Mobasher Maysa A, Germoush Mousa O, Galal El-Tantawi Hala, Samy El-Said Karim
Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, Sakaka 41412, Saudi Arabia.
Department of Clinical Pathology, El Ahrar Educational Hospital, Ministry of Health, Zagazig 44511, Egypt.
Pathogens. 2021 Jan 11;10(1):59. doi: 10.3390/pathogens10010059.
Hepatocellular carcinoma (HCC) is one of the world's most widely recognized malignant tumors that accounts for 90% of all the primary liver cancers and is a major cause of death from cancer, representing half a million deaths per year. Obesity and associated metabolic irregularities, particularly diabetes mellitus (DM) and insulin resistance, are important risk factors for the advancement of HCC. Recently, retrospective studies showed that metformin (MET) could protect the hepatic tissues in pre-existing diabetes mellitus from HCC. The purpose of this study was to assess the role of MET treatment in the pre-existing diabetic rats before and after HCC induction by diethylnitrosamine (DEN). Thirty-five male Sprague Dawley albino rats were partitioned into the following groups: Group 1 (Gp1) was the control. Gp2 was injected intraperitoneally (i.p) with streptozotocin (STZ) (80 mg/kg) and DEN (50 mg/kg/7 weeks). Gp3, Gp4, and Gp5 were injected as in Gp2 and treated with MET (150 mg/kg) before and/or after HCC induction. Biochemical parameters including liver functions, lipid profile, and oxidative stress biomarkers were determined. Furthermore, histological and immunohistochemical changes were assessed in all groups. Our results illustrated that the group of rats that were treated with STZ and DEN had significant changes in both liver functions and were associated with alterations in the liver histopathological architectures. Treatment with MET before or after HCC induction ameliorated the cellular changes in the liver tissues; however, the utmost protection was found in a group of rats, which were treated with MET before and after HCC induction.
肝细胞癌（HCC）是全球公认的恶性肿瘤之一，占所有原发性肝癌的90%，是癌症死亡的主要原因，每年导致约50万人死亡。肥胖及相关代谢紊乱，尤其是糖尿病（DM）和胰岛素抵抗，是HCC进展的重要危险因素。最近，回顾性研究表明，二甲双胍（MET）可保护糖尿病前期患者的肝组织免受HCC侵害。本研究旨在评估MET治疗在二乙基亚硝胺（DEN）诱导HCC前后对糖尿病前期大鼠的作用。将35只雄性Sprague Dawley白化大鼠分为以下几组：第1组（Gp1）为对照组。第2组腹腔注射链脲佐菌素（STZ）（80 mg/kg）和DEN（50 mg/kg/7周）。第3组、第4组和第5组注射方式同第2组，并在HCC诱导前后用MET（150 mg/kg）治疗。测定肝功能、血脂谱和氧化应激生物标志物等生化参数。此外，评估所有组的组织学和免疫组化变化。我们的结果表明，接受STZ和DEN治疗的大鼠组肝功能均有显著变化，且与肝脏组织病理学结构改变有关。在HCC诱导前后用MET治疗可改善肝组织中的细胞变化；然而，在HCC诱导前后均接受MET治疗的大鼠组中发现了最大程度的保护作用。
