N Somchit1, F Sanat, E H Gan, I A W Shahrin, A Zuraini. 1. Pharmacology and Toxicology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Malaysia. nhareet@medic.upm.edu.my
Abstract
INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat musculoskeletal disorders, inflammation and to control pain. Virtually all NSAIDs are capable of producing liver injury ranging from mild reversible elevation of liver enzymes to severe hepatic necrosis. METHODS: Mice were dosed intraperitoneally with mefenamic acid either one day at 100mg/kg and 200mg/kg, or 14 days dosing at 50mg/kg/day and 100mg/kg/day. Plasma was taken for alanine aminotransferase activity. Mice were sacrificed at the end of the study. Livers were removed and weighed. Liver samples were taken for histology. results: One-day doses of mefenamic acid revealed dose-dependent hepatocyte degeneration in the liver parenchyma. There were no significant changes in plasma alanine aminotransferase activity. Interestingly, 14-day daily doses induced hepatocellular necrosis, massive degeneration and inflammation. This was accompanied by a significant increase in plasma alanine aminotransferase activity and significant increase in the liver weight in the 100mg/kg/day mefenamic acid-dosed mice. CONCLUSION: Results from this study suggest that mefenamic acid is capable of producing hepatotoxicity and care should be taken when prescribing or using this drug.
INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat musculoskeletal disorders, inflammation and to control pain. Virtually all NSAIDs are capable of producing liver injury ranging from mild reversible elevation of liver enzymes to severe hepatic necrosis. METHODS:Mice were dosed intraperitoneally with mefenamic acid either one day at 100mg/kg and 200mg/kg, or 14 days dosing at 50mg/kg/day and 100mg/kg/day. Plasma was taken for alanine aminotransferase activity. Mice were sacrificed at the end of the study. Livers were removed and weighed. Liver samples were taken for histology. results: One-day doses of mefenamic acid revealed dose-dependent hepatocyte degeneration in the liver parenchyma. There were no significant changes in plasma alanine aminotransferase activity. Interestingly, 14-day daily doses induced hepatocellular necrosis, massive degeneration and inflammation. This was accompanied by a significant increase in plasma alanine aminotransferase activity and significant increase in the liver weight in the 100mg/kg/day mefenamic acid-dosed mice. CONCLUSION: Results from this study suggest that mefenamic acid is capable of producing hepatotoxicity and care should be taken when prescribing or using this drug.
Authors: Daniel P Hall; Nicholas G Cost; Shailaja Hegde; Emily Kellner; Olga Mikhaylova; Yiwen Stratton; Birgit Ehmer; William A Abplanalp; Raghav Pandey; Jacek Biesiada; Christian Harteneck; David R Plas; Jarek Meller; Maria F Czyzyk-Krzeska Journal: Cancer Cell Date: 2014-11-10 Impact factor: 31.743
Authors: Mary Alexandra Schleiff; Noah R Flynn; Sasin Payakachat; Benjamin Mark Schleiff; Anna O Pinson; Dennis W Province; S Joshua Swamidass; Gunnar Boysen; Grover P Miller Journal: Drug Metab Dispos Date: 2020-11-25 Impact factor: 3.922