UNIPROT:P17174 - FACTA Search

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Query: UNIPROT:P17174 (aspartate aminotransferase)
14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cocaine remains a widely abused substance. While most addicts take cocaine intranasally, a considerable number abuse cocaine by mouth. It has been assumed that after oral exposure cocaine is hydrolyzed in the stomach rendering it ineffective. This study investigated the effect of orally administered cocaine on liver function and integrity as well as its effect on liver and blood antioxidative enzymes. Male CF-1 mice were orally administered either 0, 5, 10 or 20 mg cocaine/kg body weight and sacrificed 24 h after the last treatment. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured as markers of liver injury. Blood and liver glutathione (GSH) levels were determined as well as the activities of glutathione peroxidase (GPx) and catalase (CAT). In addition, the activity of liver glutathione reductase (GRx) was also measured. The results demonstrated that oral cocaine caused hepatotoxicity in a dose dependent manner. Serum ALT and AST were elevated while blood GSH concentration decreased in all cocaine treated animals. In addition, there was a significant dose dependent decrease in the activities of GPx and CAT in blood and liver of cocaine treated animals. However, hepatic GSH content and GRx activity manifested a significant increase, particularly in the group, which received 20 mg/kg cocaine. This study is the first to demonstrate that cocaine-induced hepatotoxicity results following the oral route of administration.
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PMID:Oral cocaine produces dose-related hepatotoxicity in male mice. 1170 Dec 20

This study was designed to investigate the effect of hyperthyroidism and/or iron supplementation or cardiac oxidative stress parameters--the lipid peroxidation end product glutathione (GSH), glutathione peroxidase (CSH-Px), and superoxide dismutase (CuZnSOD)--in rats. In plasma, ferritin as an indicator of iron status and glutamate oxaloacetate transaminase (GOT) as an indicator of damage to the heart tissue were analyzed. Our findings show that hyperthyroidism increased lipooxidative damage as reflected by higher lipid peroxidation end product levels and elevated antioxidant defense parameters-GSH and GSH-Px. Iron supplementation per se does not affect oxidative stress parameters studied in the euthyroid state. Although iron increased lipid peroxidation in the hyperthyroid state, this effect was less than that seen in euthyroidism. Iron supplementation to hyperthyroid rats significantly lowered plasma ferritin levels, suggesting increased iron elimination with consequently reduced oxidative stress.
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PMID:Oxidative stress in heart tissue of hyperthyroid and iron supplemented rats. 1173

This work examines the effects of lyophilized extracts of the medicinal plants Rhazya stricta, Balanites aegyptiaca and Haplophylum tuberculatum on liver damage induced by paracetamol in mice. Rapid HPLC finger prints for some of these extracts were made. The hepatoprotective effects of the plant extracts were compared with that of the standard hepatoprotective agent silymarin. The extracts (1 g/kg) and silymarin (0.1 g/kg) were given orally for 5 consecutive days. On the last day of treatment a hepatotoxic oral dose of paracetamol (0.6 g/kg) was given, and 3 h later, the hepatic function of mice was evaluated using pentobarbitone -induced sleeping time, the concentration of reduced glutathione (GSH) in liver, and the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and cholesterol concentration in plasma. The livers were weighed and examined for macro- and microscopic changes. Pretreatment with R. stricta or with silymarin protected the livers of treated mice against paracetamol hepatotoxicity as evidenced by a significant improvement of the above liver function tests. B. Aegyptiaca had a relatively modest hepatoprotective activity, while H. tuberculatum was almost ineffective. Oral pretreatment of mice for 5 consecutive days with an extract of R. stricta or silymarin protected about 57% and 92% of the treated mice, respectively, against the lethal effect of paracetamol (1 g/kg). B. aegyptiaca and H. tuberculatum protected only 27% and 16% of the animals, respectively.
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PMID:Effect of the traditional medicinal plants Rhazya stricta, Balanitis aegyptiaca and Haplophylum tuberculatum on paracetamol-induced hepatotoxicity in mice. 1174 41

