Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current study was designed to assess the effect of immobilization stress on liver toxicity induced by topical as well as oral administration of 7,12-dimethyl benz(a)anthracene (DMBA) in Swiss Albino rats. The experimental animals were divided into six groups. Group 1 animals were exposed to chronic restraint stress alone for 10 days (3h/day), shaved back of animals in group II were painted with 0.5% solution of DMBA twice a week for 4 weeks. Group III animals were first exposed to restraint stress similar to group I followed by DMBA application as in group II, group IV animals were orally administered four doses of 0.5% DMBA solution. (1ml/rat) at weekly intervals, while group V animals were first exposed to restraint stress as in group I followed by oral dose of DMBA similar to group IV. The untreated Group VI animals served as controls. Rats were sacrificed after a period of 4 weeks following DMBA administration. Biochemical measurements were carried out on liver tissues and serum/plasma of control and treated animals. Restraint stress was found to have marked effect on DMBA induced alteration of liver function as revealed by the increase in tissue marker enzymes viz glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP), acid phosphatase (ACP), lactate dehydrogenase (LDH) with a significant further decrease in antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GR) as compared to controls and DMBA alone(topical/oral) or stress alone treated rats. Increased lipid peroxidation was accompanied by a significant decrease in the level of total reduced glutathione (GSH). The changes in the levels of marker enzymes and in vivo antioxidants in serum/plasma were comparable to that of liver. The results of the present study indicate that immobilization stress markedly enhances DMBA induced alteration of liver and circulatory antioxidant status of the rats irrespective of the mode of DMBA administration though with a predominant effect on orally infused DMBA.
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PMID:Enhancement of pro-oxidant effect of 7,12-dimethylbenz (a) anthracene (DMBA) in rats by pre-exposure to restraint stress. 1627 Dec 82

The liver plays an important role in the modulation of the process of carcinogenesis, as it is the primary site for the biotransformation of xenobiotics including carcinogens as well as anticancer drugs. The present study was designed to evaluate the biochemical alterations occurring in the liver of 7,12-dimethylbenz(a)anthracene (DMBA) induced skin tumor bearing male Balb/c mice and their modulation by aqueous Azadirachta indica leaf extract (AAILE). It was observed that skin tumor induction caused hepatic damage characterized by a decreased hepatosomatic index and significantly increased (p < 0.001) activities of the hepatic tissue injury marker enzymes, namely alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase. However, upon treatment with AAILE, the above-mentioned alterations, including the increased activities of hepatic tissue injury marker enzymes, were significantly reversed, which signified the hepato-protective efficacy of Azadirachta indica. Increased oxidative stress was also observed in the hepatic tissue of skin tumor bearing mice as revealed by a significant increase (p < 0.001) in lipid peroxidation levels and a decrease in reduced glutathione contents and activities of various antioxidant enzymes studied, namely glutathione-S-transferase, glutathione peroxidase and glutathione reductase. The AAILE treatment reduced oxidative stress by decreasing lipid peroxidation levels and enhancing the reduced glutathione contents and activities of various antioxidant enzymes. The activities of the xenobiotic biotransformation enzymes, namely cytochrome P450, cytochrome b5 and glutathione-S-transferase, were found to be decreased in the hepatic tissue of tumor bearing mice. Treatment with AAILE further caused a decrease in the activity of cytochrome P450 and cytochrome b5, whereas it up-regulated the activity of glutathione-S-transferase. The significance of these observations with respect to the progress of the process of carcinogenesis is explained in the present research article.
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PMID:Chemomodulatory effects of Azadirachta indica on the hepatic status of skin tumor bearing mice. 1652 Nov 6

