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

The hepatoprotective action of orally dosed putrescine was investigated using rat models of liver injury. When rats received putrescine orally soon after a dose of carbon tetrachloride or D-galactosamine, deranged serum alanine aminotransferase values and prothrombin times were significantly attenuated compared with control levels, with improved histologic extent of liver injury. Putrescine addition to the medium of rat hepatocytes in primary culture reduced cell killing induced by D-galactosamine or the membrane detergents chenodeoxycholic acid and Triton X-100. Similar reduction was seen in cells exposed to tert-butyl hydroperoxide (TBHP), an agent producing cell death through lipid peroxidation, with attenuation of cellular malondialdehyde content. Putrescine also significantly attenuated the extent of increased plasma membrane microviscosity as assessed with 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene in TBHP-treated cells. These results suggest that orally given putrescine protects against liver injury. Plasma membrane stabilization and reduction of lipid peroxidation may contribute to this hepatoprotection.
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PMID:Protective action of putrescine against rat liver injury. 817 Dec 86

Piperine, an active alkaloidal constituent of the extract obtained from Piper longum and Piper nigrum, was evaluated for its antihepatotoxic potential in order to validate its use in traditional therapeutic formulations. This plant principle exerted a significant protection against tert-butyl hydroperoxide and carbon tetrachloride hepatotoxicity by reducing both in vitro and in vivo lipid peroxidation, enzymatic leakage of GPT and AP, and by preventing the depletion of GSH and total thiols in the intoxicated mice. Silymarin, a known hepatoprotective drug was tested simultaneously for comparison. Piperine showed a lower hepatoprotective potency than silymarin.
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PMID:Evaluation of the liver protective potential of piperine, an active principle of black and long peppers. 825 33

The hepatotoxicity of acetaminophen is believed to be mediated by the reactive metabolite N-acetyl-p-benzoquinone imine; however, the mechanism by which this metabolite produces the toxicity is unknown. The metabolite, which is both an electrophile and an oxidizing agent, may covalently bind to critical proteins, or it may initiate oxidative damage. We have previously developed a Western blot assay for detection of acetaminophen covalently bound to protein and have reported the relationship between covalent binding and the development of hepatotoxicity. Recently, we developed a Western blot assay for protein aldehyde formation, which may occur via the reactive oxygen species, the hydroxyl radical. In this paper, we have compared covalent binding to protein aldehyde formation. Toxic doses of acetaminophen (400 mg/kg) were administered to mice, and the mice were subsequently killed at 0, 1, 2, 4, and 6 h. Since the oxidizing agent FeSO4 has been reported to potentiate lipid peroxidation when administered with acetaminophen, other mice received FeSO4 (100 mg/kg) plus acetaminophen. Compared to saline-treated control mice, acetaminophen treatment significantly increased serum alanine aminotransferase levels, an index of hepatotoxicity, at 4 and 6 h, but not at 1 or 2 h. Acetaminophen plus FeSO4 treatment of mice significantly increased serum alanine aminotransferase levels at 2, 4, and 6 h compared to controls. Levels of alanine aminotransferase in serum of acetaminophen plus ferrous sulfate-treated mice were higher at 4 and 6 h than those of acetaminophen-treated mice, but not significantly different. FeSO4 alone did not increase alanine aminotransferase levels. Western blot assays revealed that acetaminophen did not cause an increase in protein aldehydes over control at any time, nor did acetaminophen plus FeSO4; however, FeSO4 alone increased the intensity of staining of the immunoblot for protein aldehydes over control at all times after 0 time. Acetaminophen-protein adducts were detected in acetaminophen- and acetaminophen plus FeSO4-treated mice. In vitro experiments indicated that FeSO4 plus tert-butyl hydroperoxide in the presence of bovine serum albumin increased protein aldehyde formation. Inclusion of acetaminophen in the incubation mixture inhibited protein oxidation of bovine serum albumin in a concentration dependent manner. The data indicate that acetaminophen quenches protein oxidation, presumably by reacting with the hydroxyl radical. These data are consistent with the theory that acetaminophen covalent binding is the primary mechanism of toxicity and argue against a role for protein oxidation in acetaminophen hepatotoxicity.
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PMID:Mechanism of acetaminophen-induced hepatotoxicity: covalent binding versus oxidative stress. 872 1

