INDIRECT REVASCULARIZATION IN DIABETIC MICROANGIOPATHY – FROM EXPERIMENTAL MODELS TO CLINICAL USE
Introduction. Indirect revascularization in diabetic microangiopathy is considered as a promising direction for the treatment and prevention of complications of diabetes, but the theoretical background of this approach is insufficiently elaborated.
The aim of the study – to evaluate the effectiveness of combined indirect revascularization in rats with microangiopathy of the extremities on the background of experimental streptozocin diabetes.
Research Methods. Experimental studies were carried out in a chronic experiment on 100 Wistar rats weighing 180–250 g. After administration of streptozocin, animals with increased resistance to pancreatotropic toxicity were excluded from the experiment according to the criterion of the absence of hyperglycemia, after which they were bred for 6 weeks 2 animals for morphological studies. At week 7, another 10 animals were removed from the experiment to evaluate the effectiveness of the experimental model. Three experimental groups were formed from the remaining animals (n = 60). Group I (control) – rats with streptozotocin-induced angiopathy without treatment (n=10); group 2 – rats with streptozotocin-induced angiopathy, were given pentoxifylline (100 mg/kg ip for 10 days) for therapeutic purposes (n=25); group 3 – rats with streptozotocin-induced angiopathy, which together with the treatment were injected with platelet-rich plasma (in the right hind limb, once, with a volume of 0.2 ml, linearly, retrograde, from two points) and pentoxifylline (100 mg/kg intraperitoneally within 10 days) (n=25). 4 weeks after the start of the experimental therapy, 5 animals were removed from the experiment. The duration of the experiment was 110 days.
Results and Discussion. It was shown that in experimental streptozocin diabetes at 8 weeks in animals, microangiopathy of the extremities develops. It is proved that the isolated administration of pentoxifylline in the terms of revascularizing activity is inferior to combination therapy. Combined therapy with pentoxifylline and plasmofilling leads to a decrease in perivascular edema and an increase in effective vascular volume mainly due to a decrease in the intensity of inflammatory manifestations.
Conclusion. The feasibility of the clinical use of a combination of pentoxifylline and plasma enriched with platelets in the treatment of manifestations of diabetic microangiopathy as a means of indirect revascularization is discussed.
Ahmed, A.M. (2002). History of diabetes mellitus. Saudi Med. J., 23 (4), 373-378.
Guaraldi, F., & Pasquali, R. (2015). Diabetes: From Ancient Egypt to the 18th century. J. Assoc. Physicians India, 63 (3), 128.
Karamanou, M., Protogerou, A., Tsoucalas, G., Androutsos, G., & Poulakou-Rebelakou, E. (2016). Milestones in the history of diabetes mellitus: The main contributors. World J. Diabetes, 7 (1), 1-7.
Medvei, V.C. (1993). The history of clinical endocrinology: a comprehensive account of endocrinology from earliest times to the present day. Carnforth: Parthenon.
Laios, K., Karamanou, M., Saridaki, Z., & Androutsos, G. (2012). Aretaeus of Cappadocia and the first description of diabetes. Hormones (Athens), 11 (1), 109-113.
Valenti, G., & Tamma, G. (2016). History of diabetes insipidus. G. Ital. Nefrol., 33 (66), 33, 66.1
Von Mehring, J., & Minkowski, O. (1890). “Diabetes mellitus nach pankreasexstirpation”. Arch. Exp. Pathol. Pharmakol., 26 (5-6), 371-387.
Tao, Z., Shi, A., & Zhao, J. (2015). Epidemiological perspectives of diabetes. Cell Biochem. Biophys., 73 (1), 181-185.
Wild, S., Roglic, G., Green, A., Sicree, R., & King, H. (2004). Global prevalence of diabetes:estimates for the year 2000 and projections for 2030. Diabetes Care, 27 (5), 1047-1053.
Germanyuk, T.A., Ivko, T.I., & Bobrytska, L.O. (2018). The study of the effectiveness of the combined therapy of diabetes mellitus based on the pharmacoeconomic analysis in Ukraine. Visnyk farmatsii – News of Pharmacy, 3, 49-53.
