PMID:
Oxid Med Cell Longev. 2018 ;2018:1421438. Epub 2018 May 2. PMID: 29854073
Abstract Title:
Carnosic Acid, a Natural Diterpene, Attenuates Arsenic-Induced Hepatotoxicity via Reducing Oxidative Stress, MAPK Activation, and Apoptotic Cell Death Pathway.
Abstract:
The present studies have been executed to explore the protective mechanism of carnosic acid (CA) against NaAsO-induced hepatic injury. CA exhibited a concentration dependent (1-4 M) increase in cell viability against NaAsO(12 M) in murine hepatocytes. NaAsOtreatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both inandsystems. Significant activation of MAPK, NF-B, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO-exposed hepatic cells. CA could significantly counteract with redox stress and ROS-mediated signaling and thereby attenuated NaAsO-mediated hepatotoxicity. NaAsO(10 mg/kg) treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice (= 6). The serum biochemical and haematological parameters were significantly altered in the NaAsO-exposed mice (= 6). Simultaneous treatment with CA (10 and 20 mg/kg) could significantly reinstate the NaAsO-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.
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