Contrasting effects of treatment with ω-3 and ω-6 essential fatty acids on peripheral nerve function and capillarization in streptozotocin-diabetic ratsn
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Essential fatty acid metabolism is impaired by diabetes mellitus and this may be important in the aetiology of peripheral nerve dysfunction. The effects of γ-linolenic acid (ω-6) and fish oil (ω-3) alone, and in combination, on nerve function and capillarization were examined in 2-month streptozotocin-diabetic rats. Diabetes resulted in approximately 15% and 23% decreases in saphenous sensory and sciatic motor nerve conduction velocities, respectively (p<0.001). Motor and sensory conduction velocities were in the non-diabetic range after both preventive and reversal ω-6 treatment of diabetic rats (p<0.001). No significant changes occurred in ω-6 treated non-diabetic rats. Preventive ω-3 treatment was largely ineffective. Reversal treatment with a combination of ω-6 and ω-3 fatty acids was marginally effective and improved motor (p<0.05), but not sensory conduction velocity. In vitro measurement of sciatic nerve resistance to hypoxic conduction failure in diabetic rats revealed a 56% increase in the time taken for the compound action potential amplitude to be reduced by 80% (p<0.01) compared to non-diabetic rats. This was partially prevented by ω-6 treatment (29% increase, p<0.01). Reversal ω-6 treatment had a lesser effect (37% increase, p<0.05 compared to untreated diabetic rats). ω-3 treatment had no significant effect on conduction failure time. Sciatic endoneurial capillary density increased by 11% with preventive ω-6 treatment (p<0.05), but was unaffected by reversal ω-6 and by ω-3 treatments. These results demonstrate the specificity of ω-6 essential fatty acids in improving diabetic nerve function and highlight an antagonism exerted by ω-3 components, which may have therapeutic implications.
Key wordsStreptozotocin diabetes neuropathy nerve conduction essential fatty acids fish oil γ-linolenic acid ischaemia angiogenesis
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