Atractylon, a main sesquiterpenic constituent of Atractylodes rhizomes, was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in primary culture of rat hepatocytes. In the preliminary study, atractylon showed an effective antioxidant property tested by its capacity for quenching 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). Further investigations showed that atractylon at the concentrations of 0.01, 0.1 and 1.0 mg/ml decreased the formation of malondialdehyde (MDA), leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) and repair synthesis of DNA induced by 30-min treatment of t-BHP (1.5 mM) in primary cultured rat hepatocytes. Addition of atractylon also attenuated the genotoxicity of t-BHP evaluated by unscheduled DNA synthesis. The sum of the results suggested that the protective effect of atractylon against oxidative stress induced by t-BHP is via its ability to quench free radicals.
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PMID:Inhibitory effect of atractylon on tert-butyl hydroperoxide induced DNA damage and hepatic toxicity in rat hepatocytes. 887 Sep 57

Thymoquinone, the active constituent of Nigella sativa, was tested in isolated rat hepatocytes as a hepatoprotective agent against tert-butyl hydroperoxide (TBHP) toxicity. TBHP (2 mM) was used to produce oxidative injury in isolated rat hepatocytes and caused progressive depletion of intracellular glutathione (GSH), loss of cell viability as evidenced by trypan blue uptake and leakage of cytosolic enzymes, alanine transaminase (ALT) and aspartic transaminase (AST). Preincubation of hepatocytes with 1 mM of either thymoquinone or silybin, which is a known hepatoprotective agent, resulted in the protection of isolated hepatocytes against TBHP induced toxicity evidenced by decreased leakage of ALT and AST, and by decreased trypan blue uptake in comparison to TBHP treated hepatocytes. Both thymoquinone and silybin prevented TBHP induced depletion of GSH to the same extent. Although thymoquinone protected the liver enzymes leakage, the degree of protection was less than that caused by silybin.
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PMID:Hepatoprotective activity of thymoquinone in isolated rat hepatocytes. 965 Jun 43

In the present work, we followed an in vitro protective action of cyclosporin A (CsA) against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in hepatocytes. Various parameters (cell viability, cytosolic calcium level, rhodamine 123 accumulation as indicator of mitochondrial membrane potential and alanine-aminotransferase leakage from cells) were measured as an index of cytotoxicity. Tert-butyl hydroperoxide (1 mM) significantly increased cytosolic Ca2+ and affected mitochondrial membrane potential. Pretreatment with cyclosporin A (0.5 microM) reduced t-BHP-induced cytosolic Ca2+ increase and ALT (alanine-aminotransferase) leakage, but had no protective effect on t-BHP-induced changes of mitochondrial membrane potential. Our data thus suggest that the mechanism of cytoprotection of CsA on the cytosolic Ca2+ changes and ALT leakage induced by t-BHP, does not directly correlate with protection of t-BHP-induced changes of mitochondrial membrane potential.
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PMID:Modulatory effect of cyclosporin A on tert-butyl hydroperoxide-induced oxidative damage in hepatocytes. 1132 48

Berberine, a main protoberberine component of Coptidis Rhizoma, was studied for the mechanism of its inhibitory effects on the tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity and lipid peroxidation in rat liver. In the preliminary study, berberine expressed an antioxidant property by its capacity for quenching the free radicals of 1,1-diphenyl-2-picrylhydrazyl (DPPH). Further investigations were conducted using t-BHP-induced cytotoxicity in rat primary hepatocytes and hepatotoxicity in rats to evaluate the antioxidative bioactivity of berberine. The results in rat primary hepatocytes demonstrated that berberine, at the concentrations of 0.01-1.0 mM, significantly decreased the leakage of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and the formation of malondialdehyde (MDA) induced by 30 min treatment of t-BHP (1.5 mM). Berberine also attenuated the t-BHP-induced depletion of glutathione (GSH) and induced a high level of DNA repair synthesis. The in vivo study showed that the intraperitoneal pretreatment with berberine (0.5 and 5 mg/kg) for 5 days before a single dose of t-BHP (0.1 mmol/kg) significantly lowered the serum levels of hepatic enzyme markers (ALT and aspartate aminotransferase) and reduced oxidative stress in the liver. The histopathological evaluation of the livers revealed that berberine reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltrations, and necrosis induced by t-BHP. These results lead us to speculate that berberine may play a chemopreventive role via reducing oxidative stress in living systems.
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PMID:Inhibitory effect of berberine on tert-butyl hydroperoxide-induced oxidative damage in rat liver. 1241 30

