1) analogue + 1 mg/kg endotoxin 24 hr prior to sacrifice. Ethanol/endotoxin-treated rats had significantly higher liver enzyme levels (ALT: 1064 +/- 355 IU/liter, AST: 2024 +/- 515 IU/liter) compared with isocaloric/endotoxin controls (ALT: 237 +/- 54 IU/liter, AST: 602 +/- 80 IU/liter). Ethanol/endotoxin rats also had significantly higher peak serum TNF concentrations (992 +/- 200 units/ml) compared with isocaloric/endotoxin controls (344 +/- 96 units/ml). Pretreatment of ethanol/endotoxin rats with PGE1 caused significant attenuation of liver injury (ALT: 267 +/- 64 IU/liter, AST: 612 +/- 77 IU/liter) and a diminished serum TNF response. In contrast to chronic ethanol administration, acute gavage with 2 mg/kg ethanol (30% w/v) followed by intravenous injection of 2 mg/kg endotoxin produced significantly lower peak serum TNF concentrations (401 +/- 76 units/ml) than gavage with distilled water (1152 +/- 208 units/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor in alcohol enhanced endotoxin liver injury. 153 Jan 27

Although it has been reported that vanadate is effective in diminishing the expression of diabetes in the rat, the severe toxic side effects noted in the vanadate-treated animals suggest that chronic oral administration of vanadate argues against its use in human diabetes. The present study was conducted to evaluate the effects of the chelator Tiron on the mobilization of vanadium after administration of sodium metavanadate in the drinking water (0.20 mg/ml) of streptozotocin-induced diabetic rats for 35 days. Intraperitoneal treatment with Tiron (300 or 600 mg/kg) was initiated after three weeks of vanadate administration and continued for two weeks. The ameliorative effects of vanadium with respect to diabetes were not diminished by the administration of Tiron, but the accumulation of vanadium in kidney and bone was significantly decreased in the Tiron-treated groups and diabetes associated increases in serum GOT, GPT and cholesterol were diminished with Tiron treatment. It is concluded that the coadministration of metavanadate and Tiron may be of potential value for treatment of diabetes mellitus.
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PMID:Tiron administration minimizes the toxicity of vanadate but not its insulin mimetic properties in diabetic rats. 153 46

Groups of 20 rats and 20 mice of each sex were administered monochloroacetic acid (MCAA) once daily, 5 days per week, in water by gavage for up to 13 weeks. Doses used were 0, 30, 60, 90, 120, or 150 mg/kg for rats and 0, 25, 50, 100, 150, or 200 mg/kg for mice. Compound-related deaths occurred at the four highest dose levels in rats and at the highest dose level in mice. Mean body weights of treated groups of rats and mice surviving until the end of the study were similar to those of the controls. A dose-related increase in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, as well as a dose-related increase in the relative liver and kidney weights was observed in rats but not in mice. A dose-related increase in the incidence and severity of cardiomyopathy occurred in rats. This lesion may be related to the inhibition of heart mitochondrial aconitase activity. No compound-related lesions were observed in mice. The results of this study indicate that F344 rats are more sensitive than B6C3F1 mice; sexes within the species were equally sensitive. The no-observable-effect level was estimated as 30 mg MCAA/kg body weight for rats and 100 mg MCAA/kg body weight for mice.
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PMID:Toxicity of monochloroacetic acid administered by gavage to F344 rats and B6C3F1 mice for up to 13 weeks. 153 74

Five species of crude drugs are used as "Thang-kau-tin" on Taiwan market: (1) the stem of Mallotus repandus (Willd.) Muell.-Arg, (2) the stem and root of M. repandus (Willd.) Muell.-Arg, (3) the stem of Bauhinia championii Benth, (4) the stem with hooks of Uncaria hirsuta Haviland and (5) the stem with hooks of U. rhynchophylla Miquel. To clarify the effect of these crude drugs as anti-inflammatory and liver-protective agents, studies were conducted on water extracts of these five crude drugs. The statistical analysis (ANOVA) indicated that the stem of M. repandus showed the best anti-inflammatory activity against the paw edema induced by carrageenan. Nevertheless, the acute increase of GOT and GPT levels caused by CCl4 were markedly decreased by the treatment of M. repandus (stem), B. championii and U. hirsuta as a recipe group. The pathological changes around the central vein including fatty change, ballooning degeneration, cell necrosis, the increase in lymphocytes and Kupffer cells were improved by the treatment with the group of crude drugs as mentioned above.
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PMID:Studies on folk medicine "thang-kau-tin" from Taiwan. (I). The anti-inflammatory and liver-protective effect. 160 29

Adding less than 0.5% w/w of culture material of strain MRC 826 of the fungus Fusarium moniliforme to a carbohydrate diet low in fat resulted in an atherogenic plasma lipid profile in a non-human primate. Simultaneously increased plasma fibrinogen and activity of blood coagulation factor VII could enhance atherogenesis. This unique potential for promotion of atherosclerosis was probably secondary to chronic hepatotoxicity as indicated by liver fibrosis and elevated cholesterol, albumin and the enzymes AST, ALT, LD, GGT and ALP in serum. The cholesterol and enzymes responded in proportion to the calculated doses of fumonisin mycotoxins in the F. moniliforme MRC 826 cultures. Fumonisins are water soluble and heat stable. Thrombotic, hepatotoxic, carcinogenic and cerebral effects of MRC 826 culture material and fumonisins are well known in non-primates. The estimated fumonisin concentrations tested fall within a range due to natural contamination of human foods. The results suggest that all maize grain products should be analysed for fumonisins.
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PMID:Atherogenic effects in a non-human primate of Fusarium moniliforme cultures added to a carbohydrate diet. 163 55


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