Propolis, a natural beehive product has been known for centuries for a variety of beneficial traditional medicinal properties. The present study was conducted to ascertain the antineoplastic potential of propolis along with paclitaxel against experimental mammary carcinogenesis. Female Sprague Dawley rats at 55 days of age were treated with dimethylbenz(a)anthracene to induce breast cancer. Paclitaxel at a dose of 33 mg/kg body mass intraperitoneally and propolis 50 mg/kg body weight orally was administered to the experimental animals, immediately after the carcinogen treatment and continued until the termination of the study. At the end of the treatment activities of phase I and II xenobiotic metabolizing enzymes and liver marker enzymes were measured. A significant increase in carcinogen activating enzymes, cytochrome P(450), cytochrome b(5) and NADPH cytochrome C reductase with concomitant decrease in phase II enzymes, glutathione transferase and UDP-glucuronyl transferase were observed in animals with mammary cancer. Furthermore there was a significant decrease in alanine aminotransferase, aspartate aminotransferase with a sharp increase in alkaline phosphatase, acid phosphatase and 5' nucleotidase. Propolis treatment caused the activity of these enzymes return to almost normal control levels, indicating the protective effect of propolis against dimethyl benz(a) anthracene induced carcinogenesis. On the basis of the observed results propolis can be considered a promising chemotherapeutic agent and can be administered as an adjuvant with paclitaxel chemotherapy.
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PMID:Therapeutic effect of propolis and paclitaxel on hepatic phase I and II enzymes and marker enzymes in dimethylbenz(a)anthracene-induced breast cancer in female rats. 1672 Jan 5

Pine needles (Pinus densiflora Siebold et Zuccarini) have long been used as a traditional health-promoting medicinal food in Korea. To investigate their potential anticancer effects, antioxidant, antimutagenic, and antitumor activities were assessed in vitro and/or in vivo. Pine needle ethanol extract (PNE) significantly inhibited Fe(2+)-induced lipid peroxidation and scavenged 1,1-diphenyl- 2-picrylhydrazyl radical in vitro. PNE markedly inhibited mutagenicity of 2-anthramine, 2-nitrofluorene, or sodium azide in Salmonella typhimurium TA98 or TA100 in Ames tests. PNE exposure effectively inhibited the growth of cancer cells (MCF-7, SNU-638, and HL-60) compared with normal cell (HDF) in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In in vivo antitumor studies, freeze-dried pine needle powder supplemented (5%, wt/wt) diet was fed to mice inoculated with Sarcoma-180 cells or rats treated with mammary carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA, 50 mg/kg body weight). Tumorigenesis was suppressed by pine needle supplementation in the two model systems. Moreover, blood urea nitrogen and aspartate aminotransferase levels were significantly lower in pine needle-supplemented rats in the DMBA-induced mammary tumor model. These results demonstrate that pine needles exhibit strong antioxidant, antimutagenic, and antiproliferative effects on cancer cells and also antitumor effects in vivo and point to their potential usefulness in cancer prevention.
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PMID:Antioxidant, antimutagenic, and antitumor effects of pine needles (Pinus densiflora). 1747 62

The protective role of two synthetic organoselenium compounds 1-isopropyl-3-methylbenzimidazole-2-selenone (SeI) and 1, 3-di-p-methoxybenzylpyrimidine-2-selenone (Sell) was examined against the 7,12-dimethylbenz[a]anthracene (DMBA)-induced changes in biochemical parameters in blood of rats. Albino Winstar rats (150-200 g body wt) were treated with single dose of DMBA (50 mg/kg body wt) and organoselenium compounds (25 micromol/kg) for 4 weeks at two days internal. Blood was taken from the anaesthetized rats ventricle from their hearts for biochemical analysis. Administration of DMBA resulted in elevation of urea, uric acid and creatinine levels as well as AST, ALT and LDH activities and decrease in levels of total proteins, albumin and globulin. SeI and SeII caused a significant (p<0.05) decrease in urea, uric acid and creatinine levels and alanine aminotransferase (ALT); aspartate aminotransferase; (AST) and lactate dehydrogenase (LDH) activities and significantly increased the levels of total protein and albumin (p<0.05). These organoselenium compounds are likely to be beneficial in human health.
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PMID:Modulation of DMBA-induced biochemical changes by organoselenium compounds in blood of rats. 1797 Feb 85

