Ahmed Khaled Abdul-Aziz, Al-Qaisi Talal Salem, A J Jabbar Ahmed, Ismail Parween Abdul-Samad, Hussein M Raouf Mohammed M, Althagbi Hanan Ibrahmi, Wahab Bassam Ali Abed, Hassan Rawaz Rizgar, Abdulla Mahmood Ameen, Al-Dabhawi Ahmed Hameed, Saleh Musher Ismael
Department of Basic Dental Sciences, Faculty of Dentistry, Al-Ahliyya Amman University, Amman, 19328, Jordan.
Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, P.O. Box 59911, Abu Dhabi, United Arab Emirates.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 30. doi: 10.1007/s00210-025-04147-2.
Liver cirrhosis is posing a global public health concern despite improvements in early diagnosis and therapeutic innovations. The present work evaluates the acute toxicity and prophylactic effects of an O-methylated flavonoid (Ombuin) in thioacetamide (TAA)-induced liver injury in rats and its underlying mechanisms. Thirty Sprague-Dawley rats were aligned into five cages and treated for two months as follows: group A ingested orally 1% CMC + distilled water (i.p.); group B had 1% CMC + 200 mg/kg TAA i.p. (three times weekly); group C had 50 mg/kg silymarin + 200 mg/kg TAA; group D had 30 mg/kg Ombuin + TAA; group E had 60 mg/kg Ombuin + mg/kg TAA. The non-toxic effects of Ombuin were evidenced by the lack of any toxicity incidence in rats ingested with up to 500 mg/kg. The TAA inoculation provoked significant hepatic intoxication confirmed by histopathological indications, alteration of tissue architecture, cellular proliferation, endothelial injury, enlarged hepatic nucleus, cytoplasmic vacuolation, collagen deposition, and elevated necrotizing tissues. The oxidative stress and inflammation process was noticeably initiated following TAA delivery to rats evidenced by down-regulation of SOD, CAT, GPx, and IL- 10, while, up-regulating the MDA and TNF-α and IL- 6 cytokines. TAA injection stimulated cellular proliferation and apoptotic actions in injured liver tissues, indicated by increased proliferating cell nuclear antigen (PCNA) and elevated expression of Bcl- 2-associated X (Bax) proteins. Ombuin supplementation showed significant resistance against TAA-mediated hepatotoxicity, reversed those cellular alterations, and restored liver functions. These results demonstrate significant ameliorative effects of Ombuin in TAA hepatotoxic rats, which could be attributed to its anti-apoptotic, antioxidant, and anti-inflammatory potentials, making it a possible viable hepatoprotective agent for inflammatory-related hepatitis.
尽管在早期诊断和治疗创新方面有所改善，但肝硬化仍在全球范围内引起公共卫生关注。本研究评估了一种O-甲基化黄酮（奥姆布因）对硫代乙酰胺（TAA）诱导的大鼠肝损伤的急性毒性和预防作用及其潜在机制。将30只Sprague-Dawley大鼠分成五个笼子，并进行为期两个月的如下处理：A组口服1%羧甲基纤维素钠+蒸馏水（腹腔注射）；B组腹腔注射1%羧甲基纤维素钠+200mg/kg TAA（每周三次）；C组腹腔注射50mg/kg水飞蓟宾+200mg/kg TAA；D组腹腔注射30mg/kg奥姆布因+TAA；E组腹腔注射60mg/kg奥姆布因+TAA。在摄入高达500mg/kg奥姆布因的大鼠中未发生任何毒性事件，证明了奥姆布因的无毒作用。TAA接种引发了显著的肝中毒，组织病理学指标证实了组织结构改变、细胞增殖、内皮损伤、肝细胞核增大、细胞质空泡化、胶原沉积以及坏死组织增多。向大鼠注射TAA后，氧化应激和炎症过程明显启动，表现为超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和白细胞介素-10（IL-10）下调，同时丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）细胞因子上调。TAA注射刺激了受损肝组织中的细胞增殖和凋亡作用，表现为增殖细胞核抗原（PCNA）增加以及Bcl-2相关X蛋白（Bax）表达升高。补充奥姆布因显示出对TAA介导的肝毒性具有显著抗性，逆转了这些细胞改变，并恢复了肝功能。这些结果表明奥姆布因对TAA诱导的肝毒性大鼠具有显著的改善作用，这可能归因于其抗凋亡、抗氧化和抗炎潜力，使其成为一种可能对炎症相关肝炎有效的肝保护剂。
