The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice
Joint Authors
Wang, Yong
Pang, Qing
Jin, Hao
Man, Zhongran
Liu, Huichun
Ke, Xiquan
Tan, Yi
Lu, Zheng
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-01-06
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
Serotonin is involved in the pathological processes of several liver diseases via the regulation of inflammatory response and oxidative stress.
We aimed to investigate the role of serotonin in Concanavalin A- (Con A-) induced acute liver injury (ALI).
ALI was induced in C57B/6 wild-type (WT) mice and tryptophan hydroxylase 1 (TPH1) knockout mice through tail vein injection of Con A (15 mg/kg body weight).
Another group of TPH1 knockout ALI mice was supplied with 5-hydroxytryptophan (5-HTP) in advance to recover serotonin.
The blood and liver tissues of mice were collected in all groups.
Markedly increased serum levels of serotonin were identified after the injection of Con A.
Increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and stronger hepatic tissue pathology were detected, suggesting that serotonin could mediate Con A-induced liver damage.
Serotonin significantly facilitated the release of serum and intrahepatic inflammatory cytokines, including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-17A (IL-17A), interferon-gamma (IFN-γ), and tumor necrosis-alpha (TNF-α), after the administration of Con A.
In addition, serotonin significantly increased the intrahepatic levels of oxidative stress markers malonaldehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) and decreased antioxidant stress indicator glutathione (GSH) in Con A-treated mice.
Additionally, serotonin promoted hepatocyte apoptosis and autophagy based on B-cell lymphoma-2 (Bcl-2), Bcl-2-asociated X protein (Bax), and Beclin-1 levels and TUNEL staining.
More importantly, serotonin activated nuclear factor kappa B (NF-κB) and upregulated the hepatic expressions of high mobility group protein B1 (HMGB1), toll-like receptor-4 (TLR4), and downstream molecules in Con A-mediated liver injury.
Serotonin 2A receptor was upregulated in liver tissue after Con A injection, and serotonin 2A receptor antagonist Ketanserin protected against Con A-induced hepatitis.
These results indicated that serotonin has the potential to aggravate Con A-induced ALI via the promotion of inflammatory response, oxidative stress injury, and hepatocyte apoptosis and the activation of hepatic HMGB1-TLR signaling pathway and serotonin 2A receptor.
American Psychological Association (APA)
Pang, Qing& Jin, Hao& Ke, Xiquan& Man, Zhongran& Wang, Yong& Tan, Yi…[et al.]. 2020. The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1205382
Modern Language Association (MLA)
Pang, Qing…[et al.]. The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-16.
https://search.emarefa.net/detail/BIM-1205382
American Medical Association (AMA)
Pang, Qing& Jin, Hao& Ke, Xiquan& Man, Zhongran& Wang, Yong& Tan, Yi…[et al.]. The Role of Serotonin in Concanavalin A-Induced Liver Injury in Mice. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1205382
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205382