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

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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)

Chemopreventive agents are compounds that inhibit carcinogenesis when administered prior or subsequent to a course of carcinogen administration. The effects of dietary administration of crocin dyes on the hepatic damage induced by aflatoxin B1 (AFB1) and dimethylnitrosamine (DMN) in rats were investigated. Female Sprague-Dawley rats were treated with different dosages of AFB1 (0.9 or 4.5 mg/kg) or DMN (8 or 20 mg/kg) by i.p. administration, and the different degrees of hepatic damage were revealed by the elevations of levels of serum marker enzymes such as aspartate amino-transferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and lactic dehydrogenase. Pre-treatment of the animals with crocin dyes 50 mg/kg daily for three consecutive days, the enzyme elevations were significantly suppressed. This suggested that the crocin dyes possessed chemopreventive effects on the early acute hepatic damage induced by AFB1 or DMN. Feeding experiments demonstrated that crocin dyes at 0.1% in the diet could suppress partially the chronic hepatic damage induced by multiple dosages of AFB1 or DMN, but at a higher concentration of 1% crocin dye failed to do so because of their host toxicity. Crocin dyes are extracted from the fruits of Gardenia jasminoides and consist of carotenoids and geniposides as active principles. The protective mechanisms of crocin dyes may be attributed to their carotenoids which are converted metabolically to retinoids in rats.
Carcinogenesis 1986 Apr
PMID:Protection of crocin dyes on the acute hepatic damage induced by aflatoxin B1 and dimethylnitrosamine in rats. 287 Aug 20

An in vivo model of liver hyperplastic noduligenesis was induced in rats by long-term administration of thioacetamide (TAM) (50 mg/kg/day i.p.). Three doses of 50 mg/kg of an antitumoral Rh(III) complex were administered at 14, 9 and 5 days before the end of TAM treatment. Plasma and urine were obtained from either TAM or Rh(III) complex or TAM plus Rh(III) complex treated rats to determine the interactions of both substances with the biochemical parameters related to liver function. The rise in alkaline phosphatase (ALP), leucine aminopeptidase (LAP), gamma-glutamyl transferase (GGT) and the unchanged activities in the aspartate and alanine aminotransferases (AST, ALT) in plasma of TAM-treated rats indicated that the disease induced by this substance can be considered as a chronic obstructive biliary disease with indices of cell proliferation and tumors. The increased concentration of bilirubin both in the plasma and urine of TAM-treated rats suggested liver cholestasis and hepatobiliary obstruction. The very low values of creatinine clearance indicated that there was some degree of kidney failure due to the effect of TAM. The increased concentration of ammonia both in plasma and urine were probably a consequence of the decreased flux in the urea cycle in the liver. The Rh(III) complex alone did not produce significant changes in the plasma enzyme activities. The only significant changes were found in the concentrations of uric acid and ammonia in the urine. When the Rh(III) complex was administered to TAM-treated rats, significant restoration of the following parameters were observed: plasma enzymatic activities, blood bilirubin and ammonia, uric acid and creatinine in the urine and the creatinine clearance. These results suggest that the altered liver function induced by TAM can be restored by Rh(III) complex. The mechanisms by which this complex acts to counteract the TAM-induced changes are not yet established.
Carcinogenesis 1987 Nov
PMID:Effect of a rhodium complex on alterations of hepatic function in thioacetamide-induced hyperplastic noduligenesis in rats. 288 38

