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.
Highlights
Inorganic arsenic is a major environmental pollutant with multiple toxic effects in animal and human populations [1, 2]
The presented study describes the effects of EGCG on the NaAsO2-induced nuclear factor erythroid 2-related factor 2 (Nrf2) signaling for hepatotoxicity
Literatures have reported that the toxic effects of arsenic are due to its ability to induce reactive oxygen species [13]
Summary
Inorganic arsenic is a major environmental pollutant with multiple toxic effects in animal and human populations [1, 2]. Arsenic entering to human body may lead to exceed the permissible limit and cause serious toxicity to human body. Arsenic causes marked damage in various organs, including the liver [5]. The molecular mechanisms of hepatotoxicity caused by arsenic are not fully unclear. At present, emerging evidences have indicated that toxic manifestations of arsenic are mainly attributed to oxidative stress [6,7,8]. It has widely been accepted mechanism to explain the toxicity induced by arsenic [8]. In order to reduce arsenic-induced oxidative stress, the development of effective therapeutic strategies is urgently needed. Medications with antioxidants are potentially to decrease the hepatotoxicity induced by arsenic
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