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Therapeutic efficacy of methazolamide against intermittent hypoxia-induced excessive erythrocytosis in rats.\n                    <jats:italic toggle=\"yes\">High Alt Med Biol<\/jats:italic>\n                    19:69\u201380, 2018.\u2014This study aimed to determine whether methazolamide is effective for the treatment of chronic mountain sickness. Forty-eight male Wistar rats were randomly divided into eight groups: normoxia control, hypoxia control, hypoxia\u2009+\u2009acetazolamide (30\u2009mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7d\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), and five hypoxia + methazolamide groups (5, 10, 30, 90, and 120\u2009mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7d\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). Excessive erythrocytosis was induced through 4 weeks of hypobaric hypoxia (8 hours O\n                    <jats:sub>2<\/jats:sub>\n                    10%\/16 hours O\n                    <jats:sub>2<\/jats:sub>\n                    21%). Rats were then treated for 4 weeks, and their body weight was measured. Hematological, hemorheological, and biochemical parameters were analyzed. Renal hypoxia-inducible factor-1alpha (HIF-1\u03b1) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry. Proteomic analysis of plasma was conducted to determine the most differentially expressed proteins. Methazolamide with doses lower than 30\u2009mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7d\n                    <jats:sup>\u22121<\/jats:sup>\n                    had no significant effects on body weight compared with the hypoxia control group (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&gt;\u20090.05). Methazolamide dose-dependently reduced the hemoglobin concentration, hematocrit (Hct), and blood viscosity. Hct\/blood viscosity, an oxygen delivery index, dose-dependently increased after methazolamide treatment. A methazolamide dose of 10\u2009mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7d\n                    <jats:sup>\u22121<\/jats:sup>\n                    showed similar efficacy to an acetazolamide dose of 30\u2009mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7d\n                    <jats:sup>\u22121<\/jats:sup>\n                    for all the above parameters. Plasma levels of low-density lipoprotein cholesterol, total cholesterol, creatinine, and hemoglobin increased substantially after long-term hypoxia, but decreased after methazolamide treatment. HIF-1\u03b1 and VEGF both increased substantially after long-term hypoxia and decreased in the kidney after methazolamide treatment. The most differentially expressed protein was haptoglobin, an endogenous protective factor, which was depleted in rats with excessive erythrocytosis and increased substantially after methazolamide treatment. In summary, methazolamide exhibits dose-dependent efficacy for the treatment of excessive erythrocytosis induced by long-term hypoxia. It also has beneficial effects on oxygen transport and lipid metabolism, which are encouraging with regard to the development of methazolamide-based chronic mountain sickness therapies.\n                  <\/jats:p>","DOI":"10.1089\/ham.2017.0044","type":"journal-article","created":{"date-parts":[[2017,10,27]],"date-time":"2017-10-27T14:49:03Z","timestamp":1509115743000},"page":"69-80","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Therapeutic Efficacy of Methazolamide Against Intermittent Hypoxia-Induced Excessive Erythrocytosis in Rats"],"prefix":"10.1177","volume":"19","author":[{"given":"Zhiqing","family":"Zhang","sequence":"first","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghai","family":"Xiao","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingnan","family":"Deng","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjing","family":"Nie","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Li","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoli","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danfeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifeng","family":"Duan","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Health and Environmental Medicine","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,10,27]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.07.023"},{"key":"e_1_3_3_3_1","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1002\/elps.200900764","article-title":"Effect of sialic acid content on glycoprotein pI analyzed by two-dimensional electrophoresis","volume":"31","author":"Barrab\u00e9s S","year":"2010","unstructured":"Barrab\u00e9s S, , Sarrats A, , Fort E, , De Llorens R, , Rudd PM, , and Peracaula R. 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