Deep sea minerals ameliorate diabetic-induced inflammation via inhibition of TNFα signaling pathways

Chieh Hsiang Lu, Hsiu Chung Ou, Cecilia Hsuan Day, Hsiu I. Chen, Pei Ying Pai, Cheng Yu Lee, Ray Jade Chen, Ruey Lin Chang, Vijaya PadmaViswanadha, Dennis Jine Yuan Hsieh, Chih Yang Huang

Research output: Contribution to journalArticle

Abstract

It has been well-documented that the consumption of deep sea water (DSW) has beneficial effects on myocardial hypertrophy and cardiac apoptosis induced by hypercholesterolemia. However, the molecular mechanisms for the anti-inflammatory 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-inflammatory effects through the suppression of the TNF-α-mediated signaling pathways. IP injection of streptozotocin (STZ) at the dose of 65 mg/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 weeks. These dosages are DSW-1X (equivalent to 37 mg Mg2+/kg/day), 2X (equivalent to 74 mg Mg2+/kg/day) and 3X (equivalent to 111 mg Mg2+ mg/kg/day). Immunofluorescence staining and Western blot showed that the protein expression level of TNF-α was markedly higher in the STZ-induced diabetic rat hearts than in the control group. Consequently, the phosphorylation levels of the TNF-α-modulated downstream signaling molecules and P38 mitogen-activated protein kinases (MAPKs) were notably elevated in heart tissues of STZ-induced diabetes. These higher phosphorylation levels subsequently upregulated NF-κB-modulated inflammatory mediators, such as cyclooxygenase (COX)-II and inducible nitric oxide synthase (iNOS). However, treatment with DSW as well as MgSO4, the main mineral in DSW, significantly reversed all the alterations. These findings suggest that DSW has potential as a therapeutic agent for preventing diabetes-related cardiovascular diseases.

Original languageEnglish
JournalEnvironmental Toxicology
DOIs
Publication statusAccepted/In press - Jan 1 2019

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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    Lu, C. H., Ou, H. C., Day, C. H., Chen, H. I., Pai, P. Y., Lee, C. Y., Chen, R. J., Chang, R. L., PadmaViswanadha, V., Hsieh, D. J. Y., & Huang, C. Y. (Accepted/In press). Deep sea minerals ameliorate diabetic-induced inflammation via inhibition of TNFα signaling pathways. Environmental Toxicology. https://doi.org/10.1002/tox.22882