Nutr Res Pract.  2019 Oct;13(5):377-383. 10.4162/nrp.2019.13.5.377.

Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice

• Lee H
• Lim Y

• KMID: 2464116
• DOI: http://doi.org/10.4162/nrp.2019.13.5.377

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.

Keyword

Gamma-tocopherol; hyperglycemia; liver; inflammasome; inflammation

MeSH Terms

Alloxan
Animals
Blood Glucose
Catalase
Corn Oil
Diet
Fasting
gamma-Tocopherol*
Glucose
Hyperglycemia
Inflammasomes*
Inflammation*
Injections, Intraperitoneal
Liver
Mice*
Mice, Inbred ICR
Oxidative Stress
Oxidoreductases
Peroxidase
Alloxan
Blood Glucose
Catalase
Corn Oil
Glucose
Inflammasomes
Oxidoreductases
Peroxidase
gamma-Tocopherol

Figure

• 

  Fig. 1 Effect of GT supplementation on hepatic protein levels of 4-hydroxynonenal (4-HNE) (A) and oxidative stress related markers (B): nuclear Nrf2, NQO1, catalase, GPx and MnSOD in alloxan-induced diabetic mice (n = 6). The hepatic protein was measured by western blot. A representative image is shown in the below panel, the bands were normalized to the band levels of α-tubulin (cytosol) or Lamin B1 (nucleus). Data are presented as means ± SEM. Values with the same superscript letter are not significantly different (P < 0.05). CON, non-diabetic mice; DMC, diabetic control mice; GT, diabetic mice supplemented with gamma-tocopherol 35 mg/kg BW.

• 

  Fig. 2 Effect of GT supplementation on hepatic protein levels of NLRP3 inflammasome related markers: NLRP3, ASC, pro-caspase-1, caspase-1, pro-IL-1β and IL-1β in alloxan-induced diabetic mice (n = 6). The hepatic protein was measured by western blot. A representative image is shown in the below panel, the bands were normalized to the band levels of α-tubulin (cytosol). Data are presented as means ± SEM. Values with the same superscript letter are not significantly different (P < 0.05). CON, non-diabetic mice; DMC, diabetic control mice; GT, diabetic mice supplemented with gamma-tocopherol 35 mg/kg BW.

• 

  Fig. 3 Effect of GT supplementation on protein levels of inflammatory response related markers: NFκB, SIRT1, TNF-α, MCP-1, IL-6, iNOS and COX-2 in alloxan-induced diabetic mice (n = 6). The hepatic protein was measured by western blot. A representative image is shown in the below panel, the bands were normalized to the band levels of α-tubulin (cytosol) or Lamin B1 (nucleus). Data are presented as means ± SEM. Values with the same superscript letter are not significantly different (P < 0.05). CON, non-diabetic mice; DMC, diabetic control mice; GT, diabetic mice supplemented with gamma-tocopherol 35 mg/kg BW.

• 

  Fig. 4 Effect of GT supplementation on hepatic protein levels of apoptosis related markers: caspase-3 (A), caspase-8 (B) and Bax-Bcl2 ratio (C) in alloxan-induced diabetic mice (n = 6). The hepatic protein was measured by western blot. A representative image is shown in the below panel, the bands were normalized to the band levels of α-tubulin (cytosol). Data are presented as means ± SEM. Values with the same superscript letter are not significantly different (P < 0.05). CON, non-diabetic mice; DMC, diabetic control mice; GT, diabetic mice supplemented with gamma-tocopherol 35 mg/kg BW.

• 

  Fig. 5 Effect of GT supplementation on hepatic protein levels of fibrosis: α-SMA, TGFβ1, PKC and collagen in alloxan-induced diabetic mice (n = 6). The hepatic protein was measured by western blot. A representative image is shown in the below panel, the bands were normalized to the band levels of α-tubulin (cytosol). Data are presented as means ± SEM. Values with the same superscript letter are not significantly different (P < 0.05). CON, non-diabetic mice; DMC, diabetic control mice; GT, diabetic mice supplemented with gamma-tocopherol 35 mg/kg BW.

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