Oxidative stress, a pervasive condition induced by stress has been implicated and recognized to be a prominent feature of various pathological states including cancer and their progression. The present study sought to validate the effectiveness of chronic unpredictable stress (CUS) on hepatic and renal toxicity in terms of alterations of various in vivo biochemical parameters, oxidative stress markers and the extent of DNA damage in Swiss albino mice. Animals were randomized into different groups based on their exposure to CUS alone, 7,12-dimethylbenz (a) anthracene (DMBA) alone (topical), DMBA-12-O-tetradecanoylphorbol-13-acetate (TPA) (topical), and exposure to CUS prior to DMBA or DMBA-TPA treatment, and sacrificed after 16 weeks of treatment. Prior exposure to CUS increased the pro-oxidant effect of carcinogen as depicted by significantly compromised levels of antioxidants; superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase, reduced glutathione in hepatic and renal tissues accompanied by a significant elevation of thiobarbituric acid reactive species (TBARS) as compared to DMBA alone or DMBA-TPA treatments. Loss of structural integrity at the cellular level due to stress-induced oxidative damage was demonstrated by significant increases in the hepatic levels of intracellular marker enzymes such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase, and significantly reduced levels of uric acid in kidney tissues. The results of DNA damage studies further positively correlated with all the above biochemical measurements. Thus, exposure to physical or psychological stress may significantly enhance the hepatotoxic and nephrotoxic potential of carcinogens through enhanced oxidative stress even if the treatment is topical.
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PMID:Chronic unpredictable stress exacerbates 7,12-dimethylbenz (a) anthracene induced hepatotoxicity and nephrotoxicity in Swiss albino mice. 2153 68

