Aminoguanidine, which prevents formation of advanced glycation end products and is a relatively selective potent inhibitor of the inducible (versus constitutive) isoform(s) of nitric oxide synthase, has been reported to ameliorate structural and functional abnormalities in peripheral somatic nerves in rats with streptozocin (STZ)-induced diabetes. In the present studies, the effects of aminoguanidine treatment on ultrastructural changes in the autonomic nervous system of rats with STZ-induced diabetes were examined. The frequency of neuroaxonal dystrophy, the neuropathological hallmark of sympathetic autonomic neuropathy in diabetic rats, increased 9- to 11-fold in the superior mesenteric ganglia of 7- and 10-month STZ-diabetic rats compared with that in age-matched controls. Administration of aminoguanidine continuously from the time of induction of diabetes at a dose equal to or in excess of that providing a salutary effect in the diabetic somatic peripheral nervous system did not alter the severity of diabetes as assessed by plasma glucose level, 24-h urine volume, and levels of glycated hemoglobin. Chronic aminoguanidine therapy did not diminish the frequency or affect the ultrastructural appearance of neuroaxonal dystrophy in diabetic or age-matched control rat sympathetic ganglia after 7 or 10 months of continuous administration. Our findings (under these experimental conditions) do not support a role for aminoguanidine-sensitive processes in the development of sympathetic neuroaxonal dystrophy in diabetic rats. Glycation-linked aminoguanidine-insensitive processes, however, such as the formation of early glucose adducts (Schiff bases and Amadori products) with intracellular and/or extracellular proteins and amine-containing lipids, superoxide anion generation during subsequent autoxidation of these glucose adducts, and non-glycative processes, remain potential pathogenetic mechanisms for diabetic autonomic neuropathy.
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March 01 1996
Effect of Aminoguanidine on the Frequency of Neuroaxonal Dystrophy in the Superior Mesenteric Sympathetic Autonomic Ganglia of Rats With Streptozocin-Induced Diabetes
Robert E Schmidt;
Robert E Schmidt
Department of Pathology
California
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Denise A Dorsey;
Denise A Dorsey
Department of Pathology
California
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Lucie N Beaudet;
Lucie N Beaudet
Department of Pathology
California
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Karen M Reiser;
Karen M Reiser
Divisions of Neuropathology and Anatomic Pathology Washington University School of Medicine, St. Louis, Missouri
California
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Joseph R Williamson;
Joseph R Williamson
Department of Pathology and Laboratory Medicine The University of Texas, Houston Health Science Center, Houston, Texas
California
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Ronald G Tilton
Ronald G Tilton
Department of Medicine University of California Davis School of Medicine, Davis
California
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Address correspondence and reprint requests to Dr. Robert E. Schmidt, Department of Pathology (Division of Neuropathology), Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110
Diabetes 1996;45(3):284–290
Article history
Received:
March 17 1995
Received:
October 24 1995
Accepted:
October 24 1995
PubMed:
8593931
Citation
Robert E Schmidt, Denise A Dorsey, Lucie N Beaudet, Karen M Reiser, Joseph R Williamson, Ronald G Tilton; Effect of Aminoguanidine on the Frequency of Neuroaxonal Dystrophy in the Superior Mesenteric Sympathetic Autonomic Ganglia of Rats With Streptozocin-Induced Diabetes. Diabetes 1 March 1996; 45 (3): 284–290. https://doi.org/10.2337/diab.45.3.284
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