title: Primary preventive and secondary interventionary effects of acetyl-L-carnitine on diabetic neuropathy in the bio-breeding Worcester rat.
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.
authors.affiliation: Department of Pathology, University of Michigan Medical Center, Ann Arbor, 48109, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Sima
authors.forename: H
authors.initials: H
authors.lastname: Ristic
authors.forename: A
authors.initials: A
authors.lastname: Merry
authors.forename: M
authors.initials: M
authors.lastname: Kamijo
authors.forename: S A
authors.initials: SA
authors.lastname: Lattimer
authors.forename: M J
authors.initials: MJ
authors.lastname: Stevens
authors.forename: D A
authors.initials: DA
authors.lastname: Greene
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000108:Acetylcarnitine / Q000627:therapeutic use*; D000527:Alprostadil / Q000378:metabolism; D000818:Animals; D003929:Diabetic Neuropathies / Q000503:physiopathology / Q000517:prevention & control*; D015232:Dinoprostone / Q000378:metabolism; D005632:Fructose / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D011913:Rats, Inbred BB; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism; D013997:Time Factors
chemical_list: D005632:Fructose; D007294:Inositol; D013012:Sorbitol; D015121:6-Ketoprostaglandin F1 alpha; D000108:Acetylcarnitine; D000254:Sodium-Potassium-Exchanging ATPase; D000527:Alprostadil; D015232:Dinoprostone