PMID- 35339478 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220426 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 923 DP - 2022 May 15 TI - A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases. PG - 174910 LID - S0014-2999(22)00171-6 [pii] LID - 10.1016/j.ejphar.2022.174910 [doi] AB - Liver fibrosis is a common chronic hepatic disease. This study was done to examine the effect of pyridoxamine against thioacetamide-induced hepatic fibrosis. Animals were divided into four groups (1) control group; (2) Thioacetamide group (200 mg/kg, i.p.) twice a week for eight weeks; (3) Pyridoxamine-treated group treated with pyridoxamine (100 mg/kg/day, i.p.) for eight weeks; (4) Thioacetamide and pyridoxamine group, in which pyridoxamine was given (100 mg/kg/day, i.p.) during thioacetamide injections. Thioacetamide treatment resulted in hepatic dysfunction manifested by increased serum levels of bilirubin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Oxidative stress was noted by increased hepatic lipid peroxidation and decreased glutathione (GSH). Increased concentrations of total nitrite/nitrate, advanced glycation end products (AGEs), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), matrix metalloproteinases (MMP-2&9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were noticed in hepatic tissues. Immunostaining sections also revealed overexpression of MMP-2, MMP-9 and collagen IV. Liver fibrosis was confirmed by severe histopathological changes. Pyridoxamine improved the assessed parameters. Moreover, histopathological and immunohistological studies supported the ability of pyridoxamine to reduce liver fibrosis. The findings of the present study provide evidence that pyridoxamine is a novel target for the treatment of liver fibrosis. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Alshanwani, Aliah R AU - Alshanwani AR AD - Physiology Department, College of Medicine & King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia. FAU - Hagar, Hanan AU - Hagar H AD - Physiology Department, College of Medicine & King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia. Electronic address: hhagar@ksu.edu.sa. FAU - Shaheen, Sameerah AU - Shaheen S AD - Anatomy Department and Stem Cell Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia. FAU - Alhusaini, Ahlam M AU - Alhusaini AM AD - Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Arafah, Maha M AU - Arafah MM AD - Pathology Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia. FAU - Faddah, Laila M AU - Faddah LM AD - Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alharbi, Fatima Mb AU - Alharbi FM AD - Biochemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia. FAU - Sharma, Arun K AU - Sharma AK AD - Pharmacology Department, Amity Institute of Pharmacy, Amity University, Gurugram, Haryana, 122413, India. FAU - Fayed, Amel AU - Fayed A AD - Clinical Sciences Department, College of Medicine, Princess Nourah Bint Abdulrahman University, Saudi Arabia. Electronic address: aafayed@pnu.edu. FAU - Badr, Amira M AU - Badr AM AD - Pharmacology and Toxicology Department, Faculty of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Pharmacology and Toxicology Department, College of Pharmacy, Ain Shams University, Cairo, Egypt. LA - eng PT - Journal Article DEP - 20220323 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Glycation End Products, Advanced) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 075T165X8M (Thioacetamide) RN - 6466NM3W93 (Pyridoxamine) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Animals MH - Glycation End Products, Advanced/pharmacology MH - Liver MH - Liver Cirrhosis/chemically induced/drug therapy/pathology MH - *Matrix Metalloproteinase 2/metabolism MH - Matrix Metalloproteinases/metabolism MH - Oxidative Stress MH - Pyridoxamine/metabolism/pharmacology/therapeutic use MH - *Thioacetamide/pharmacology MH - Tissue Inhibitor of Metalloproteinase-1/metabolism OTO - NOTNLM OT - Advanced glycation end products OT - Liver fibrosis OT - Matrix metalloproteinases OT - Pyridoxamine OT - Tissue inhibitor of matrix metalloproteinase-1 OT - Transforming growth factor-beta EDAT- 2022/03/28 06:00 MHDA- 2022/04/27 06:00 CRDT- 2022/03/27 20:20 PHST- 2022/03/06 00:00 [received] PHST- 2022/03/18 00:00 [accepted] PHST- 2022/03/28 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/03/27 20:20 [entrez] AID - S0014-2999(22)00171-6 [pii] AID - 10.1016/j.ejphar.2022.174910 [doi] PST - ppublish SO - Eur J Pharmacol. 2022 May 15;923:174910. doi: 10.1016/j.ejphar.2022.174910. Epub 2022 Mar 23.