title: 7,8-dihydroxycoumarin has a dual mechanism of action in hepatic ischemia reperfusion injury.
abstract: The present study was designed to investigate the protective effect of 7,8-dihydroxycoumarin on hepatic ischemia/reperfusion (I/R) injury in the rats. The rats were divided in three groups of 10 each; normal control, untreated and the 7,8-dihydroxycoumarin treatment groups. The rats in the treatment group received 7,8-dihydroxycoumarin at doses of 15 mg/kg body weight 1 h prior to ischemia and then daily for 2 days. The animals were sacrificed after 1, 12, 24, 36, and 48 h of reperfusion. The results revealed that 7,8-dihydroxycoumarin protected the liver against I/R injury via inhibition of inflammatory response at the early stage (0-24 h). However, in 7,8-dihydroxycoumarin treatment group autophagy was inhibited resulting in intensified I/R injury following 36 h of reperfusion. 7,8-dihydroxycoumarin treatment caused reduction in the level of serum aminotransferase, liver inflammatory cytokines and showed minor liver histopathologic alterations. However, after 36 h of reperfusion treatment group showed similar I/R injury as that of untreated group. It was observed that 7,8-dihydroxycoumarin enhanced the activation of mitogen-activated protein kinase, decreased nuclear release of high-mobility group box 1 and production of inflammatory cytokines. After 36 h 7,8-dihydroxycoumarin promoted hepatic injury through suppression of autophagy and induction of hepatic apoptosis. Therefore, 7,8-dihydroxycoumarin exhibits inhibitory effect on hepatic ischemia during 0-24 h but causes its promotion after 36 h.
authors.affiliation: Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan, China.
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan, China.
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan, China.
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D014468:Umbelliferones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D020011:Protective Agents; D014468:Umbelliferones; D020928:Mitogen-Activated Protein Kinases; C039952:daphnetin
keywords: 7; 8-dihydroxycoumarin; apoptosis; cytokines; ischemic injury; reperfusion