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

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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) haveshown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigateeffects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic micewith 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-diabeticmice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl ≤ FBG ≤ 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 FBGlevels (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 NFκB associated inflammatory response(phosphorylated inhibitory kappa B-α, interleukin-1β, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumorgrowth factor β-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. Onthe 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 weightin m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuatedFBG 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 nutrientsto modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirmbeneficial effects of tocopherols in diabetes with different FBG levels for clinical applications

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) haveshown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigateeffects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic micewith 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-diabeticmice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl ≤ FBG ≤ 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 FBGlevels (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 NFκB associated inflammatory response(phosphorylated inhibitory kappa B-α, interleukin-1β, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumorgrowth factor β-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. Onthe 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 weightin m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuatedFBG 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 nutrientsto modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirmbeneficial effects of tocopherols in diabetes with different FBG levels for clinical applications

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