Effects of carbon tetrachloride, menadione, and paraquat on the urinary excretion of malondialdehyde, formaldehyde, acetaldehyde, and acetone in rats.
Excretions of the lipid peroxidation products, formaldehyde (FA), acetaldehyde (ACT), malondialdehyde (MDA), and acetone (ACON), were simultaneously identified and quantitated in the urine of female Sprague-Dawley rats by gas chromatography-mass spectroscopy (GC-MS) and high pressure liquid chromatography (HPLC) following the acute administration of carbon tetrachloride, a model alkylating agent that does not induce glutathione depletion, and the redox cycling compounds paraquat and menadione. All three xenobiotics are well-known inducers of oxidative stress. Oxidative stress was induced by oral administration of single doses of 2.5 mL of carbon tetrachloride/kg, 60 mg menadione/kg, and 75 mg paraquat/kg. These doses are approximately 50% of the LD50's for the three xenobiotics. Urinary excretion of FA, ACT, MDA, and ACON increased relative to control animals following treatment with all xenobiotics. Over the 48 hours of the study, the greatest increases in the excretion of MDA, FA, ACT, and ACON occurred after paraquat administration, with increases of approximately 2.7-, 2.6-, 4.3-, and 11.0-fold, respectively. This technique may have wide-spread applicability as an effective biomarker for investigating altered lipid metabolism in disease states and exposure to environmental pollutants/xenobiotics.
Bagchi
D
D
Department of Pharmaceutical Sciences, Creighton University Health Sciences Center, Omaha, NE 68178.
Bagchi
M
M
Hassoun
E
E
Moser
J
J
Stohs
S J
SJ
D000079:Acetaldehyde / Q000652:urine*; D000096:Acetone / Q000652:urine*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000652:urine*; D008055:Lipids / Q000652:urine; D008315:Malondialdehyde / Q000652:urine*; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014812:Vitamin K / Q000633:toxicity*
D008055:Lipids; D014812:Vitamin K; D000096:Acetone; D005557:Formaldehyde; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D000079:Acetaldehyde; D010269:Paraquat