Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cutaneous xenobiotic metabolizing enzymes including aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECD), epoxide hydrolase (EH) and glutathione S-transferase (GST) activities were examined in SKH hairless mice chronically irradiated with UVB to induce squamous cell carcinoma (SCC). Enzyme activities in irradiated tumor-bearing skin were compared to those present in the skin of nonirradiated control animals as well as in unirradiated non-tumor bearing skin sites of the SCC-bearing mice. The inducibility of skin AHH and ECD in each set of animals was assessed following a single topical application of coal tar (1 ml/100 g). Enzyme-mediated binding of [3H]benzo(a)pyrene (BP) and its metabolite 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE-I) to epidermal DNA was also evaluated. Basal AHH and ECD activities in microsomes from UVB-irradiated SCC-bearing dorsal skin were 4.6- and 4.8-fold lower than those in dorsal skin of nonirradiated control animals. Enzyme activities in non-tumor bearing ventral skin from the UVB-irradiated SCC-bearing mice also were 2.2 to 2.8-fold lower as compared to activities in the nonirradiated control animals. The reduction in AHH activity paralleled the levels of enzyme-mediated binding of radiolabeled BP metabolites and of BPDE-I to epidermal DNA. GST activity was found to be increased (173%) in non-tumor bearing ventral skin of UVB-irradiated mice whereas no difference in activity between SCC-bearing dorsal skin and dorsal skin of control animals could be detected. EH activity was unchanged in each group of animals. Treatment with topically applied coal tar resulted in higher inducibility of AHH and ECD in both SCC-bearing (13-fold) as well as in non-tumor skin sites (6-fold) of UVB-irradiated mice than in skin of control animals (3-fold). Coal tar application also increased the covalent binding of [3H]BP and of the metabolite BPDE-I to skin DNA. This was greater in SCC-bearing dorsal skin (119-129%) than in nonirradiated skin of control animals (48-62%). Our studies suggest that the metabolism of BP by cutaneous cytochrome P-450 dependent monooxygenases is impaired in skin of mice irradiated chronically with UVB. The higher inducibility of these monooxygenases by topically applied coal tar and the enhancement of the associated enzyme-mediated covalent binding of BP metabolites and BPDE-I to epidermal DNA indicate that repetitive exposure of mammalian skin to UVB radiation can profoundly alter the activity and the inducibility of drug and carcinogen metabolizing enzymes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Altered patterns of cutaneous xenobiotic metabolism in UVB-induced squamous cell carcinoma in SKH-1 hairless mice. 399 3

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