Allicin Decreases Lipopolysaccharide-Induced Oxidative Stress and Inflammation in Human Umbilical Vein Endothelial Cells through Suppression of Mitochondrial Dysfunction and Activation of Nrf2
| Autor: | Li Jiang, Yinjie Xu, Xueting Wang, Zhaohui Qiu, Min Zhang, Huichao Pan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Physiology Neutrophils Apoptosis Pharmacology medicine.disease_cause lcsh:Physiology Lipid peroxidation chemistry.chemical_compound 0302 clinical medicine HUVEC Malondialdehyde lcsh:QD415-436 Disulfides Liver X Receptors chemistry.chemical_classification Membrane Potential Mitochondrial lcsh:QP1-981 Chemistry Cytochromes c Mitochondria Endothelial stem cell Biochemistry 030220 oncology & carcinogenesis RNA Interference NF-E2-Related Factor 2 Oxidative phosphorylation Nrf2 lcsh:Biochemistry 03 medical and health sciences medicine Cell Adhesion Human Umbilical Vein Endothelial Cells Humans Viability assay Inflammation Reactive oxygen species Allicin Tumor Necrosis Factor-alpha Interleukin-8 Sulfinic Acids Atherosclerosis Oxidative Stress 030104 developmental biology Lipid Peroxidation Reactive Oxygen Species Mitochondrial dysfunction Oxidative stress |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 41, Iss 6, Pp 2255-2267 (2017) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background: Allicin, a major component of garlic, is regarded as a cardioprotective agent and is associated with increased endothelial function. Methods: The effects of allicin on lipopolysaccharide (LPS)-induced vascular oxidative stress and inflammation in cultured human umbilical vein endothelial cells (HUVECs) and the mechanisms underlying these effects were studied. The protective effects were measured using cell viability, a lactate dehydrogenase (LDH) assay and cell apoptosis as indicators, and the anti-oxidative activity was determined by measuring reactive oxygen species (ROS) generation, oxidative products and endogenous antioxidant enzyme activities. HUVEC mitochondrial function was assessed by determining mitochondrial membrane potential (MMP) collapse, cytochrome c production and mitochondrial ATP release. To investigate the potential underlying mechanisms, we also measured the expression of dynamic mitochondrial proteins using western blotting. Furthermore, we evaluated the Nrf2 antioxidant signaling pathway using an enzyme-linked immunosorbent assay (ELISA). Results: Our results demonstrated that allicin enhanced HUVEC proliferation, which was suppressed by LPS exposure, and LDH release. Allicin ameliorated LPS-induced apoptosis, suppressed ROS overproduction, reduced lipid peroxidation and decreased the endogenous antioxidant enzyme activities in HUVECs. These protective effects were associated with the inhibition of mitochondrial dysfunction as indicated by decreases in the MMP collapse, cytochrome c synthesis and mitochondrial ATP release. In addition, allicin attenuated the LPS-induced inflammatory responses, including endothelial cell adhesion and TNF-α and IL-8 production. Furthermore, allicin increased the expression of LXRα in a dose-dependent manner. Allicin-induced attenuation of inflammation was inhibited by LXRα siRNA treatment. Finally, allicin activated NF-E2-related factor 2 (Nrf2), which controls the defense against oxidative stress and inflammation. Conclusions: Taken together, the present data suggest that allicin attenuated the LPS-induced vascular injury process, which may be closely related to the oxidative stress and inflammatory response in HUVECs. Allicin modulated Nrf2 activation and protected the cells against LPS-induced vascular injury. Our findings suggest that allicin attenuated the LPS-induced inflammatory response in blood vessels. |
| Databáze: | OpenAIRE |
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