The antihistamine methapyrilene (MP) was widely used as a component of cold, allergy and sleep-aid medications in the 1970s until it was identified as a potent rat liver carcinogen. MP does not induce positive responses in most short-term genotoxicity assays, which suggests that it is carcinogenic by a non-genotoxic mechanism. We have evaluated the potential of MP to induce unscheduled DNA synthesis (UDS), a genetic end point and S-phase synthesis (SPS), and indicator of cell proliferation, in Fischer-344 (F344) rat and B6C3F1 mouse liver. We also examined the response of MP in hepatocytes from two species treated in vitro. MP failed to induce UDS in rat or mouse liver following in vivo treatment, or in hepatocytes from rat and adult human treated in vitro. Control rats and mice yielded less than 0.3% of cells in S-phase (%S). In contrast, MP induced significant elevations in SPS both in male F344 rat (6.3%S) and female B6C3F1 mice (1.4%S). In the male rat, sorbitol dehydrogenase (SDH), bilirubin, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvate transaminase (SGPT) showed elevations of 9-, 10-. 17- and 28-fold over controls respectively, indicating that significant hepatotoxicity was induced by MP. This was confirmed by histopathologic examination, which revealed significant periportal and focal necrosis followed by an increased presence of mitotic figures. These results indicate that MP is not genotoxic in rat liver, but is a potent inducer of hepatic cell proliferation by inducing toxicity and subsequent regeneration, which may be an important mechanism of hepatocarcinogenesis.
Carcinogenesis 1988 Jun
PMID:Examination of genotoxicity, toxicity and morphologic alterations in hepatocytes following in vivo or in vitro exposure to methapyrilene. 337 Jul 59

To further evaluate the role of tryptophan and vitamin B6 in bladder carcinogenesis, male Fischer 344 rats were fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) in semipurified diet or were given semipurified diet alone for 4 weeks. One week later, rats from each group were assigned for the remainder of the experiment to one of four experimental diets, labeled as follows: group 1, control semipurified; group 2, L-tryptophan excess (2%); group 3, vitamin B6-deficient (1.0 mg/kg diet); or group 4, L-tryptophan excess, plus vitamin B6-deficient diet. All surviving rats were killed at 80 weeks of the experiment. Throughout the study, body weights were reduced in the groups fed FANFT and, at 70 and 80 weeks, body weights were reduced in the groups given tryptophan excess. The incidence of urinary bladder carcinoma was highest in the group treated with FANFT, followed by diet with control tryptophan and vitamin B6 levels (40%). The disease incidence was reduced in the vitamin B6-deficient group (13%) and of an intermediate range in the groups fed a tryptophan excess with or without vitamin B6 deficiency (28-29%). Tumors at other sites were greatest in number in FANFT-treated rats fed vitamin B6-deficient diet with excess tryptophan and were significantly fewer in FANFT-treated rats fed vitamin B6-deficient diet alone. Animals given diet deficient in vitamin B6 consistently had depressed levels of alanine aminotransferase activity and plasma pyridoxyl phosphate. FANFT pretreatment decreased alanine aminotransferase activities in rats in some groups and the feeding of tryptophan had variable effects on alanine aminotransferase and plasma pyridoxyl phosphate levels. Urinary tryptophan metabolites were influenced by all treatments, but the results did not correlate with tumor yields. Urinary bladder ornithine decarboxylase activity was not altered in vitamin B6-deficient female rats. These results do not support the hypothesis that increased dietary L-tryptophan promotes bladder carcinogenesis in rats, but other dietary factors might modify the process following FANFT initiation.
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PMID:Effect of L-tryptophan excess and vitamin B6 deficiency on rat urinary bladder cancer promotion. 381 36

In the present experiments, we studied the effect of poly(ADP-ribose) polymerase inhibitors on the early stage of liver carcinogenesis by diethylnitrosamine (DEN) in rat liver in order to clarify the biological role of this enzyme in cancer induction. We used 3-aminobenzamide(ABA), 5-methylnicotinamide(MNam), and thymidine as the inhibitors and measured the numbers and sizes of gamma-glutamyltranspeptidase (gamma-GTP) positive foci as a marker of initiated cell populations. When ABA was given within 4 hr after DEN treatment, it had almost the same effect as a partial hepatectomy and caused dose-dependent enhancement of the induction of gamma-GTP positive foci. The administration of ABA at a dose of 600 mg/kg was effective to enhance the induction of the foci 1 day before to 1 day after 20 mg/kg DEN initiation. The enhancing effect of MNam and thymidine at a dose of 600 mg/kg was observed to the same extent as that of ABA. Based on these results the experiments were extended to the mechanisms of the enhancing effect of ABA. Liver cell necrosis was not detected by measuring serum GOT and GPT levels and histology after DEN and ABA administration. Further, the initiating and promoting activities of ABA in liver carcinogenesis were studied and ABA per se was not found to take part in either activity. These results indicate that poly(ADP-ribose) polymerase plays an important role in the early stage of liver carcinogenesis by DEN and provides a new avenue for studying the mechanisms of the initiation process in chemical carcinogenesis.
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PMID:Possible role of poly(ADP-ribose) polymerase on the early stage of liver carcinogenesis by diethylnitrosamine in rats. 614 Feb 58

