Summary
It has been shown that parameters of oxidative stress are increased in experimental diabetic neuropathy. The glutathione redox system is one of the intracellular scavenger systems for neutralizing free oxygen radicals. In this investigation we studied the effect of glutathione-treatment on the development of diabetic neuropathy in streptozotocin-induced diabetic rats by measuring sensory and motor nerve conduction velocities. The total study period was 10 weeks. Four groups of rats were studied: Group 1 consisted of non-diabetic, age-matched control rats; Group 2, of diabetic rats treated with placebo from week 0 to 10; Group 3, of diabetic rats treated with 200 mg glutathione/kg body weight i. v. two times per week from weeks 0 to 10; and Group 4, of diabetic rats treated with placebo from weeks 0 to 4 and as Group 3 from weeks 4 to 10. The sensory and motor nerve conduction velocity of rats treated prophylactically with glutathione (Group 3) were significantly different from those of rats treated with placebo (Group 2) or with glutathione administered at a later time point (Group 4). Complete restoration of sensory and motor nerve conduction velocity was not reached. There was a significant improvement in motor nerve conduction velocity from weeks 4 to 6 (p<0.005), but not in sensory nerve conduction velocity in the delayed treatment group (Group 4). In conclusion, treatment with glutathione, a free radical scavenger, is partially effective in the prevention of diabetic neuropathy in streptozotocin-induced diabetic rats, but is of limited value when the neuropathy is already present.
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Dyck PJ, James J, O'Brien PC (1987) Diagnosis, staging and classification of diabetic neuropathy and association with other complications. In: Dyck PJ, Thomas PK, Asbury AK, Winegrad AI, Porte D (eds) Diabetic neuropathy. WB Saunders Co., Philadelphia, pp 36–44
Greene DA, DeJesus PV Jr, Winegrad AI (1975) Effects of insulin and dietary myo-inositol on impaired peripheral motor nerve conduction velocity in acute streptozotocin diabetes. J Clin Invest 55: 1326–1336
Finegold D, Lattimer SA, Nolle S, Bernstein M, Greene DA (1983) Polyol pathway activity and myo-inositol metabolism: a suggested relationship in pathogenesis of diabetic neuropathy. Diabetes 32: 988–992
Vlassara H, Brownlee M, Cerami A (1983) Excessive non enzymatic glycosylation of peripheral and central nervous system myelin components in diabetic rats. Diabetes 32: 670–674
Vlassara H, Brownlee M, Cerami A (1985) Recognition and uptake of human diabetic peripheral nerve myelin by macrophages. Diabetes 34: 553–557
Tuck RR, Schmelzer JD, Low PA (1984) Endoneurial blood flow and oxygen tension in sciatic nerves of rats with experimental diabetic neuropathy. Brain 107: 935–950
Low PA, Tuck RR, Dyck PJ, Schmelzer JD, Yao JK (1984) Prevention of some electrophysiologic and biochemical abnormalities with oxygen-supplementation in experimental diabetic neuropathy. Proc Natl Acad Sci USA 81: 6894–6898
Low PA, Schmelzer JD, Ward KK, Yao JK (1986) Experimental chronic hypoxic neuropathy: relevance to diabetic neuropathy. Am J Physiol 250: E94-E99
Low PA, Nickander KK (1991) Oxygen free radical effects in sciatic nerve in experimental diabetes. Diabetes 40: 873–877
Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40: 405–412
Loven D, Schedl H, Wilson H et al. (1986) Effect of insulin and oral glutathione levels and superoxide dismutase activities in organs of rats with streptozotocin-induced diabetes. Diabetes 35: 503–507
Romero FJ, Segura-Aguilar J, Monsalve E et al. (1990) Antioxidant and glutathione-related enzymatic activities in rat sciatic nerve. Neurotoxicol Teratol 12: 603–605
De Koning P, Gispen WH (1987) Org 2766 improves functional and electrophysiological aspects of regenerating sciatic nerve in the rat. Peptides 8: 415–422
Waxman SG (1980) Determination of conduction velocity in myelinated nerve fibres. Muscle Nerve 3: 141–150
Stanley EF (1981) Sensory and motor nerve conduction velocities and the latency of the H-reflex during growth of the rat. Exp Neurol 71: 497–506
Fleiss JL (1986) The design and analysis of clinical experiments. John Wiley, Chichester, New York
Halliwell B, Gutteridge JMC (1989) Free radicals in biology and medicine, 2nd edn. Oxford University Press, Oxford
Loven DP, Oberly LW (1989) Free radicals, insulin action, and diabetes. In: Superoxide dismutase. Pathological states. Oberly LW (ed) CRC Press, Boca Raton, pp 151–190
Morel DW, Chisolm GM (1989) Antioxidant treatment of diabetic rats inhibits lipoprotein oxidation and cytotoxicity. J Lipid Res 30: 1827–1834
Wohaieb SA, Godin V (1987) Alterations in free radical tissuedefense mechanisms in streptozotocin-induced diabetes in rat. Effects of insulin treatment. Diabetes 36: 1014–1018
Murakami K, Kondo T, Ohtsuka Y, Fujiwara Y, Shimada M, Kawakami Y (1989) Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. Metabolism 38: 753–758
Tomlinson DR, Moriarty RJ, Mayer JH (1984) Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor sorbinil. Diabetes 33: 470–476
Van der Zee CEEM, Gerritsen van der Hoop R, Gispen WH (1989) Beneficial effect of Org 2766 in treatment of peripheral neuropathy in streptozotocin-induced diabetic rats. Diabetes 38: 225–230
Bravenboer B, Kappelle AC, van Buren T, Erkelens DW, Gispen WH (1991) ACTH-analogue ORG 2766 can ameliorate existing neuropathy in diabetic rats. Diabetologia 34 [Suppl 2]: A21 (Abstract)
Cameron NE, Cotter MA, Robertson S (1991) Essential fatty acid diet supplementation. Effects on peripheral nerve and skeletal muscle function and capillarization in streptozotocininduced diabetic rats. Diabetes 40: 532–539
Sonobe M, Yasuda H, Hisanaga T et al. (1991) Amelioration of nerve Na+-K+-ATPase activity independently of myo-inositol level by PGE1 analogue OP-1206.α-CD in streptozotocininduced diabetic rats. Diabetes 40: 726–730
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Bravenboer, B., Kappelle, A.C., Hamers, F.P.T. et al. Potential use of glutathione for the prevention and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat. Diabetologia 35, 813–817 (1992). https://doi.org/10.1007/BF00399926
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DOI: https://doi.org/10.1007/BF00399926