Abstract
Sodium arsenite (NaAsO2) has been recognized as a worldwide health concern. Hydrangea macrophylla (HM) is used as traditional Chinese medicine possessing antioxidant activities. The study was performed to investigate the therapeutic role and underlying molecular mechanism of HM on NaAsO2-induced toxicity in human liver cancer (HepG2) cells and liver in mice. The hepatoprotective role of HM in HepG2 cells was assessed by using 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT), reactive oxygen species (ROS), and lactate dehydrogenase (LDH) assays. Histopathology, lipid peroxidation, serum biochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blot analyses were performed to determine the protective role of HM against NaAsO2 intoxication in liver tissue. In this study, we found that co-treatment with HM significantly attenuated the NaAsO2-induced cell viability loss, intracellular ROS, and LDH release in HepG2 cells in a dose-dependent manner. Hepatic histopathology, lipid peroxidation, and the serum biochemical parameters alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were notably improved by HM. HM effectively downregulated the both gene and protein expression level of the mitogen-activated protein kinase (MAPK) cascade. Moreover, HM well-regulated the Bcl-2-associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) ratio, remarkably suppressed the release of cytochrome c, and blocked the expression of the post-apoptotic transcription factor caspase-3. Therefore, our study provides new insights into the hepatoprotective role of HM through its reduction in apoptosis, which likely involves in the modulation of MAPK/caspase-3 signaling pathways.
Highlights
Inorganic arsenic compounds are heavy metal toxicants recognized as human carcinogens [1,2]
Based on the traditional uses and pharmacological actions of the active component of Hydrangea macrophylla (HM), our study investigates the hepatoprotective activities of HM and underlying molecular mechanisms involved in the action of NaAsO2-induced oxidative stress in liver
We demonstrated that HM can be used as a novel indigenous phytomedicine due to its strong hepatoprotective effects against NaAsO2-mediated oxidative stress in vitro and in vivo
Summary
Inorganic arsenic compounds are heavy metal toxicants recognized as human carcinogens [1,2]. Sodium arsenite is the most hazardous inorganic arsenic compound for human and animal health [3]. Arsenic is found in the environment surrounding the industrial and natural sources, raising eco-friendly public health concerns due to modern globalization [4]. Trivalent arsenical (arsenite) in ground water is the foremost source of arsenicosis, affecting more than 140 million people globally, in India, Bangladesh, and neighboring countries [5]. Epidemiological investigations reveal links between arsenicosis and pathogenesis of various adverse health effects such as liver disorders, vascular diseases, diabetes, and cancer [6,7]. Oxidative stress due to the excessive release of free radicals has been implicated in NaAsO2-mediated damage in liver, kidney, heart, brain, skin and other tissues [10]
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