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Hepatoprotective Effect of Curcumin on Hepatocellular Carcinoma Through Autophagic and Apoptic Pathways

Ahmed M. Elmansi, Amro A. El-Karef, Mamdouh M. El-Shishtawy, Laila A. Eissa


Background and rationale. Microtubule-associated protein light chain 3-II (LC3-II), and Sequestosome-1 (SQSTM1) are proteins that can be used as markers for autophagic pathway. Bcl-2 protein is reported to be inversely correlated with apoptosis. We aimed to investigate the effects of curcumin on liver inflammation and fibrosis up to the first dysplastic stage of Hepatocellular carcinoma (HCC) induced by Thioacetamide (TAA) in rats and to clarify the effects of curcumin on LC3-II, SQSTM1, and Bcl-2. Male Sprague-Dawley rats were randomized into four groups: Control group, TAA group, Curcumin low-dose group, and Curcumin highdose group. The last three groups received TAA 200 mg/kg i.p. twice weekly for 18 weeks. Oxidative stress markers as hepatic malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity were measured by colorimetric methods. Hepatic SQSTM1 concentration was measured by ELISA, and gene expression levels of Bcl-2, and LC3-II were measured by RT-PCR. We also investigated the in vitro effect of curcumin on HepG2 cells viability through MTT assay, and the involvement of autophagy in this effect. Results. Curcumin increased the survival percent in rats, decreased -fetoprotein (AFP) concentration, and serum aspartate aminotransferase (AST) activity, and increased serum albumin concentration. Curcumin also significantly reduced oxidative stress in liver, inhibited apoptosis, and induced autophagy. In vitro, curcumin (50 μM) decreased HepG2 cells viabilityand the concentration of SQSTM1. Conclusions. Curcumin leads to protection against TAA induced HCC up to the first dysplastic stage through activating autophagic pathway and inhibiting apoptosis. Also, the antioxidant activity of curcumin almost prevents liver fibrosis.

Key words. Liver fibrosis., LC3-II., SQSTM1., Bcl-2. ROS.

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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