Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 22

Experimental diabetic neuropathy has a number of features in common with the human disease, including a reduction of nerve conduction velocity (NCV) and Na+, K+-ATPase activity in nerve fibers, and alteration of the essential fatty acid metabolism leading to changes in membrane composition. N-3 polyunsaturated fatty acids (PUFA) are beneficial in different pathological conditions including diabetic complications. Since the PUFA composition of cell membranes largely depends on the diet, most studies have supplemented the diet with fish oil (FO), particularly rich in docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, or DHA and EPA ethyl esters. We have prepared a new formulation of n-3 PUFA wax esters (WE) enriched in DHA and EPA that have a bioavailability comparable to oil and esters, are easily digestible and are free from most of the previous drawbacks. The present study was designed to measure Na+, K+-ATPase activity, NCV, and FA content in plasma phospholipids (PL) and to assess the preventive effect of newly formulated n-3 PUFA-WE, and individual EPA and DHA-WE (as compared with standard and FO-supplemented diets) on these abnormalities. Diabetes was induced by streptozotocin (STZ, 60 mg/kg/ip). After STZ injection, diabetic and non-diabetic control rats were fed the standard diet (St) without supplementation or supplemented with either FO or n-3 PUFA-WE or individual EPA and DHA-WE, to reach a daily dose of 0.15 g/kg, the experiment continued for five weeks. Analysis of the FA composition of plasma PL, which better reflects FA intake and content in biological membranes, showed that the sums of n-3 PUFA were double the St diet after n-3 supplement of independent of the dietary regimen, whereas those of FA of the n-6 family were not affected by n-3 supplementation. Thus, the n-6/n-3 ratios were reduced from 15:1 with the St diet to 7:1 for the FO and WE diets. Na+, K+-ATPase activity was significantly lower in diabetic rats (−30–35%), significantly restored in diabetic rats that received FO, n-3 PUFA and EPA-WE supplementation, and partially restored by DHA-WE (9% lower than with non-diabetic controls). These effects were partially associated with a significant beneficial effect on NCV which was reduced by 20% in diabetic rats. FO protected against this decrease (3%), n-3 PUFA-WE were only partially protective (11%), and EPA and DHA-WE had scant effect. This study indicates that, like FO, n-3 PUFA-EPA and DHA-WE have beneficial effects on diabetic-induced alterations in sciatic nerve ATPase+-ATPase activity and, partially, also on NCV. The newly formulated n-3 PUFA WE offer a potential advantage over products in current use, on account of their greater stability.