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However, the molecular mechanisms for the anti\u2010inflammatory effects of DSW on diabetic cardiomyopathy are still largely unclear. The main purpose of this present study was to test the hypothesis that DSW exerts anti\u2010inflammatory effects through the suppression of the TNF\u2010\u03b1\u2010mediated signaling pathways. IP injection of streptozotocin (STZ) at the dose of 65\u2009mg\/kg was used to establish a diabetes rat model. DSW mineral extracts that diluted in desalinated water were prepared in three different dosages and administered to the rats through gavages for 4\u2009weeks. These dosages are DSW\u20101X (equivalent to 37\u2009mg\u2009Mg<jats:sup>2+<\/jats:sup>\/kg\/day), 2X (equivalent to 74\u2009mg\u2009Mg<jats:sup>2+<\/jats:sup>\/kg\/day) and 3X (equivalent to 111\u2009mg\u2009Mg<jats:sup>2+<\/jats:sup> mg\/kg\/day). Immunofluorescence staining and Western blot showed that the protein expression level of TNF\u2010\u03b1 was markedly higher in the STZ\u2010induced diabetic rat hearts than in the control group. Consequently, the phosphorylation levels of the TNF\u2010\u03b1\u2010modulated downstream signaling molecules and P38 mitogen\u2010activated protein kinases (MAPKs) were notably elevated in heart tissues of STZ\u2010induced diabetes. These higher phosphorylation levels subsequently upregulated NF\u2010\u03baB\u2010modulated inflammatory mediators, such as cyclooxygenase (COX)\u2010II and inducible nitric oxide synthase (iNOS). However, treatment with DSW as well as MgSO<jats:sub>4<\/jats:sub>, the main mineral in DSW, significantly reversed all the alterations. These findings suggest that DSW has potential as a therapeutic agent for preventing diabetes\u2010related cardiovascular diseases.<\/jats:p>","DOI":"10.1002\/tox.22882","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T14:47:05Z","timestamp":1575384425000},"page":"468-477","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Deep sea minerals ameliorate diabetic\u2010induced inflammation via inhibition of TNF\u03b1 signaling pathways"],"prefix":"10.1002","volume":"35","author":[{"given":"Chieh\u2010Hsiang","family":"Lu","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine Ditmanson Medical Foundation Chia\u2010Yi Christian Hospital  Chiayi Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiu\u2010Chung","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, 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