In order to confirm the close association between chronic hepatitis B virus (HBV) infection and primary hepatocellular carcinoma (PHC) in Japan, 8,646 male hepatitis B surface antigen (HBs Ag)-positive blood donors (GPT less than or equal to 35 Karmen units) were followed up. Twenty liver cancer cases were observed during the follow-up period (average 6.2 years), the expected number calculated on the basis of age-specific incidence rates among the general population being 3.03. Therefore, the observed to expected ratio of liver cancer was 6.60, that is significantly higher than 1.0. During the same follow-up period, a total of 76 deaths were observed, of which 20 were due to liver cancers and 9 to liver cirrhoses, meaning that nearly 40% of deaths among the study subjects due to chronic liver diseases. Drinking and smoking habits in the liver cancer cases were compared with those observed in healthy male HBV carriers. A strong positive association between drinking habits and liver cancer was observed and there was a significant dose-response relationship after adjustment for cigarette smoking habits. A high risk of liver cancer was also observed among heavy smokers, but a significant dose-response relationship could not be found between smoking habits and liver cancer, partly because of the limited number of the study subjects. These findings suggest that HBV is a major etiologic agent of PHC in Japan where the HBs Ag prevalence rate is about 2%, and alcohol drinking and cigarette smoking may promote the process of HB viral hepato-carcinogenesis.
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PMID:Follow-up study of HBs Ag-positive blood donors with special reference to effect of drinking and smoking on development of liver cancer. 651 Nov 24

Patients with chronic active hepatitis C and cirrhosis often develop hepatocellular carcinoma. Interferon (IFN) seems to be effective in some patients but whether it prevents carcinogenesis is unknown. In a prospective randomised controlled trial, we evaluated the effects of IFN-alpha in cirrhotic patients with HCV infection because of their high risk of hepatocellular carcinoma. 90 patients with compensated chronic active hepatitis C with cirrhosis were randomly allocated to receive IFN-alpha (6 MU three times weekly for 12-24 weeks) (45 patients) or symptomatic treatment (45 controls), and were followed up for 2-7 years. In nine controls, alanine aminotransferase (ALT) decreased to less than 80 IU/L but did not stay in the normal range. In 19 patients given IFN-alpha, ALT decreased to less than 80 IU/L (in seven patients, it became and stayed normal; p = 0.011, Wilcoxon rank-sum test). However, the mean change in ALT was not significantly different between the two groups. The mean change in peak alpha-fetoprotein values was smaller in patients given IFN-alpha than in controls (p = 0.021). The mean change in the serum albumin level was higher in the IFN-alpha group (p < 0.001). The histological activity index in the 12 IFN-alpha patients undergoing a second biopsy after therapy was improved (p = 0.031). Hepatitis C viral RNA disappeared in seven (16%) of the 45 IFN-alpha patients (95% CI, 7-29%) and in none of the 45 controls (0-8%; p = 0.018). Hepatocellular carcinoma was detected in two (4%, 1-15%) IFN-alpha patients and 17 (38%, 24-54%) controls (p = 0.002, Wilcoxon signed-rank test). The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 (0.009-0.530; p = 0.010 Cox's proportional hazards). IFN-alpha improved liver function in chronic active hepatitis C with cirrhosis, and its use was associated with a decreased incidence of hepatocellular carcinoma.
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PMID:Randomised trial of effects of interferon-alpha on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis. 854 66

