Prior induction of heme oxygenase-1 with glutathione depletor ameliorates the renal ischemia and reperfusion injury in the rat.
Heme oxygenase (HO)-1 catalyzes the rate-limiting step in heme degradation releasing iron, carbon monoxide, and biliverdin. Induction of HO-1 occurs as an adaptive and protective response to oxidative stress. Ischemia and reperfusion (IR) injury seems to be mainly caused by the oxidative stress. In this study, we have examined whether prior induction of HO-1 with buthionine sulfoximine (BSO), a glutathione (GSH) depletor, affects the subsequent renal IR injury. BSO (2 mmol/kg body weight) was administered intraperitoneally into rats, the levels of HO-1 protein increased within 4 h after the injection. When BSO was administered into rats at 5 h prior to the renal 45 min of ischemia, the renal IR injury was assessed by determining the levels of blood urea nitrogen and serum creatinine, markers for renal injury, after 24 h of reperfusion. The renal injury was significantly improved as compared to the rats treated with IR alone. Administration of zinc-protoporphyrin IX, an inhibitor of HO activity, reduced the efficacy of BSO pretreatment on the renal IR injury. Our findings suggest that the prior induction of HO-1 ameliorates the subsequent renal IR injury.
Horikawa
Saburo
S
Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, Japan. hori-pbc@mri.tmd.ac.jp
Yoneya
Rika
R
Nagashima
Yoji
Y
Hagiwara
Kiyokazu
K
Ozasa
Hisashi
H
D000818:Animals; D001806:Blood Urea Nitrogen; D015153:Blotting, Western; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004790:Enzyme Induction / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*
D011524:Protoporphyrins; C017803:zinc protoporphyrin; D019328:Buthionine Sulfoximine; D003404:Creatinine; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione