Ketsa O V, Marchenko M M
Yuriy Fedkovych Chernivtsi National University, Chernivtsy, Ukraine.
Vopr Pitan. 2019;88(2):32-39. doi: 10.24411/0042-8833-2019-10015. Epub 2019 Mar 13.
Oxidative stress is a universal mechanism of cellular damage of hepatocytes, leading to a decrease in the detoxification function of the liver, which is especially important during oncogenesis. An early correction of these mechanisms by lipophilic essential nutrients could increase the effectiveness of antitumor treatment and prevent the development and progress of cancer. to study the effect of separate and combined use of ω-3 PUFA and vitamin D on the intensity of free radical processes, mitochondrial swelling and cytochrome c content in the liver mitochondrial fraction of the tumor-bearing rats during the intensive growth of the tumor has been studied. . Studies were carried out on white outbred female rats weighing 130-150 g, which were divided into 5 groups (each n=12). Guerin's carcinoma was used as a model of malignant neoplasm. Carcinoma transplantation was carried out by subcutaneous injection of 0.5 ml of a 30% suspension of cancer cells into saline in the upper thigh region of the right limb. ω-3 PUFAs (120 mg/kg of body weight, per os) and vitamin D (600 IU/kg of body weight, per os) were pre-administered for 28 days before the transplantation of Guerin's carcinoma and after transplantation for the entire period of tumor growth in the body (14 days). Liver mitochondrial fraction was isolated by differential centrifugation. The intensity of lipid peroxidation was judged by using spectrophotometry by the content of primary, secondary, and tertiary products in isopropanol extracts. The rate of formation of the superoxide radical was recorded in a test with nitro-blue tetrazolium, the swelling of mitochondria was assessed by a decrease in the optical density of isolated mitochondria, the content of cytochrome c in the mitochondrial and cytosolic fractions was determined by multi-wavelength visible light spectroscopy. . An increase in the content of primary (diene and triene conjugates), secondary (ketodienes; conjugated trienes; TBA-active products) and terminal (Schiff bases) lipid peroxidation products with a simultaneous increase in the generation of superoxide anion-radical was found in the liver mitochondrial fraction of the tumorbearing rats. With the administration of ω-3 PUFA and vitamin D, both separately and especially when used together, a decrease in the intensity of free radical processes in liver mitochondrial fraction of tumor-bearing rats has been observed. At the same time, mitochondrial swelling decreased, this prevented the release of cytochrome c from mitochondria into cytosol. . The administration of the complex ω-3 PUFA and vitamin D reduces the processes of lipid peroxidation in the mitochondrial fraction of the liver of tumor-bearing rats while simultaneously restoring the functional ability of mitochondria.
氧化应激是肝细胞细胞损伤的普遍机制，会导致肝脏解毒功能下降，这在肿瘤发生过程中尤为重要。通过亲脂性必需营养素对这些机制进行早期纠正，可提高抗肿瘤治疗的效果，并预防癌症的发生和发展。本研究旨在探讨在肿瘤快速生长期间，单独及联合使用ω-3多不饱和脂肪酸（PUFA）和维生素D对荷瘤大鼠肝脏线粒体部分自由基过程强度、线粒体肿胀及细胞色素c含量的影响。研究选用体重130 - 150 g的白化远交雌性大鼠，分为5组（每组n = 12）。采用格林氏癌作为恶性肿瘤模型。通过在右下肢大腿上部皮下注射0.5 ml癌细胞在生理盐水中的30%悬浮液进行癌移植。在移植格林氏癌前28天及移植后肿瘤在体内生长的整个时期（14天），预先给予ω-3多不饱和脂肪酸（120 mg/kg体重，经口）和维生素D（600 IU/kg体重，经口）。通过差速离心分离肝脏线粒体部分。通过分光光度法根据异丙醇提取物中初级、次级和三级产物的含量判断脂质过氧化强度。用硝基蓝四唑试验记录超氧阴离子自由基的形成速率，通过分离线粒体光密度的降低评估线粒体肿胀，用多波长可见光光谱法测定线粒体和细胞溶质部分细胞色素c的含量。在荷瘤大鼠的肝脏线粒体部分发现，初级（二烯和三烯共轭物）、次级（酮二烯；共轭三烯；TBA活性产物）和终末（席夫碱）脂质过氧化产物含量增加，同时超氧阴离子自由基生成增加。给予ω-3多不饱和脂肪酸和维生素D后，无论是单独使用还是尤其联合使用时，均观察到荷瘤大鼠肝脏线粒体部分自由基过程强度降低。同时，线粒体肿胀减轻，这阻止了细胞色素c从线粒体释放到细胞溶质中。给予ω-3多不饱和脂肪酸和维生素D复合物可减少荷瘤大鼠肝脏线粒体部分的脂质过氧化过程，同时恢复线粒体的功能能力。
