Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ≥ 250 mg/dL), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear factor-κB pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.
Abstract
BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ≥ 250 mg/dL), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear factor-κB pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.
참고문헌 (37)
- Pagano E, "The relative burden of diabetes complications on healthcare costs: the populationbased CINECA-SID ARNO Diabetes Observatory", Nutr Metab Cardiovasc Dis, 26, pp.944~950 (2016)
- Regnell SE, "Hepatic steatosis in type 1 diabetes", Rev Diabet Stud, 8, pp.454~467 (2011)
- Käräjämäki AJ, "Non-alcoholic fatty liver disease with and without metabolic syndrome: different long-term outcomes", Metabolism, 66, pp.55~63 (2017)
- Maritim AC, "Diabetes, oxidative stress, and antioxidants: a review", J Biochem Mol Toxicol, 17, pp.24~38 (2003)
- Loboda A, "Role of Nrf2", HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism, 2016, pp.73, 3221~3247
- Mohamed J, "Mechanisms of diabetes-induced liver damage: the role of oxidative stress and inflammation", Sultan Qaboos Univ Med J, 16, pp.e132~e141 (2016)
- Hu C, "NLRP3 deficiency protects from type 1 diabetes through the regulation of chemotaxis into the pancreatic islets", Proc Natl Acad Sci U S A, 112, pp.11318~11323 (2015)
- Abderrazak A, "NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases", Redox Biol, 4, pp.296~307 (2015)
- Kang HH, "Chronic intermittent hypoxia induces liver fibrosis in mice with diet-induced obesity via TLR4", MyD88, NF-kB signaling pathways, pp.Biochem Biophys Res Commun, 2017[DOI]
- Kauppinen A, "Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders", Cell Signal, 25, pp.1939~1948 (2013)
- Cao Y, "SIRT1 and insulin resistance", J Diabetes Complications, 30, pp.178~183 (2016)
- Alegre F, "Inflammasomes in liver fibrosis", Semin Liver Dis, 37, pp.119~127 (2017)
- Koyama Y, "Liver inflammation and fibrosis", J Clin Invest, 127, pp.55~64 (2017)
- Li J, "The role of vitamins in the pathogenesis of non-alcoholic fatty liver disease", Integr Med Insights, 11, pp.19~25 (2016)
- Lee H, "Tocotrienol-rich fraction supplementation reduces hyperglycemia-induced skeletal muscle damage through regulation of insulin signaling and oxidative stress in type 2 diabetic mice", J Nutr Biochem, 57, pp.77~85 (2018)
- Smolarek AK, "Chemopreventive activity of vitamin E in breast cancer: a focus on γ- and δ-tocopherol", Nutrients, 3, pp.962~986 (2011)
- Jiang Q, "Gamma-tocopherol, but not alpha-tocopherol, decreases proinflammatory eicosanoids and inflammation damage in rats", FASEB J, 17, pp.816~822 (2003)
- Yunsook Lim, "Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation", Nutrition Research and Practice, 10(1), pp.33~41 (2016), 한국영양학회
- Shin J, "Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice", Exp Biol Med (Maywood), 242, pp.505~515 (2017)
- Peh HY, "Vitamin E therapy beyond cancer: Tocopherol versus tocotrienol", Pharmacol Ther, 162, pp.152~169 (2016)
- Himmelfarb J, "Alpha and gamma tocopherol metabolism in healthy subjects and patients with end-stage renal disease", Kidney Int, 64, pp.978~991 (2003)
- Uusitalo L, "Serum alpha- and gamma-tocopherol concentrations and risk of advanced beta cell autoimmunity in children with HLA-conferred susceptibility to type 1 diabetes mellitus", Diabetologia, 51, pp.773~780 (2008)
- Jiang Q, "gammatocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells", Proc Natl Acad Sci U S A, 97, pp.11494~11499 (2000)
- Roldi LP, "Vitamin E (alpha-tocopherol) supplementation in diabetic rats: effects on the proximal colon", BMC Gastroenterol, 9, pp.88~ (2009)
- 김기현, "Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study", Clinical and Molecular Hepatology, 21(4), pp.379~386 (2015), 대한간학회
- Agca CA, "Taurine ameliorates neuropathy via regulating NF-κB and Nrf2", HO-1 signaling cascades in diabetic rats, 2014, pp.71, 116~121
- Gupte AA, "Nuclear factor (erythroid-derived 2)-like-2 factor (Nrf2), a key regulator of the antioxidant response to protect against atherosclerosis and nonalcoholic steatohepatitis", Curr Diab Rep, 13, pp.362~371 (2013)
- Harijith A, "Reactive oxygen species at the crossroads of inflammasome and inflammation", Front Physiol, 5, pp.352~ (2014)
- Esposito K, "Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress", Circulation, 106, pp.2067~2072 (2002)
- Li X, "Diabetes mellitus is a significant risk factor for the development of liver cirrhosis in chronic hepatitis C patients", Sci Rep, 7, pp.9087~ (2017)
- Rath PC, "TNF-induced signaling in apoptosis", J Clin Immunol, 19, pp.350~364 (1999)
- Ingaramo PI, "Tumor necrosis factor alpha pathways develops liver apoptosis in type 1 diabetes mellitus", Mol Immunol, 48, pp.1397~1407 (2011)
- Carnovale CE, "Role of nitric oxide in liver regeneration", Ann Hepatol, 11, pp.636~647 (2012)
- Zheng QY, "LIGHT", IFN-γ triggers β cells apoptosis via NF-κB, J Cell Mol Med, pp.2016, 20[DOI]
- Boumela I, "Involvement of BCL2 family members in the regulation of human oocyte and early embryo survival and death: gene expression and beyond", Reproduction, 141, pp.549~561 (2011)
- Ju J, "Cancer-preventive activities of tocopherols and tocotrienols", Carcinogenesis, 31, pp.533~542 (2010)
- Wree A, "NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice", Hepatology, 59, pp.898~910 (2014)