Mohd Efendy Goon Mohd Danial, Zulkanain Nur Izzati, Sheikh Abdul Kadir Siti Hamimah, Ab Rahim Sharaniza, Mazlan Musalmah, Abd Latip Normala, Abdul Aziz Mardiana, Mohd Noor Norizal
Department of Biochemistry, Faculty of Medicine, Universiti Teknologi MARA (UiTM), Cawangan Selangor, Sungai Buloh, Selangor, Malaysia.
Institute for Pathology, Laboratory and Forensics (I-PPerForM), Universiti Teknologi MARA (UiTM), Cawangan Selangor, Sungai Buloh, Selangor, Malaysia.
Transl Gastroenterol Hepatol. 2022 Jan 25;7:2. doi: 10.21037/tgh.2020.02.20. eCollection 2022.
The prevalence of non-alcoholic fatty liver disease (NAFLD) in Asian countries is increasing at concerning level. Currently, no specific treatment available to prevent its oxidative stress and progression except for diet and lifestyle changes. Vitamin E such as tocotrienol-rich fraction (TRF) has a promising potential in preventing NAFLD progression. TRF is a potent antioxidant but has low bioavailability due to the use of long-chain triglycerides (LCT) as its carrier. Testing of potential therapeutic agents such as TRF are commonly carried out using animal models. These animal models are often costly due to limited access to the supply especially Asian countries and predisposed to high transportation cost. Lower expenditure of NAFLD model should be investigated without forfeiting the outcome of study. Therefore, this study addresses the gap by utilizing the ICR mice as NAFLD model through dietary modification and testing on the newly formulated TRF with combination of palm kernel oil (PKO) as a medium-chain triglycerides (MCT) carrier.
Fifteen ICR strain mice were randomly group into two control and one treatment group. Control groups received high-fat diet (HFD) only and standard diet while treatment group was given HFD with TRF (200 mg/kg/day). Study was carried out for 10 weeks. Weights were recorded twice a week. At the end of study, all mice were euthanized and data such weights, waist circumference and random blood glucose were recorded. Liver from each mouse were prepared for histology assessment.
Mice mean weights and random blood sugar showed no difference between group (P>0.05) while significance waist circumference was larger in HFD and TRF groups compared to SD (P<0.05). Histology assessment showed steatosis in TRF group had lower severity compared to HFD group. NAFLD activity score (NAS) was lower in treatment group compared to HFD group.
TRF showed promising potential as an agent to reduce NAFLD progression in ICR mice. Further study at gene and protein levels are required to fully elucidate the mechanism of this new TRF formulation in reducing NAFLD progression.
亚洲国家非酒精性脂肪性肝病（NAFLD）的患病率正以令人担忧的速度上升。目前，除了饮食和生活方式改变外，没有可用于预防其氧化应激和进展的特定治疗方法。维生素E，如富含生育三烯酚的组分（TRF），在预防NAFLD进展方面具有潜在的前景。TRF是一种有效的抗氧化剂，但由于使用长链甘油三酯（LCT）作为其载体，生物利用度较低。对潜在治疗剂如TRF的测试通常使用动物模型进行。这些动物模型由于供应有限，特别是在亚洲国家，获取困难且运输成本高，往往成本高昂。应研究在不影响研究结果的情况下降低NAFLD模型的费用。因此，本研究通过将ICR小鼠作为NAFLD模型，通过饮食调整，并测试新配制的以棕榈仁油（PKO）作为中链甘油三酯（MCT）载体的TRF来填补这一空白。
将15只ICR品系小鼠随机分为两个对照组和一个治疗组。对照组仅接受高脂饮食（HFD）和标准饮食，而治疗组给予含TRF（200毫克/千克/天）的HFD。研究进行10周。每周记录两次体重。在研究结束时，对所有小鼠实施安乐死，并记录体重、腰围和随机血糖等数据。对每只小鼠的肝脏进行组织学评估。
各组小鼠的平均体重和随机血糖无差异（P>0.05），而与标准饮食组相比，HFD组和TRF组的腰围显著更大（P<0.05）。组织学评估显示，TRF组的脂肪变性严重程度低于HFD组。治疗组的NAFLD活动评分（NAS）低于HFD组。
TRF显示出作为降低ICR小鼠NAFLD进展的药物的潜在前景。需要在基因和蛋白质水平上进行进一步研究，以充分阐明这种新的TRF制剂降低NAFLD进展的机制。
