{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:06:19Z","timestamp":1792674379268,"version":"4.5.0"},"reference-count":29,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T00:00:00Z","timestamp":1399420800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Toxicol"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:p>\n                    Using rats fed 22 g\/d of a control diet containing 0.005% zinc (Zn) or 2 Zn-excess diets containing 0.05% or 0.2% Zn for 4 weeks, we examined the mechanisms involved in the deterioration of renal function induced by Zn-excess intake. An increase in Zn intake elevated mean blood pressure (BP) and reduced renal blood flow (RBF) and inulin clearance in a dose-dependent manner. This decline in inulin clearance may be derived from a fall in RBF. Administration of the nitric oxide (NO) synthase inhibitor, N\n                    <jats:sup>\u03c9<\/jats:sup>\n                    -nitro-l-arginine methyl ester, markedly increased mean BP and significantly decreased RBF in the 3 groups of rats. Administration of the exogenous superoxide radical (OO\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) scavenger, tempol, significantly decreased mean BP and substantially increased RBF in all groups of rats. These observations suggest that both an elevation in systemic BP and a reduction in RBF seen in the 2 Zn-excess diet groups result from a decrease in the action of the vasodilator, NO, through the formation of peroxynitrite based on the nonenzymatic reaction of NO and increased OO\n                    <jats:sup>\u2212<\/jats:sup>\n                    . Indeed, the activity of the endogenous OO\n                    <jats:sup>\u2212<\/jats:sup>\n                    scavenger, copper\/Zn-superoxide dismutase, was significantly reduced in the vessel wall of rats fed 2 Zn-excess diets versus a control diet. 8-Hydroxy-2\u2032-deoxyguanosine formation caused by OO\n                    <jats:sup>\u2212<\/jats:sup>\n                    generation was notably elevated in the kidneys of rats fed 2 Zn-excess diets relatively to rats fed a control diet. Thus, Zn-excess intake leads to the aggravation of renal function concomitantly with an increase in systemic BP predominantly through the oxidative stress caused by OO\n                    <jats:sup>\u2212<\/jats:sup>\n                    .\n                  <\/jats:p>","DOI":"10.1177\/1091581814532958","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T22:46:29Z","timestamp":1399502789000},"page":"288-296","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":36,"title":["Zinc-Excess Intake Causes the Deterioration of Renal Function Accompanied by an Elevation in Systemic Blood Pressure Primarily Through Superoxide Radical-Induced Oxidative Stress"],"prefix":"10.1177","volume":"33","author":[{"given":"Hiroyuki","family":"Yanagisawa","sequence":"first","affiliation":[{"name":"Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Community Health Science Center, Saitama Medical University, Moroyama, Iruma-gun, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Nodera","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Health, Saitama Medical University, Hidaka City, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Miyajima","sequence":"additional","affiliation":[{"name":"School of Medical Technology and Health, Saitama Medical University, Hidaka City, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takamasa","family":"Kido","sequence":"additional","affiliation":[{"name":"Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machi","family":"Suka","sequence":"additional","affiliation":[{"name":"Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,5,7]]},"reference":[{"key":"bibr1-1091581814532958","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1993.73.1.79"},{"issue":"1","key":"bibr2-1091581814532958","first-page":"3","volume":"18","author":"Yanagisawa H","year":"2007","journal-title":"Biomed Res Trace 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