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Effectiveness of Human Erythropoietin Analogues in an Ex Vivo Model of Experimental Intestinal Ischemia
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PAVEL D. KOLESNICHENKO, SERGEY A. ALEKHIN, KONSTANTIN M. REZNIKOV, ELENA B. ARTYUSHKOVA, ANNA P. VASILEVA, NATALIA A. BYSTROVA, GALINA A. LAZAREVA, ALEXANDER A. STEPCHENKO, ALEXANDER V. FAITELSON
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| Abstract:
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Introduction: Prevention of hypoxia, protective effect of a short-term, intermittent hypoxic or ischemic episode and subsequent more severe hypoxic episodes have been known for more than thirty years when studying cardiac muscle ischemia. Currently, the concept of hypoxic preconditioning has expanded, but the condition of smooth muscles of visceral organs paid little attention to, despite their obvious importance to health. Taking into account the fact that the researchers have so far determined only the fact of ambiguous effectiveness of ischemic preconditioning for smooth muscle organs, the study of effectiveness of pharmacological preconditioning with hematopoietic and non-hematopoietic analogues of erythropoietin in the model of experimental intestinal hypoxia is being carried out for the first time and, therefore, is vital. Materials and Methods: The study was conducted on 40 Wistar male rats. Erythropoietinalpha and its non-hematopoietic analogue, carbamylated darbepoetin, were preliminarily introduced in two doses for the preconditioning effect. Subject to applicable law, sections of the large intestine were removed, and spontaneous peristalsis, a contractile response to increased potassium and acetylcholine ions were studied in vitro at the Tissue Bath Station 4-chan Sys (Biopac Systen Inc.). To simulate hypoxia, Krebs solution devoid of glucose and oxygen was used; reperfusion was simulated with a standard Krebs solution.
Results: Preconditioning induced by erythropoietin analogues does not affect “hypoxic” inhibition of spontaneous peristalsis, contractile activity induced by hyper-potassium and acetylcholine stimuli. However, high doses of erythropoietin analogues accelerate restoration of functional activity during the reperfusion period. The effectiveness of the non-hematopoietic analogue of erythropoietin carbamylated darbepoetin is comparable to that of erythropoietin alpha.
Conclusion: The obtained results confirm the ambiguous results obtained by researchers in the study of ischemic preconditioning in models of smooth muscle hypoxia. The established facts of improving recovery of the isolated intestine function during the reperfusion period will undoubtedly attract the attention of specialists in the development of protocols for further studies.
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carbamylated darbepoetin, intestinal ischemia, L-ethoxidol.
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| DOI:
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https://doi.org/10.31838/ijpr/2020.SP1.163
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