During water treatment, potentially hazardous chemical by-products may be formed. Alachlor (2-chloro-N-(2, 6-diethylphenyl)-N-(methoxymethyl) acetamide) is a widely used pre-emergence herbicide. The present study investigated the toxicity of alachlor and its disinfection by-products on freshly isolated rat hepatocytes. Hepatocytes were harvested by a collagenase perfusion technique and were exposed to different concentrations of alachlor and its by-products for up to 2 h. Cell viability, the leakage of aspartate transaminase (AST) and alanine transaminase (ALT) and glutathione (GSH) depletion were determined throughout the incubation period. The cell viability of the hepatocytes exposed to 100 microg ml(-1) alachlor was decreased by 20% compared with the control after 60 min of incubation. At the same concentration of alachlor the leakage of ALT and AST was increased by 56% and 45%, respectively. Cell viability of the hepatocytes was decreased upon exposure to 2-chloro-N-(3-chloro-2,6-diethylphenyl)-N-(methoxymethyl) acetamide (CCDMA) and 2-chloro-N-(3-chloro-2,6-diethylphenyl) acetamide (CCDA)--the by-products of alachlor and chlorine--after 60 min of exposure. At 100 microg ml(-1) CCDMA the AST leakage was increased significantly (73%) after 30 min of incubation. The reaction mixture of alachlor (100 microg ml(-1)) and chlorine dioxide (1 ppm) caused significant increases in cell loss and ALT and AST levels by 22%, 40% and 34%, respectively, as early as 15 min incubation. Alachlor (100 and 200 microg ml(-1)) caused significant decreases in GSH contents (62%) in isolated hepatocytes. The reaction mixture of alachlor and chlorine dioxide led to significant glutathione depletion (44%) after 60 min of incubation. The by-products of alachlor and chlorine--CCDMA and CCDA--depleted GSH almost completely (93%). This investigation suggested that the by-products formed from the reaction of alachlor and chlorine decreased GSH and increased the leakage of liver enzymes, especially AST.
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PMID:In vitro hepatotoxicity of alachlor and its by-products. 1180 27

Tobacco smoke is involved in the pathogenesis of several diseases regarding different body systems, mainly cardiovascular and respiratory in addition to its local toxic effect in the oral cavity. The noxious effects of smoke compounds justify the high incidence of periodontal diseases, caries, and neoplastic diseases of oral tissues in smokers. Some toxic components of tobacco smoke, unsaturated and saturated aldehydes, could interact with thiol rich compounds, leading to structural and functional modification of these molecules. Previous papers have demonstrated an in vitro significant decrease of some enzymatic activities, both in plasma and in saliva, following external addition of aldehydes or exposure to cigarette smoke (CS). Furthermore, the same studies underlined the protective effect exerted by the addition of glutathione (GSH) against the damaging role of smoke aldehydes. In this study some salivary enzymes (lactic dehydrogenase [LDH], aspartate aminotransferase [AST] and amylase), and total GSH were measured in 20 volunteers smokers, before and just after smoking a single cigarette. All enzymatic activities showed a significant inhibition following a single cigarette, probably due to the interaction between smoke aldehydes and -SH groups of the enzyme molecules. Moreover, the percentage of the enzymatic inhibition showed a negative correlation with the basal level of salivary GSH. Our results emphasize that not only one cigarette is sufficient to impair the salivary enzymatic activities but also strengthen the proposed protective role of GSH against the noxious biochemical effects of CS.
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PMID:Inhibition of salivary enzymes by cigarette smoke and the protective role of glutathione. 1204 26

