J Korean Diabetes Assoc.  2007 Nov;31(6):488-497. 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

• Piao MH
• Jin HY
• Song SK
• Kang SM
• Kim SY
• Park JH
• Baek HS
• Park TS

• KMID: 2177562
• DOI: http://doi.org/10.4093/jkda.2007.31.6.488

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.

Keyword

Alpha-Lipoic Acid; Diabetic Neuropathy; Intraepidermal Nerve Fiber; Microvascularity

MeSH Terms

Animals
Capillaries
Diabetic Neuropathies
Diet
Humans
Injections, Intraperitoneal
Mice
Microvessels
Nerve Fibers*
Neural Conduction
Peripheral Nervous System Diseases
Polyneuropathies
Rats*
Risk Factors
Streptozocin
Thioctic Acid*
Streptozocin
Thioctic Acid

Figure

• 

  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.

• 

  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.

• 

  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.

• 

  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.

• 

  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).

• 

  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.

• 

  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).

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