Nutr Res Pract.  2016 Feb;10(1):33-41. 10.4162/nrp.2016.10.1.33.

Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation

• Shin H
• Eo H
• Lim Y

• KMID: 2313898
• DOI: http://doi.org/10.4162/nrp.2016.10.1.33

Abstract

BACKGROUND/OBJECTIVES
Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG).
MATERIALS/METHODS
Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl < or = FBG < or = 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation.
RESULTS
Both AT and GT supplementations showed similar beneficial effects on NFkappaB associated inflammatory response (phosphorylated inhibitory kappa B-alpha, interleukin-1beta, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor beta-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM.
CONCLUSIONS
The results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.

Keyword

Diabetic kidney; tocopherol; oxidative stress; inflammation; pre-fibrosis

MeSH Terms

Alloxan
alpha-Tocopherol*
Animals
Blood Glucose
C-Reactive Protein
Catalase
Chronic Disease
Diabetes Mellitus
Diet
Fasting
Fibrosis
gamma-Tocopherol*
Glutathione Peroxidase
Hand
Heme Oxygenase-1
Hyperglycemia*
Inflammation*
Interleukin-1beta
Kidney*
Malondialdehyde
Mice
Mice, Inbred ICR
Monocytes
Oxidative Stress*
Protein Kinases
Tocopherols
Alloxan
Blood Glucose
C-Reactive Protein
Catalase
Glutathione Peroxidase
Heme Oxygenase-1
Interleukin-1beta
Malondialdehyde
Protein Kinases
Tocopherols
alpha-Tocopherol
gamma-Tocopherol

Figure

• 

  Fig. 1 Effects of AT and GT supplementations on body weight change and kidney weight in diabetic mice.Body weight change in mild DMC group (A), body weight change in severe DMC group (B), kidney weight per 100g body weight in mild DMC group (C), and kidney weight per 100g weight in severe DMC group (D). Values are means ± SEM (N = 6). Mean values with unlike letters were significantly different (P < 0.05). CON: non-diabetic mice, m-DMC: diabetic control mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-AT: alpha-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-GT: gamma-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), s-DMC: diabetic control mice (450 mg/dl < FBG), s-AT: alpha-tocopherol supplemented diabetic mice (450 mg/dl < FBG), s-GT: gamma-tocopherol supplemented diabetic mice (450 mg/dl < FBG)

• 

  Fig. 2 Effects of AT and GT supplementations on fasting blood glucose levels in diabetic mice.Fasting blood glucose levels in mild DMC group (A), and fasting blood glucose levels in severe DMC group (B) Values are means ± SEM (N = 6). Mean values with unlike letters were significantly different (P < 0.05). CON: non-diabetic mice, m-DMC: diabetic control mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-AT: alpha-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-GT: gamma-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), s-DMC: diabetic control mice (450 mg/dl < FBG), s-AT: alpha-tocopherol supplemented diabetic mice (450 mg/dl < FBG), s-GT: gamma-tocopherol supplemented diabetic mice (450 mg/dl < FBG)

• 

  Fig. 3 Effects of AT and GT supplementations on BUN (A), and plasma creatinine (B) levels in diabetic mice. Values are means ± SEM (N = 6).Mean values with unlike letters were significantly different (P < 0.05). CON: non-diabetic mice, m-DMC: diabetic control mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-AT: alpha-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-GT: gamma-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), s-DMC: diabetic control mice (450 mg/dl < FBG), s-AT: alpha-tocopherol supplemented diabetic mice (450 mg/dl < FBG), s-GT: gamma-tocopherol supplemented diabetic mice (450 mg/dl < FBG)

• 

  Fig. 4 Effects of AT and GT supplementations on kidney MDA concentrations (A) protein levels of HO-1, GPx, and catalase (B) in diabetic mice.Values are means ± SEM (N = 6). Mean values with unlike letters were significantly different (P < 0.05). CON: non-diabetic mice, m-DMC: diabetic control mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-AT: alpha-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-GT: gamma-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), s-DMC: diabetic control mice (450 mg/dl < FBG), s-AT: alpha-tocopherol supplemented diabetic mice (450 mg/dl < FBG), s-GT: gamma-tocopherol supplemented diabetic mice (450 mg/dl < FBG)

• 

  Fig. 5 Effects of AT and GT supplementations on kidney protein levels of pIkBα, IL-1β, CRP, MCP-1, and TNF-α in diabetic mice. Values are means ± SEM (N = 6).Means values with unlike letters were significantly different (P < 0.05). CON: non-diabetic mice, m-DMC: diabetic control mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-AT: alpha-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-GT: gamma-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), s-DMC: diabetic control mice (450 mg/dl < FBG), s-AT: alpha-tocopherol supplemented diabetic mice (450 mg/dl < FBG), s-GT: gamma-tocopherol supplemented diabetic mice (450 mg/dl < FBG)

• 

  Fig. 6 Effects of AT and GT supplementations on kidney protein levels of PKC-β II, and TGF-βI in diabetic mice. Values are means ± SEM (N = 6).Mean values with unlike letters were significantly different (P < 0.05). CON: non-diabetic mice, m-DMC: diabetic control mice (250 mg/dl ≤ FBG ≤ 45 0mg/dl), m-AT: alpha-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), m-GT: gamma-tocopherol supplemented diabetic mice (250 mg/dl ≤ FBG ≤ 450 mg/dl), s-DMC: diabetic control mice (450 mg/dl < FBG), s-AT: alpha-tocopherol supplemented diabetic mice (450 mg/dl < FBG), s-GT: gamma-tocopherol supplemented diabetic mice (450 mg/dl < FBG)

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