Pharmacological preconditioning protects lung injury induced by intestinal ischemia/reperfusion in rat.
Intestinal ischemia/reperfusion (IIR) is a critical and triggering event in the development of distal organ dysfunction, frequently involving the lungs. Respiratory failure is a common cause of death and complications after intestinal I/R. Stress protein heme oxygenase-1 (HO-1) confers the protection against a variety of oxidant-induced cell and tissue injuries. The aim of this study was to investigate the hypothesis that the induced HO-1 expression by pharmacological preconditioning with anticancer drug doxorubicin (Dox) could protect the lung injury induced by intestinal I/R. Intravenous administration of Dox induced HO-1 expression in the lungs and high levels of the expression were sustained at least to 48 h after the injection. Therefore, as pharmacological preconditioning, a low dose of Dox was injected intravenously into rats at 48 h before the start of intestinal ischemia. Rats underwent intestinal I/R by superior mesenteric artery occlusion for 120 min followed by 120 min of reperfusion. Preconditioning with Dox significantly ameliorated the lung injury induced by the intestinal I/R. Administration of a specific inhibitor of HO activity reduced the efficacy of the preconditioning. Our results suggest that this improvement may be mediated at least in part by the HO-1 induction. These findings may offer interesting perspectives for patient management In Intestinal surgical operation and intestine transplantation.
Department of Pathological Biochemistry, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.
Koji
K
Ito
Hisashi
H
Ozasa
Naosuke
N
Kojima
Mitsutaka
M
Miura
Takehisa
T
Iwa
Haruki
H
Senoo
Saburo
S
Horikawa
D000818:Animals; D004195:Disease Models, Animal; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D007422:Intestines / Q000098:blood supply; D019194:Ischemic Preconditioning / Q000379:methods*; D008168:Lung / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*
D009195:Peroxidase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1