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Comparison of the effects of ascorbyl γ-linolenic acid and γ-linolenic acid in the correction of neurovascular deficits in diabetic rats

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Summary

Essential fatty acid metabolism is impaired by diabetes mellitus and γ-linolenic acid rich treatments such as evening primrose oil correct deficits in nerve conduction and endoneurial blood flow in diabetic rats. Other mechanistically unrelated treatments, such as antioxidants and aldose reductase inhibitors have a similar effect and there may be positive interactions with multiple treatments. Our aim was to compare the efficacy of a novel essential fatty acid derivative, ascorbyl γ-linolenic acid, with that of γ-linolenic acid in correcting diabetic neurovascular deficits. Eight weeks of diabetes caused 20.4 and 48.2% reductions in sciatic motor conduction velocity and nutritive endoneurial blood flow, respectively. Treatment was given for the last 2 weeks with γ-linolenic acid (100 mg · kg−1 · day−1) either in pure form or as ascorbyl γ-linolenic acid, an equivalent dose of ascorbate (21 mg · kg−1 · day−1) or jointly with ascorbate and γ-linolenic acid. Conduction velocity was corrected by 39.8, 87.4, 13.2 and 66.8% with γ-linolenic acid, ascorbyl γ-linolenic acid, ascorbate and γ-linolenic acid plus ascorbate, respectively. Corresponding ameliorations of the nutritive blood flow deficit were 44.0, 87.4, 13.2 and 65.7%. For the γ-linolenic acid plus ascorbate combination, and especially for ascorbyl γ-linolenic acid, the magnitude of correction for conduction velocity and blood flow was greater than expected for simple addition of ascorbate and γ-linolenic acid, indicating a synergistic interaction. Thus, with an efficacy 40 times that of evening primrose oil in rats, ascorbyl γ-linolenic acid may be a suitable candidate for clinical trials of diabetic neuropathy.

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Abbreviations

ARI:

Aldose reductase inhibitor

GLA:

γ-linolenic acid

NCV:

nerve conduction velocity

NO:

nitric oxide

ROS:

reactive oxygen species

PG:

prostaglandin

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

    N. E. Cameron & M. A. Cotter

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Cameron, N.E., Cotter, M.A. Comparison of the effects of ascorbyl γ-linolenic acid and γ-linolenic acid in the correction of neurovascular deficits in diabetic rats. Diabetologia 39, 1047–1054 (1996). https://doi.org/10.1007/BF00400653

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