Free radical processes in rat liver in experimental diabetes, malignant growth and their combination

I. Goroshinskaya, E. Frantsiyants, I. Kaplieva, L. Nemashkalova, L. Trepitaki, P. Kachesova, E. Surikova, V. Bandovkina, M. Morozova, I. Kotieva
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Abstract

Purpose of the study. To study the intensity of lipid peroxidation (LPO) and indicators of antioxidant protection in the liver of rats of different sexes with combined pathology – the growth of Guerin's carcinoma in presence of experimental type 1 diabetes mellitus.Materials and methods. The levels of malondialdehyde (MDA) and diene conjugates (DC), the activities of superoxide dismutase (SOD) and catalase, and the levels of vitamins A and D were studied by conventional spectrophotometric methods in liver tissue samples from males and females with alloxan‑induced diabetes mellitus (DM), transplanted Guerin’s carcinoma (GC) and in animals with combined pathologies (GC growth in presence of diabetes mellitus), as well as in intact rats.Results. The levels of both LPO markers in intact females were significantly higher than in males: MDA by 3 times, DC by 2 times. The development of DM led to an increase in the content of MDA and DC in the liver of males compared with intact animals, which indicated an intensification of LPO. At the same time, there was an almost twofold increase in SOD activity, a decrease in catalase activity, and an increase in the ratio of enzymes by 2.8 times. In females, there was no increase in LPO in the liver; there was only a less pronounced increase in SOD activity than in males. At the same time, SOD activity in males was 37 % higher than in females, and catalase activity, on the contrary, was lower by 33 %, which caused a twofold excess of the ratio of enzymes in males relative to females. Among animals with GC, only males had an increase in SOD by 2.5 times, a decrease in catalase activity, and an increase in the SOD/Catalase ratio by 3 times relative to intact animals, which may be due to pronounced sex differences the SOD activity and SOD/Catalase ratio in males were 3–4 times higher than that of females. The levels of MDA and DC in males with GC growing in presence of DM remained elevated, although to a somewhat lesser extent than in DM alone, while in females both indicators were reduced. The ratio of vitamins E and A increased only in males. SOD activity and SOD/Catalase coefficient in animals of both sexes with combined pathologies were significantly lower than in groups with only DM or GC.Conclusions. The data showed that diabetes mellitus changes the specificity of oncogenesis depending on the sex of the animals. Males with the growth of Guerin's carcinoma in presence of diabetes in conditions of inhibition of SOD activity and a decrease in the ratio of conjugated enzymes of the first line of antioxidant defense demonstrate an intensification of LPO accompanied by an increase in the non‑enzymatic unit of the antioxidant system, while there is no increase in LPO in females, and the indicators of antioxidant activity change to a lesser extent.
实验性糖尿病大鼠肝脏自由基过程、恶性生长及其联合
研究目的:目的:研究实验性1型糖尿病合并病理- Guerin癌生长的不同性别大鼠肝脏脂质过氧化(LPO)强度及抗氧化保护指标。材料和方法。采用常规分光光度法测定了四氧嘧啶诱导的糖尿病(DM)、移植Guerin癌(GC)、合并病变动物(糖尿病伴GC生长)及正常大鼠肝组织中丙二醛(MDA)和二烯偶联物(DC)的含量、超氧化物歧化酶(SOD)和过氧化氢酶的活性以及维生素A和D的含量。两种LPO标记物的水平均显著高于雄性:MDA高3倍,DC高2倍。DM的发生导致雄性大鼠肝脏中MDA和DC含量较正常大鼠增加,表明LPO增强。同时,SOD活性升高近2倍,过氧化氢酶活性降低,酶比升高2.8倍。在女性中,肝脏中的LPO没有增加;与男性相比,雌性的SOD活性增加不那么明显。与此同时,雄性的SOD活性比雌性高37%,过氧化氢酶活性却比雌性低33%,导致雄性的酶比是雌性的两倍。在GC动物中,只有雄性的SOD比正常动物增加了2.5倍,过氧化氢酶活性降低,SOD/过氧化氢酶比值增加了3倍,这可能是由于明显的性别差异,雄性的SOD活性和SOD/过氧化氢酶比值比雌性高3 - 4倍。在患有糖尿病的男性胃癌患者中,MDA和DC的水平仍然升高,尽管升高程度略低于单独患有糖尿病的男性,而在女性中,这两个指标都降低了。维生素E和维生素A的比例只在男性中增加。两性合并病变动物的SOD活性和SOD/过氧化氢酶系数均显著低于仅DM或gc组。数据显示,糖尿病改变了肿瘤发生的特异性,这取决于动物的性别。在糖尿病存在的情况下,在SOD活性受到抑制和抗氧化第一道防线共轭酶比例降低的情况下,雄性Guerin癌的生长表现出LPO的增强,同时抗氧化系统的非酶单位增加,而雌性的LPO没有增加,抗氧化活性指标的变化程度较小。
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