title: Apocynin and raisanberine alleviate intermittent hypoxia induced abnormal StAR and 3β-HSD and low testosterone by suppressing endoplasmic reticulum stress and activated p66Shc in rat testes.
abstract: We hypothesized that hypoxia induced testicular damage is mediated by an activated NADPH oxidase (NOX), therefore, APO (apocynin) an inhibitor of NOX and raisanberine (RS), a calcium influx inhibitor were tested if they could attenuate hypoxic toxicity to the testis. Male Sprague-Dawley rats were exposed to hypoxia (10±0.5% O₂) for 17d and intervened with APO and RS in the last 6d. Histological changes and expression of pro-inflammation factors were evaluated in vivo. Biomarkers in isolated Leydig cells incubated with H₂O₂ were also assayed in vitro. Hypoxic rats displayed lower serum testosterone and higher LH and FSH. Upregulation of p22/p47(phox), NOX2, MMP9, PERK and p66Shc was associated with downregulation of StAR, 3β-HSD and Cx43 in the hypoxia testis, revealed by Western blot and immunohistochemical assay, respectively. APO and RS at least partially normalize hypoxia caused male hypogonadism by suppressing ER stress, and p66Shc in testes.
authors.affiliation: College of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Zhang
authors.forename: De-Zai
authors.initials: DZ
authors.lastname: Dai
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.forename: Yin
authors.initials: Y
authors.lastname: Dai
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000098:Acetophenones / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005058:Eunuchism / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D055765:Shc Signaling Adaptor Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: C400084:4-chlorobenzyltetrahydroberberine; D000098:Acetophenones; D015415:Biomarkers; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D000098682:Steroidogenic Acute Regulatory Protein; D001599:Berberine; D013739:Testosterone; C056165:acetovanillone; D015096:3-Hydroxysteroid Dehydrogenases; D019255:NADPH Oxidases