Detection of paraquat-induced in vivo lipid peroxidation by gas chromatography/mass spectrometry and high-pressure liquid chromatography.
The cyclic oxidation-reduction of paraquat results in the formation of oxygen free radicals, which are believed to mediate the toxic manifestations of this herbicide. Because of paraquat's profound effects on lipid peroxidation, the effect of oral administration of 75 mg paraquat/kg to rats has been examined on the urinary excretion of the lipid metabolites malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT), and acetone (ACON) over 48 hours post-treatment. The urinary metabolites were identified by gas chromatography/mass spectrometry and quantitated by high-pressure liquid chromatography. Time-dependent increases in the urinary excretion of the four metabolites were observed after paraquat administration. Over the 48 hours of the study, the paraquat-induced urinary excretion of MDA, FA, ACT, and ACON increased by approximately 218, 155, 331, and 995%, respectively, relative to control animals. The data were expressed in nmol/kg body weight/4.5 h. The results clearly demonstrate that paraquat increases the urinary excretion of four lipid metabolites, which may have widespread applicability as biomarkers of altered lipid metabolism in disease states and cases of exposure to environmental pollutants and xenobiotics that induce enhanced lipid peroxidation.
Bagchi
D
D
Department of Pharmaceutical Sciences and Pharmacology, Creighton University Health Sciences Center, Omaha, NE 68178.
Bagchi
M
M
Hassoun
E A
EA
Stohs
S J
SJ
D000079:Acetaldehyde / Q000652:urine; D000096:Acetone / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005557:Formaldehyde / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000652:urine; D010084:Oxidation-Reduction / Q000187:drug effects; D010269:Paraquat / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D000096:Acetone; D005557:Formaldehyde; D008315:Malondialdehyde; D000079:Acetaldehyde; D010269:Paraquat