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Mitochondrial nutrients improve immune dysfunction in the type 2 diabetic Goto-Kakizaki rats.

Hao J, Shen W, Tian C, Liu Z, Ren J, Luo C, Long J, Sharman E, Liu J - J. Cell. Mol. Med. (2008)

Bottom Line: We first studied the effects of the combination of these four nutrients on immune function by examining cell proliferation in immune organs (spleen and thymus) and immunomodulating factors in the plasma.These effects are comparable to, or greater than, those of the anti-diabetic drug pioglitazone.These data suggest that a rational combination of mitochondrial-targeting nutrients may be effective in improving immune function in type 2 diabetes through enhancement of mitochondrial function, decreased oxidative damage, and delayed cell death in the immune organs and blood.

View Article: PubMed Central - PubMed

Affiliation: Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China.

ABSTRACT
The development of type 2 diabetes is accompanied by decreased immune function and the mechanisms are unclear. We hypothesize that oxidative damage and mitochondrial dysfunction may play an important role in the immune dysfunction in diabetes. In the present study, we investigated this hypothesis in diabetic Goto-Kakizaki rats by treatment with a combination of four mitochondrial-targeting nutrients, namely, R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide and biotin. We first studied the effects of the combination of these four nutrients on immune function by examining cell proliferation in immune organs (spleen and thymus) and immunomodulating factors in the plasma. We then examined, in the plasma and thymus, oxidative damage biomarkers, including lipid peroxidation, protein oxidation, reactive oxygen species, calcium and antioxidant defence systems, mitochondrial potential and apoptosis-inducing factors (caspase 3, p53 and p21). We found that immune dysfunction in these animals is associated with increased oxidative damage and mitochondrial dysfunction and that the nutrient treatment effectively elevated immune function, decreased oxidative damage, enhanced mitochondrial function and inhibited the elevation of apoptosis factors. These effects are comparable to, or greater than, those of the anti-diabetic drug pioglitazone. These data suggest that a rational combination of mitochondrial-targeting nutrients may be effective in improving immune function in type 2 diabetes through enhancement of mitochondrial function, decreased oxidative damage, and delayed cell death in the immune organs and blood.

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Related in: MedlinePlus

Effect of treatments on the total antioxidant capacities (T-AOC), glutathione (GSH), glutathione S-transferase (GST), and superoxide dismutase (SOD) in plasma and thymus. (A) T-AOC in plasma, n= 6; (B) T-AOC in thymus, n= 6; (C) GSH in plasma, n= 10; (D) Glutathione (GSH) in thymus, n= 8; (E) glutathione S-transferase (GST) in plasma, n= 10; (F) GST in thymus, n= 10; (G) Superoxide dismutase (SOD) in plasma, n= 10 and (H) SOD in thymus, n= 10. Data are means ± SEM. *P < 0.05 and **P < 0.01 versus Wistar group; #P < 0.05, ##P < 0.01 versus GK untreated group.
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fig05: Effect of treatments on the total antioxidant capacities (T-AOC), glutathione (GSH), glutathione S-transferase (GST), and superoxide dismutase (SOD) in plasma and thymus. (A) T-AOC in plasma, n= 6; (B) T-AOC in thymus, n= 6; (C) GSH in plasma, n= 10; (D) Glutathione (GSH) in thymus, n= 8; (E) glutathione S-transferase (GST) in plasma, n= 10; (F) GST in thymus, n= 10; (G) Superoxide dismutase (SOD) in plasma, n= 10 and (H) SOD in thymus, n= 10. Data are means ± SEM. *P < 0.05 and **P < 0.01 versus Wistar group; #P < 0.05, ##P < 0.01 versus GK untreated group.

Mentions: T-AOC levels in plasma (Fig. 5A) and thymocytes (Fig. 5B) were significantly decreased in the GK rats, compared with the Wistar rats. The low-dose nutrient treatment significantly inhibited the decrease in T-AOC in both plasma and thymocytes while the high-dose nutrient and pioglitazone treatments did not show significant inhibition.


