The effects of evening primrose oil on nerve function and capillarization in streptozotocin‐diabetic rats: modulation by the cyclo‐oxygenase inhibitor flurbiprofen

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Abstract
1 The aims of this study were first, to examine whether deficits in nerve conduction in streptozotocin-diabetic rats could be reversed by a 10% dietary supplement of evening primrose oil. Second, to determine the time-course of reversal, and third, to assess whether the effects could be blocked by the cylco-oxygenase inhibitor flurbiprofen (5 mg kg−1 day−1). 2 One-month diabetes produced 20% and 15% deficits in sciatic motor and saphenous sensory conduction velocity respectively, which were maintained over 2 months diabetes. 3 The effect of 1-month evening primrose oil treatment on abnormalities caused by an initial month of untreated diabetes was examined. Motor and sensory nerve conduction velocity were restored to the non-diabetic level. 4 Resistance to hypoxic conduction failure was investigated for sciatic nerve trunk in vitro. The 80% conduction failure times were 29% and 55% prolonged by 1- and 2-month diabetes respectively. Evening primrose oil did not reverse the increased hypoxic resistance following 1-month untreated diabetes. 5 Sciatic nerve endoneurial capillary density was not significantly affected by diabetes, but was 16% increased in diabetic rats with reversal by evening primrose oil treatment for 1 month compared to 2-month untreated diabetes. 6 Serial motor conduction velocity measurement after 3-month untreated diabetes revealed complete normalization by evening primrose oil within 4 days. Cessation of treatment resulted in a rapid decline in conduction velocity over 24 h. 7 In a preventive study of 2-month duration, 6 groups of rats were used. These comprised non-diabetic controls, diabetic rats, and evening primrose oil-treated diabetic rats, both with and without flurbiprofen treatment. Flurbiprofen had no significant effect in non-diabetic rats, but produced an 11% worsening of motor conduction velocity and a 21% reduction of sciatic capillary density in diabetic rats. Evening primrose oil prevented the decreases in conduction velocity and increased hypoxic resistance with diabetes, and caused a 23% increase in capillary density. Flurbiprofen completely blocked the effect of evening primrose oil on conduction velocity, resistance to hypoxia, and capillarization. 8 Six main conclusions were reached. First, evening primrose oil rapidly reverses conduction deficits in diabetic rats. Second, the effects of treatment may be very short-lived, suggesting a primary metabolic action. Third, evening primrose oil cannot reverse established changes in hypoxic resistance over 1-month treatment. Fourth, long-term treatment causes angiogenesis, suggesting a vascular action. Fifth, products of cyclo-oxygenase-mediated metabolism are necessary for maintaining vasa nervorum integrity in diabetic rats. Sixth, evening primrose oil probably acts by providing substrate for vasodilator prostanoid synthesis by vasa nervorum.