Higenamine reduces apoptotic cell death by induction of heme oxygenase-1 in rat myocardial ischemia-reperfusion injury

Abstract

Pharmacological modulation of heme oxygenase (HO) gene expression may have significant therapeutic potential in oxidant-induced disorders, such as ischemia reperfusion (I/R) injury. Higenamine is known to reduce ischemic damages by unknown mechanism(s). The protective effect of higenamine on myocardial I/R-induced injury was investigated. Ligation of rat left anterior descending coronary artery for 30 min under anesthesia was done and followed by 24 h reperfusion before sacrifice. I/R-induced myocardial damages were associated with mitochondria-dependent apoptosis as evidenced by the increase of cytochrome c release and caspase-3 activity. Administration of higenamine (bolus, i.p) 1 h prior to I/R-injury significantly decreased the release of cytochrome c, caspase-3 activity, and Bax expression but up-regulated the expression of Bcl-2, HO-1, and HO enzyme activity in the left ventricles, which were inhibited by ZnPP IX, an enzyme inhibitor of HO-1. In addition, DNA-strand break-, immunohistochemical-analysis, and TUNEL staining also supported the anti-apoptotic effect of higenamine in I/R-injury. Most importantly, administration of ZnPP IX inhibited the beneficial effect of higenamine. Taken together, it is concluded that HO-1 plays a core role for the protective action of higenamine in I/R-induced myocardial injury.

Protective effect of higenamine ameliorates collagen-induced arthritis through heme oxygenase-1 and PI3K/Akt/Nrf-2 signaling pathways

“…The present study demonstrated that pretreatment with higenamine significantly recovered abnormal CIA-induced MDA and GSH activities in CIA mice. Lee et al (18) concluded that higenamine reduces apoptotic cell death through suppression of oxidation in rat myocardial ischemia-reperfusion injury.…”

“…Caspase is activated by the mitochondria's morphologic and functional change, which results in the release of cytochrome c. The present data clearly demonstrate that higenamine significantly weakens CIA-induced caspase-3/9 activities of CIA mice. In addition, Lee et al (18) concluded that higenamine reduces apoptotic cell death through suppression of oxidation and caspase-3 activity in rat myocardial ischemia-reperfusion injury.…”

Protective Effects of Glycyrrhizin against .BETA.2-Adrenergic Receptor Agonist-Induced Receptor Internalization and Cell Apoptosis

“…They play a major role in determining cell's survival or death after apoptotic stimuli. 49,50) It was reported that changes in the ratio of proapoptotic and antiapoptotic members of the Bcl-2 family, rather than the absolute expression level of any single Bcl-2 member protein, could determine apoptotic sensitivity. 51) In the present study, we found that treatment with glycyrrhizin increased ratio of Bcl-2/Bax (Fig.…”

(S)-1-(α-Naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CKD712) Reduces Rat Myocardial Apoptosis against Ischemia and Reperfusion Injury by Activation of Phosphatidylinositol 3-Kinase/Akt Signaling and Anti-inflammatory Action in Vivo

“…Next, we focused our attention on the anti-inflammatory or antioxidant action of CKD712 that may also reduce myocardial damage during I/R. Previously, CKD712 and its congeners reduced proinflammatory cytokines in LPS-treated macrophages (Kang et al, 1999;Tsoyi et al, 2008) and induced heme oxygenase (HO)-1 in many cells, including I/R hearts (Lee et al, 2006). We demonstrated that CKD712 showed powerful antioxidant activity in a cell-free system.…”