Diabetic neuropathy in the rat: 1. Alcar augments the reduced levels and axoplasmic transport of substance P.
This study examined the sciatic nerve axonal transport of substance P-like immunoreactivity (SPLI) and its basal content in stomach, sciatic nerve and lumbar spinal cord of 8- and 12-week alloxan-diabetic rats, respectively. One group of diabetic rats received acetyl-l-carnitine (ALCAR) throughout the experimental period. Alloxan treatment caused hyperglycemia and reduced boy growth. Axonal transport of SPLI was studied by measurement of 24-hour accumulation at a ligature on the sciatic nerve. There was a marked reduction (from 50% to 100% according to the nerve segment examined) of anterograde and retrograde accumulation of SPLI in the constricted nerve of 8-week diabetic rats. In the sciatic nerve of ALCAR-treated diabetic rats, the accumulation of SPLI was comparable to control values. In the sciatic nerve, lumbar spinal cord and stomach of 12-week diabetic rats, there is a significant reduction of SPLI content. ALCAR treatment prevented SPLI loss in these tissues. Sciatic nerves showed the typical sorbitol increase and myo-inositol loss that were significantly counteracted by ALCAR. This study suggests that ALCAR treatment prevents diabetes-induced sensory neuropathy by improving altered metabolic pathways such as polyol activity and myo-inositol synthesis, and by preventing the reduction of synthesis and axonal transport of substance P.
Di Giulio
A M
AM
Department of Medical Pharmacology, University of Milano, Italy.
Lesma
E
E
Gorio
A
A
D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000378:metabolism*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002331:Carnitine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003929:Diabetic Neuropathies / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000276:immunology; D013373:Substance P / Q000378:metabolism*
D001786:Blood Glucose; D013373:Substance P; D000496:Alloxan; D002331:Carnitine