Primary preventive and secondary interventionary effects of acetyl-L-carnitine on diabetic neuropathy in the bio-breeding Worcester rat

J Clin Invest. 1996 Apr 15;97(8):1900-7. doi: 10.1172/JCI118621.

Abstract

The abnormalities underlying diabetic neuropathy appear to be multiple and involve metabolic neuronal and vasomediated defects. The accumulation of long-chain fatty acids and impaired beta-oxidation due to deficiencies in carnitine and/or its esterified derivatives, such as acetyl-L-carnitine, may have deleterious effects. In the present study, we examined, in the diabetic bio-breeding Worcester rat, the short- and long-term effects of acetyl-L-carnitine administration on peripheral nerve polyols, myoinositol, Na+/K+ -ATPase, vasoactive prostaglandins, nerve conduction velocity, and pathologic changes. Short-term prevention (4 mo) with acetyl-L-carnitine had no effects on nerve polyols, but corrected the Na+/K+ -ATPase defect and was associated with 63% prevention of the nerve conduction defect and complete prevention of structural changes. Long-term prevention (8 mo) and intervention (from 4 to 8 mo) with acetyl-L-carnitine treatment normalized nerve PGE(1) whereas 6-keto PGF(1-alpha) and PGE(2) were unaffected. In the prevention study, the conduction defect was 73% prevented and structural abnormalities attenuated. Intervention with acetyl-L-carnitine resulted in 76% recovery of the conduction defect and corrected neuropathologic changes characteristic of 4-mo diabetic rats. Acetyl-L-carnitine treatment promoted nerve fiber regeneration, which was increased two-fold compared to nontreated diabetic rats. These results demonstrate that acetyl-L-carnitine has a preventive effect on the acute Na+/- K+_ATPase defect and a preventive and corrective effect on PGE1 in chronically diabetic nerve associated with improvements of nerve conduction velocity and pathologic changes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / metabolism
  • Acetylcarnitine / therapeutic use*
  • Alprostadil / metabolism
  • Animals
  • Diabetic Neuropathies / physiopathology
  • Diabetic Neuropathies / prevention & control*
  • Dinoprostone / metabolism
  • Fructose / metabolism
  • Inositol / metabolism
  • Male
  • Neural Conduction / drug effects
  • Rats
  • Rats, Inbred BB
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / physiology
  • Sciatic Nerve / physiopathology
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Sorbitol / metabolism
  • Time Factors

Substances

  • Fructose
  • Inositol
  • Sorbitol
  • 6-Ketoprostaglandin F1 alpha
  • Acetylcarnitine
  • Sodium-Potassium-Exchanging ATPase
  • Alprostadil
  • Dinoprostone