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Alteration of AP-endonuclease1 expression in curcumin-treated fibrotic rats

Ahmad R. Bassiouny, Amira Zaky, Faten Fawky, Kamal M. Kandeel

Abstract

Background. Apurinic/apyrimidinic endonuclease1/ redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA base excision repair and redox regulation of many transcription factors. It is an important pro-survival protein activated in response to oxidative stress. Increased level of this essential redox sensitive protein correlates closely with cellular survival against oxidative insults. Curcumin (diferuloylmethane) a naturally occurring compound derived from turmeric has attracted interest because of its anti-inflammatory, anti-oxidative, and chemopreventive activities. Material and methods. The current study evaluates the in vivo role of curcumin in protecting and treating liver injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats. It also addresses the possible involvement of the multifunctional protein APE1 in hepatoprotection. Analysis of APE1 expression was performed at mRNA and protein levels by reverse transcriptase (RT)-PCR and western blotting respectively. Profile of HSCs-activation related genes were assayed by RT-PCR and pro-inflammatory cytokines levels were determined by enzyme-linked immune assays. Results. Here we show that oral administration of curcumin was accompanied by a robust increase in APE1 protein and mRNA levels, and improved the histological architecture of rat liver. In addition, curcumin attenuated oxidative stress by increasing the content of hepatic glutathione within normal values, leading to the reduction in the level of lipid hydroperoxide. Curcumin remarkably suppressed inflammation by reducing levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB) and interleukin-6 (IL-6). It also inhibited hepatic stellate cells (HSCs) activation by elevating the level of PPARγ and reducing the abundance of transforming growth factor-β (TGF-β). We found that oral administration of curcumin at 200 mg/kg dose not only protected against CCl4-induced hepatic injury, but also resulted in more than two-fold induction of APE1 protein expression in CCl4-induced rat group. Conclusions. It can be concluded that curcumin reduced markers of liver damage in rats treated with CCl4, with concomitant elevation in APE1 protein level indicating a possible protective effect with unknown mechanism. The induction of DNA repair enzymes may be an important and novel strategy for hepatic protection against oxidative injury.

Key words. Apurinic/apyrimidinic endonuclease 1, Hepatic stellate cells, Curcumin, Tumor necrosis factor-α TNF-α, Nuclear factor-kappaB - NF-κB, Transforming growth factor-β TGF-β

Article Metrics

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

ALEH Hepatología CASL ACEF Médica Sur
Index Copernicus PubMed

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