Basic Study
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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
Abstract
BACKGROUND

Fluoxetine is one of the most widely prescribed anti-depressant drugs belonging to the category of selective serotonin reuptake inhibitors. Long-term fluoxetine treatment results in hepatotoxicity. Baicalin, a natural compound obtained from the Chinese herb Scutellaria baicalensis is known to have antioxidant, hepatoprotective and anti-inflammatory effects. However, the beneficial effects of baicalin against fluoxetine-induced hepatic damage have not previously been reported.

AIM

To evaluate the protective action of baicalin in fluoxetine-induced liver toxicity and inflammation.

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 oral baicalin (50 mg/kg and 100 mg/kg, respectively) while group 5 received silymarin (100 mg/kg), a standard hepatoprotective compound for comparison. Groups 6 and 7 were used as a positive control for baicalin (100 mg/kg) and silymarin (100 mg/kg), respectively. All treatments were carried out for 28 d. After sacrifice of the rats, 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-based kits. The effect of baicalin on liver was also analyzed by histopathological examination of tissue sections.

RESULTS

Fluoxetine-treated rats showed elevated levels of the 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. 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.

CONCLUSION

These findings suggested that long-term treatment with fluoxetine leads to oxidative stress via the formation of free radicals that consequently cause inflammation and liver damage. Concurrent treatment with baicalin alleviated fluoxetine-induced hepatotoxicity and liver injury by regulating oxidative stress and inflammation.

Keywords: Fluoxetine; Hepatotoxicity; Oxidative stress; Baicalin; Anti-inflammatory; Hepatoprotective and antioxidant

Core Tip: Prolonged treatment with the antidepressant drug fluoxetine causes severe hepatic damage. This study evaluated fluoxetine-induced liver damage in male albino Wistar rats. Oral fluoxetine was administered (10 mg/kg) for 28 d and caused significant alterations in serum and tissue biomarkers. Baicalin and silymarin were co-administered to facilitate the amelioration of oxidative stress-mediated hepatic damage and inflammation. The biochemical markers (total protein, albumin, total bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase, superoxide dismutase, catalase, glutathione, glutathione-S-transferase, malondialdehyde and advanced oxidation protein products) and inflammatory markers [tumor necrosis factor-α, interleukin (IL)-6, IL-10 and interferon-γ] were markedly restored to near normal levels after treatment with the natural flavonoid compound baicalin. Histopathological examination of liver slices showing cellular degeneration and increased vacuolation in the fluoxetine-treated rats also corroborated the results obtained for biomarkers of liver function, oxidative stress and inflammation. The baicalin-treated rats demonstrated normal vacuolation and cellular pattern. Thus, baicalin acts as an antioxidant, anti-inflammatory and hepatoprotective agent in mitigating fluoxetine-induced toxicity. To the best of our knowledge, this is the first study to report the hepatoprotective efficacy of baicalin in fluoxetine-induced liver damage.