Changes in plasma lipoproteins as toxicity markers for carbon tetrachloride, chloroform, and dichloromethane.
Effects of single intraperitoneal (i.p.) administration of carbon tetrachloride (CCl4), chloroform (CHCl3), and dichloromethane (CH2Cl2) on lipoproteins in plasma and liver were investigated in rats. Changes in lipoproteins caused by these solvents were compared with changes in traditional hepatotoxicity markers such as GPT (ALT). Following the administration, concentrations of lipoproteins (VLDL, LDL, HDL), triglyceride, cholesterol, and GPT activity in plasma were determined through changes in liver weight, liver content of triglyceride, malon dialdehyde (MDA), and glutathione (GSH). Time-course study revealed that changes in plasma and liver reached their peaks at 19 or 32 hr following the administration of CCl4 or CHCl3. Peaks of changes were observed at 8 or 19 hr following the administration of CH2Cl2. Dose dependency of these changes was investigated at dosages of 3, 30, and 300 mg/kg of CCl4 or CHCl3, and 300, and 1,000 mg/kg of CH2Cl2. Significant decreases in triglyceride and apolipoproteins in VLDL fraction were observed at 3 mg/kg of CCl4. Such VLDL components decreased at 30 mg/kg of CHCl3. HDL decreased significantly at 300 mg/kg of CH2Cl2 and marked increase in LDL occurred at 1,000 mg/kg of the solvent. Liver weight and liver content of triglyceride and MDA significantly increased at 30 mg/kg of CCl4, while significant increase in GPT activity was observed at 300 mg/kg of CCl4 and CHCl3. GPT increased significantly at 1,000 mg/kg of CH2Cl2. These results revealed that changes in plasma lipoproteins can serve as sensitive and simple markers for liver disorders caused by chlorinated hydrocarbon solvents such as CCl4, CHCl3, or CH2Cl2.
Honma
T
T
Department of Occupational Diseases, National Institute of Industrial Health, Kawasaki, Japan.
Suda
M
M
D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers; D002251:Carbon Tetrachloride / Q000494:pharmacology / Q000633:toxicity*; D002725:Chloroform / Q000494:pharmacology / Q000633:toxicity*; D008074:Lipoproteins / Q000097:blood*; D008099:Liver / Q000187:drug effects*; D008297:Male; D008752:Methylene Chloride / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D015415:Biomarkers; D008074:Lipoproteins; D008752:Methylene Chloride; D002725:Chloroform; D002251:Carbon Tetrachloride