Inhibition of NF-κB and the oxidative stress -dependent caspase-3 apoptotic pathway by betaine supplementation attenuates hepatic injury mediated by cisplatin in rats.

Background: Cisplatin is a major anti-cancer drug commonly used in the treatment of various cancers; nevertheless, the associated hepatotoxicity has limited its clinical application. The aim of this investigation is to test the impact of betaine supplementation on cisplatin-induced hepatotoxicity.
Methods: Animals were allocated into four groups; normal control group (control betaine group (250 mg/kg/day, po for twenty six days), cisplatin group (single injection of 7 mg/kg, ip) and betaine + cisplatin group (received betaine for twenty one days before cisplatin injection and daily after cisplatin for five days).
Results: Cisplatin-induced liver injury was confirmed by increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Cisplatin elevated lipid peroxides, and reduced the concentrations of reduced glutathione (GSH), glutathione peroxidase (GSH-Px), catalase and superoxide dismutase (SOD) in hepatic tissues. Cisplatin increased the inflammatory mediators; nitrite and tumor necrosis factor-α (TNF- α) in hepatic tissues. Increased gene expressions of the apoptotic marker, caspase-3 and nuclear factor-kappa B (NF-κB) were observed in hepatic tissues of cisplatin-treated rats. All these changes were further confirmed by histopathological findings in cisplatin group. Pre-treatment with betaine reduced serum aminotransferases (ALT and AST), and lowered hepatic concentrations of lipid peroxides, nitrite and TNF-α while increased SOD, GSH, catalase, and GSH-Px concentrations. Moreover, the histological and immunohistochemical changes were improved.
Conclusion: The suppression of NF-κβ-mediated inflammation, oxidative stress, and caspase-3 induced apoptosis are possible mechanisms to the observed hepatoprotective effect of betaine.
(Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)