THE EFFECTS OF KADSURENONE IN ISCHEMIA-REPERFUSION-INDUCED LIVER INJURY IN RATS_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

Shi Liubin , Chen Huairen , Wang Erhui , et al.

Department of Hepatobiliary Surgery, First Affiliated Hospital, Nanjing Railway Medical College,Nanjing 210009;

Corresponding author：

Keywords：

Platelet; activating factorLiverIschemia; reperfusion injuryKadsurenone

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To investigate the role of platelet-activating factor (PAF), neutrophils in ischemia-reperfusion-induced liver injury and their possible mechanism, PAF and the degree of neutrophil infiltration in liver tissue and the preventive effects of PAF antagonist kadsurenone were evaluated in this study by means of a partial liver ischemia model, in which it was induced by clamping only left and median lobes of the liver without causing intestinal congestion. The present study was undertaken to find out the mechanism of liver ischemia-reperfusion injury and preventive effect of kadsurenone. The results indicate that in early stage of reperfusion liver injury possibly caused by the generation of free radicals, declined of autioxidant defence and increased Ca２＋ influx, and in the later stage of reperfusion injury was mainly mediated by accumulation of PAF in the liver, which elicits the release of polymorphonuclear leukocytes induced toxical free radical, endothelial damage, microcirculatory collapse. The authors conclude that the effectiveness of antagonist kadsurenone in protecting against ischemiareperfusioninduced liver injury is due not only to their action in preventing the direct effects of PAF, but also to their ability to inhibit both PAF priming and PAF dependent feedback processes, thus preventing escalation of auto generated inflammatory damage.

Citation： Shi Liubin,Chen Huairen,Wang Erhui,et al.. THE EFFECTS OF KADSURENONE IN ISCHEMIA-REPERFUSION-INDUCED LIVER INJURY IN RATS. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 1998, 5(4): 195-198. doi: Copy

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7.	Kobayashi H, Nonami T, Kurokawa T, et al. Mechanism and prevention of ischemiareperfusion induced liver injury in rats. J Surg Res, 1991; 51(1)∶240.
8.	Born GVR. Aggregation of blood platelets by adenosine diphosphate and it’s reversal. Nature, 1962; 194(4832)∶927.
9.	Whittle BJR, BoughtonSmith NK, Hutcheson IR, et al. Increased intestinal formation of PAF in endotoxininduced damage in the rat. Br J Pharmac, 1987; 92(1)∶3.
10.	Ontell SJ. Pharmacologic modulation of experimental postischemic hepatic function. Ann Surg, 1989; 209(2)∶200.
11.	Jaeschk H. Neutophils and kupffer cell induced oxidant stress and IR injury in the rat liver. Am J Physiol, 1991; 260(3)∶G335.
12.	陈清，冬利家，苏静怡等.血小板激活因子在小肠缺血再灌注损伤中的意义及山莨菪碱的保护作用.基础医学与临床， 1993； 13(4)∶56.
13.	Ludwig JC, McManus LM, Clark PO, et al. Modulation of plateletactivating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMNs)∶ role of extracellular Ca2+. Arch Biochem Biophys, 1984; 232(1)∶102.
14.	Kochanek PM, Dntka AJ, Kumaroo KK, et al. Plateletactivating factor receptor blockers enhances recovery after mutifocal brain ischemia. Life Science, 1987; 41(24)∶2639.

1. McCord JM. Oxygenderived free redicals in post ischemic tissue injury. New Engl J Med, 1985; 312(3)∶159.
2. Kane AB, Young EE, Schanne FAX, et al. Calcium dependence of phalloidininduced liver cell death. Proc Natl Acad Sci USA, 1980; 77(2)∶1177.
3. Braquet P, Koltai M, Bourgain R, et al. Is there a care for PAF antagonists in the treatment of ischemic states? TIPs, 1989; 10(1)∶23.
4. Gardner CR, Laskin JD, Laskin DL. Plateletactivatingfactor induced calcium mobilization and oxiditive metabolism in hepatic macrophagesand endothelial cells. J Leukoc Biol, 1993; 53(1)∶190.
5. Jaeschke H, Farhood A, Smith CW. Neutrophils contribute to ischemia/reperfusion injury in rat liver invivo. FASEB J, 1990; 4(A120)∶3353.
6. Shen TY, Hwang SB, Chang MN, et al. Characterization of a plateletactivating factor receptor antagonist isolated from haifenteng (piper futokedsura): specific inhibition of in vitro and in vivo plateletactivating factor induced effects. Pro Natl Acad Sci USA, 1985; 82(3)∶672.
7. Kobayashi H, Nonami T, Kurokawa T, et al. Mechanism and prevention of ischemiareperfusion induced liver injury in rats. J Surg Res, 1991; 51(1)∶240.
8. Born GVR. Aggregation of blood platelets by adenosine diphosphate and it’s reversal. Nature, 1962; 194(4832)∶927.
9. Whittle BJR, BoughtonSmith NK, Hutcheson IR, et al. Increased intestinal formation of PAF in endotoxininduced damage in the rat. Br J Pharmac, 1987; 92(1)∶3.
10. Ontell SJ. Pharmacologic modulation of experimental postischemic hepatic function. Ann Surg, 1989; 209(2)∶200.
11. Jaeschk H. Neutophils and kupffer cell induced oxidant stress and IR injury in the rat liver. Am J Physiol, 1991; 260(3)∶G335.
12. 陈清，冬利家，苏静怡等.血小板激活因子在小肠缺血再灌注损伤中的意义及山莨菪碱的保护作用.基础医学与临床， 1993； 13(4)∶56.
13. Ludwig JC, McManus LM, Clark PO, et al. Modulation of plateletactivating factor (PAF) synthesis and release from human polymorphonuclear leukocytes (PMNs)∶ role of extracellular Ca2+. Arch Biochem Biophys, 1984; 232(1)∶102.
14. Kochanek PM, Dntka AJ, Kumaroo KK, et al. Plateletactivating factor receptor blockers enhances recovery after mutifocal brain ischemia. Life Science, 1987; 41(24)∶2639.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

THE EFFECTS OF KADSURENONE IN ISCHEMIA-REPERFUSION-INDUCED LIVER INJURY IN RATS

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