Mechanistic study of the inhibition of aflatoxin b1-induced hepatotoxicity by dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy biphenyl-2, 2'-dicarboxylate.
The mechanism of DDB (dimethyl 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxy biphenyl-2,2'-dicarboxylate) prevention of aflatoxin B1 (AFB1)-induced hepatotoxicity in rats has been investigated. Pretreatment of DDB (200 mg/kg) daily for 4 days significantly suppressed (P < 0.05) the AFB1-induced hepatic damage as evidenced by the increase of serum marker enzymes. DDB induced rat hepatic cytochrome P450IA1, IIB1 and glutathione S-transferase activities. The hepatic microsomes derived from DDB treated rats increased the mutation frequency of AFB1 and enhanced the binding of AFB1 to DNA. However, the hepatic S9 fraction from DDB treated rats showed a protective effect against AFB1-induced damage. It is concluded that the protective effect of DDB against AFB1-induced damage might be mediated by the induced glutathione S-transferase activity and not from the accelerated hepatic cytochrome P450 detoxification pathway of AFB1 which was previously believed.
Liu
T Y
TY
Department of Medical Research, Veterans General Hospital, Taipei, Taiwan, ROC.
Hwua
Y S
YS
Chao
T W
TW
Chi
C W
CW
D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004149:Dioxoles / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
D001713:Biphenyl Compounds; D004149:Dioxoles; D003577:Cytochrome P-450 Enzyme System; C043146:7-hydroxy-7'-methoxy-4,4'-bis(1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; D016604:Aflatoxin B1; D005982:Glutathione Transferase