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Validity of the Models of Experimental Diabetes for Oxidative Stress Studies. P. 66–78

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Section: Medical and biological sciences

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UDC

616.379-008.64-092.11

DOI

10.17238/issn2542-1298.2019.7.1.66

Authors

Mariya I. Yashanova*, Tat’yana G. Shcherbatyuk*, Vadim Yu. Nikolaev**
*Privolzhsky Research Medical University (Nizhny Novgorod, Russian Federation)
**Nizhny Novgorod State Agricultural Academy (Nizhny Novgorod, Russian Federation)

Abstract

Oxidative stress plays an important role in the pathogenesis of diabetes mellitus (DM) and the development of its complications. It was not until fairly recently that DM began to be studied as a freeradical pathology. Thus, there are currently no unified methodological approaches to assessing the effect of oxidative stress on the pathogenesis of DM and to analysing the effectiveness of antioxidant therapy. For this reason, new models are required for assessing the antioxidant effect of new drugs. We performed a comparative analysis of the activity of free-radical processes in 49 white outbred male rats with diabetes induced by intraperitoneal injection of alloxan (120 mg/kg) and streptozotocin (40 mg/kg), the latter preceded by a high-calorie diet (STZ DM). The research found that the formation of lipid and protein oxidation products is more intensive in rats with STZ DM than in those with alloxan-induced DM. Moreover, animals with experimental STZ DM stay alive longer, which makes it possible to use this model in evaluating long-term effects of various drugs. In order to estimate the validity of the STZ DM model for oxidative stress studies, saxagliptin (Onglyza) at a dosage of 3 mg/kg was administered by intragastric gavage for 14 days to animals with STZ DM (10 rats). After 14 days of administration, the drug decreased the total free-radical activity, concentration of malondialdehyde and all products of oxidative modification of proteins during spontaneous oxidation, which proves that the STZ DM model can be used to evaluate the antioxidant effect of antidiabetic drugs.

Keywords

experimental diabetes, alloxan, streptozotocin, oxidative modification of proteins and lipids, ketone-dinitrophenylhydrazones, aldehydе-dinitrophenylhydrazones, malondialdehyde, saxagliptin

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