Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a part of our program aimed at exploring the biological activity of symmetrical substitution of side chains into the anthracene-9,10-dione chromophore, we have synthesized a series of 1,5-bisthioanthraquinones 2 and 1,5-bisacyloxyanthraquinones 3 that are related to the antitumor agent mitoxantrone. Since the telomerase enzyme is a novel target for potential anticancer therapy and stem cell expansion, we explore the biological effects of these compounds by evaluating their effects on telomerase activity and telomerase expression. Telomerase is required for telomere maintenance and is active in most human cancers and in germinal cells but not in most of the normal human somatic tissues. We found that most of the 1,5-disubstituted anthraquinones did not exhibit inhibitory activity at the concentration ranging from 20 to 30 microM. To facilitate the analysis of the expression of telomerase, we used cancer and normal cell lines that carry secreted alkaline phosphatase (SEAP) gene under the control of human telomerase reverse transcriptase (hTERT). The effects of these compounds on the expression of telomerease were analyzed using the cell-based reporter systems. While most of these compounds did not appear to selectively repress the expression of hTERT in cancer cells, compounds 3a, 3d, and 3i activated hTERT expression in normal cells. The effects of these three compounds on hTERT expression appear to be specific because they did not increase the expression of a CMV promoter-driven SEAP. Thus, in addition to anticancer functions, our finding raises the possibility that these compounds might also have a role in cell immortalization. The application of these anthraquinone derivatives in stem cell research and tissue engineering is also discussed.
 ...
PMID:Activation of human telomerase reverse transcriptase expression by some new symmetrical bis-substituted derivatives of the anthraquinone. 1285 60

A single dose of 10 mg of 7,12-dimethylbenz[a]anthracene (DMBA), administered to rats through intragastric intubation, was sufficient to induce many biochemical and histopathological changes in their mammary tissue. Significant increases were observed in the activity levels of the enzymes acid ribonuclease, 5-nucleotidase, alkaline phosphatase, and beta-glucuronidase in mammary tissue homogenates of DMBA-treated rats after an experimental period of five months. Histopathological studies of the mammary tissue also revealed malignant epithelial tumors (cribriform carcinoma) induced among 85% of the treated rats, with an incidence of 4 tumors in 12 mammary glands. Nevertheless, administration of 30% soybean in the diet of rats or 5,000 ppm ascorbic acid in their drinking water in addition to DMBA revealed a significant chemoprotective effect against the carcinogenesis induced by DMBA alone. This chemoprotective effect was demonstrated by the normalization of the activity levels of the enzymes studied in mammary tissue homogenates, because most of the enzymes were maintained at near the levels in the control animals. The incidence and number of tumors were also decreased. Cribriform carcinoma was observed in 50% of the rats, and the incidence of the affected glands was 2 in 12 mammary glands among both groups. On the other hand, a less chemoprotective effect was observed due to Vicia faba administration.
 ...
PMID:Effect of soybean, Vicia faba, and vitamin C on the carcinogenicity of DMBA. 1450 48

Break-Free CLP((R)) is a commercial cleaning, lubricating and preserving compound used in both the military and civilian sectors for maintenance of small- and large-caliber weapons. Like many commercial mixtures, there is very little information available on the toxicity of Break-Free CLP. Studies were conducted to characterize the biological effects of single or repeat dermal application of Break-Free CLP to the clipped backs of CD-1 mice. Break-Free CLP was applied neat, 50 microl three times of week for up to 2 weeks. Foci of epithelial ulceration were observed in skin sections from 22% of Break-Free CLP-treated animals in conjunction with markedly thickened epithelium suggesting that robust epithelial regeneration was occurring in these animals. Skin histopathology of Break-Free CLP-treated animals closely matched the histopathology from mice treated repeatedly with 2% croton oil in acetone (dermal irritation positive control). Serum alkaline phosphatase activity was significantly (P < 0.05) lower for mice treated with Break-Free CLP, 2% croton oil or 7,12-dimethylbenz[a]anthracene (DMBA) compared with negative and vehicle control mice. Skin nitric oxide (NO) levels were not significantly elevated for mice treated with Break-Free CLP but were significantly elevated for mice treated with dermal irritation positive control compound DMBA. The cumulative skin changes in Break-Free CLP-treated animals support conducting a subchronic dermal application study. The observed decreases in serum alkaline phosphatase activity suggest that future studies should include the liver and bone as possible target organs. Additionally, dermal penetration studies could provide key health risk assessment information for characterizing the potential health risks associated with chronic dermal exposure to Break-Free CLP.
 ...
PMID:Acute and subacute dermal toxicity of Break-Free CLP: a weapons cleaning and maintenance compound. 1602 32