Forty halogenated hydrocarbons of known rodent carcinogenicity (24 carcinogens, 16 noncarcinogens), including many promoters of carcinogenesis, nongenotoxic carcinogens, and hepatocarcinogens, were selected for study. The chemicals were administered by gavage in two dose levels to female Sprague-Dawley rats. The effects of these 40 chemicals on four biochemical assays [hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase activity (ODC), serum alanine aminotransferase activity (ALT), and hepatic cytochrome P-450 content (P450)] were determined. Composite predictive parameters are defined as follows: CP = [ODC and P450], CT = [ALT and ODC], and TS = [DD or CP or CT]. The operational characteristics of TS for predicting rodent cancer were sensitivity 58%, specificity 81%, positive predictivity 82%, negative predictivity 57%, and concordance 68%. The concordance for the Ames test (45%) and structural alerts (SA; 46%) was much lower. TS also outperformed the Ames test and SA in producing fewer false positives (the specificity of TS was 81% vs. only 63% for the Ames test and 57% for SA). For predicting the carcinogenicity of the most difficult halogenated hydrocarbons (Ames and SA negative chemicals), TS was capable of successfully predicting the carcinogenicity of 8 (carbon tetrachloride, chloroform, alpha-hexachlorocyclohexane, kepone, mirex, monuron, p,p'-DDE, and 2,4,6-trichlorophenol) out of 16 of these non-DNA-reactive halogenated hydrocarbon carcinogens. All 8 of these halogenated hydrocarbons were positive in either CP or CT. This evidence shows that nongenotoxic carcinogenesis is best predicted by nongenotoxic parameters such as CP or CT (components of the predictor TS).
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PMID:Predicting rodent carcinogenicity of halogenated hydrocarbons by in vivo biochemical parameters. 790 85

Inducers of Phase II enzymes, already consumed by humans as food additives, medicines or as constituents of vegetables, can prevent experimental carcinogenesis. Since protection is neither carcinogen- nor organ-specific, clinical trials are already underway to establish the efficacy of 'anticarcinogenic enzyme inducers' (i.e. oltipraz). However, efficient and cost-effective assays to establish the dose wherein a putative anticarcinogen can raise Phase II enzyme levels are lacking. We tested the proposal that serum Phase II enzyme activities would be dependent on relative tissue levels by measuring quinone reductase and glutathione S-transferase activities in sera of mice treated with dietary 2(3)-tert-butyl-4-hydroxyanisole (BHA) or dimethyl fumarate. Serum activities were significantly elevated in animals with increased tissue specific activities of these Phase II enzymes. Increasing concentrations of BHA in the diet from 0.05-0.5% increased hepatic specific activities of both QR and GST from two to six-fold, and increases in serum activities were well correlated to increases observed in the liver (r2 > or = 0.95). There was no evidence for an elevation of serum alanine aminotransferase levels. Thus, in the absence of serological evidence for hepatocellular damage, increased serum Phase II enzyme activities can be correlated to tissue levels. Our results suggest that similar assays tailored to human sera will not only be useful in the execution of chemoprevention trials, but also to assess the role that Phase II enzyme induction plays in the prevention of cancer by fruits and vegetables.
Carcinogenesis 1993 Dec
PMID:Elevation of serum phase II enzymes by anticarcinogenic enzyme inducers: markers for a chemoprotected state? 826 10

Sodium arsenite and cadmium chloride, were administered orally to adult female rats at 21 and 4 h prior to sacrifice. Liver, lung, skin and urinary bladder were the tissues studied. DNA damage, cytochrome P450, glutathione content (GSH), ornithine decarboxylase (ODC), serum alanine aminotransferase and heme oxygenase activity were measured. Sodium arsenite increased rat hepatic ODC activity at 1.6 and 24.6 mg/kg and hepatic heme oxygenase activity at 8.2 and 24.6 mg/kg, but did not cause any DNA damage. Cadmium chloride did not affect any of the six parameters tested. These findings suggest that sodium arsenite may be a promoter rather than an initiator of carcinogenesis.
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PMID:Arsenite, but not cadmium, induces ornithine decarboxylase and heme oxygenase activity in rat liver: relevance to arsenic carcinogenesis. 855 13


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