title: Simvastatin induces the expression of hemeoxygenase-1 against ischemia-reperfusion injury on the testes in rats.
abstract: We evaluate the protective role of simvastatin-induced HO-1 in remote preconditioning against testis ischemia-reperfusion (IR) injury in vivo. Simvastatin was intraperitoneally (i.p.) injected 24 h before IR injury. Testis was occluded in the right testis for 40 min and followed by 30 min of reperfusion to induce IR injury. Tin protoporphyrin (Snpp), a competitive inhibitor of hemeoxygenase, was i.p. injected 1 h before the IR injury in separate groups of rats. The rat testes were harvested 24 h later. Induction of HO-1 expression by simvastatin was significantly increased at 24 and 48 h. Rats pre-treated with simvastatin showed higher expression of HO-1 protein by Western blotting and immunohistochemistry (IHC), and presented lower caspases-3 activity by caspase-3 activity assay. TUNEL staining analysis revealed simvastatin pretreatment significantly reduced IR induced cellular apoptosis. Contrarily, the simvastatin-induced cytoprotective effect was entirely abolished by administrations of Snpp. Further, lower caspase-3 activities were also noted in simvastatin plus Snpp (SS) group than the control plus Snpp (CS) group. After IR injury, eNOS immunoreactivity was markedly increased in the germ cell and Leydig cell of testicular tissues. Pretreatment of simvastatin significantly decreased eNOS immunoreactivity in the germ cell of the tubules in the rat testes. In conclusion, we suggest HO-1 plays a protective role in IR-induced injury in the testes of rats.
authors.affiliation: Department of Urology, Tao-Yuan General Hospital, Department of Health, Taoyuan 330, Taiwan.
authors.forename: Yuan-Po
authors.initials: YP
authors.lastname: Tu
authors.forename: Shu-Ju
authors.initials: SJ
authors.lastname: Chuang
authors.forename: Shyh-Chyan
authors.initials: SC
authors.lastname: Chen
authors.forename: Yi-Hsia
authors.initials: YH
authors.lastname: Liu
authors.forename: Chau-Fong
authors.initials: CF
authors.lastname: Chen
authors.forename: Tzyh-Chyuan
authors.initials: TC
authors.lastname: Hour
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D013737:Testis / Q000098:blood supply / Q000187:drug effects*
chemical_list: D008665:Metalloporphyrins; D011524:Protoporphyrins; D019821:Simvastatin; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; D053148:Caspase 3