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The Influence of Sulindac on Experimental Streptozotocin-Induced Diabetic Neuropathy

Published online by Cambridge University Press:  18 September 2015

Douglas W. Zochodne*
Affiliation:
Peripheral Nerve Research Laboratory, Neuroscience Research Group, Department of Clinical Neurosciences, University of Calgary, Calgary
Lam T. Ho
Affiliation:
Peripheral Nerve Research Laboratory, Neuroscience Research Group, Department of Clinical Neurosciences, University of Calgary, Calgary
*
University of Calgary, Department of Clinical Neurosciences, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1
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Abstract:

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We studied the influence of sulindac, a nonsteroidal anti-inflammatory agent on experimental streptozotocin-induced diabetic neuropathy. Untreated diabetic rats were compared with nondiabetic rats, diabetic rats treated with low dose insulin and diabetic rats given sulindac (6.0 mg/kg by gavage 5 of 7 days weekly). Neuropathy was assessed by following serial in vivo motor and sensory caudal conduction, resistance to ischemic conduction failure, and in vitro conduction in sural myelinated and unmyelinated sensory fibers. The impact of low dose insulin and sulindac treatment on the microenvironment of the L4 dorsal root ganglion and sciatic endoneurium was asssessed by measuring local perfusion and oxygen tension after 16 weeks of diabetes. Sulindac normalized conduction velocity in caudal sensory fibers, sural myelinated fibers and sural unmyelinated fibers, and reduced the number of diabetic cataracts. Sulindac also normalized a deficit in dorsal root ganglion blood flow and a reduction in sciatic endoneurial oxygen tension in diabetic rats. Low dose insulin improved neuropathy as well but the pattern of benefits was less robust than that of sulindac. Sulindac may be a candidate for a clinical trial in human diabetic polyneuropathy.

Type
Original Articles
Copyright
Copyright © Canadian Neurological Sciences Federation 1994

