Paraquat-generated oxidative stress in rat liver induces heme oxygenase-1 and aminolevulinic acid synthase.
The in vivo effect of the known herbicide, paraquat, on both hepatic oxidative stress and heme metabolism was studied. A marked increase in lipid peroxidation and a decrease in reduced glutathione (GSH) content were observed 1 h after paraquat administration. The activity of liver antioxidant enzymes, superoxide dismutase, catalase and glutathione peroxidase was decreased 3 h after paraquat injection. Heme oxygenase-1 induction started 9 h after treatment, peaking at 15 h. delta-aminolevulinic acid synthase induction occurred once heme oxygenase had been enhanced, reaching its maximum (1.5-fold of control) at 16 h. delta-aminolevulinic acid dehydratase activity was 40% inhibited at 3 h showing a profile similar to that of GSH, while porphobilinogenase activity was not modified along the whole period of the assay. Administration of alpha-tocopherol (35 mmol/kg body weight) 2 h before paraquat treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels as well as heme oxygenase-1 and delta-aminolevulinic acid synthase induction. This study shows that oxidative stress produced by paraquat leads to an increase in delta-aminolevulinic acid synthase and heme oxygenase-1 activities, indicating that the herbicide affects both heme biosynthesis and degradation.
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Guillermo O
GO
Noriega
Soledad
S
Gonzales
María L
ML
Tomaro
Alcira M Del C
AM
Batlle
D000624:5-Aminolevulinate Synthetase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004798:Enzymes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects* / Q000378:metabolism; D051547:Heme Oxygenase-1; D006540:Herbicides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology
D000975:Antioxidants; D004798:Enzymes; D006540:Herbicides; D017392:Thiobarbituric Acid Reactive Substances; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D000624:5-Aminolevulinate Synthetase; D005978:Glutathione; D024502:alpha-Tocopherol; D010269:Paraquat