Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Apr 27, 2022; 14(4): 729-743
Published online Apr 27, 2022. doi: 10.4254/wjh.v14.i4.729
Baicalin provides protection against fluoxetine-induced hepatotoxicity by modulation of oxidative stress and inflammation
Risha Ganguly, Ramesh Kumar, Abhay K Pandey
Risha Ganguly, Ramesh Kumar, Abhay K Pandey, Department of Biochemistry, University of Allahabad, Prayagraj 211002, India
Author contributions: Ganguly R performed the research and wrote the manuscript; Ganguly R and Kumar R analyzed the data; Pandey AK designed the research study, critically reviewed and revised the manuscript; and all authors have read and approved the final manuscript.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals, registered IAEC approval is No. IAEC/AU/2017(1)/003.
Conflict-of-interest statement: The authors declare 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Abhay K Pandey, PhD, Professor, Department of Biochemistry, University of Allahabad, University Road, Katra, Prayagraj 211002, India. akpandey23@rediffmail.com
Received: July 23, 2021
Peer-review started: July 23, 2021
First decision: September 5, 2021
Revised: September 17, 2021
Accepted: March 25, 2022
Article in press: March 25, 2022
Published online: April 27, 2022
Processing time: 273 Days and 0.6 Hours
ARTICLE HIGHLIGHTS
Research background

Fluoxetine is one of the most commonly prescribed drugs for depression and anxiety disorders. Prolonged use of fluoxetine results in hepatic toxicity. Baicalin is a natural compound obtained from the ancient Chinese herb Scutellaria baicalensis. Baicalin is known to possess several antioxidant, anti-inflammatory, anticancer, neuroprotective, cardioprotective and hepatoprotective effects.

Research motivation

The hepatotoxic effects of fluoxetine following prolonged treatment have been reported previously. As baicalin has anti-inflammatory and hepatoprotective properties, the aim of this study was to evaluate the hepatoprotective and anti-inflammatory properties of baicalin when co-administered with fluoxetine.

Research objectives

The objective of this study was to assess the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.

Research methods

Male albino Wistar rats were divided into seven groups. Group 1 was the normal control. Oral fluoxetine was administered at 10 mg/kg body weight to groups 2, 3, 4 and 5. In addition, groups 3 and 4 were also co-administered with oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg). Groups 6 and 7 were used as positive controls for baicalin (100 mg/kg) and silymarin (100 mg/kg). All treatments were carried out for 28 d. Biomarkers of oxidative stress [superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione-S-transferase (GST), advanced oxidation protein products (AOPP), malondialdehyde (MDA)], and liver injury [alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein, albumin, bilirubin] were studied in serum and tissue using standard protocols and diagnostic kits. Inflammatory markers [tumor necrosis factor (TNF-α), interleukin (IL)-6, IL-10 and interferon (IFN)-γ] in serum were evaluated using ELISA kits. The effect of baicalin on the liver was also analyzed by histopathological examination of tissue sections.

Research results

Fluoxetine-treated rats showed elevated levels of serum liver function markers (total bilirubin, ALT, AST, and ALP) and inflammatory markers (TNF-α, IL-6, IL-10 and IFN-γ), with a decline in total protein and albumin levels. The biochemical markers of oxidative stress such as SOD, CAT, GST, GSH, MDA and AOPP in the liver tissue homogenate were also altered indicating a surge in reactive oxygen species leading to oxidative damage. Histological examination of liver tissue also showed degeneration of hepatocytes. Concurrent administration of baicalin (50 and 100 mg/kg) restored the biomarkers of oxidative stress, inflammation and hepatic damage in serum as well as in liver tissues to near normal levels.

Research conclusions

The results suggested that prolonged fluoxetine treatment leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Co-administration of baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.

Research perspectives

Baicalin exhibited considerable hepatoprotective activity at a dose of 100 mg/kg and it was found to be comparable to the standard compound silymarin at the same dose. Therefore, baicalin can be used along with fluoxetine to prevent hepatic toxicity and inflammation. However, further research is needed for a better understanding of the key pathways and mechanisms that could explain the protective effects of baicalin against fluoxetine-induced liver injury, oxidative damage and particularly the anti-inflammatory response.