The present investigation focused on the possible hepatoprotective potential of captopril on carbon tetrachloride (CCl4)-induced acute liver injury in mice. Twenty-four hours after a single intraperitoneal injection of CCl4 (20 microl/Kg), hepatotoxicity was evidenced in the serum by elevated levels of aspartate transaminase (AST; EC: 2.6.1.1), alanine transaminase (ALT; EC: 2.6.1.2) and lactate dehydrogenase (LDH; EC: 1.1.1.27) and in the liver by depleted level of reduced glutathione (GSH), enhanced activity of glutathione peroxidase (GSH-Px; EC: 1I.11.1.9) and elevated level of lipid peroxides (LP). Captopril was given orally at three dose levels viz., 10, 25 and 50 mg/Kg/day for three consecutive days before subjecting the animals to the hepatotoxin. With the exception of the lowest dose namely, 10 mg/Kg/day, captopril afforded protection against CCl4-induced hepatotoxicity to different extents. Thus, the elevated activities of the enzymes AST, ALT, LDH and GSH-Px as well as the enhanced lipid peroxidation were markedly reduced below those elicited by the hepatotoxin, reaching values closer to the control, though still statistically higher. Captopril, however, did not ameliorate the depletion of GSH produced by CCl4. The data reported herein reveal a protective potential of captopril against the acute hepatotoxicity induced by CCl4 in mice. This hepatoprotection could be attributed, at least in part, to the free radical scavenging properties of the drug.
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PMID:Prior treatment with captopril attenuates carbon tetrachloride-induced liver injury in mice. 1209 Mar 55

Cocaine produces hepatotoxicity by a mechanism that remains undefined but that has been linked to its oxidative metabolism. Endotoxin (lipopolysaccharide, LPS) is also a well-known cause of hepatic damage, where exposure to non-injurious doses of LPS increases the toxicity of certain hepatotoxins. This study was conducted to investigate the possible potentiation of cocaine-mediated hepatotoxicity (CMH) by LPS. Male CF-1 mice were administered oral cocaine hydrochloride for 5 consecutive days at a dose of 20 mg/kg with and without 12 x 10(6) EU LPS/kg given intraperitoneally 4 h after the last cocaine injection. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured as markers of liver injury. Blood and liver glutathione (GSH) levels were determined, as well as the activities of glutathione peroxidase (GPx) and catalase (CAT). In addition, the activity of liver glutathione reductase (GRx) was measured. The results demonstrate that endotoxin potentiated the hepatotoxicity of cocaine. Serum ALT and AST were significantly elevated with the combined cocaine and LPS treatment versus all other treatments. While cocaine alone resulted in centrilobular necrosis, the cocaine and LPS combination produced submassive necrosis. The increased hepatic GSH content and GRx activity observed with cocaine alone were not observed with the combination treatment, rendering the liver more susceptible to oxidative stress. Moreover, there was a significant decrease in the activities of hepatic GPx and CAT, particularly with the combination treatment. In conclusion, this study demonstrates that LPS potentiates the hepatotoxicity of cocaine as revealed by an array of biochemical and morphological markers.
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PMID:Endotoxin potentiates the hepatotoxicity of cocaine in male mice. 1213 32

The radioprotective effect of silymarin using different modes of treatment against radiation (3 or 6 Gy) induced hepatotoxicity 1, 3 and 7 days post-irradiation was studied. Whole-body gamma-irradiation revealed an increase in serum alkaline phosphatase (AP) activity as well as liver glutathione reductase (GR) and glutathione peroxidase (GSH-PX) activities on the first post-exposure day with respect to the control value. However, 3 days after radiation exposure, these parameters showed a significant decrease below the control level which persisted till the end of the experimental time except for serum AP activity that showed another increase on the seventh post-exposure day at 3 Gy dose of radiation. A gradual increase in serum alanine and aspartate aminotransferase (ALT&AST) as well as gamma glutamyl transpeptidase activities were observed due to irradiation throughout the experimental time. Administration of silymarin as single (70 mg kg (-1)), fractionated (490 mg kg (-1)) oral doses or as intravenous (i.v.) injection (50 mg kg (-1)), caused significant protection. Intravenous treatment showed the most pronounced protection. The protective effect of silymarin was attributed to its antioxidant and free radicals scavenging properties.
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PMID:Radioprotective effect of silymarin against radiation induced hepatotoxicity. 1216 44

