Carnosic Acid, a Natural Diterpene, Attenuates Arsenic-Induced Hepatotoxicity via Reducing Oxidative Stress, MAPK Activation, and Apoptotic Cell Death Pathway. (2nd May 2018)

• Record Type: Journal Article
• Authors: Das, Sonjit; Joardar, Swarnalata; Manna, Prasenjit; Dua, Tarun K.; Bhattacharjee, Niloy; Khanra, Ritu; Bhowmick, Shovonlal; Kalita, Jatin; Saha, Achintya; Ray, Supratim; De Feo, Vincenzo; Dewanjee, Saikat
• Other Names: Carneiro Maria F. H. Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2018(2018)
• Publication Date: 2018-05-02
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2018/1421438
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : The present studies have been executed to explore the protective mechanism of carnosic acid (CA) against NaAsO2 -induced hepatic injury. CA exhibited a concentration dependent (1–4 μ M) increase in cell viability against NaAsO2 (12 μ M) in murine hepatocytes. NaAsO2 treatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both in in vitro and in vivo systems. Significant activation of MAPK, NF- κ B, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO2 -exposed hepatic cells. CA could significantly counteract with redox stress and ROS-mediated signaling and thereby attenuated NaAsO2 -mediated hepatotoxicity. NaAsO2 (10 mg/kg) treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice (n = 6 ). The serum biochemical and haematological parameters were significantly altered in the NaAsO2 -exposed mice (n = 6 ). Simultaneous treatment with CA (10 and 20 mg/kg) could significantly reinstate the NaAsO2 -mediated toxicological effects in the liver. Molecular docking and dynamics predicted the possible interaction patterns and the stability of interactions between CA and signal proteins. ADME prediction anticipated the drug-likeness characteristics of CA. Hence, there would be an option to employ CA as a new therapeutic agent against As-mediated toxic manifestations in future.