Abstract
Oxidative stress is a common mechanism in the cytotoxicity of cisplatin, a widely used antineoplastic agent related to hepatotoxicity. In this context, we highlight galectin-3 (Gal-3), a β-galactoside-binding protein that regulates the inflammatory response and oxidative stress, and modified citrus pectin (MCP), an inhibitor of Gal-3. Thus, this study evaluates the effect of Gal-3 inhibition with MCP on cisplatin-induced acute liver injury in Wistar rats. Animals were divided into four groups (n = 5/group): SHAM–intraperitoneal (i.p.) injection of saline for 3 days; CIS–i.p. injection of cisplatin (10 mg/kg/day) for 3 days; MCP-orogastric gavage with MCP (100 mg/kg/day) for 7 days, followed by saline via i.p.; and MCP+CIS-gavage with MCP for 7 days, followed by cisplatin via i.p. for 3 days. Cisplatin administration caused a significant weight loss in the animals from CIS and MCP+CIS, an effect corroborated by a marked reduction in the glycogen storage in hepatocytes compared to their control groups. Cisplatin also provoked a marked increase in the influx of leukocytes, liver degeneration, ROS production, and STAT3 activation in the hepatocytes, plasma levels of cytokines (IL-6, IL-10), and hepatic toxicity biomarkers (ARG1, GSTα, SDH). Cisplatin per se reduced Gal-3 levels, especially in the mitochondria of hepatocytes. On the other hand, the MCP+CIS group also showed increased levels of IL-1β, TNF-α, and GOT1, as well as raised hepatic levels of MDA production and mitochondrial respiratory complex I. In conclusion, the inhibition of Gal-3 with MCP did not protect the liver against the deleterious effects of cisplatin, indicating that Gal-3 is important for tissue, cellular, and molecular maintenance of the liver.
Author Contributions
Conceptualization, D.D.d.S. and C.D.G.; methodology, D.D.d.S., N.M.B., R.A.d.S., A.A.F.C., G.R.d.S.S. and C.D.G.; formal analysis, D.D.d.S.; resources, C.D.G.; data curation, D.D.d.S., N.M.B. and C.D.G.; writing—original draft preparation, D.D.d.S. and C.D.G.; writing—review and editing, D.D.d.S. and C.D.G.; supervision, C.D.G.; project administration, C.D.G.; funding acquisition, C.D.G. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by Fundação de Amparo à Pesquisa do Estado 9 de São Paulo—FAPESP [grant number 20/03565-2]. Diego Dias dos Santos is supported by CAPES 10 scholarship [code No. 001].
Institutional Review Board Statement
The experimental rat model was conducted according to the rules issued by the National Council for Control of Animal Experimentation (CONCEA) and approved by the Ethics Committee on Animal Use of the Federal University of São Paulo (CEUA/UNIFESP) in the meeting of 20 January 2021 (protocol code 5533211220).
Informed Consent Statement
Not applicable.
Data Availability Statement
Data will be made available upon request.
Conflicts of Interest
The authors declare no conflict of interest.
Abbreviations
| ARG1 | hepatic arginase 1 |
| GOT1 | aspartate transaminase 1 |
| GSTα | α-glutathione S-transferase |
| IL | interleukin |
| MCP | modified citrus pectin |
| MDA | malondialdehyde |
| ROS | reactive oxygen species |
| SDH | sorbitol dehydrogenase |
| TNF-α | tumor necrosis factor-α |
| STAT3 | signal transducer and activator of transcription 3 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).