Pharmaceutical composition of 1,2,4-trioxolanes with betulin in fish oil. Effect on oxidative and energy metabolism in the treatment of burns in rats

D. Malygina, P. V. Yastrebov, A. E. Fayans, I. Spitskaya, A. L. Esipovich, А. G. Soloveva, P. V. Peretyagin, N. Melnikova
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Abstract

Background. Ozonation products of unsaturated fatty acids in fats and oils – 1,2,4-trioxolanes – which contribute to the normalization of oxidative and energy metabolism in various diseases, may be a promising substance for the creation of new combined anti-burn drugs.The aim. To study the effect of 1,2,4-trioxolanes in a pharmaceutical composition with betulin, which exhibits wound-healing properties, on indicators of oxidative stress and on energy metabolism in the treatment of burns in an experiment onrats. Methods. The experiments were carried out on 50 male Wistar rats with seconddegree skin burns. We assessed the activity of glutathione reductase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, aldehyde dehydrogenase, superoxide dismutase and catalase, as well as the level of lipid peroxidation indicators.Results. The properties of 1,2,4-trioxolanes were studied and a pharmaceutical composition of 1,2,4-trioxolanes with betulin from birch bark in fish oil was developed. The effect of this composition on oxidative and energy metabolism in rats during the treatment of burns was studied. The activation of NADP/H and NAD/H dependent enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, aldehyde dehydrogenase), as well as superoxide dismutase and catalase, and the normalization of lipid peroxidation parameters under the influence of the studied composition in the treatment of burns were revealed. The effect of the composition on the energy metabolism of erythrocytes was noted, which was assessed by changes in the ratio of lactate dehydrogenase activity in the reverse and direct reactions. Morphohistological studies showed that using the composition under normal conditions and in case of a burn had no effect on the structure of the stomach wall, and also improved the condition of the burn wound on the day 10 compared to the wound condition in animals without treatment.Conclusion. The proposed composition of 1,2,4-trioxolanes and betulin in fish oil, which allows normalizing oxidative and energy metabolism and improving the condition of a burn wound without toxic effects on the stomach wall, can be used as an element of additional therapy in the treatment of burns.
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1,2,4-三氧杂环戊烷与鱼油中的白桦脂的药物成分。治疗大鼠烧伤时对氧化和能量代谢的影响
背景。油脂中不饱和脂肪酸的臭氧分解产物--1,2,4-三氧杂环戊烷--有助于各种疾病中氧化和能量代谢的正常化,可能是一种很有前途的物质,可用于制造新的抗烧伤联合药物。目的是通过在大鼠身上进行的实验,研究 1,2,4-三氧杂烷与具有伤口愈合特性的白桦脂组成的药物组合物在治疗烧伤时对氧化应激指标和能量代谢的影响。实验方法实验对象是 50 只二度皮肤烧伤的雄性 Wistar 大鼠。我们评估了谷胱甘肽还原酶、葡萄糖-6-磷酸脱氢酶、乳酸脱氢酶、醛脱氢酶、超氧化物歧化酶和过氧化氢酶的活性以及脂质过氧化指标的水平。对 1,2,4-三氧杂环戊烷的特性进行了研究,并在鱼油中添加了 1,2,4-三氧杂环戊烷和桦树皮中的桦木醇。研究了这种成分在治疗烧伤期间对大鼠氧化和能量代谢的影响。结果显示,在所研究的烧伤治疗成分的影响下,NADP/H 和 NAD/H 依赖酶(谷胱甘肽还原酶、葡萄糖-6-磷酸脱氢酶、乳酸脱氢酶、醛脱氢酶)以及超氧化物歧化酶和过氧化氢酶被激活,脂质过氧化参数恢复正常。该成分对红细胞能量代谢的影响通过逆反应和直接反应中乳酸脱氢酶活性比率的变化进行评估。形态组织学研究表明,在正常情况下和烧伤情况下使用该成分对胃壁结构没有影响,而且与未经处理的动物的伤口情况相比,第 10 天烧伤伤口的情况有所改善。鱼油中的 1,2,4-三氧杂环戊烷和白桦脂的拟议组合物可以使氧化和能量代谢正常化,改善烧伤创面的状况,而不会对胃壁产生毒性影响,可作为治疗烧伤的一种附加疗法。
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