Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2020; 12(11): 949-964
Published online Nov 27, 2020. doi: 10.4254/wjh.v12.i11.949
Aceclofenac-induced hepatotoxicity: An ameliorative effect of Terminalia bellirica fruit and ellagic acid
Ashutosh Gupta, Abhay K Pandey
Ashutosh Gupta, Abhay K Pandey, Department of Biochemistry, University of Allahabad, Prayagraj 211002, Uttar Pradesh, India
Author contributions: Pandey AK conceptualized and designed the study; Gupta A performed the experiments, collected the data, and wrote the manuscript; Gupta A and Pandey AK analyzed and interpreted the data; Pandey AK critically reviewed and finalized the manuscript. All authors have read and approved the final manuscript.
Institutional animal care and use committee statement: The study was reviewed and approved by the Institutional Animal Ethics Committee, University of Allahabad, Prayagraj, India (IAEC/AU/2019(1)/16).
Conflict-of-interest statement: The authors declare that there are no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Abhay K Pandey, PhD, Professor, Department of Biochemistry, University of Allahabad, Prayagraj - 211002, Uttar Pradesh, India. akpandey23@rediffmail.com
Received: June 16, 2020
Peer-review started: June 16, 2020
First decision: August 22, 2020
Revised: September 5, 2020
Accepted: September 22, 2020
Article in press: September 22, 2020
Published online: November 27, 2020
ARTICLE HIGHLIGHTS
Research background

Hepatotoxicity is one of the common side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Aceclofenac , a prodrug in the aryl-acetic acid class, is an oral NSAID effective in the treatment of painful inflammatory diseases. Chronic use of aceclofenac damages gastrointestinal mucosa by irritant action, causing an alteration in mucosal permeability and/or suppression of prostaglandin synthesis.

Research motivation

Previous studies on Terminalia bellirica fruit revealed that it possesses a wide range of bioactive compounds that are accountable for its antioxidant and radical scavenging potential against various types of experimental models. Moreover, its fruit has a positive impact on NSAIDs-induced liver injury. Therefore, in this study we explored the therapeutic attributes of T. bellirica fruit and ellagic acid against aceclofenac-induced hepatotoxicity and oxidative stress.

Research objectives

The major objectives were to evaluate the antioxidant and hepatoprotective activities of T. bellirica fruit ethyl acetate (Eth) and aqueous (AQ) extracts and its constituent ellagic acid against aceclofenac-induced hepatotoxicity in albino Wistar rats.

Research methods

The antioxidant activities of T. bellirica fruit extracts were measured in vitro by metal ion chelation and nitric oxide radical scavenging assays. The in vivo antioxidant and hepatoprotective effects of T. bellirica extracts (200 mg/kg) and ellagic acid (40 mg/kg) in aceclofenac-induced hepatotoxic rats were evaluated in serum and liver tissue. The ferric reducing ability of plasma and lipid peroxidation inhibition were measured in blood. Liver function markers such as ALP, GPT, GOT, LDH, γ-glutamyl transferase, creatinine, total protein, and uric acid were evaluated in rat serum and superoxide dismutase, catalase and malondialdehyde were analyzed in liver tissues using standard protocols.

Research results

T. bellirica fruit Eth extract (IC50 168 µg/mL) showed higher ion chelating ability than the AQ extract (IC50 220 µg/mL). Similarly, the Eth extract (IC50 48 µg/mL) showed comparatively better NO scavenging activity than the AQ extract (IC50 57 µg/mL). The Eth extract also decreased lipid peroxidation by 75% indicating its lipoprotective ability. The ferric reducing ability of plasma value in the EA treated rat group was significantly higher (P < 0.05) than that in the T. bellirica fruit extract treated groups in vivo. T. bellirica fruit extracts and ellagic acid treatment suppressed the toxic effect of aceclofenac in rats and improved the body weight coupled with restoration of serum liver function markers and tissue specific antioxidants.

Research conclusions

The results of the current study suggest that the administration of T. bellirica fruit extracts and ellagic acid exhibited considerable hepatoprotective efficacy against aceclofenac-induced oxidative stress and hepatic damage in Wistar rats. Abnormal levels of biomarkers may have occurred due to peroxidation reactions and biotransformation of aceclofenac in liver. These reactions were responsible for oxidative damage to cellular components. T. bellirica fruit extracts and ellagic acid treatment significantly ameliorated the hepatic injury induced by aceclofenac.

Research perspectives

T. bellirica fruit extracts and its phytoconstituent ellagic acid exhibited appreciable radical scavenging, antioxidant and hepatoprotective activity in aceclofenac-induced liver injury. However, further evaluation is warranted to reveal the complete mechanism of action of different phytoconstituents present in T. bellirica fruit which might be helpful in the development of a new therapeutic agent of natural origin.