The metabolism and liver toxicity of N,N-dimethylformamide in the isolated perfused rat liver

Sangbaek Koh, Bong Suk Cha, Jong Ku Park, Soung Hoon Chang, Sei Jin Chang

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Abstract

N,N-dimethylformamide (DMF) is metabolized by the microsomal cytochrome p-450 into mainly N-hydroxymethyl-N-methylformamide (HNF), which further breaks down to N-methyformide (NMF). However, the detailed mechanism of its toxicity remains unclear. We investigated the metabolism and the toxicity of DMF using the isolated perfused liver model. DMF was added to the recirculating perfusate of the isolated perfused rat liver at concentrations of 0, 10 and 25 mM. Samples were collected from the inferior vena cava at 0, 30, 45, 60, 75, and 90 minutes following addition of the DMF. The metabolites of DMF were analyzed using Gas-chromatography (GC). The changes in the rate of oxygen consumption by the DMF were monitored during perfusion. The enzyme activities (aspartic aminotransferase: AST, alanine aminotransferase:ALT, and lactic dehydrogenase:LDH)) in the perfusate were monitored to see if DMF caused bepatotoxicity. As the perfusion progressed, the DMF concentration in the perfusate decreased, but the level of NMF increased to a maximum of 1.16 mM. The rate of oxygen consumption increased at DMF concentrations of 10 mM and 25 mM. However, when a known inhibitor of cytochrome p-450, SKF 525A (300 μ M), was used to pretreat the perfusate prior to the addition of the DMF, the rate of oxygen consumption was significantly inhibited, indicating the cytochrome p-450 system was responsible for the conversion of DMF to NMF. On addition of the DNF, the activities of the enzymes AST, ALT and LDH were significantly increased a time and dose dependent manner. However, following pretreatment with SKF 525A, their releases were inhibited.

Original languageEnglish
Pages (from-to)491-499
Number of pages9
JournalYonsei Medical Journal
Volume43
Issue number4
DOIs
Publication statusPublished - 2002 Jan 1

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Dimethylformamide
Liver
Cytochromes
Oxygen Consumption
Proadifen
Perfusion
Inferior Vena Cava
Enzymes
Transaminases
Alanine Transaminase
Gas Chromatography
Oxidoreductases
Milk

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Koh, Sangbaek ; Cha, Bong Suk ; Park, Jong Ku ; Chang, Soung Hoon ; Chang, Sei Jin. / The metabolism and liver toxicity of N,N-dimethylformamide in the isolated perfused rat liver. In: Yonsei Medical Journal. 2002 ; Vol. 43, No. 4. pp. 491-499.
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The metabolism and liver toxicity of N,N-dimethylformamide in the isolated perfused rat liver. / Koh, Sangbaek; Cha, Bong Suk; Park, Jong Ku; Chang, Soung Hoon; Chang, Sei Jin.

In: Yonsei Medical Journal, Vol. 43, No. 4, 01.01.2002, p. 491-499.

Research output: Contribution to journalArticle

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