Enhanced expression of microsomal epoxide hydrolase and glutathione S-transferase by imidazole correlates with the radioprotective effect.
Previous studies have shown that induction of microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) by oltipraz correlated with the radioprotective effect. The present study was designed to investigate the expression of the antioxidant enzymes and the radioprotective effect by imidazole (IM). Northern blot analysis revealed that IM increased the mEH and GST mRNA levels in the rat liver in a dose-dependent manner. Rats irradiated with 3 Gy of gamma-rays in combination with IM showed enhanced increases in mEH and rGSTA2 mRNAs, as compared to either IM or irradiation alone. IM prevented elevations in the hepatic GSH content by gamma-irradiation. In contrast to IM, cysteine blocked radiation-inducible increases in the mRNAs with no suppression of the GSH content. The radioprotective effect by IM was greater than that by cysteine, as assessed by the 30-day survival rate of mice (i.e. 80% and 69%, respectively, vs. 48% in control). These results demonstrated that IM enhanced radiation-inducible mEH and GST expression with prevention of the increase in GSH content, which correlated with the radioprotective effect, and that the mechanistic basis of radioprotection by IM differed from that by cysteine.
Lee
A K
AK
College of Pharmacy, Seoul National University, Korea.
Cho
C K
CK
Kim
M S
MS
Kim
S G
SG
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004851:Epoxide Hydrolases / Q000235:genetics*; D005720:Gamma Rays; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics*; D007093:Imidazoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D007093:Imidazoles; D012333:RNA, Messenger; D011837:Radiation-Protective Agents; C029899:imidazole; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D005978:Glutathione; D003545:Cysteine