Pérez-Díaz, I. (2016). Diabetes mellitus. Gac. Med. Mex, 152 (1), 50-55.
Polsky, S., & Ellis, S.L. (2015). Obesity, insulin resistance, and type 1 diabetes mellitus. Curr. Opin. Endocrinol. Diabetes Obes., 22 (4), 277-282.
Barrett, E.J., Liu, Z., Khamaisi, M., King, G.L., Klein, R., Klein, B.E.K., …, & Casellini, C.M. (2017). Diabetic microvascular disease: An Endocrine Society Scientific Statement. J. Clin. Endocrinol. Metab., 102 (12), 4343-4410.
Elraiyah, T., Tsapas, A., Prutsky, G., Domecq, J.P., Hasan, R., Firwana, B., … Murad, M.H. (2016). A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers. J. Vasc. Surg., 63 (2), 46S-58S.e1-2
Agrawal, N.K., & Kant, S. (2014). Targeting inflammation in diabetes: Newer therapeutic options. World J. Diabetes, 5 (5), 697-710.
Mokhort, T.V. (2015). Khronicheskiye oslozhneniya sakharnogo diabeta: fokus na pentoksifillin [Chronic complications of diabetes mellitus: focus on pentoxifylline]. Meditsinskiye novosti – Medical News, 4, 4-9 [in Russian].
Ahmed, M., Reffat, S.A., Hassan, A., & Eskander, F. (2017). Platelet-rich plasma for the treatment of clean diabetic foot ulcers. Ann. Vasc. Surg., 38, 206211.
Martinez-Zapata, M.J., Martí-Carvajal, A.J., Solà, I., Expósito, J.A., Bolíbar, I., Rodríguez, L., ..., Zaror, C. (2016). Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst. Rev., (5), CD006899.
Mazo, V.K. Sidorova, Yu.S., Zorin, S.N., & Kochetkova, A.A. (2016). Streptozototsinovyye modeli sakharnogo diabeta [Streptozotocin models of diabetes mellitus]. Voprosy pitaniya – Problems of Nutrition, 85, 4, 14-21 [in Russian].
Al-Awar, A., Kupai, K., Veszelka, M., Szűcs, G., Attieh, Z., Murlasits, Z., ..., & Varga, C. (2016). Experimental Diabetes Mellitus in Different Animal Models. J. Diabetes Res., 2016, 9051426.
Fenske, R.J., Cadena, M.T., Harenda, Q.E., Wienkes, H.N., Carbajal, K., Schaid, M.D., …, Kimple, M.E. (2017). The inhibitory G protein α-subunit, gαz, promotes type 1 diabetes-like pathophysiology in NOD mice. Endocrinology, 158 (6), 1645-1658.
Furman, B.L. (2015). Streptozotocin-induced diabetic models in mice and rats. Curr. Protoc. Pharmacol., 70, 1, 5.47.1-20.
Heinonen, S.E., Genové, G., Bengtsson, E., Hübschle, T., Åkesson, L., Hiss, K., …, Gomez, M.F. (2015). Animal models of diabetic macrovascular complications: key players in the development of new therapeutic approaches. J. Diabetes Res., 2015, 404085.
King, A., & Bowe, J. (2016). Animal models for diabetes: Understanding the pathogenesis and finding new treatments. Biochem. Pharmacol., 99, 1-10.
King, A.J. (2012). The use of animal models in diabetes research. Br. J. Pharmacol., 166 (3), 877-894.
Kundiiev, Yu. (Ed.) (2003). Antolohiia bioetyky [Anthology of bioethics]. Lviv: Bak [in Ukrainian].
Kishkun, A.A. (2008). Klinicheskaya laboratornaya diagnostika [Clinical laboratory diagnostics]. Moscow: GEOTAR-Media [in Russian].
Borovikov, V.P., & Borovikov, I.P. (1998). Statistica – Statisticheskiy analiz i obrabotka dannykh v srede Windows [Statistica – Statistical analysis and data processing in Windows]. Moscow: Informats, izdat. dom “Filin” [in Russian].