References

1.Zochodne, DW, Ho, LT.The influence of indomethacin and guanethidine on experimental streptozotocin diabetic neuropathy. Can J Neurol Sci 1992; 19: 433441.CrossRefGoogle ScholarPubMed
2.Parry, GJ, Kozu, H.Piroxicam may reduce the rate of progression of experimental diabetic neuropathy. Neurology 1990; 40: 14461449.CrossRefGoogle ScholarPubMed
3.Ward, KK, Low, PA, Schmelzer, JD, Zochodne, DW.Prostacyclin and noradrenaline in peripheral nerve of chronic experimental diabetes in rats. Brain 1989; 112: 197208.CrossRefGoogle ScholarPubMed
4.Low, PA.Recent advances in the pathogenesis of diabetic neuropathy. Muscle and Nerve 1987; 10: 121128.CrossRefGoogle ScholarPubMed
5.Tuck, RR, Schmelzer, JD, Low, PA.Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy. Brain 1984; 107: 935950.CrossRefGoogle ScholarPubMed
6.Zochodne, DW, Ho, LT.Normal blood flow but lower oxygen tension in diabetes of young rats: microenvironment and the influence of sympathectomy. Can J Physiol Pharmacol 1992; 70: 651659.CrossRefGoogle ScholarPubMed
7.Newrick, PG, Wilson, AJ, Jakubowski, J, Boulton, AJM, Ward, JD.Sural nerve oxygen tension in diabetes. Br Med J 1986; 293: 10531054.CrossRefGoogle ScholarPubMed
8.Low, PA, Tuck, RR, Dyck, PJ, Schmelzer, JD, Yao, JK.Prevention of some electrophysiologic and biochemical abnormalities with oxygen supplementation in experimental diabetic neuropathy. Proc Nat Acad Sci U.S.A. 1984; 81: 68946898.CrossRefGoogle ScholarPubMed
9.Low, PA, Schmelzer, JD, Ward, KK, Curran, GL, Poduslo, JF.Effect of hyperbaric oxygenation on normal and chronic streptozotocin diabetic peripheral nerves. Exp Neurol 1988; 99: 201212.CrossRefGoogle ScholarPubMed
10.Zollman, P, Sahenk, Z, Low, PA.The effects of hyperbaric oxygenation on fast axonal trasport in streptozotocin-induced diabetes. Neurology 40 (Suppl 1): 1990; 124.Google Scholar
11.Low, PA, Schmelzer, JD, Ward, KK, Yao, JK.Experimental chronic hypoxic neuropathy: relevance to diabetic neuropathy. Am J Physiol 1986; 250: E94-E99.Google ScholarPubMed
12.Benstead, TJ, Dyck, PJ, Low, P.Chronic hypoxia induces selective maldevelopment of peripheral myelin in rat. J Neuropathol Exp Neurol 1988; 47:599608.CrossRefGoogle ScholarPubMed
13.Hampton, KK, Alani, SM, Wilson, JI, Price, DE.Resistance to ischaemic conduction failure in chronic hypoxaemia and diabetes. J Neurol Neurosurg Psychiatry 1989; 52: 13031305.CrossRefGoogle ScholarPubMed
14.Masson, EA, Church, SE, Woodcock, AA, Hanley, SP, Boulton, AJM.Is resistance to ischemic conduction failure induced by hypoxia? Diabetologia 1988; 31: 762765.CrossRefGoogle ScholarPubMed
15.Brogden, RN, Heel, RC, Speight, TM, Avery, GS.Sulindac: a review of its pharmacological properties and therapeutic efficacy in rheumatic diseases. Drugs 1978; 16: 97114.CrossRefGoogle ScholarPubMed
16.Sharma, YR, Cotlier, E.Inhibition of lens and cataract aldose reductase by protein-bound anti-rheumatic drugs: salicylate, indomethacin, oxyphenbutazone, sulindac. Exp Eye Res 1982; 35:2127.CrossRefGoogle ScholarPubMed
17.Chaudhry, PS, Cabrera, J, Juliani, HR, Varma, SD.Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochemical Pharmacology 1983; 32: 19951998.CrossRefGoogle ScholarPubMed
18.Tomlinson, DR, Moriarty, RJ, Mayer, JH.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 1984; 33: 470476.CrossRefGoogle ScholarPubMed
19.Yue, DK, Hanwell, MA, Satchell, PM, Turtle, JR.The effect of aldose reductase inhibition on motor nerve conduction velocity in diabetic rats. Diabetes 1982; 31: 789794.CrossRefGoogle ScholarPubMed
20.Tilton, RG, Chang, K, Pugliese, G, et al. Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. Diabetes 1989; 37: 12581270.CrossRefGoogle Scholar
21.Pugliese, G, Tilton, RG, Speedy, A, et al. Effects of very mild versus overt diabetes on vascular haemodynamics and barrier function in rats. Diabetologia 1989; 32: 845857.CrossRefGoogle ScholarPubMed
22.Cameron, NE, Cotter, MA, Low, PA.Nerve blood flow in early experimental diabetes in rats: relation to conduction deficits. Am J Physiol 1991; 261: E1-E8.Google ScholarPubMed
23.Zochodne, DW, Ho, LT.Unique microvascular characteristics of the dorsal root ganglion in the rat. Brain Res 1991; 559: 8993.CrossRefGoogle ScholarPubMed
