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Prevention and reversal of motor and sensory peripheral nerve conduction abnormalities in streptozotocin-diabetic rats by the prostacyclin analogue iloprost

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Summary

The effects of the prostacyclin analogue iloprost on nerve function were examined in streptozotocin-diabetic rats. Rats were treated either with iloprost from induction of diabetes over 2 months in a preventive experiment, or for 1 month following a 1 month untreated period of diabetes in a reversal experiment. One and 2 months untreated diabetic control, non-diabetic control, and iloprost-treated non-diabetic groups were also used.

Diabetes of 1 month duration caused a 21% (P < 0.001) reduction in sciatic motor conduction velocity and a 14% (P (0.001) deficit in saphenous sensory conduction. This was not significantly changed over a subsequent month without treatment. Diabetic rats given iloprost treatment in both preventive and reversal studies had motor and sensory conduction velocities not significantly different from those of non-diabetic controls, but greater than for untreated diabetes (P < 0.01). Iloprost treatment did not have a significant effect on nerve conduction in non-diabetic rats. The time taken for sciatic nerve compound action potential amplitude to be reduced by 80% under hypoxic conditions in vitro was progressively elevated by 19% and 57% after 1 and 2 months diabetes respectively. Iloprost treatment significantly attenuated this for both preventive (47%, P < 0.001) and reversal (50%, P < 0.001) studies. There was no effect on hypoxic resistance for non-diabetic rats. In the preventive group there was a 28010 increase in sciatic nerve endoneurial capillary density (P < 0.001), a lesser effect (16%, P < 0.05) in the reversal group, and no effect in non-diabetic rats. Sciatic nerve sorbitol, fructose and myo-inositol levels were measured in 2 month diabetic control and reversal iloprost-treated groups. Treatment had no significant effect on the elevation of polyol pathway metabolites or myo-inositol concentration.

We conclude that iloprost treatment may compensate for reduced prostacyclin production by vasa nervorum. Although short durations of experimental diabetes do not result in the severe degenerative changes found in clinical neuropathy, it is nevertheless possible that iloprost may have therapeutic potential for vascular-related diabetic complications.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Aberdeen, Marischal College, Aberdeen AB9 1AS, Scotland, UK

    M. A. Cotter, K. C. Dines & N. E. Cameron

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  1. M. A. Cotter
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  2. K. C. Dines
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  3. N. E. Cameron
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Correspondence to N. E. Cameron at the above address

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Cotter, M.A., Dines, K.C. & Cameron, N.E. Prevention and reversal of motor and sensory peripheral nerve conduction abnormalities in streptozotocin-diabetic rats by the prostacyclin analogue iloprost. Naunyn-Schmiedeberg's Arch Pharmacol 347, 534–540 (1993). https://doi.org/10.1007/BF00166747

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