The Metabolism and Liver Toxicity of N,N-dimethylformamide in the Isolated Perfused Rat Liver

• DOI: 10.3349/ymj.2002.43.4.491
• Publication Date: 2014-09-27T04:48:05Z
• Authors: Sang Baek Koh; Bong Suk Cha; Jong Ku Park; Soung Hoon Chang; Sei Jin Chang
• Keywords: Male; Perfusion; Rats, Sprague-Dawley; 0301 basic medicine; 03 medical and health sciences; Oxygen Consumption; Liver; Animals; Dimethylformamide; Rats; 3. Good health

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