Mitochondrial nutrients improve immune dysfunction in the type 2 diabetic Goto-Kakizaki rats.

Hao J, Shen W, Tian C, Liu Z, Ren J, Luo C, Long J, Sharman E, Liu J - J. Cell. Mol. Med. (2008)

Effect of treatments on the total antioxidant capacities (T-AOC), glutathione (GSH), glutathione S-transferase (GST), and superoxide dismutase (SOD) in plasma and thymus. (A) T-AOC in plasma, n= 6; (B) T-AOC in thymus, n= 6; (C) GSH in plasma, n= 10; (D) Glutathione (GSH) in thymus, n= 8; (E) glutathione S-transferase (GST) in plasma, n= 10; (F) GST in thymus, n= 10; (G) Superoxide dismutase (SOD) in plasma, n= 10 and (H) SOD in thymus, n= 10. Data are means ± SEM. *P < 0.05 and **P < 0.01 versus Wistar group; #P < 0.05, ##P < 0.01 versus GK untreated group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822877&req=5

fig05: Effect of treatments on the total antioxidant capacities (T-AOC), glutathione (GSH), glutathione S-transferase (GST), and superoxide dismutase (SOD) in plasma and thymus. (A) T-AOC in plasma, n= 6; (B) T-AOC in thymus, n= 6; (C) GSH in plasma, n= 10; (D) Glutathione (GSH) in thymus, n= 8; (E) glutathione S-transferase (GST) in plasma, n= 10; (F) GST in thymus, n= 10; (G) Superoxide dismutase (SOD) in plasma, n= 10 and (H) SOD in thymus, n= 10. Data are means ± SEM. *P < 0.05 and **P < 0.01 versus Wistar group; #P < 0.05, ##P < 0.01 versus GK untreated group.
Mentions: T-AOC levels in plasma (Fig. 5A) and thymocytes (Fig. 5B) were significantly decreased in the GK rats, compared with the Wistar rats. The low-dose nutrient treatment significantly inhibited the decrease in T-AOC in both plasma and thymocytes while the high-dose nutrient and pioglitazone treatments did not show significant inhibition.

Bottom Line: We first studied the effects of the combination of these four nutrients on immune function by examining cell proliferation in immune organs (spleen and thymus) and immunomodulating factors in the plasma.These effects are comparable to, or greater than, those of the anti-diabetic drug pioglitazone.These data suggest that a rational combination of mitochondrial-targeting nutrients may be effective in improving immune function in type 2 diabetes through enhancement of mitochondrial function, decreased oxidative damage, and delayed cell death in the immune organs and blood.

View Article: PubMed Central - PubMed

Affiliation: Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, China.

ABSTRACT
The development of type 2 diabetes is accompanied by decreased immune function and the mechanisms are unclear. We hypothesize that oxidative damage and mitochondrial dysfunction may play an important role in the immune dysfunction in diabetes. In the present study, we investigated this hypothesis in diabetic Goto-Kakizaki rats by treatment with a combination of four mitochondrial-targeting nutrients, namely, R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide and biotin. We first studied the effects of the combination of these four nutrients on immune function by examining cell proliferation in immune organs (spleen and thymus) and immunomodulating factors in the plasma. We then examined, in the plasma and thymus, oxidative damage biomarkers, including lipid peroxidation, protein oxidation, reactive oxygen species, calcium and antioxidant defence systems, mitochondrial potential and apoptosis-inducing factors (caspase 3, p53 and p21). We found that immune dysfunction in these animals is associated with increased oxidative damage and mitochondrial dysfunction and that the nutrient treatment effectively elevated immune function, decreased oxidative damage, enhanced mitochondrial function and inhibited the elevation of apoptosis factors. These effects are comparable to, or greater than, those of the anti-diabetic drug pioglitazone. These data suggest that a rational combination of mitochondrial-targeting nutrients may be effective in improving immune function in type 2 diabetes through enhancement of mitochondrial function, decreased oxidative damage, and delayed cell death in the immune organs and blood.

Show MeSH
Related in: MedlinePlus