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Role of Gal-3 on cisplatin-induced acute liver injury model
* 1, 2 , 2 , 1 , 2 , 2 , 1, 2
1  Biosciences Graduate Program, Institute of Biosciences, Letters and Exact Sciences, São Paulo State University (IBILCE/Unesp), São José do Rio Preto, SP, Brazil
2  Structural and Functional Biology Graduate Program, Paulista School of Medicine, Federal University of São Paulo (EPM/UNIFESP), São Paulo, SP, Brazil
Academic Editor: Alexander E. Kalyuzhny


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 4 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 cisplastin 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, 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.

Keywords: cytokines, hepatotoxicity, inflammation, mitochondria, modified citrus pectin, ROS.