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.
 ...
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.
 ...
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.
 ...
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

Two new anthracene glycosides (1, 2) were isolated from aerial parts of Rhodomyrtus tomentosa, along with three known compounds (3-5). The structures of two new compounds were established to be 4,8,9,10-tetrahydroxy-2,3,7-trimethoxyanthracene-6-O-beta-D-glucopyranoside (1) and 2,4,7,8,9,10-hexahydroxy-3-methoxyanthracene-6-O-alpha-L-rhamnopyranoside (2) based on spectroscopic and chemical methods. Among them, compound 1, 2, and 5 significantly (P<0.05) increased the alkaline phosphatase activity, collagen synthesis, and mineralization of the nodules of MC3T3-E1 osteoblastic cells compared to those of the control, respectively.
 ...
PMID:New anthracene glycosides from Rhodomyrtus tomentosa stimulate osteoblastic differentiation of MC3T3-E1 cells. 1940 68

The present study was designed to evaluate the modulatory effects of lycopene against 7, 12 Dimethylbenz (a) anthracene induced clastogenicity and oxidative stress in male Balb/c mice. The animals were divided into four groups; group I served as control (vehicle treated). Animals of group III and IV were administered lycopene orally at a dose of 4 mg/kg body weight for 10 weeks. Groups II and IV were administered DMBA, i.p., at a dose level of 40 mg/kg body weight, 48 hrs before the sacrifice of animals. Exposure to DMBA clearly induced hepatic cell injury as was evident by an increase in micronucleated cell score, lactate dehydrogenase and alkaline phosphatase activities, and Lipid Peroxidation levels. When the lycopene pre-treated animals were challenged with DMBA, a decrease in micronucleated cell score was observed, which was in corroboration with the observed decrease in LDH and ALP activities and LPO levels. DMBA treatment caused an increase in the oxidative stress with consequent alterations in enzymatic antioxidant defense system. Lycopene pre-treatment boosted the antioxidant defense in group IV. Thus, the antioxidant role of lycopene could be plausible in the protective action conferred by lycopene, enabling it to be used an effective natural free radical scavenger.
 ...
PMID:Lycopene mediated modulation of 7,12 Dimethlybenz (a) anthracene induced hepatic clastogenicity in male Balb/c mice. 2044 42

Epithelial cells from urinary bladders of pigs were isolated and cultured under serum-free conditions. For these cells it was previously shown that they developed morphologic polarity resembling the epithelium in vivo. Lactate dehydrogenase release was low, chromosome set and activities of marker enzymes (alkaline phosphatase, acid phosphatase, g-glutamyltranspeptidase) were stable over a period of 4 wk. In this study, metabolic competence was evaluated by measuring activities of phase I and phase II enzymes. Activity of prostaglandin H-synthase was expressed in freshly isolated cells as well as in cultured cells, as were activities of the conjugating enzymes glutathione transferase, UDP-glucuronyltransferase and N-acetyltransferase. Cytochrome P4501A1 activity in freshly isolated cells amounted to 10-15% of the respective activity in the porcine liver, this activity was not detectable in cultured cells. No activity was seen in cultured cells after induction with methylcholanthrene and benz[a]anthracene. This cell culture system was used to detect genotoxic effects of substances suspected to induce bladder cancer by measuring the induction of sister chromatid exchanges (SCE). The aromatic amines 4-aminobiphenyl and 2-aminofluorene induced a concentration dependent increase of SCEs at non-cytotoxic concentrations. These results imply that urinary bladder epithelial cells are capable to perform metabolic activation which is required to generate genotoxic effects of aromatic amines. Therefore, this new cell culture system, representing the urinary bladder epithelium, is an effective tool in in vitro toxicology to investigate adverse effects of compounds, regarded or suspected to induce toxic effects in the bladder.
 ...
PMID:An in vitro model of the urinary bladder: cultured porcine urinary bladder epithelial cells. 2065 31

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.
 ...
PMID:Chronic unpredictable stress exacerbates 7,12-dimethylbenz (a) anthracene induced hepatotoxicity and nephrotoxicity in Swiss albino mice. 2153 68


<< Previous 1 2 3 4 Next >>