24.Low, PA, Schmelzer, JD, Ward, KK.The effect of age on energy metabolism and resistance to ischaemic conduction failure in rat peripheral nerve. J Physiol (London) 1986; 374: 263271.CrossRefGoogle ScholarPubMed
25.Cameron, NE, Cotter, MA, Robertson, S.The effect of aldose reductase inhibition on the pattern of nerve conduction deficits in diabetic rats. Quart J Exp Physiol 1989; 74: 917926.CrossRefGoogle ScholarPubMed
26.Yagihashi, S, Kamijo, M, Ido, Y, Mirrlees, DJ.Effects of long-term aldose reductase inhibition on development of experimental diabetic neuropathy. Diabetes 1990; 39: 690696.CrossRefGoogle ScholarPubMed
27.Yasuda, H, Sonobe, M, Yamashita, M, et al. Effect of prostaglandin El analogue TFC 612 on diabetic neuropathy in streptozocin-induced diabetic rats. Diabetes 1989; 38: 832838.CrossRefGoogle Scholar
28.Sutera, SP, Chang, K, Marvel, J, Williamson, JR.Concurrent increases in regional hematocrit and blood flow in diabetic rats: prevention by sorbinil. Am J Physiol 1992; 263: H945-H950.Google ScholarPubMed
29.Pries, AR, Ley, K, Claassen, M, Gaehtgens, P.Red cell distribution at microvascular bifurcations. Microvasc Res 1989; 38: 81101.CrossRefGoogle ScholarPubMed
30.Kowluru, R, Bitensky, MW, Kowluru, A, et al. Reversible sodium pump defect and swelling in the diabetic rat erythrocyte: effects on filterability and implications for microangiopathy. Proc Nat Acad Sci (USA) 1989; 86: 33273331.CrossRefGoogle ScholarPubMed
31.Rillaerts, EG, Vertommen, JJ, De Leeuw, IH.Effect of statu (ICI 128436) on erythrocyte viscosity in vitro. Diabetes 1988; 37: 471475.CrossRefGoogle Scholar
32.Ditzel, J.Oxygen transport impairment in diabetes. Diabetes 1976; 25(2): 832838.Google ScholarPubMed
33.Greene, DA, Winegrad, AI, Carpentier, JL, et al. Rabbit sciatic nerve fascicle and “endoneurial” preparations for in vitro studies of peripheral nerve glucose metabolism. J Neurochem 1979; 33: 10071018.CrossRefGoogle ScholarPubMed
34.Kadekaro, M, Crane, AM, Sokoloff, L.Differential effects of electrical stimulation of sciatic nerve on metabolic activity in spinal cord and dorsal root ganglion in the rat. Proc Nat Acad Sci (U.S.A.) 1985; 82:60106013.CrossRefGoogle ScholarPubMed
35.Bohlen, HG, Hankins, KD.Early arteriolar and capillary changes in streptozotocin-induced diabetic rats and intraperitoneal hyper-glycaemic rats. Diabetologia 1982; 22: 344348.CrossRefGoogle Scholar
36.Sullivan, S, Sparks, HB.Diminished contractile response of aortas from diabetic rabbits. Am J Physiol 1979; 236: H301-H306.Google ScholarPubMed
37.Turlapaty, PDMV, Lum, G, Altura, BM.Vascular responsiveness and serum biochemical parameters in alloxan diabetes mellitus. Am J Physiol 1980; 239: E412-E421.Google ScholarPubMed
38.Mayhan, WG.Impairment of endothelium-dependent dilatation of cerebral arterioles during diabetes mellitus. Am J Physiol 1989; 265: H621-H625.Google Scholar
39.Williamson, JR, Ostrow, E, Eades, D, et al. Glucose-induced microvascular functional changes in non-diabetic rats are stere-ospecific and are prevented by an aldose reductase inhibitor. J Clin Invest 1990; 85: 11671172.CrossRefGoogle Scholar
40.Bucala, R, Tracey, KJ, Cerami, A.Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Invest 1991; 87: 432438.CrossRefGoogle ScholarPubMed
41.Bareford, D, Jennings, PE, Stone, PCW, et al. Effects of hyperglycaemia and sorbitol accumulation on erythrocyte deformability in diabetes mellitus. J Clin Pathol 1986; 39: 722727.CrossRefGoogle ScholarPubMed
42.Sharma, AK, Thomas, PK.Peripheral nerve structure and function in experimental diabetes. J Neurol Sci 1974; 23: 115.CrossRefGoogle ScholarPubMed
43.Yasuda, H, Sonobue, M, Yamashita, M, et al. Effect of prostaglandin El analogue TFC612 on diabetic neuropathy in streptozotocin-induced diabetic rats. Comparison with aldose reductase inhibitor ONO 2235. Diabetes 1989; 38: 832838.CrossRefGoogle Scholar
44.Robison, WG, Kador, PF, Akagi, Y, et al. Prevention of basement membrane thickening in retinal capillaries by a novel inhibitor of aldose reductase, tolrestat. Diabetes 1986; 35: 295299.CrossRefGoogle ScholarPubMed
45.Brooks, PM, Day, RO.Nonsteroidal antiinflammatory drugs-differences and similarities. N Engl J Med 1991; 324: 17161725.Google ScholarPubMed