The effects of acetyl-L-carnitine and sorbinil on peripheral nerve structure, chemistry, and function in experimental diabetes.
Nerve conduction velocity (NCV) increased with age in nondiabetic male Wistar rats for the first 26 weeks of life. The NCV of animals made hyperglycemic at age 6 weeks by administration of streptozotocin (STZ) also increases, but at a slower rate. Animals with 4 weeks of hyperglycemia and reduced NCV treated with an aldose reductase inhibitor (sorbinil) or a short-chain acyl-carnitine (acetyl-L-carnitine [ALC]) daily for 16 weeks showed an improvement in NCV. Morphometric studies of tibial nerves collected from animals after 20 weeks of hyperglycemia (age 26 weeks) showed a consistent reduction in the width of the myelin sheath and little change in axon area. The number of large myelinated fibers (>6.5 microns) found in nerves collected from hyperglycemic animals was less than the number found in nondiabetic animals. Treatment of hyperglycemic rats with either sorbinil or ALC was associated with increased NCV, myelin width, and large myelinated fibers. The apparent metabolic effect of these agents was similar for fatty acid metabolism, but different for polyol pathway activity. We conclude that in animals hyperglycemic long enough to slow NCV, sorbinil and/or ALC treatment reduces the functional, structural, and biochemical changes associated with hyperglycemia that occur in the myelin sheath.
Malone
J I
JI
Diabetes Center and the Department of Pediatrics, University of South Florida, Tampa, FL 33612-4799, USA.
Lowitt
S
S
Salem
A F
AF
Miranda
C
C
Korthals
J K
JK
Carver
J
J
D000108:Acetylcarnitine / Q000494:pharmacology*; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male; D009186:Myelin Sheath / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004791:Enzyme Inhibitors; D005227:Fatty Acids; D007093:Imidazoles; D048289:Imidazolidines; D018697:Nootropic Agents; D000108:Acetylcarnitine; D000449:Aldehyde Reductase; C026411:sorbinil