Sinomenine pretreatment attenuates cold ischemia/reperfusion injury in rats: the role of heme oxygenase-1.
Ischemia/reperfusion (I/R) injury can be characterized as an inflammatory response including recruitment of inflammatory cells to a post-ischemic organ or tissue and a cascade of mediators. Sinomenine (SIN), a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum, has been used to treat various inflammatory diseases including rheumatism and arthritis. However, whether SIN can attenuate I/R injury has not previously been examined. Using a syngeneic orthotopic liver transplantation model in rats, we investigated the effect of SIN on hepatic I/R injury, in particular its effect on heme oxygenase-1 (HO-1) induction and its hepatocellular protective effect. To our knowledge, our results were the first to show that: (a) SIN pretreatment was able to induce HO-1 expression in donor livers in a dose dependent manner; (b) SIN pretreatment protected the liver graft from cold I/R injury; and (c) the protective effect of SIN was, at least in part, mediated by HO-1, as proved by the fact that inhibiting HO-1 activity with zinc protoporphyrin (ZnPP) reduced the protection. Thus, SIN deserves further exploration as a novel agent to attenuate I/R injury.
Song
Shaohua
S
Organ Transplantation Center, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People's Republic of China.
Shen
Xiaoyun
X
Tang
Yi
Y
Wang
Zhengxin
Z
Guo
Wenyuan
W
Ding
Guoshan
G
Wang
Quanxing
Q
Fu
Zhiren
Z
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D050377:Cold Ischemia; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology; D008297:Male; D009019:Morphinans / Q000008:administration & dosage*; D011524:Protoporphyrins / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009019:Morphinans; D011524:Protoporphyrins; C017803:zinc protoporphyrin; C009271:sinomenine; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat