| Autor: |
Elhadidy MG; Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.; Department of Medical Physiology, Faculty of Medicine, Al-Baha University, Al Baha, Kingdom of Saudi Arabia., Elmasry AI; Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt., El Nashar EM; Department of Anatomy, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia.; Department of Histology and Cell Biology, Faculty of Medicine, Benha University, Benha, Egypt., Alghamdi MA; Department of Anatomy, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia.; Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia., Al-Khater KM; Department of Anatomy, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia., Alasmari WA; Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia., Eladl AE; Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Hamed EM; Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Almohawes ZN; Biology Department, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Kingdon of Saudi Arabia., El-Kott AF; Department of Biology, Science College, King Khalid University, Abha, Saudi Arabia. elkottaf@kku.edu.sa.; Department of Zoology, Faculty of Science, Damanhour University, Damanhor, Egypt., Shati AA; Department of Biology, Science College, King Khalid University, Abha, Saudi Arabia., Rabei MR; Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt Kong Saloman International University, South Sinai, Egypt., Elalfy MM; Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt. |
| Abstrakt: |
Liver fibrosis is a chronic progressive disease, its resolution still unclear, and the current study explored the role of melatonin in modulation of interleukin-6 (IL-6), interleukin-4 (IL-4), transforming growth factor beta1 (TGF-β1) and urokinase plasminogen activator receptor-associated protein/Endo180 (uPARAP/Endo180) pathway in thioacetamide (TAA)-induced hepatotoxicity. Thirty two adult Sprague-Dawley rats were divided into four groups: vehicle control group, TAA-induced liver fibrosis group that was left untreated, melatonin administration before and along with TAA and melatonin along with TAA group. TTA-induced massive liver necrosis, fibrosis around portal tract and increases serum levels of liver enzymes and total bilirubin when compared with control vehicle group. While both melatonin pretreatment and treatment retained liver parenchyma and liver enzymes quite similar to control group and reduced TAA-induced liver injury. Notably, melatonin pretreatment and treatment increased collagen degradation in TAA liver injury by19, 31.7-fold respectively evidence by collagen percentage area. Melatonin also decreased the amount of thiobarbituric acid reactive compounds and retained the reduced glutathione and superoxide dismutase to basal level quite similar to control group. Additionally, melatonin significantly (P value ≤0.05) decreased the levels of TGF-β1, epidermal growth factor (EGF), hydroxyproline, tissues IL-6, caspase-3, and receptor interacting serine/threonine kinase1 (RIPK1), fibrillin-1, and - smooth muscle actin in the liver tissues while significantly (P value ≤0.05) increasing the levels of IL-4 and uPARAP/Endo180. Due to its anti-inflammatory, anti-apoptotic, and antioxidant capabilities as well as its ability to decrease hepatic stellate cell activation and fibrogenesis, these data imply that melatonin has a powerful anti-fibrotic effect. |
