Deep sea minerals ameliorate diabetic-induced inflammation via inhibition of TNFα signaling pathways.
Chieh-Hsiang LuHsiu-Chung OuCecilia-Hsuan DayHsiu-I ChenPei-Ying PaiCheng-Yu LeeRay-Jade ChenRuey-Lin ChangVijaya PadmaViswanadhaDennis Jine-Yuan HsiehChih-Yang HuangPublished in: Environmental toxicology (2019)
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.
Keyphrases
- diabetic rats
- oxidative stress
- type diabetes
- cardiovascular disease
- nitric oxide synthase
- signaling pathway
- rheumatoid arthritis
- high glucose
- nitric oxide
- heart failure
- left ventricular
- glycemic control
- pi k akt
- drug induced
- induced apoptosis
- south africa
- epithelial mesenchymal transition
- metabolic syndrome
- inflammatory response
- cardiovascular events
- cell death
- cardiovascular risk factors
- weight loss
- protein kinase
- endoplasmic reticulum stress
- lps induced
- skeletal muscle
- insulin resistance
- climate change
- diabetic nephropathy