Altered neuroexcitability in experimental diabetic neuropathy: effect of acetyl-L-carnitine.
Sciatic nerve conduction velocity (NCV) is reduced in rats made hyperglycaemic with streptozotocin (STZ). This neurophysiological dysfunction has been associated with increased nerve sorbitol and reduced nerve inositol. Treatment of STZ diabetic rats with aldose reductase inhibitors (ARIs) which reduce sorbitol and increase inositol in the nerve results in normalization of NCVs. Male Wistar rats were made diabetic with 50 mg/kg of streptozotocin given intraperitoneally. Those animals with blood glucose > 300 mg/dl two weeks later were included in this study. The STZ-diabetic rats were treated with either the ARI sorbinil (40 mg/kg per day), or acetyl-L-carnitine (ALC) (300 mg/kg per day) or sterile 0.15% aqueous NaCl for 16 weeks after 4 or 8 weeks of untreated hyperglycaemia. A control group of non-diabetic rats received no treatment during the interval. Sciatic-nerve sorbitol was elevated (1.08 +/- 0.13 nanomol/mg wet weight vs. 0.19 +/- 0.03 nm/mg wet weight) and inositol was reduced (1.21 +/- 0.12 nm/mg ww vs. 2.02 +/- 0.08 nm/mg ww) in the STZ diabetic rats, which were untreated for 4 weeks. Treatment with sorbinil was associated with normalization of the tissue sorbitol (0.10 +/- 0.05 nm/mg ww), while ALC treatment also significantly reduced the nerve sorbitol but only to a level (0.34 +/- 0.08 nm/mg ww) more elevated than the normal level. The nerves of STZ animals treated with sorbinil or ALC had inositol levels no different from untreated diabetic rats. Thus, hyperglycaemic animals treated with either ALC or sorbinil had similar improvements in NCVs as the diabetic, even though the effect on nerve sorbitol was different and nerve inositol was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Malone
J I
JI
University of South Florida, Tampa.
Lowitt
S
S
Corsico
N
N
Orfalian
Z
Z
D000108:Acetylcarnitine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000503:physiopathology
D007093:Imidazoles; D048289:Imidazolidines; D000108:Acetylcarnitine; C026411:sorbinil