Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New biologically active compounds (BAC) created on the basis of nicotinic acid possess hepatoprotective action. The preparations were introduced preventively in doses of 10 mg/kg during 14 days. Litonit and nicogamol increased survival of experimental animals by 36.8% and nicotinic acid by 26.8%. ALT, AST, GGT activity in the blood serum was reduced. The activity of the main antioxidant enzymes (SOD and catalase) grew in the rat liver tissue in parallel with inhibition of DK and MDA activity. Morphological picture of the rat liver, most evident after application of litonit improved. Hepatoprotective action of these BAC are attributed to their membrano stabilizing effects.
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PMID:[Mechanisms of hepatoprotective action of new nicotinic acid derivatives in experimental CCL4-induced liver injury]. 142 11

Rat livers were perfused at 37 degrees C, 41 degrees C, 42 degrees C, 42.5 degrees C, and 43 degrees C for 2 hr. Among perfusate constituents analyzed were urea, total amino acids, N-acetyl-beta-glucosaminidase (NAG), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), allantoin, potassium, phosphate, and glucose. After perfusion, livers were homogenized and analyzed for xanthine oxidase (XO) activity, GSH content, and lysosomal lability. Perfusate AST, LDH, NAG, potassium, glucose, and phosphate increased significantly with time, and there were significant differences in the final values between 37 degrees C and 42 degrees C, 42.5 degrees C and 43 degrees C (P less than .05). GSH levels increased significantly at all temperatures after 90 and 120 min, whereas GSSG levels differed significantly at 60, 90, and 120 min for 37 degrees C vs. 42 degrees C, 42.5 degrees C, and 43 degrees C (P less than .05). Mean MDA levels at 37 degrees C differed from those at 41 degrees C and 43 degrees C (P less than .05) at each temperature. Allantoin levels increased significantly with time of perfusion; mean levels at 37 degrees C were significantly different from mean levels at each temperature at 60, 90, and 120 min. GSH liver tissue levels decreased with perfusion at hyperthermic temperatures; mean values at 41 degrees C, 42 degrees C, and 42.5 degrees C, and 43 degrees C differed from 37 degrees C mean values (P less than .01). Type O XO increased after 120 min perfusion from 6.4% +/- 2.0% at 37 degrees C to 55% +/- 30%, 43% +/- 27%, and 63% +/- 29% at 42 degrees C, 42.5 degrees C, and 43 degrees C, respectively. Lysosomal lability increased after perfusion at 42.5 degrees C. There was a significant increase in nonsedimentable NAG activity at 42.5 degrees C (P less than .05). These data support the premise that hyperthermic toxicity to the liver may be a consequence of oxidative stress brought about by enhanced adenosine triphosphate (ATP) consumption and conversion of XO to type O. Such conversion results in superoxide formation and subsequent depletion of cellular GSH, labilization of the lysosomes, and plasma membrane damage.
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PMID:Hyperthermic liver toxicity: a role for oxidative stress. 279 43

In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.
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PMID:A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis. 822 95

Morphological and biochemical changes in mitochondrial have been reported early in the course of cocaine-induced hepatotoxicity. This study was designed to examine the effects of repeated cocaine exposure in vivo on mitochondrial respiration, activities of respiratory chain enzymes, and lipid peroxide measures in liver. Male Sprague-Dawley rats were exposed to cocaine (5 i.p. injections of 25 mg/kg; 3-day period). Blood and liver samples were taken, and hepatic mitochondria were isolated by differential centrifugation. The cocaine-treated rats developed oxidative stress in hepatic mitochondria as evidenced by a significant increase in malonaldialdehyde (MDA; 52%; p < 0.0001) and a decreased glutathione (GSH; 22%; p < 0.0003). Blood aspartate aminotransferase (AST) and glutathione s-transferase (GST) levels in cocaine groups were significantly elevated (2.6 and 3.2 fold, respectively; p < 0.0001 for both). Cocaine caused a decrease in state-3 respiration and respiratory control ratio (RCR) ratio when exposed to site I and II substrates; these changes were parallelled by a decrease in complex I (22%; p < 0.003), succinate cytochrome c reductase (27%; p < 0.004), and complex IV (24%; p < 0.003). In conclusion, functional abnormalities of hepatic mitochondria accompany lipid peroxidation caused by cocaine, supporting the hypothesis that the mitochondria is one of the major intracellular targets of cocaine hepatotoxicity.
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PMID:Impairment of mitochondrial respiration and electron transport chain enzymes during cocaine-induced hepatic injury. 907 24

