Protective effects of antioxidants against endrin-induced hepatic lipid peroxidation, DNA damage, and excretion of urinary lipid metabolites.
Oxidative stress is believed to play a pivotal role in endrin-induced hepatic and neurologic toxicity. Therefore, the effects of the antioxidants vitamin E succinate and ellagic acid have been examined on hepatic lipid peroxidation, DNA single-strand breaks (SSB), and the urinary excretion of lipid metabolites following an acute oral dose of 4.5 mg endrin/kg. Groups of rats were pretreated with 100 mg/kg vitamin E succinate for 3 d followed by 40 mg/kg on day 4, or 6.0 mg ellagic acid/kg for 3 d p.o. followed by 3.0 mg/kg on day 4 or the vehicle. Endrin was administered p.o. on day 4 2 hr after treatment with the antioxidant. All animals were killed 24 h after endrin administration. Vitamin E succinate pretreatment decreased the endrin-induced increase in hepatic mitochondrial and microsomal lipid peroxidation by approximately 60% and 40%, respectively. Ellagic acid pretreatment reduced the endrin-induced increased in mitochondrial and microsomal lipid peroxidation by approximately 76 and 79%, respectively. Both vitamin E succinate and ellagic acid alone produced small but nonsignificant decreases in hepatic mitochondrial and microsomal lipid peroxidation. A 3.3-fold increase in the incidence of hepatic nuclear DNA single-strand breaks was observed 24 h after endrin administration. Pretreatment of rats with vitamin E succinate, vitamin E, and ellagic acid decreased endrin-induced DNA-SSB by approximately 47%, 22%, and 21%, respectively. Pretreatment of rats with vitamin E succinate decreased the endrin-induced increase in the urinary excretion of malondialdehyde, acetaldehyde, formaldehyde, and acetone by approximately 68, 65, 70, and 55%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Bagchi
D
D
Department of Pharmaceutical Sciences and Pharmacology, Creighton University Health Sciences Center, Omaha, NE 68178.
Hassoun
E A
EA
Bagchi
M
M
Stohs
S J
SJ
D000079:Acetaldehyde / Q000652:urine; D000096:Acetone / Q000652:urine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D004610:Ellagic Acid / Q000494:pharmacology; D004732:Endrin / Q000494:pharmacology*; D005260:Female; D005557:Formaldehyde / Q000652:urine; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000652:urine*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008315:Malondialdehyde / Q000652:urine; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D024505:Tocopherols; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology
D000975:Antioxidants; D008055:Lipids; D000096:Acetone; D014810:Vitamin E; D004610:Ellagic Acid; D005557:Formaldehyde; D008315:Malondialdehyde; D000079:Acetaldehyde; D004732:Endrin; D024505:Tocopherols