The aim of this study was to investigate the protective effect of acanthoic acid, a diterpene isolated from the root bark of Acanthopanax koreanum, on liver injury induced by either tert-butyl hydroperoxide (tBH) or carbon tetrachloride in vitro and in vivo. In vitro, the cellular leakage of lactate dehydrogenase (LDH) following treatment with 1.5 mM tBH for 1 h, was significantly inhibited by co-treatment with acanthoic acid (25 and 5 microg/mL) and the ED (50) of acanthoic acid was 2.58 microg/mL (8.5 microM). The cellular leakage of LDH following one hour of treatment with 2.5 mM CCl (4) was significantly inhibited by co-treatment with acanthoic acid (25 microg/mL) and the ED (50) of acanthoic acid was 4.25 microg/mL (14.1 microM). Co-treatment with acanthoic acid significantly inhibited the generation of intracellular reactive oxygen species (ROS) and intracellular glutathione (GSH) depletion induced by tBH or CCl (4). Acanthoic acid pretreatment (100 mg/kg per day for four consecutive days, p. o.) significantly reduced levels of aspartate transaminase and alanine transaminase in acute liver injury models induced by either tBH or carbon tetrachloride. Treatment with acanthoic acid (100 mg/kg, p. o.) at 6, 24, and 48 hours after carbon tetrachloride subcutaneous injection significantly reduced the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in CCl (4)-injured liver were improved upon treatment with acanthoic acid. In vivo treatment with acanthoic acid was not able to modify CYP2E1 activity and protein expression in liver microsomes at the dose used, showing that the hepatoprotective effect of acanthoic acid was not mediated through inhibition of CCl (4) bioactivation. From the results above, acanthoic acid had a protective effect against tBH- or CCl (4)-induced hepatotoxicity in vitro and in vivo.
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PMID:Acanthoic acid from Acanthopanax koreanum protects against liver injury induced by tert-butyl hydroperoxide or carbon tetrachloride in vitro and in vivo. 1509 47

There is increasing evidence that oxidative stress is implicated in the pathogenesis of various diseases, including alcoholic liver injury. In the present work, we investigate the protective effects of the saponins isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the tert-butyl hydroperoxide (t-BHP)-induced oxidative injury (hepatotoxicity) in cultured rat primary hepatocytes and in rat livers. CKS significantly reduced t-BHP-induced oxidative injuries in cultured rat hepatocytes, as determined by cell cytotoxicity, intracellular glutathione (GSH) content and lipid peroxidation in a dose-dependent manner. CKS provided good protection from the t-BHP-induced production of intracellular reactive oxygen species and DNA damage. In addition, CKS was able to quench 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals and the superoxide radical. The in vivo study showed that the pretreatment with CKS prior to the administration of t-BHP significantly prevented the increase in the serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced oxidative stress, such as GSH content and lipid peroxidation, in the liver in a dose-dependent manner. These results support the anti-oxidative role of CKS, and demonstrate that CKS can scavenge oxygen free radicals and protect cells from oxidative stress.
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PMID:Protective effect of saponins derived from roots of Platycodon grandiflorum on tert-butyl hydroperoxide-induced oxidative hepatotoxicity. 1510 19

Sabina przewalskii is a Tibetan medicinal plant. Pretreatment with an ethyl acetate-soluble fraction of the plant suppressed the plasma alanine aminotransferase activity in menadione-intoxicated mice. In vitro studies showed that the Sabina extract could inhibit NADH-induced superoxide production in isolated hepatocytes as indicated by a decrease of lucigenin-amplified chemiluminescence. In addition, the extract inhibited tert-butyl hydroperoxide-induced lipid peroxidation in isolated hepatocytes dose-dependently. These results suggested that the protective action of the Sabina extract against menadione-induced hepatotoxicity is associated with its antioxidant activities including the scavenging of superoxide anion radicals and inhibition of lipid peroxidation.
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PMID:Hepatoprotective effect of Sabina przewalskii against menadione-induced toxicity. 1516 70


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