Different administration patterns of docosahexaenoic acid in combating cytotoxic manifestations due to arsenic trioxide (acute promyelocytic leukemia drug) induced redox imbalance in hepatocytes

作者：Abhilash S; Siviyasankar R; Binu P; Arathi P; Nair R Harikumaran^*

来源：Prostaglandins & Other Lipid Mediators, 2018, 136: 64-75.

DOI：10.1016/j.prostaglandins.2018.05.002

• Arsenic trioxide
• Hepatotoxicity
• Docosahexaenoic acid
• Chang liver cells
• Oxidative stress

Docosahexaenoic acid (DHA) obtained from fish and plant sources is an essential dietary fatty acid and an important cell membrane structural component. The acute promyelocytic leukemia (APL) drug arsenic trioxide (As2O3), causes hepatotoxicity. We evaluated the protective potential of DHA as pre/combination/post-administration patterns against As2O3 induced toxicity. The therapeutic concentration of As2O3 (10 mu M) resulted in cytotoxicity with a significant (p < 0.05) variation from the control group. Reduced cell viability, morphological alterations, enhanced LDH release and apoptosis were observed. The oxidative stress markers (lipid per oxidation, nitric oxide, and ROS) and hepatic enzymes (AST and ALT) and intracellular calcium levels were found to be elevated by the As2O3 administration. Reduction in levels of mitochondrial membrane potential, cellular free radical scavenging potential, intracellular proteins, ATPases and major antioxidants (catalase, SOD, GSH, and GPx) were also observed. Administration of DHA along with As2O3 as pre/combination administration patterns offered protection against As2O3 induced cytotoxicity at significant levels (p < 0.05) from As2O3 alone treated group. The cell viability and morphology were protected with reduced LDH release and apoptosis. The hepatic enzymes and oxidative stress markers were reduced with replenishment of mitochondrial membrane potential, free radical scavenging potential, intracellular proteins, ATPases and antioxidant levels. DHA pre/combination administration patterns showed protective potential against As2O3 with pre-treatment being the best and the post-treatment method failed to produce any protective effect.

• 出版日期2018-5