Institute of Pathophysiology "Ljubodrag Buba Mihailovic", Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Center for Endocrine Surgery, Clinical Center of Serbia, Belgrade, Serbia.
Curr Med Chem. 2021;28(16):3249-3268. doi: 10.2174/0929867327666201104151025.
Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that contributes to the inflammatory response to chemical liver injury. This cytokine exhibits pro- and anti-inflammatory effects depending on the etiology and stage of liver disease.
Our study aimed to investigate the role of MIF in oxidative stress and inflammation in the liver, and modulatory effects of betaine on MIF in thioacetamide (TAA)-induced chronic hepatic damage in mice.
The experiment was performed on wild type and knockout MIF-/- C57BL/6 mice. They were divided into the following groups: control; Bet-group that received betaine (2% wt/v dissolved in drinking water); MIF-/- mice group; MIF-/-+Bet; TAA-group that received TAA (200 mg/kg b.w.), intraperitoneally, 3x/week/8 weeks); TAA+Bet; MIF-/-+TAA, and MIF-/-+TAA+Bet. In TAA- and Bet-treated groups, animals received the same doses. After eight weeks of treatment, blood samples were collected for biochemical analysis, and liver specimens were prepared for the assessment of parameters of oxidative stress and inflammation.
In MIF-/-mice, TAA reduced transaminases, γ-glutamyltranspeptidase, bilirubin, malondialdehyde (MDA), oxidative protein products (AOPP), total oxidant status (TOS), C-reactive protein (CRP), IL-6, IFN-γ, and increased thiols and total antioxidant status (TAS). Betaine attenuated the mechanism of MIF and mediated effects in TAA-induced liver injury, reducing transaminases, γ-glutamyltranspeptidase, bilirubin, MDA, AOPP, TOS, CRP, IL-6, IFN-g, and increasing thiols.
MIF is a mediator in hepatotoxic, pro-oxidative, and proinflammatoryeffects of TAA-induced liver injury. MIF-targeted therapy can potentially mitigate oxidative stress and inflammation in the liver, but the exact mechanism of its action requires further investigation. Betaine increases anti-oxidative defense and attenuates hepatotoxic effects of MIF, suggesting that betaine can be used for the prevention and treatment of liver damage.
巨噬细胞移动抑制因子（MIF）是一种多功能细胞因子，可引发化学性肝损伤的炎症反应。该细胞因子在疾病的病因和阶段的不同，表现出促炎和抗炎的双重作用。
本研究旨在探讨 MIF 在肝脏氧化应激和炎症中的作用，以及甜菜碱对硫代乙酰胺（TAA）诱导的慢性肝损伤小鼠中 MIF 的调节作用。
该实验在野生型和 MIF-/- C57BL/6 敲除型小鼠中进行。它们被分为以下几组：对照组；给予甜菜碱（2%wt/v，溶于饮用水中）的 Bet 组；MIF-/- 组；MIF-/-+Bet 组；给予 TAA（200mg/kg b.w.），腹腔内注射，每周 3 次/共 8 周）的 TAA 组；TAA+Bet 组；MIF-/-+TAA 组和 MIF-/-+TAA+Bet 组。在 TAA 和甜菜碱处理组中，动物给予相同剂量。治疗 8 周后，采集血液样本进行生化分析，并制备肝组织标本，评估氧化应激和炎症参数。
在 MIF-/- 小鼠中，TAA 降低了转氨酶、γ-谷氨酰转肽酶、胆红素、丙二醛（MDA）、氧化蛋白产物（AOPP）、总氧化剂状态（TOS）、C 反应蛋白（CRP）、白细胞介素 6（IL-6）、干扰素 γ（IFN-γ），并增加了硫醇和总抗氧化状态（TAS）。甜菜碱减弱了 MIF 的作用机制，并介导了 TAA 诱导的肝损伤，降低了转氨酶、γ-谷氨酰转肽酶、胆红素、MDA、AOPP、TOS、CRP、IL-6、IFN-γ，增加了硫醇。
MIF 是 TAA 诱导的肝损伤中致肝毒性、促氧化和促炎作用的介质。针对 MIF 的治疗方法可能潜在减轻肝脏的氧化应激和炎症，但确切的作用机制仍需进一步研究。甜菜碱增加了抗氧化防御，减弱了 MIF 的肝毒性作用，提示甜菜碱可用于预防和治疗肝损伤。
