Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous study, we found that sodium arsenite increased hepatic ornithine decarboxylase (ODC) activity and hepatic heme oxygenase (HO) activity, but did not cause any DNA damage in adult female rat liver or lung, suggesting that arsenite may be a promoter of carcinogenesis. In this study sodium arsenate, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) were administered orally in equitoxic doses to adult female rats at 21 and 4 h prior to sacrifice. DNA damage (DD), cytochrome P450 content (P450), glutathione content (GSH), ODC, serum alanine aminotransferase (ALT) and HO were measured in liver and/or lung tissue. At 60 mg/kg in rat liver, sodium arsenate increased hepatic HO fivefold. MMA decreased ALT at 226 mg/kg, decreased ALT and GSH at 679 mg/kg and also increased P450 at 679 mg/kg in rat liver. DMA decreased ALT and hepatic GSH and increased hepatic HO at 387 mg/kg. In the lung, DMA decreased ODC at both 129 and 387 mg/kg. DD in lung tissue was significantly higher at 387 mg/kg DMA, demonstrating organ specific DNA damage. The biochemical effects and the inferred oncologic potential of the four major forms of arsenic (arsenate, arsenite, MMA and DMA) differ dramatically. The inorganic forms (arsenate and arsenite) are similar to each other (both good HO inducers); the methylated organic forms of arsenic (MMA and DMA) also share a similar pattern of biochemical effects (decreased GSH and ALT, increased P450). All six of the biochemical parameters studied were altered by DMA in either rat liver or lung.
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PMID:Dimethylarsinic acid treatment alters six different rat biochemical parameters: relevance to arsenic carcinogenesis. 926 21

Rat heme oxygenase (HO) activity was used as a specific (among forms of arsenic) and sensitive biomarker of effect for orally administered sodium arsenite in rats. Time course studies showed that HO was induced in rat liver from 2 to 48 h in both rat liver and kidney. Hepatic and renal inorganic arsenic (iAs) concentrations were high at times preceding a high degree of HO induction. At times following pronounced HO induction, tissue dimethylarsinic acid concentrations were high. Dose-response studies of arsenite showed substantial HO induction in liver at doses of 30 micromol/kg and higher and in the kidney at doses of 100 micromol/kg and higher. Doses of 10 (in liver) and of 30 micromol/kg (in kidney) sodium arsenite given by gavage did not significantly induce rat HO activity. Speciation of tissue total arsenic into iAs, methylarsonic acid (MMA), and dimethylarsinic acid (DMA) permits us to link tissue iAs and HO enzyme induction. There was a linear relationship between tissue inorganic arsenic (iAs) concentration and tissue HO in individual rats (r(2) = 0.780 in liver and r(2) = 0.797 in kidney). Nonlinear relationships were observed between administered arsenite dose and either liver or kidney iAs concentration. Overall, there was a sublinear relationship between administered arsenite and biological effect in rats. Teratogenesis Carcinog. Mutagen. 19:385-402, 1999. Published 1999 Wiley-Liss, Inc.
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PMID:An integrated pharmacokinetic and pharmacodynamic study of arsenite action. 1. Heme oxygenase induction in rats. 1058 9