Affiliation:
1. Inter-Department Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok, Thailand
2. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
3. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
Abstract
Abstract
Objectives
Indomethacin (INDO) and diclofenac (DIC) can induce intestinal cell death through induction of oxidative stress-mediated ER stress and mitochondrial dysfunction. This study investigated the cytoprotective potential of 11 polyphenols, namely caffeic acid (CAF), curcumin (CUR), epigallocatechin gallate (EGCG), gallic acid (GAL), hypophyllanthin (HYPO), naringenin (NAR), phyllanthin (PHY), piperine (PIP), quercetin (QUE), rutin (RUT) and silymarin (SLY) against these two NSAIDs in Caco-2 cells.
Methods
Reactive oxygen species (ROS) production was determined with fluorescence spectroscopy using specific probes (DHE, DCFH-DA, HPF). Cell viability and mitochondrial function were assessed by MTT and TMRE assays. The mRNA levels of Bax, Bcl-2 and CHOP proteins were determined by quantitative real-time polymerase chain reaction technique.
Key findings
All test polyphenols reduced NSAIDs-mediated ROS production. Only EGCG, QUE and RUT protected INDO-/DIC-induced cell death. These three polyphenols suppressed Bax/Bcl-2 mRNA ratio, CHOP up-regulation and MMP disruption in NSAIDs-treated cells. CAF and NAR prevented cytotoxicity from INDO, but not DIC. The cytoprotective effect of NAR, but not CAF, involved alteration of Bax/Bcl-2 mRNA ratio or MMP disruption, but not CHOP transcription.
Conclusion
The cytoprotective activity of polyphenols against NSAIDs-induced toxicity stemmed from either suppression of CHOP-related ER and mitochondria stresses or other CHOP-independent pathways, but not from the intrinsic ROS scavenging capacity.
Funder
Chulalongkorn University
100th Anniversary Chulalongkorn University Fund for Doctoral Scholarship
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
26 articles.
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