Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2016; 22(21): 4999-5011
Published online Jun 7, 2016. doi: 10.3748/wjg.v22.i21.4999
Phosalone-induced inflammation and oxidative stress in the colon: Evaluation and treatment
Seyedeh Farnaz Ghasemi-Niri, Faheem Maqbool, Maryam Baeeri, Mahdi Gholami, Mohammad Abdollahi
Seyedeh Farnaz Ghasemi-Niri, Faheem Maqbool, Maryam Baeeri, Mahdi Gholami, Mohammad Abdollahi, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411, Iran
Faheem Maqbool, Mohammad Abdollahi, International Campus, Tehran University of Medical Sciences, Tehran 1417614411, Iran
Author contributions: Ghasemi-Niri SF performed the majority of experiments and analyzed the data; Baeeri M performed the molecular investigations; Gholami M participated in treatment of animals; Ghasemi-Niri SF, Maqbool F and Abdollahi M designed, coordinated the research and wrote the paper; and Abdollahi M conceived the study.
Supported by Tehran University of Medical Sciences, No. 93-02-45-26666 (in part).
Institutional review board statement: The study was reviewed and approved by the Tehran University of Medical Sciences Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the (Tehran University of Medical Sciences) (IACUC protocol: [http://research.tums.ac.ir/informatics/77/Animal%20Research.doc]).
Conflict-of-interest statement: The authors received the partial research funding from Tehran University of Medical Sciences (TUMS). Mohammad Abdollahi is a Professor of Pharmacology and Toxicology at TUMS.
Data sharing statement: Everything about the methods, statistics, and results data are clearly stated in the article with details. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Mohammad Abdollahi, PhD, Professor, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Enghelab Avenue, Tehran 1417614411, Iran. mohammad@tums.ac.ir
Telephone: +98-21-66959104 Fax: +98-21-66959104
Received: February 11, 2016
Peer-review started: February 13, 2016
First decision: March 31, 2016
Revised: April 8, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: June 7, 2016
Abstract

AIM: To investigate the side effects of phosalone on intestinal cells and to evaluate benefits of ellagic acid (EA) as a remedy.

METHODS: In order to conduct an in vivo study, a rat model was used. The rats were divided into ten groups based on the materials used in the experiment and their dosage. The first group was fed normally. The second group was administered EA through gavage. Next Four groups were given (1/3, 1/5, 1/10, 1/20) LD50 phosalone; an organophosphorus compound. The last four groups received (1/3, 1/5, 1/10, 1/20) LD50 phosalone and of EA. After one month, the rats were sacrificed and their colon cells were examined to evaluate the level of inflammation, proteins and oxidative stress markers.

RESULTS: The results of this research show that phosalone elevates oxidative stress and changes the level of tumor necrosis factor-a (TNF-α), interlukin-6β (IL-6β) and nuclear factor (NF)-κB proteins. EA administration reduced phosalone toxicity and changed oxidative stress and inflammatory markers for all phosalone doses. Overall changes in reduction of TNF-α (230.47 ± 16.55 pg/mg protein vs 546.43 ± 45.24 pg/mg protein, P < 0.001), IL-6β (15.85 ± 1.03 pg/mg protein vs 21.55 ± 1.3 pg/mg protein, P < 0.05), and NF-κB (32.47 ± 4.85 pg/mg protein vs 51.41 ± 0.71 pg/mg protein, P < 0.05) manifest that the efficacy of EA is more viable for 1/3 LD50 dose of phosalone. Furthermore, EA is effective to counteract the negative outcomes of oxidative stress. When EA was used to treat 1/3 LD50 of phosalone’s side effects, it improved the level of AChE activity (48.5% ± 6% vs 25% ± 7%, P < 0.05), TTM (0.391 ± 0.008 mmol/L vs 0.249 ± 0.032 mmol/L, P < 0.05), FRAP (46.04 ± 5.005 μmol/L vs 18.22 ± 1.9 μmol/L, P < 0.01) and MPO (0.222 ± 0.019 U/mg protein vs 0.387 ± 0.04 U/mg protein, P < 0.05).

CONCLUSION: This research highlights that EA is effective to alleviate the side effects of phosalone by reducing the level of oxidative stress and inflammatory proteins.

Keywords: Organophosphorus, Phosalone, Ellagic acid, Inflammation, Oxidative stress, Colon

Core tip: This research uses a rat model to evaluate the colon related side effects of phosalone which is a member of the organophosphorus family. After feeding different dosages of phosalone to the rats for one month, the colon tissue of the rats were studied using oxidative stress and pathology tests. Both tests show that the higher doses of phosalone elevate reactive oxygen species (ROS), tumor necrosis factor-α, interlukin-6β and nuclear factor-κB proteins which result in more inflammation. In our study, ellagic acid (EA) which is a strong antioxidant reduced phosalone-induced side effects. The oxidative stress and pathology results concluded that EA helps reducing inflammation and ROS.