Abstract
Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, we examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy. Four groups of adult Sprague-Dawley rats were studied: group I received STZ plus AG (25 mg.kg-1.day-1), group II received STZ plus AG (50 mg.kg-1.day-1), group III received STZ alone, and group IV was a control. We monitored conduction and action potential amplitudes serially in sciatic-tibial and caudal nerves, nerve blood flow, oxygen free radical activity (conjugated dienes and hydroperoxides), and the product of the permeability coefficient and surface area to 125I-labeled albumin. STZ-induced diabetes (group III) caused a 57% reduction in nerve blood flow and in abnormal nerve conduction and amplitudes and a 60% increase in conjugated dienes. Nerve blood flow was normalized by 8 weeks with AG (groups I and II) and conduction was significantly improved, in a dose-dependent manner, by 16 and 24 weeks in sciatic-tibial and caudal nerves, respectively. The permeability coefficient was not impaired, suggesting a normal blood-nerve barrier function for albumin, and the oxygen free-radical indices were not ameliorated by AG. We suggest that AG reverses nerve ischemia and more gradually improves their electrophysiology by an action on nerve microvessels. AG may have potential in the treatment of diabetic neuropathy.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brownlee M., Cerami A., Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988 May 19;318(20):1315–1321. doi: 10.1056/NEJM198805193182007. [DOI] [PubMed] [Google Scholar]
- Buege J. A., Aust S. D. Microsomal lipid peroxidation. Methods Enzymol. 1978;52:302–310. doi: 10.1016/s0076-6879(78)52032-6. [DOI] [PubMed] [Google Scholar]
- FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
- Gerrard J. M., Stuart M. J., Rao G. H., Steffes M. W., Mauer S. M., Brown D. M., White J. G. Alteration in the balance of prostaglandin and thromboxane synthesis in diabetic rats. J Lab Clin Med. 1980 Jun;95(6):950–958. [PubMed] [Google Scholar]
- Greene D. A. Metabolic abnormalities in diabetic peripheral nerve: relation to impaired function. Metabolism. 1983 Jul;32(7 Suppl 1):118–123. doi: 10.1016/s0026-0495(83)80024-9. [DOI] [PubMed] [Google Scholar]
- Halushka P. V., Rogers R. C., Loadholt C. B., Colwell J. A. Increased platelet thromboxane synthesis in diabetes mellitus. J Lab Clin Med. 1981 Jan;97(1):87–96. [PubMed] [Google Scholar]
- Kihara M., Low P. A. Regulation of rat nerve blood flow: role of epineurial alpha-receptors. J Physiol. 1990 Mar;422:145–152. doi: 10.1113/jphysiol.1990.sp017977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Low P. A., Schmelzer J. D. Peripheral nerve conduction studies in galactose-poisoned rats. Demonstration of increased resistance to ischemic conduction associated with endoneurial edema due to sugar alcohol accumulation. J Neurol Sci. 1983 Jun;59(3):415–421. doi: 10.1016/0022-510x(83)90026-6. [DOI] [PubMed] [Google Scholar]
- Low P. A., Schmelzer J. D., Ward K. K., Yao J. K. Experimental chronic hypoxic neuropathy: relevance to diabetic neuropathy. Am J Physiol. 1986 Jan;250(1 Pt 1):E94–E99. doi: 10.1152/ajpendo.1986.250.1.E94. [DOI] [PubMed] [Google Scholar]
- Low P. A., Tuck R. R., Dyck P. J., Schmelzer J. D., Yao J. K. Prevention of some electrophysiologic and biochemical abnormalities with oxygen supplementation in experimental diabetic neuropathy. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6894–6898. doi: 10.1073/pnas.81.21.6894. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Low P. A., Ward K., Schmelzer J. D., Brimijoin S. Ischemic conduction failure and energy metabolism in experimental diabetic neuropathy. Am J Physiol. 1985 Apr;248(4 Pt 1):E457–E462. doi: 10.1152/ajpendo.1985.248.4.E457. [DOI] [PubMed] [Google Scholar]
- O'Brien P. C. The appropriateness of analysis of variance and multiple-comparison procedures. Biometrics. 1983 Sep;39(3):787–794. [PubMed] [Google Scholar]
- Pugliese G., Tilton R. G., Speedy A., Santarelli E., Eades D. M., Province M. A., Kilo C., Sherman W. R., Williamson J. R. Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol. Diabetes. 1990 Mar;39(3):312–322. doi: 10.2337/diab.39.3.312. [DOI] [PubMed] [Google Scholar]
- Recknagel R. O., Ghoshal A. K. Lipoperoxidation as a vector in carbon tetrachloride hepatotoxicity. Lab Invest. 1966 Jan;15(1 Pt 1):132–148. [PubMed] [Google Scholar]
- Tilton R. G., Chang K., Pugliese G., Eades D. M., Province M. A., Sherman W. R., Kilo C., Williamson J. R. Prevention of hemodynamic and vascular albumin filtration changes in diabetic rats by aldose reductase inhibitors. Diabetes. 1989 Oct;38(10):1258–1270. doi: 10.2337/diab.38.10.1258. [DOI] [PubMed] [Google Scholar]
- Tuck R. R., Schmelzer J. D., Low P. A. Endoneurial blood flow and oxygen tension in the sciatic nerves of rats with experimental diabetic neuropathy. Brain. 1984 Sep;107(Pt 3):935–950. doi: 10.1093/brain/107.3.935. [DOI] [PubMed] [Google Scholar]
- Vlassara H., Brownlee M., Cerami A. Nonenzymatic glycosylation: role in the pathogenesis of diabetic complications. Clin Chem. 1986 Oct;32(10 Suppl):B37–B41. [PubMed] [Google Scholar]
- Ward K. K., Low P. A., Schmelzer J. D., Zochodne D. W. Prostacyclin and noradrenaline in peripheral nerve of chronic experimental diabetes in rats. Brain. 1989 Feb;112(Pt 1):197–208. doi: 10.1093/brain/112.1.197. [DOI] [PubMed] [Google Scholar]
- Weerasuriya A., Curran G. L., Poduslo J. F. Blood-nerve transfer of albumin and its implications for the endoneurial microenvironment. Brain Res. 1989 Aug 7;494(1):114–121. doi: 10.1016/0006-8993(89)90149-2. [DOI] [PubMed] [Google Scholar]
- Ziboh V. A., Maruta H., Lord J., Cagle W. D., Lucky W. Increased biosynthesis of thromboxane A2 by diabetic platelets. Eur J Clin Invest. 1979 Jun;9(3):223–228. doi: 10.1111/j.1365-2362.1979.tb00927.x. [DOI] [PubMed] [Google Scholar]