Tetralin is used as an industrial solvent primarily for naphthalene, fats, resins, oils, and waxes; as a solvent and stabilizer for shoe polishes and floor waxes; as a solvent for pesticides, rubber, asphalt, and aromatic hydrocarbons (e.g., anthracene); as a dye solvent carrier in the textile industry; as a substitute for turpentine in lacquers, paints, and varnishes; in paint thinners and as a paint remover; in alkali-resistant lacquers for cleaning printing ink from rollers and type; as a constituent of motor fuels and lubricants; for the removal of naphthalene in gas distribution systems; and as an insecticide for clothes moths. Tetralin was nominated by the National Cancer Institute for carcinogenicity and disposition studies because of its structure, high production volume, and high potential for worker and consumer exposure. Male and female F344/N rats and B6C3F1 mice were exposed to tetralin (at least 97% pure) by inhalation for 2 weeks, 3 months, or 2 years; male NCI Black Reiter (NBR) rats were exposed to tetralin by inhalation for 2 weeks. Male NBR rats do not produce 2u-globulin; the NBR rats were included to study the relationship of 2u-globulin and renal lesion induction. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male (F344/N and NBR) and five female (F344/N) rats were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 12 exposures. All rats survived to the end of the studies. The final mean body weight of female rats exposed to 120 ppm and mean body weight gains of female rats exposed to 30 ppm or greater were significantly less than those of the chamber controls. Final mean body weights of exposed groups of male NBR rats and mean body weight gains of all exposed groups of male rats were significantly less than those of the chamber controls. Dark-stained urine was observed in all 120 ppm rats. Squinting, weeping, or matted fur around the eyes were noted in the majority of F344/N rats exposed to 120 ppm. The 2u-globulin concentrations in the kidney of male F344/N rats were significantly greater in all exposed groups than in the chamber control group. The absolute kidney weight of 60 ppm females and the relative kidney weights of male F344/N rats exposed to 30 ppm or greater and female rats exposed to 15 ppm or greater were significantly increased. The absolute liver weight of 120 ppm NBR male rats and the relative liver weights of male and female rats exposed to 60 or 120 ppm were significantly increased. In the nose, the incidences of mononuclear cell cellular infiltration were generally significantly increased in all exposed groups of rats, and incidences of olfactory epithelium degeneration and glandular hypertrophy occurred in all male F344/N rats exposed to 120 ppm. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 13 exposures. All mice survived to the end of the study. Mean body weights of male and female mice were similar to those of the chamber controls. Dark-stained urine was observed in most of the exposed mice. The absolute and relative liver weights of 60 and 120 ppm males and 30 and 120 ppm females and the relative liver weights of 60 ppm females were significantly greater than those of the chamber controls. In the nose, the incidences of olfactory epithelium atrophy were significantly increased in 60 and 120 ppm males and females. Glandular dilatation occurred in all 120 ppm females, and glandular hyperplasia occurred in all 120 ppm males and females. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 14 weeks. The same exposure concentrations were given to additional groups of 10 male and 10 female clinical pathology study rats for up to 6 weeks and five male renal toxicity rats for 2 weeks. All rats survived to the end of the study. During the first 4 weeks of exposure, dark-stained urine was observed in the catch pans of rats exposed to 30, 60, or 120 ppm. Tetralin induced a minimal decrease in the erythron in both sexes that resulted in a hematopoietic response. Tetralin increased urine aspartate aminotransferase and urine lactate dehydrogenase activities (males and females) and glucose/creatinine ratio (males), suggestive of renal injury. The absolute kidney weights of 60 and 120 ppm females and the relative kidney weights of males and females exposed to 15 ppm or greater were significantly greater than those of the chamber controls. Concentrations of 2u-globulin in the kidney of exposed male rats were generally greater than those of the chamber controls at all time points and greater at 6 and 14 weeks than at 2 weeks. There were significantly increased incidences of olfactory epithelium necrosis in rats exposed to 30 ppm or greater and of olfactory epithelium regeneration in 60 and 120 ppm rats. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to tetralin at air concentrations of 0, 7.5, 15, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 14 weeks. All mice survived to the end of the study. Mean body weights of 120 ppm males were significantly less than those of the chamber controls. Dark-stained urine was observed in the catch pans of mice exposed to 30, 60, or 120 ppm during the first month of the study. Tetralin induced a minimal decrease in the erythron in both sexes that resulted in a hematopoietic response. The relative liver weights of 120 ppm males and 30 ppm or greater females were significantly greater than those of the chamber controls. Incidences of olfactory epithelium metaplasia in 60 and 120 ppm males and females, respiratory epithelium hyaline droplet accumulation in 120 ppm males and 60 and 120 ppm females, cytoplasmic eosinophilic granules within the transitional epithelium lining the urinary bladder in all exposed groups of males and females, and ovarian atrophy and uterine atrophy in 60 and 120 ppm females were significantly increased. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to tetralin at air concentrations of 0, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 105 weeks. Additional groups of five male and five female rats were exposed to the same concentrations for 12 months. Survival of all exposed groups of rats was similar to that of the chamber controls. Mean body weights of 120 ppm females were 6% less than those of the chamber controls after week 29. Dark-stained urine was observed in all exposed groups of rats. Creatinine-adjusted levels of all urinary metabolites increased with increasing exposure concentration in males and females. In the standard evaluation of the kidney, there were slightly increased incidences of cortical renal tubule adenoma in male rats. In the combined analysis of single and step sections, the incidence of cortical renal tubule adenoma was significantly increased in the 120 ppm group. In the combined analysis, there was also a significantly increased incidence of renal tubule hyperplasia in the 120 ppm group. In 120 ppm males in the standard evaluation, the severity of chronic nephropathy was increased and the incidence of transitional epithelial hyperplasia in the renal pelvis was significantly increased. Three hepatocellular adenomas occurred in 120 ppm females, and one hepatocellular carcinoma each was observed in the 60 and 120 ppm groups. The incidences of uterine stromal polyp and endometrium hyperplasia were significantly increased in 120 ppm females. Incidences of interstitial cell adenoma and germinal epithelium atrophy of the testis in 30 and 120 ppm males were significantly greater than those in the chamber controls. The incidences of olfactory epithelium degeneration, metaplasia, basal cell hyperplasia, suppurative inflammation, and mineralization (except 30 ppm females) in the nose were significantly increased in all exposed groups of rats. The incidences of glandular dilatation were significantly increased in 120 ppm males and all exposed groups of females. The incidences of respiratory epithelium chronic inflammation were significantly increased in males exposed to 60 or 120 ppm and all exposed groups of females. The incidences of lens cataract in 120 ppm females were significantly increased. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to tetralin at air concentrations of 0, 30, 60, or 120 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 105 weeks. Additional groups of five male and five female mice were exposed to the same concentrations for 12 months. Survival of 60 and 120 ppm female mice was significantly greater than that of the chamber controls. The mean body weights of all exposed groups of male and female mice were similar to those of the chamber controls by the end of the study. Dark-stained urine was observed in all exposed groups of male mice and in females exposed to 60 or 120 ppm. Creatinine-adjusted levels of all urinary metabolites increased with increasing exposure concentration in males and females. The incidence of hemangiosarcoma of the spleen was increased in 120 ppm females and exceeded the historical control range for inhalation studies. The incidences of olfactory epithelium atrophy, respiratory metaplasia, glandular hyperplasia, and suppurative inflammation in exposed groups of mice were significantly greater than those in the chamber controls. Transitional epithelium cytoplasmic eosinophilic granules were present in the urinary bladder of all exposed mice. (ABSTRACT TRUNCATED)
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PMID:Toxicology and carcinogenesis studies of tetralin (CAS No. 119-64-2) in F344/N rats and B6C3F1 mice (inhalation studies). 2168 56

