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Oxid Med Cell Longev. 2018 May 2;2018:1421438. doi: 10.1155/2018/1421438. eCollection 2018.

Carnosic Acid, a Natural Diterpene, Attenuates Arsenic-Induced Hepatotoxicity via Reducing Oxidative Stress, MAPK Activation, and Apoptotic Cell Death Pathway.

Author information

1
Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
2
Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam 785006, India.
3
Department of Chemical Technology, University of Calcutta, Kolkata 700009, India.
4
Department of Pharmaceutical Sciences, Assam University, Silchar 788011, India.
5
Department of Pharmacy, University of Salerno, Fisciano 84084, Italy.

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 μM) increase in cell viability against NaAsO2 (12 μM) 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-κB, 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.

PMID:
29854073
PMCID:
PMC5954942
DOI:
10.1155/2018/1421438
[Indexed for MEDLINE]
Free PMC Article

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