Pathophysiological aspects of wound healing in normal and diabetic foot The main cause of long-term healing of ulcers in patients with diabetic foot is considered to be direct mechanical damage when walking due to reduced sensitivity to due to neuropathy, hyperglycemia, infection and peripheral artery disease. These factors determine the standard approaches to the treatment of diabetic foot, which include: offloading, glycemic control, debridement of ulcers, antibiotic therapy and revascularization. Recently, however, disturbances in the healing process of the skin in diabetes recognized an additional factor affecting the timing of healing patients with diabetic foot. Improved understanding and correction of cellular, molecular and biochemical abnormalities in chronic wound in combination with standard of care for affords new ground for solving the problem of ulcer healing in diabetes.
The use of the anticancer drug doxorubicin (Dox) is limited due to its cardiotoxic effect. Using the method of automatic solid-phase peptide synthesis, we obtained a synthetic agonist of galanin receptors GalR1-3 [RAla14, His15]-galanine (2-15) (G), exhibiting cardioprotective properties. It was purified by high performance liquid chromatography (HPLC). The homogeneity and structure of the peptide was confirmed by HPLC, 1H-NMR spectroscopy and mass spectroscopy. The purpose of this study was to study the effect of G on the metabolism and cardiac function of rats with chronic heart failure (CHF) caused by Dox. Experiments were performed using male Wistar rats weighing 280-300 g. The control group of animals (C) was intraperitoneally treated with saline for 8 weeks; the doxorubicin group (D) of rats was intraperitoneally treated with Doх; the group of Doх + peptide G (D+G) received intraperitoneally injections of Doх and subcutaneously injections of peptide G; the peptide G group (G) was subcutaneously treated with G. At the beginning and at the end of the study, the concentration of thiobarbituric acid reactive substances (TBARS) and the activity of creatine kinase-MB (CK-MB) were determined in blood plasma; the animals were weighed, and cardiac function was assessed using echocardiography. At the end of the experiments, the hearts were used for determination of metabolites and assessment of oxidative phosphorylation in mitochondria. After 8-week treatment, animals of group D were characterized by severe heart failure, the lack of weight gain and an increase in plasma TBARS concentration and CK-MB activity. These disorders were accompanied by a decrease in the content of myocardial high-energy phosphates, a reduction inmitochondrial respiratory parameters, accumulation of lactate and glucose in the heart, and disturbances in the metabolism of alanine and glutamic and aspartic acids. Coadministration of G and Dox prevented the increase in plasma CK-MB activity and significantly reduced the plasma TBARS concentration. At the end of the experiments animals of group D+G had higher myocardial energy state and the respiratory control index of mitochondria than animals of group D, there was a decrease in anaerobic glycolysis and no changes in the amino acid content compared to the control. The peptide G significantly improved the parameters of cardiac function and caused weight gain in animals of group D+G in comparison with these parameters in group D. The obtained results demonstrate the ability of a novel agonist of galanin receptors GalR1-3 to attenuate Dox-indiced cardiotoxicity.
Резюме Цель исследования. Изучить влияние внутривенной инфузии инновационного препарата метилин, разработанного в ФГБУ «НМИЦ кардиологии» Минздрава России, обладающего антиишемическими и антиоксидантными свойствами на показатели функции сердца кроликов in vivo, поврежденных длительным введением доксорубицина. Материалы и методы. Животным опытной группы внутривенно вводили доксорубицин (2 мг на 1 кг массы тела 1 раз в неделю) в течение 8 нед, животным контрольной группы-изотонический раствор натрия хлорида. Повреждение миокарда оценивали по содержанию малонового диальдегида (МДА), тропонина I (TnI), фракции MB креатинкиназы (КК-MB) в венозной крови и по изменениям структуры левого желудочка (ЛЖ) сердца при морфологическом исследовании. Влияние метилина на функцию сердца оценивали с помощью эхокардиографии и катетеризациии ЛЖ Милларовским катетером. Результаты. Введение доксорубицина сопровождалось снижением массы тела животных, увеличением содержания маркеров повреждения сарколеммы КК-MB и тропонина, продукта перекисного окисления липидов МДА в венозной крови и нарушениям структуры мышечных волокон и микрососудов ЛЖ. Одновременно снижались показатели сократимости миокарда-увеличивались конечные диастолический и систолический размеры и уменьшались фракции укорочения и выброса по сравнению с исходными значениями. Эти изменения указывали на развитие у животных хронической сердечной недостаточности (ХСН). На этом фоне внутривенная инфузия метилина достоверно увеличивала фракции укорочения и выброса. Положительное действие метилина на показатели сократимости и расслабимости сердца сохранялось в течение 30 мин после прекращения инфузии. Метилин оказывал большее влияние на показатели функции сердца кроликов с ХСН по сравнению с животными контрольной группы, не получавших доксорубицин. Заключение. Полученные результаты указывают на возможность использования метилина для снижения дисфункции ЛЖ при ХСН.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.