Methionine metabolism is regulated by folate, and both folate deficiency and abnormal hepatic methionine metabolism are recognized features of alcoholic liver disease (ALD). Previously, histological features of ALD were induced in castrated male micropigs fed diets containing ethanol at 40% of kilocalories for 12 months, whereas in male micropigs fed the same diets for 12 months abnormal methionine metabolism and hepatocellular apoptosis developed. Folate deficiency may promote the development of ALD by accentuating abnormal methionine metabolism. Intact male micropigs received eucaloric diets that were folate sufficient, folate deficient, or each containing 40% of kilocalories as ethanol for 14 weeks. Folate deficiency alone reduced hepatic folates by one half, and ethanol feeding alone reduced methionine synthase, S-adenosylmethionine (SAM), and glutathione (GSH) levels and elevated plasma malondialdehyde (MDA) levels. The combined regimen elevated plasma homocysteine, hepatic S-adenosylhomocysteine (SAH), urinary 8-hydroxy-2-deoxyguanosine (oxy(8)dG), an index of DNA oxidation, and serum aspartate aminotransferase (AST) levels. Terminal hepatic histopathologic characteristics included typical features of steatonecrosis and focal inflammation in pigs fed the combined diet, with no changes in the other groups. Hepatic SAM levels correlated with those of GSH, whereas urinary oxy(8)dG and plasma MDA levels correlated with the SAM:SAH ratio and to hepatic GSH. The results demonstrate the linkage of abnormal methionine metabolism to products of DNA and lipid oxidation and to liver injury. The finding of steatonecrosis and focal inflammation only in the combined diet group supports the suggestion that folate deficiency promotes and folate sufficiency protects against the early onset of methionine cycle-mediated ALD.
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PMID:Folate deficiency, methionine metabolism, and alcoholic liver disease. 1216 45

In patients with severe alcoholic liver disease (i.e., cirrhosis), a deficiency of S-adenosylmethionine (SAMe) develops as a result of decreased SAMe synthetase activity. Whether a sizeable SAMe depletion occurs already at earlier stages of alcoholic liver disease has been the subject of debate. To address this issue, rats were fed alcohol (or isocaloric carbohydrate) in Lieber-DeCarli liquid diets containing adequate amounts of protein, vitamins, and lipotropic factors, including methionine. Alcohol feeding resulted in hepatic steatosis (without fibrosis) and unchanged SAMe synthetase activity, yet SAMe concentration was already greatly decreased. This most likely resulted from oxidative stress associated with the metabolism of alcohol and the induction of cytochrome P4502E1 (CYP2E1), which generates free radicals. Indeed, the decrease in hepatic SAMe correlated with parameters of oxidative stress, such as increased 4-hydroxynonenal (measured by gas chromatography-mass spectrometry) and diminished glutathione (GSH). Decreased GSH, occurring as a result of excessive GSH consumption caused by the oxidative stress, probably generated by enhanced utilization of SAMe, a precursor of GSH, thereby explaining the depletion of SAMe. In view of the known differences between rodents and primates in the metabolism of lipotropes, my colleagues and I have also studied the interaction between alcohol and SAMe in baboons and found again that, at early stages preceding the development of cirrhosis, there was already a significant lowering of hepatic SAMe concentration, associated with a striking oxidative stress documented by decreased levels and accelerated turnover of GSH. This was associated with increased lipid peroxidation and damage to cellular membranes, including those of the mitochondria, assessed by electron microscopy. Oral administration of SAMe resulted in its hepatic repletion with a corresponding attenuation of the ethanol-induced oxidative stress and liver injury, with significantly less GSH depletion, less increases in plasma aspartate aminotransferase (AST) levels, less leakage of mitochondrial glutamic dehydrogenase into the plasma, and fewer megamitochondria. In conclusion, (1) both in rodents and in non-human primates, significant SAMe depletion occurs already at early stages of alcoholic liver disease, despite the consumption of adequate diets; (2) the decreased hepatic SAMe concentration and the associated liver lesions, including mitochondrial injury, can be corrected with SAMe supplementation; and (3) accordingly, therapeutic administration of SAMe should be the subject of a comprehensive clinical trial to assess its capacity to attenuate early stages of alcoholic liver injury in human beings.
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PMID:S-Adenosyl-L-methionine and alcoholic liver disease in animal models: implications for early intervention in human beings. 1216 46

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