We investigated the effects of quercetin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced oxidative stress and the expression of CYP1A1 and CYP1B1 in mice. Quercetin was administered orally to mice at 100 or 250 mg/kg BW for 18 days, after which DMBA (34 mg/kg BW) was administered intragastrically twice. Quercetin showed side effects such as increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in DMBA-untreated mice. Also, quercetin induced AST and ALT in DMBA-treated, although this was not significantly different from levels in DMBA-treated controls. The thiobarbituric acid reactive substances (TBARS) value showed a tendency to decrease following quercetin treatment; these decreases were significantly greater in the DMBA-treated compared to the untreated groups. Also, catalase and superoxide dismutase (SOD) activities as well as their mRNA expression were increased by quercetin; this increase was more pronounced in DMBA-treated compared to untreated mice. DMBA induced CYP1 activity as well as expression of CYP1A1 and CYP1B1. Each of these effects was significantly reduced by quercetin; however, this reduction was observed for CYP1A1 at only the higher dose and for CYP1B1 at both doses. These data suggest that quercetin shows antioxidant activity against DMBA-induced oxidative stress. Moreover, its regulation of CYP1A1 and CYP1B1 suggests the potential of quercetin as an anticancer supplement.
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PMID:Quercetin acts as an antioxidant and downregulates CYP1A1 and CYP1B1 against DMBA-induced oxidative stress in mice. 2246 40

Oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage in a variety of liver disorders. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present investigation is to evaluate the efficacy of Moringa oleifera as a hepatoprotective and an antioxidant against 7, 12-dimethylbenz[a]anthracene induced hepatocellular damage. Single oral administration of DMBA (15 mg/kg) to mice resulted in significantly (p<0.001) depleted levels of xenobiotic enzymes like, cytochrome P450 and b5. DMBA induced oxidative stress was confirmed by decreased levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) in the liver tissue. The status of hepatic aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) which is indicative of hepatocellular damage were also found to be decreased in DMBA administered mice. Pretreatment with the Moringa oleifera (200 and 400 mg/kg) orally for 14 days significantly reversed the DMBA induced alterations in the liver tissue and offered almost complete protection. The results from the present study indicate that Moringa oleifera exhibits good hepatoprotective and antioxidant potential against DMBA induced hepatocellular damage in mice that might be due to decreased free radical generation.
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PMID:Chemopreventive efficacy of Moringa oleifera pods against 7, 12-dimethylbenz[a]anthracene induced hepatic carcinogenesis in mice. 2293 21

Coal tar is a significant product generated from coal pyrolysis. Coal tar can be utilized as raw materials for various industries. It is also a type of raw material from which phenols, naphthalenes, and anthracene can be extracted. The present study was designed to investigate the possibility of coal tar creosote to induce oxidative stress and biochemical perturbations in rat liver and the role of rosemary (Rosmarinus officinalis) in ameliorating its toxic effects. Male Wister Albino rats were randomly divided into four groups of seven each, group I served as control; group II treated with rosemary (10 mL of water extract/kg BW for 21 days), group III received coal tar creosote (200 mg/4 mL olive oil/kg BW for 3 days), and group IV treated with both rosemary and coal tar creosote. The administration of coal tar creosote significantly caused elevation in lipid peroxidation (LPO) and reduction in the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). A significant decrease in reduced glutathione (GSH) content was also observed. Liver aminotransferases aspartate transaminase (AST) and alanine transaminase (ALT)] and alkaline phosphatase (AlP) were significantly decreased while lactate dehydrogenase (LDH) was increased. Rosemary pretreatment to coal tar creosote-treated rats decreased LPO level and normalized GPx, GR, SOD, CAT, and GST activities, while GSH content was increased. Also, liver AST, ALT, AlP, and LDH were maintained near normal level due to rosemary treatment. In conclusion, rosemary has beneficial effects and could be able to antagonize coal tar creosote toxicity.
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PMID:Oxidative stress modulation by Rosmarinus officinalis in creosote-induced hepatotoxicity. 2504 95


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