{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T19:39:28Z","timestamp":1740166768594,"version":"3.37.3"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["LSHB-CT-2006-037712"],"award-info":[{"award-number":["LSHB-CT-2006-037712"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006789","name":"Halogenated Solvent Industry Alliance Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006789","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The industrial solvent trichloroethylene (TCE) and its two major metabolites trichloroethanol (TCE-OH) and trichloroacetic acid (TCA) cause formic aciduria in male F344 rats. Prior treatment of male F344 rats with 1-aminobenzotriazole a cytochrome P450 inhibitor, followed by TCE (16mk\/kg, po), completely prevented formic aciduria, but had no effect on formic acid excretion produced by TCA (8 or 16\u00a0mg\/kg, po), suggesting TCA may be the proximate metabolite producing this response. Dow and Green reported an increase in the concentration of 5-methyltetrahydrofolate (5-MTHF) in the plasma of rats treated with TCE-OH, suggesting a block in the cycling of 5-MTHF to tetrahydrofolate (THF). This pathway is under the control of the vitamin B12-dependent methionine salvage pathway. We therefore treated rats with three daily doses of methylcobalamin (CH3Cbl) or hydroxocobalamin (OHCbl), a cofactor for methionine synthase, or L-methionine, followed by TCE (16\u00a0mg\/kg) to determine if they could alleviate the formic aciduria. These pretreatments only partially reduced the excretion of formic acid in the urine. Although prior treatment with S-adenosyl-L-methionine had no effect on formic acid excretion. Consistent with these findings, the activity of methionine synthase in the liver of TCE-treated rats was not inhibited. Transcriptomic analysis of the liver-identified nine differential expressed genes, of note, was downregulation of Lmbrd1 involved in the conversion of vitamin B12 into CH3Cbl, a cofactor for methionine synthase. Our findings indicate that the formic aciduria produced by TCE-OH and TCA may be the result of a block in the recycling of 5-MTHF to THF, the effect on the methionine salvage pathway being a secondary response following acute exposure.<\/jats:p>","DOI":"10.1093\/toxres\/tfaa006","type":"journal-article","created":{"date-parts":[[2020,2,25]],"date-time":"2020-02-25T15:16:29Z","timestamp":1582643789000},"page":"117-126","source":"Crossref","is-referenced-by-count":0,"title":["The effect of trichloroethylene metabolites on the hepatic vitamin B12-dependent methionine salvage pathway and its relevance to increased excretion of formic acid in the rat"],"prefix":"10.1093","volume":"9","author":[{"given":"Noreen","family":"Yaqoob","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna M","family":"Bloch","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew R","family":"Evans","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward A","family":"Lock","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,4,24]]},"reference":[{"key":"2020050712475337300_ref1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1080\/15459620701301763","article-title":"Uses of and exposure to trichloroethylene in U.S. 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