Higher School of Strategic Planning in Dąbrowa Górnicza, Kościelna 6 St., 41-300 Dąbrowa Górnicza, Poland.
Wielkoszyński Medical Center and Laboratory, Piłsudskiego 10 St., 41-300 Dąbrowa Górnicza, Poland.
Oxid Med Cell Longev. 2020 Jun 8;2020:4751803. doi: 10.1155/2020/4751803. eCollection 2020.
Oxidized cholesterol derivatives are compounds with proven atherogenic and mutagenic effects. However, little is known about the effect of oxidized plant sterol derivatives (oxyphytosterols), whose structure is similar to the one of oxycholesterols. Our previous studies indicate that they have a similar profile of action, e.g., both exacerbate disorder of lipid metabolism and oxidative stress in experimental animals. The aim of the present study was to assess the effect of epoxycholesterol and epoxyphytosterols (mainly sitosterol) on the severity of nitrosative stress and the concentration of selected proinflammatory cytokines in blood and liver tissue of rats on a low-cholesterol diet. . Forty-five male Wistar rats were fed with feed containing 5,6-epoxyphytosterols (ES group, : 15), 5,6-epoxycholesterol (ECh group, : 15), and oxysterol-free feed (C group, : 15) for 90 days (daily dose of oxysterols: 10 mg/kg). At the end of the experiment, nitrotyrosine, TNF-, IL-1, IL-6, and lipid metabolism parameters were determined in blood serum. Furthermore, nitrotyrosine, TNF-, cholesterol, and triglyceride content were determined in liver homogenates.
Serum nitrotyrosine, IL-1, and TNF- concentrations as well as TNF- content in the liver were significantly higher in both groups exposed to oxysterols (ECh and ES groups) as compared to the C group. The serum IL-6 level and nitrotyrosine content in the liver were significantly higher in the ECh group, as compared to the C and ES groups. There was evidence to support the dyslipidemic effect of studied compounds.
The results indicate that oxidized plant sterols have a similar toxicity profile to that of oxycholesterols, including nitrosative stress induction, proinflammatory effect, and impaired lipid metabolism.
氧化胆固醇衍生物是具有明确致动脉粥样硬化和致突变作用的化合物。然而，人们对结构类似于氧化胆固醇的氧化植物固醇衍生物（氧杂固醇）的作用知之甚少。我们之前的研究表明，它们具有相似的作用模式，例如，两者都可加剧实验动物脂质代谢紊乱和氧化应激。本研究的目的是评估环氧胆固醇和环氧植物固醇（主要为谷固醇）对低胆固醇饮食大鼠血液和肝脏组织中一氧化氮应激严重程度和选定促炎细胞因子浓度的影响。 . 45 只雄性 Wistar 大鼠用含有 5,6-环氧植物固醇（ES 组，：15）、5,6-环氧胆固醇（ECh 组，：15）和不含胆甾醇的饲料（C 组，：15）喂养 90 天（每天胆甾醇剂量：10mg/kg）。实验结束时，测定血清中硝基酪氨酸、TNF-、IL-1、IL-6 和脂质代谢参数。此外，还测定了肝匀浆中的硝基酪氨酸、TNF-、胆固醇和甘油三酯含量。
与 C 组相比，暴露于胆甾醇（ECh 和 ES 组）的两组大鼠血清中硝基酪氨酸、IL-1 和 TNF-浓度以及肝中 TNF-含量均显著升高。与 C 和 ES 组相比，ECh 组血清中 IL-6 水平和肝中硝基酪氨酸含量显著升高。有证据表明研究化合物具有血脂异常作用。
结果表明，氧化植物固醇具有与氧化胆固醇相似的毒性特征，包括诱导一氧化氮应激、促炎作用和脂质代谢受损。
