MiR-155 Dysregulation Is Associated with the Augmentation of ROS/p53 Axis of Fibrosis in Thioacetamide-Induced Hepatotoxicity and Is Protected by Resveratrol
Amal F. Dawood,
Suliman Al Humayed,
Maha A. Momenah,
Mohamed El-Sherbiny,
Hend Ashour,
Samaa S. Kamar,
Asmaa M. ShamsEldeen,
Mohamed A. Haidara,
Bahjat Al-Ani,
Hasnaa A. Ebrahim
Affiliations
Amal F. Dawood
Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
Suliman Al Humayed
Department of Internal Medicine, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia
Maha A. Momenah
Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
Mohamed El-Sherbiny
Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia
Hend Ashour
Department of Physiology, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia
Samaa S. Kamar
Department of Histology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 12624, Egypt
Asmaa M. ShamsEldeen
Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 12624, Egypt
Mohamed A. Haidara
Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 12624, Egypt
Bahjat Al-Ani
Department of Physiology, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia
Hasnaa A. Ebrahim
Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia
Liver fibrosis is a hallmark of thioacetamide (TAA) intoxications. MicroRNAs (miRs), such as miR-155, have been implied in the pathogenesis of liver disease, and regulated by the antioxidant and anti-inflammatory compound resveratrol (RES). The link between reactive oxygen species (ROS), tumour suppressor p53 (p53), and liver fibrosis-during the pathogenesis of TAA-induced liver injury-associated with miR-155 dysregulation with and without RES incorporation has not been previously studied. Therefore, one group of rats received TAA injections of 200 mg/kg; twice a week at the beginning of week 3 for 8 weeks (TAA group; or model group), whereas the protective group was pretreated daily with RES suspension (20 mg/kg; orally) for the first two weeks and subsequently sustained on receiving both RES and TAA until being sacrificed at the 10th week. Liver injuries developed in the model group were confirmed by a significant (p p ≤ 0.0234) protected by resveratrol (RES + TAA). In addition, we observed a significant (p < 0.0001) correlation between ROS/p53 axis mediated liver fibrosis and miR-155. Thus, TAA intoxication induced miR-155 imbalance and ROS/p53-mediated liver fibrosis, with resveratrol, conversely displaying beneficial hepatic pleiotropic effects for a period of 10 weeks.
