title: Pre-existing liver cirrhosis reduced the toxic effect of diethylene glycol in a rat model due to the impaired hepatic alcohol dehydrogenase.
abstract: Hepatic metabolizing enzymes of diethylene glycol (DEG) are impaired in liver diseases. Thus, the purpose of this study was to increase our understandings in metabolism and toxicology of DEG by clarifying the influences of pre-existing liver disease. Forty Sprague-Dawley rats with carbon tetrachloride-induced liver cirrhosis and 20 control rats were intraperitoneally administered a single dose of DEG, and randomly killed 1, 2, 5 or 8 days following exposure. Compared with control rats, the model rats had significantly higher blood CO(2)-combining power, lower blood urine nitrogen, serum creatinine and alanine aminotransferase levels on the second day and a lower mortality rate on the eighth day following DEG exposure. Enlargements of liver and kidneys and degeneration and necrosis of hepatocytes and renal tubules in the model rats was also less serious than in the control rats. Urine DEG levels were significantly higher on the first day in the model rats than the control rats (46.65 ± 8.79 mg vs 18.88 ± 6.18 mg, p < 0.01), but DEG concentrations in the blood, liver and kidneys were lower. Hepatic alcohol dehydrogenase (ADH) activity in the model rats was significantly lower than that in the control rats, which was positively related to renal damage. The toxic effects of DEG in rats with pre-existing liver cirrhosis are significantly reduced, which may be due to the decreased hepatic ADH activity. It suggests that the metabolite of ADH is responsible for DEG poisoning, and this toxic metabolite may mainly originate in the liver.
authors.affiliation: Hepatology Laboratory, Hospital for Liver Disease, Sun Yat-Sen University, Guangdong, People's Republic of China, Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, People's Republic of China.
authors.lastname: Ming Xing Huang
authors.lastname: Xiao Mou Peng
authors.lastname: Lin Gu
authors.lastname: Gui Hua Chen
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects; D004195:Disease Models, Animal; D005026:Ethylene Glycols / Q000493:pharmacokinetics / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects; D006651:Histocytochemistry; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000139:chemically induced / Q000201:enzymology; D012307:Risk Factors
chemical_list: D005026:Ethylene Glycols; C013484:diethylene glycol; D002251:Carbon Tetrachloride; D000426:Alcohol Dehydrogenase