Oncotarget

Research Papers:

The involvement of Nrf2 in the protective effects of (-)-Epigallocatechin-3-gallate (EGCG) on NaAsO2-induced hepatotoxicity

Xiao-Dong Han, Yan-Yan Zhang, Ke-Lei Wang, Yong-Pan Huang _, Zhong-Bao Yang and Zhi Liu

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:65302-65312. https://doi.org/10.18632/oncotarget.18582

Metrics: PDF 2553 views  |   HTML 3074 views  |   ?  


Abstract

Xiao-Dong Han1,2,3,*, Yan-Yan Zhang4,*, Ke-Lei Wang5,*, Yong-Pan Huang6,7, Zhong-Bao Yang8 and Zhi Liu9

1Department of Anesthesia, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi 710049, China

2Medical College, Yan’an University, Yan’an, Shaanxi 716000, China

3Department of Anesthesia, Xianyang Rainbow Hospital, Xianyang, Shaanxi 712021, China

4Department of Pharmacology, Guizhou Medical University, Guiyang, Guizhou 550004, China

5Department of Pharmacology, Guiyang Nursing Vocational College, Guiyang, Guizhou 550025, China

6Department of Pharmacology, School of Medicine, Hunan Normal University, Changsha, Hunan 410013, China

7Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, China

8Department of Pharmacy, Affiliated Changsha Hospital of Hunan Normal University, Changsha, Hunan 410006, China

9Department of Urology Surgery, The Second Affiliated Hospital of Guizhou Medical University, Kaili, Guizhou 556000, China

*These authors have contributed equally to this work

Correspondence to:

Yong-Pan Huang, email: [email protected]

Zhong-Bao Yang, email: [email protected]

Zhi Liu, email: [email protected]

Keywords: NaAsO2, (-)-Epigallocatechin-3-gallate (EGCG), hepatotoxicity, oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2)

Received: November 24, 2016     Accepted: April 27, 2017     Published: June 21, 2017

ABSTRACT

Arsenic exposure produces hepatotoxicity. The common mechanism determining its toxicity is the generation of oxidative stress. Oxidative stress induced by arsenic leads to the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. (-)-Epigallocatechin-3-gallate (EGCG) possesses a potent antioxidant capacity and exhibits extensive pharmacological activities. This study aims to evaluate effects of EGCG on arsenic-induced hepatotoxicity and activation of Nrf2 pathway. Plasma activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were measured; Histological analyses were conducted to observe morphological changes; Biochemical indexes such as oxidative stress (Catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), reactive oxygen species (ROS)), Nrf2 signaling related genes (Nrf2, Nqo1, and Ho-1) were assessed. The results showed that EGCG inhibited arsenic-induced hepatic pathological damage, liver ROS level and MDA level. Arsenic decreases the antioxidant enzymes SOD, GPX, and CAT activity and the decrease was inhibited by treatment of EGCG. Furthermore, EGCG attenuated the retention of arsenic in liver tissues and improved the expressions of Nrf2 signaling related genes (Nrf2, Nqo1, and Ho-1). These findings provide evidences that EGCG may be useful for reducing hepatotoxicity associated with oxidative stress by the activation of Nrf2 signaling pathway. Our findings suggest a possible mechanism of antioxidant EGCG in preventing hepatotoxicity, which implicate that EGCG may be a potential treatment for arsenicosis therapy.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 18582