Prevention of processes coupled with free radical formation prevents also the development of calcium-resistance in the diabetic heart

Recently it was shown that besides their negative role in pathogenesis of diabetes, reactive oxygen species (ROS) and particularly the products of non-enzymatic glycation of proteins (NEGP) may also participate in some processes of adaptation of the myocardium to diabetes, such as in the mechanism o...

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Published in:Life sciences (1973) 1999-10, Vol.65 (18), p.1999-2001
Main Authors: Ziegelhöffer, A., Styk, J., Ravingerová, T., Šeboková, J., Volkovová, K., Waczulíková, I., Čársky, J., Džurba, A., Dočolomanský, P.
Format: Article
Language:English
Subjects:
Animals
Antioxidants - pharmacology
Calcium - metabolism
calcium resistance
Diabetes Mellitus, Experimental - metabolism
diabetic heart
Free Radicals - metabolism
fructosamine
Glycoproteins - metabolism
Guanidines - pharmacology
Male
Myocardium - metabolism
non-enzymatic protein glycation
Rats
Rats, Wistar
reactive oxygen species
Reactive Oxygen Species - metabolism
resorcylidene aminoguanidine
Sarcolemma - drug effects
Sarcolemma - metabolism
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Summary:Recently it was shown that besides their negative role in pathogenesis of diabetes, reactive oxygen species (ROS) and particularly the products of non-enzymatic glycation of proteins (NEGP) may also participate in some processes of adaptation of the myocardium to diabetes, such as in the mechanism of development of calcium resistance of the heart. Our study revealed that the hearts of rats with experimentally induced diabetes (single dose of streptozotocin, 45 mg/kg i.V., 6 U/kg insulin daily) develop considerable resistance against calcium overload (induced by means of Ca-paradox). On the day 63 after the beginning of experiment, when the diabetic cardiomyopathy became fully developed but the hearts were still not failing, their calcium resistance was increased to 83.33 %. Our results provide evidence that, when applied in a special regimen, resorcylidene aminoguanidine (RAG, 4 mg/kg) prevented both, the formation of fructosamine (a source of ROS generation), and also that of the advanced Maillard products, in the heart sarcolemma of diabetic rats. The effect of RAG was accompanied by a decrease in calcium resistance in the group of rats with chronic diabetes (63 days) from 83.3 to 46.7 %. It is concluded that NEGP and ROS formation are inevitably needed for development of calcium resistance in the diabetic hearts.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(99)00464-6