The protective effect of pyoverdins Pa A and Pf, peptidic siderophores secreted respectively by Pseudomonas aeruginosa and fluorescens, was studied in primary cultures of human hepatocytes exposed to iron (50 or 100 microM of iron-citrate). AST, ALT and MDA releases were measured as indexes of cytotoxicity. In order to demonstrate that these chelators were able to decrease iron uptake or increase iron release from the hepatocytes, labelled cells were obtained by maintaining the cultures in the presence of 1 microM 55Fe ferric chloride plus 50 microM iron citrate. One day after iron treatment, an increase in AST, ALT and MDA release was observed with 50 or 100 microM of iron citrate; it appeared that the concentrations 50 and 100 microM of iron were highly toxic for human hepatocytes. In the presence of 50 or 100 microM of iron, the addition of 50 or 100 microM of Pa A or Pf was effective to inhibit the increase observed in the enzyme leakage and the MDA production resulting from iron exposure. In human hepatocytes cultured for 1 day in the presence of 1 microM 55Fe-50 microM iron citrate plus 50 or 100 microM Pa A or Pf, a net decrease of iron uptake by the cells was observed, as demonstrated by the low intracellular iron level. When the hepatocytes were cultured for 1 day in the presence of 1 microM 55Fe-50 microM iron citrate and then for a further day in the presence of 50 or 100 microM Pa A or Pf without additional iron, the chelators increased the extracellular iron level, indicating their iron release from the loaded cells; however, the effects of Pa A and Pf on iron release did not differ significantly. In conclusion, iron loading achieved by adding iron citrate to the culture medium is highly toxic for human hepatocytes. Pyoverdins Pa A and Pf are effective in protecting human hepatocytes against the toxic effect of iron by both decreasing the uptake of the metal and increasing its release from the loaded cells.
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PMID:Inhibition of iron toxicity in human hepatocyte cultures by pyoverdins Pa A and Pf, the peptidic siderophores of Pseudomonas aeruginosa and fluorescens. 913 75

Sixteen dairy cows were studied to assess the status of the natural antioxidant vitamin E and lipid peroxidation in their livers. Cows with liver failure (n = 7) showed clinical signs of a hepatic encephalopathy and had the following values of selected blood indices: AST > 80 U/l and GLDH > 15 U/l in serum, and venous plasma ammonia > 35 mmol/l. The control group (n = 9) consisted of dairy cows which were recovering from surgery (omentopexy) and were free of any health complications. Blood was analysed for alpha-tocopherol, aspartate aminotransferase, glutamate dehydrogenase, gamma-glutamyl transferase, total bilirubin, ammonia, cholesterol, albumin, free fatty acids, glucose, and beta-hydroxybutyrate. Alpha-tocopherol, triglyceride and malondialdehyde were measured in wet liver tissue. The cows with hepatic failure were clearly low in alpha-tocopherol and had significantly lower (P < 0.01) plasma alpha-tocopherol than the controls. Both liver triglycerides and MDA were higher (P < 0.05) in the cows with fatty livers. It is concluded that the cows with liver failure had an increase in the intensity of hepatic lipoperoxidative processes and a low antioxidative status, which should be taken into consideration in cases where treatment of the disease is proposed.
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PMID:A study of lipid peroxidation and vitamin E in dairy cows with hepatic insufficiency. 1039 80

The aim of this investigation was to determine serum levels of vitamin A, E, beta carotene, glutathione peroxidase (GSHPx), lipid peroxidation (MDA) and biochemical and haematological parameters during enflurane anaesthetised dogs. Ten kangal dogs were used and all animals were anaesthetised with enflurane for two hours and blood samples were taken before and 30, 120 minutes, 24 hours and 7 days during the anaesthesia. Vitamin E and beta carotene content were significantly (p<0.05 and p<0.01) higher before anaesthesia than after whereas serum GSHPx activity was not statistically different. However, serum levels of vitamin A and MDA were significantly (p<0.05) increased during the anaesthesia. In general, serum levels of aspartate aminotransferase, alanine aminotransferase, albumin, glucose, urea and creatinine were significantly (p<0.05 and p<0.01) increased during anaesthesia and returned to near normal values after 7 days of anaesthesia, whereas the white blood cell count was significantly (p<0.05 and p<0.01) decreased during the anaesthesia. However, the red blood cell count, haemoglobin and packed cell volume values, and levels of total cholesterol, triglycerides, total protein and globulin were apparently not influenced by the anaesthesia. In conclusion, we observed that the serum level of vitamin E and beta carotene were significantly decreased, whereas serum MDA and vitamin A levels were significantly increased during the enflurane anaesthesia.
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PMID:The levels of some antioxidant vitamins, glutathione peroxidase and lipoperoxidase during the anaesthesia of dogs. 1045 42

