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Piao, Jin, Song, Kang, Kim, Park, Baek, and Park: The Effect of Alpha-Lipoic Acid on the Protection of Epidermal Nerve Fibers and Microcapillaries in the Streptozotocin-Induced Diabetic Rats
Original Articles
The Journal of Korean Diabetes Association

The Journal of Korean Diabetes Association 2007; 31(6): 488-497.

Published online: 30 November 2007

DOI: https://doi.org/10.4093/jkda.2007.31.6.488

The Effect of Alpha-Lipoic Acid on the Protection of Epidermal Nerve Fibers and Microcapillaries in the Streptozotocin-Induced Diabetic Rats

Ming Han Piao1, Heung Yong Jin, Sun Kyung Song2, Seun Mi Kang, So Young Kim, Ji Hyun Park, Hong Sun Baek, Tae Sun Park

Division of Endocrinology & Metabolism, Department of Internal Medicine, Chonbuk National University Hospital, Korea.

1Department of Medicine of the Graduate School and Research Institute of Clinical Medicine, Chonbuk National University, Korea.

2Jeon Ju Jesus Hospital, Korea.

Received 29 August 2007       Accepted 30 October 2007

Copyright © 2007 Korean Diabetes Association

Abstract

Background

Diabetic neuropathy is associated with risk factors for macrovascular diseases and other microvascular complications. Alpha-lipoic acid (ALA) administration has been reported to improve metabolic abnormalities and ameliorate peripheral polyneuropathy in diabetic patients. In addition, ALA improves endoneurial nutritive neural blood flow and nerve conduction velocity in diabetic rats. But it is not clear whether ALA has a preservation effect on microvasculature in addition to the effect on intraepidermal nerve fibers (IENFs). We investigated the effect of ALA on intraepidermal nerve fiber density (numbers/mm) and cutaneous capillary length in streptozotocin-induced diabetic rats.

Methods

The rats were randomly divided into 3 groups: diabetes without diet control, diabetes with diet control, and diabetes with ALA treatment. Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg) and the effect of ALA treatment was assessed by IENF immunostained with protein gene product 9.5 and by quantification of total cutaneous capillary length with mouse anti-rat reca-1 immunostaining.

Results

The value of IENF density significantly increased in ALA treatment group compared with other groups (P < 0.05). Quantification of microvascularity was also significantly increased in ALA treatment group compared with other groups (P < 0.05).

Conclusion

The results of this study suggest that ALA administration in diabetic rats may be beneficial in the prevention of peripheral neuropathy associated with improvement of microvascularity. And the symptomatic amelioration after ALA treatment may be attributed to this morphological improvement.

Keywords: Alpha-Lipoic Acid, Diabetic Neuropathy, Intraepidermal Nerve Fiber, Microvascularity

Figures and Tables

Fig. 1
A. Body weight changes of animals according to the management in the experimental period. B. Fasting blood glucose levels of animals according to the management in the experimental period. N = 5 in each group. ALA, alpha lipoic acid. *P < 0.05 vs DM without diet control.
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Fig. 2
A. Blood glucose level after oral glucose challenge according to the management in the experimental period. B. Blood glucose level after intraperitoneal insulin challenge according to the management in the experimental period. N = 5 in each group. ALA, alpha-lipoic Acid; ITT, insulin tolerance test. *P < 0.05 vs. DM without diet control. †P < 0.05 vs. DM with diet control.
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Fig. 3
The level of insulin secretion in the isolated beta cell in response to 20 mM glucose medium. All values are presented as mean ± SD. N = 5 in each group. ALA, alpha-lipoic Acid. *P < 0.05 vs. DM without diet control.
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Fig. 4
Intraepidermal nerve fiber density according to the experimental group. N= 5 in each group. ALA, alpha lipoic acid. *P < 0.05 vs. DM without diet control. †P < 0.05 vs. DM with diet control.
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Fig. 5
Morphological changes of dermal and epidermal nerve fibers according to the management. A. DM without diet control group. B. DM with diet control group. C. DM with ALA treatment group. ↔ Arrow indicates epidermis. → Arrow indicates intraepidermal nerve fiber (×100).
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Fig. 6
Total capillary length according to the experimental group. N = 5 in each group. ALA, alpha lipoic acid. *P < 0.05 vs. DM without diet control; †P < 0.05 vs. DM with diet control.
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Fig. 7
Morphological changes of dermal and epidermal blood vessels according to the management in the experimental animals shown by endothelial cell antibody RECA-1 immunostaining. A. DM without diet control group. B. DM with diet control group. C. DM with ALA treatment group. ALA, alpha lipoic acid. → Arrow indicates cutaneous capillary (×100).
jkda-31-488-g007
Table 1
Mean food intake in the experimental animals
jkda-31-488-i001

All values are presented as mean ± SD. N = 5 in each group. DM, STZ-induced diabetes mellitus; ALA, Alpha-Lipoic Acid; STZ, Streptozotocin.

Table 2
Insulin and C-peptide levels of experimental animals
jkda-31-488-i002

All values are presented as mean ± SD. N = 5 in each group. DM, STZ-induced diabetes mellitus; ALA, Alpha Lipoic Acid; STZ, streptozotocin. *P < 0.05 vs. DM without diet control. †P < 0.05 vs. DM with diet control.

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