Articles You Might Have Missed
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ARTICLES YOU MIGHT HAVE MISSED
Articles You Might Have Missed Alexis L. Cates 1
&
Richard J. Chen 1 & Laura B. Roper 1 & Steven J. Walsh 1
Received: 16 October 2020 / Revised: 16 October 2020 / Accepted: 19 October 2020 # American College of Medical Toxicology 2020
Keywords Acetaminophen . Acute liver failure . Opioid use disorder . Beta-adrenergic antagonists
Article #1: Rivera P, Vargas A, Pastor A, et al.: Differential hepatoprotective role of the cannabinoid CB1 and CB2 receptors in paracetamol-induced liver injury. Br J Pharmacol 2020;177(14):3309-3326. Background: It is known that an acute overdose or chronic supratherapeutic use of paracetamol (acetaminophen, APAP) can lead to drug-induced liver injury (DILI) due to the accumulation of N-acetyl-4-benzoquinoneimine (NAPQI). Hepatocytes and nonparenchymal liver cells can produce two endogenous cannabinoids, anandamide and 2-AG that are involved in a lipid signaling system. Under normal hepatic physiology, these two cannabinoids are degraded by enzymes (fatty acid amide hydrolase and monoacylglycerol lipase; respectively) and have little activity at cannabinoid (CB)1 and 2 receptors due to low levels of receptor expression. Liver injury appears to upregulate CB1 and CB2 receptors, thus leading to the hypothesis that endogenous cannabinoids might serve as a therapeutic target for liver disease. Previous studies indicated that blocking the CB1 receptor and CB2 receptor activation would result in hepatoprotective functions with antifibrogenic and antiinflammatory effects. Research Question: Does endogenous cannabinoid signaling through CB1 and CB2 receptors play a role in liver fibrosis and inflammation associated with APAP overdose? Methods: Several mouse models were used to evaluate acute and repeated APAP administration causing DILI. The APAP was orally administered at 750 mg/kg. A second (experimental) solution containing arachidonyl-2′chloroethylamide (ACEA; a CB1 receptor agonist) and JWH015 (a CB2 receptor agonist) in a DMSO solution (vehicle) was injected intraperitoneally at 10 mg/kg into the Supervising Editor: Daniel Brooks, MD * Alexis L. Cates [email protected] 1
Division of Medical Toxicology, Department of Emergency Medicine, Albert Einstein Healthcare Network, 5501 Old York Road, Korman B-14, Philadelphia, PA 19141, USA
experiment group. All animals fasted for 13 hours to avoid food-induced changes to liver. There were several different experiment groups depending on what was being analyzed. The first experimental design looked at several groups (each with 8 mice): administration of the vehicle solution and one acute APAP dose followed by euthanasia and analysis at 6 hours (group 1), 24 hours (group 2), and 48 hours (group 3). Wide-type (normal) mice and mice without CB2 receptors received either a single dose of either APAP or the experimental solution and were then killed and analyzed at 24 hours. A fifth group included wide-type mice who received the vehicle solution or JHW015 1 hour before acute APAP administration and then killed a
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