Pregnyl (hCG), a preparation of human chorionic gonadotropin, was evaluated for its effects on the endocrinological, biochemical and genotoxic changes in female Swiss albino mice. hCG treatment at different doses (25, 50 and 100 I.U./Kg/day) for 5 days was found to significantly increase the plasma levels of hCG, estradiol and progesterone in a dose-dependent manner, while the concentrations of LH and FSH remained below the detection levels. The plasma levels of ALT, CK-MB, creatinine and urea were significantly decreased, whereas the concentrations of AST were significantly increased. The treatment was found to significantly increase and decrease the hepatic concentrations of MDA and NP-SH respectively. The hepatic levels of proteins and DNA were not affected, but there was a significant increase in the concentrations of RNA. In addition, hCG treatment did not show any effect on the frequency of occurrence of micronuclei, whereas the ratio of PCE/NCE was found to be significantly increased. These results demonstrate that the hCG treatment in mice affected the pituitary-ovarian hormones in a similar pattern to that of humans. The treatment increased oxidative stress in hepatic cells without disturbing the functions of the liver as well as other organs. This finding may be of value concerning the safe use of hCG and may contribute to the overall antioxidant balance in the body.
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PMID:Evaluation of the effects of pregnyl on pituitary-ovarian hormones and biochemical markers of tissue injury in female Swiss albino mice. 1085 Mar 79

Large and small doses of drugs for improving blood circulation and removing blood stasis were used in model rats to treat mild chronic hepatic damage induced by carbon tetrachloride (CCl4). The results show that large dose of Dang Gui ([symbol: see text] Radix Angelicae Sinensis) and Dan Shen ([symbol: see text] Radix Salviae Miltiorrhizae) (drugs for regulating blood flow) and small dose of Yu Jin ([symbol: see text] Radix Curcumae) and Niu Xi ([symbol: see text] Radix Achyranthis Bidentatae) (drugs for activating blood flow) can significantly elevate the activity of SOD (P < 0.05) and/or lower the T/K ratio, markedly reduce the MDA content (P < 0.05 or P < 0.01) and significantly decrease the activities of ALT and AST (P < 0.05 or P < 0.01), demonstrating that these drugs are effective in combating oxygen free radicals (OFR) in chronic liver damage. On the contrary, large dose of Tu Bie Chong ([symbol: see text] Eupolyphaga seu Steleophaga) and E Zhu ([symbol: see text] Rhizoma Curcumae) (drugs for removing blood stasis) tend to increase the ALT and AST (P < 0.05) activities. The results suggest that the synergism of elevation of the SOD activity and reduction of T/K ratio contributes to the action of drugs for improving blood circulation and removing blood stasis in combating the liver damage induced by CCl4.
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PMID:An experimental study on drugs for improving blood circulation and removing blood stasis in treating mild chronic hepatic damage. 1178 34

The degradation of extracellular matrix during cancer invasion results from the action of several protease and protease inhibitor systems. Alpha(1)-Antitrypsin (AAT) is a serine proteinase inhibitor produced by various tumour cells, and its plasma concentration rises during inflammation, infection and malignant diseases. AAT is found in a native, inhibitory active form, but also in other, non-inhibitory forms including cleaved and/or degraded. To test a hypothesis that AAT dependent on its molecular form may have multiple effects on tumour cell behaviour, breast cancer cells, MDA-MB 468, were cultured alone or stimulated with a native AAT or its C-terminal fragment (C-36) at a concentration of 5 micromol/l for 2, 24 and 48 hours. Native AAT added to the cells for 2 hours enhanced transforming growth factor beta 1 (TGFbeta1) levels by 50%, but inhibited cell proliferation (by 61%), reduced interleukin 6 (IL-6) levels (by 87%) and activity (by about 66%), compared with non-stimulated cells. Native AAT showed similar, but less pronounced, effects when added to the cells for 24 and 48 hours. Under the same experimental conditions the cells exposed to the C-36 peptide significantly increased in proliferation, invasiveness and showed higher IL-6 levels. In addition, cells treated with the C-36 for 48 hours increased in NFkappaB (nuclear factor kappa B) activity. These results indicate that AAT, dependent on its molecular form, can both suppress and induce breast tumour cell biological activity in vitro.
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PMID:Multiple effects of alpha1-antitrypsin on breast carcinoma MDA-MB 468 cell growth and invasiveness. 1267 35


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