title: Rutin attenuates H2O2-induced oxidation damage and apoptosis in Leydig cells by activating PI3K/Akt signal pathways.
abstract: Oxidative stress is a primary factor in the pathology of male infertility. The strong antioxidative capacity of rutin has been proven by numerous studies, but a protective role in the context of male reproduction remains to be elucidated. To explore the biological role of rutin in protecting male reproductive function and the potential underlying mechanism, H2O2-induced Leydig cells were used as a cell model of oxidation damage. Our findings showed that rutin at concentrations of 10, 20, and 40μmol/L remarkably increased cell survival rate of H2O2-induced Leydig cells to 70.1%, 86.8%, and 80.3% respectively. Next, rutin with concentrations of 10, 20, and 40μmol/L decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels but increased the levels of glutathione (GSH) and testosterone in H2O2-induced Leydig cells. The activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were remarkably increased by rutin treatment with concentrations of 20 and 40μmol/L, but glutathione peroxidase (GSH-Px) activity was notably decreased. Moreover, rutin with concentrations of 10, 20, and 40μmol/L increased Bcl-2 protein levels but decreased protein levels of Bax and caspase-3. Furthermore, 20μmol/L rutin significantly abrogated the decrease in levels of phosphoinositide 3-kinase (PI3K) and phosphorylated serine/threonine kinase (p-AKT) induced by H2O2. Pretreatment with LY294002, a PI3K inhibitor, antagonized protective action of 20μmol/L rutin against H2O2-induced cell activities, intracellular oxidant, testosterone, antioxidant enzyme activities, and the apoptosis related protein expression. Taken together, these results suggest that rutin attenuates H2O2-induced oxidation damage and apoptosis in Leydig cells by activating PI3K/Akt signal pathways, providing a promising strategy to decrease oxidative stress associated with male infertility.
authors.affiliation: Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China; Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an 710003, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Gynecology and Obstetrics, Xi'an No. 4 Hospital, Affiliated Guangren Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shaanxi Ophthalmic Medical Center, Xi'an No. 4 Hospital, Affiliated Guangren Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an 710003, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Shi
authors.affiliation: Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an 710003, China.
authors.forename: Juanzi
authors.initials: J
authors.lastname: Shi
authors.affiliation: Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an 710003, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: junpingxing@163.com.
authors.forename: Junping
authors.initials: J
authors.lastname: Xing
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012431:Rutin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051033:Apoptosis Inducing Factor; D013739:Testosterone; D008315:Malondialdehyde; D012431:Rutin; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione
keywords: Cell apoptosis; Leydig cells; Male infertility; Oxidation damage; PI3K/Akt signal pathways; Rutin