J Korean Diabetes Assoc.  2006 May;30(3):170-176. 10.4093/jkda.2006.30.3.170.

The Effects of Alpha-Lipoic Acid on Epidermal Nerve Preservation in the Diabetic Neuropathy of OLETF Rats

• Piao MH
• Park JH
• Baek HS
• Park TS

• KMID: 2177609
• DOI: http://doi.org/10.4093/jkda.2006.30.3.170

Abstract

BACKGROUND: Alpha-Lipoic acid (ALA) administration has been reported to ameliorate some of symptoms of peripheral polyneuropathy in diabetic patients and to improve endoneurial nutritive neural blood flow and nerve conduction velocity in diabetic rats. But it is not clear whether ALA has the preservation effect on epidermal nerve fibers (ENFs) density.
METHODS
We tested the efficacy of ALA in preserving current perception thresholds (CPTs) and ENFs (numbers/mm) in OLETF (Otsuka Long-Evans Tokushima Fatty) rats, an animal model of type 2 diabetes, which were fed with sucrose until diabetes mellitus developed. Thereafter, one group of OLETF rats was fed with ALA and the other was not for 40 weeks. Diabetic rats were administered with ALA (80 mg/kg of body weight/day) by oral feeding for 40 weeks. The effect of ALA treatment on ENFs preservation was assessed by protein gene product 9.5 immunostaining. Quantification of neuropathic symptoms on the dorsum of hind paws of rat was measured by CPT test every 4 weeks.
RESULTS
Numbers of ENF significantly decreased in OLETF rats fed without ALA compared with OLETF rats fed with ALA (P < 0.01). The thresholds at 2000, 250 and 5 Hz in OLETF rats fed with ALA did not increased and OLETF rats without ALA significantly increased at 80 weeks (P < 0.01).
CONCLUSION
These observations suggest that administrations of ALA may be useful for preserving ENFs and CPTs in OLETF rats dorsum of hind paws skin.

Keyword

Alpha-Lipoic Acid; Current perception threshold; Diabetic neuropathy; Epidermal nerve fiber density

MeSH Terms

Animals
Diabetes Mellitus
Diabetic Neuropathies*
Humans
Models, Animal
Nerve Fibers
Neural Conduction
Polyneuropathies
Rats
Rats, Inbred OLETF*
Skin
Sucrose
Thioctic Acid*
Sucrose
Thioctic Acid

Figure

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  Fig. 1 Glucose concentration and body weight changes in ALA administration and control group during experiment. ALA, alpha lipoic acid.

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  Fig. 2 Current perception thresholds change of 2000 Hz, 250 Hz, and 5 Hz of ALA administration and control group during experiment. *P < 0.01 compare to control and ALA group; ALA, alpha lipoic acid.

• 

  Fig. 3 Morphological change of dermal (A) and epidermal nerve fibers (B) of OLETF rats dorsum of hind paws skin by protein gene product 9.5 immunostaining. A: ALA administration (a) and control (b) group show the preservation of dermal nerve fiber number and thickness(× 100); Arrow indicates dermal nerve fibers. B: Epidermal nerve fibers change in ALA administration and control group. Arrow indicates epidermis (× 200).

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  Fig. 4 Difference of epidermal nerve fiber densities between ALA administration group and control group. *P < 0.01 compare to ALA administration and control group. ALA, alpha lipoic acid.

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