Hemolysate pretreatment ameliorates ischemic acute renal injury in rats.
Heme oxygenase-1 (HO-1) is an antioxidant enzyme and is believed to protect against oxidative stress-induced tissue injury. Renal ischemia-reperfusion (IR) injury seems at least in part to be caused by the oxidative stress. The aim of this study was to improve the renal IR injury by clinically available means. When littermate hemolysate was intravenously administered into rats, HO-1 was markedly induced in the kidneys. To investigate whether prior induction of HO-1 by the hemolysate injection ameliorates the subsequent renal IR injury, we assessed the levels of blood urea nitrogen (BUN) and serum creatinine (SCr), markers for renal injury, in rats with 45 min of ischemia followed by 18 h of reperfusion. To avoid the nephrotoxicity induced by hemolysate, small but effective amounts of hemolysate was injected into rats at 48 h prior to the ischemia. The levels of BUN and SCr values were significantly improved as compared to the rats with renal IR injury alone. Administration of HO inhibitor abolished the efficacy of hemolysate pretreatment. Our findings indicated that the prior induction of HO-1 by treatment of littermate hemolysate ameliorated the subsequent renal IR injury. Prior injection of self-hemolysate would be clinically useful for the protection against the renal IR injury induced by kidney transplantation and kidney surgery without immunological and infectious problems.
Yoneya
Rika
R
Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Nagashima
Yoji
Y
Sakaki
Kyohei
K
Hagiwara
Kiyokazu
K
Teraoka
Hirobumi
H
Ozasa
Hisashi
H
Horikawa
Saburo
S
D000818:Animals; D004790:Enzyme Induction; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D051547:Heme Oxygenase-1; D006461:Hemolysis; D006801:Humans; D007511:Ischemia / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology / Q000293:injuries* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control / Q000628:therapy
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1