Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

n/a
Article Publish Status: FREE
Abstract Title:

Differential Cytotoxicity of Acetaminophen in Mouse Macrophage J774.2 and Human Hepatoma HepG2 Cells: Protection by Diallyl Sulfide.

Abstract Source:

PLoS One. 2015 ;10(12):e0145965. Epub 2015 Dec 29. PMID: 26714183

Abstract Author(s):

Haider Raza, Annie John

Article Affiliation:

Haider Raza

Abstract:

Non-steroidal anti-inflammatory drugs (NSAIDs), including acetaminophen (APAP), have been reported to induce cytotoxicity in cancer and non-cancerous cells. Overdose of acetaminophen (APAP) causes liver injury in humans and animals. Hepatic glutathione (GSH) depletion followed by oxidative stress and mitochondrial dysfunction are believed to be the main causes of APAP toxicity. The precise molecular mechanism of APAP toxicity in different cellular systems is, however, not clearly understood. Our previous studies on mouse macrophage J774.2 cells treated with APAP strongly suggest induction of apoptosis associated with mitochondrial dysfunction and oxidative stress. In the present study, using human hepatoma HepG2 cells, we have further demonstrated that macrophages are a more sensitive target for APAP-induced toxicity than HepG2 cells. Using similar dose- and time-point studies, a marked increase in apoptosis and DNA fragmentation were seen in macrophages compared to HepG2 cells. Differential effects of APAP on mitochondrial respiratory functions and oxidative stress were observed in the two cell lines which are presumably dependent on the varying degree of drug metabolism by the different cytochrome P450s and detoxification by glutathione S-transferase enzyme systems. Our results demonstrate a marked increase in the activity and expression of glutathione transferase (GST) and multidrug resistance (MDR1) proteins in APAP-treated HepG2 cells compared to macrophages. This may explain the apparent resistance of HepG2 cells to APAP toxicity. However, treatment of these cells with diallyl sulfide (DAS, 200μM), a known chemopreventive agent from garlic extract, 24 h prior to APAP (10 μmol/ml for 18h) exhibited comparable cytoprotective effects in the two cell lines. These results may help in better understanding the mechanism of cytotoxicity caused by APAP and cytoprotection by chemopreventive agents in cancer and non-cancerous cellular systems.

Print Options


Sayer Ji
Founder of GreenMedInfo.com

Subscribe to our informative Newsletter & get Nature's Evidence-Based Pharmacy

Our newsletter serves 500,000 with essential news, research & healthy tips, daily.

Download Now

500+ pages of Natural Medicine Alternatives and Information.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2019 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.