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

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. NaAsO treatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both in and systems. 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.