Toxic Effects of Docosahexaenoic Acid Treatment in the Rat Liver BRL-3A Cell.

The cytotoxicity of docosahexaenoic acid (DHA) on normal cells is still unclear. This study investigated the effects of DHA on the cytotoxicity and possible mechanism in the BRL-3A cell. The cultured rat liver BRL-3A cell line was treated with 50, 100 and 200 μM DHA for 24 h. The cell viability was increased in the 50 and 100 μM DHA treatments, but decreased in the 200 μM DHA treatment. The 50, 100 and 200 μM DHA treatments increased the proportion of the apoptotic cells, the levels of lactate dehydrogenase (LDH), alkaline phosphatase (AKP) and IL-6 in the supernatant, and the ratio of the phosphonated p38MAPK to the p38MAPK (p-p38/p38) protein in the cells. The expression of TGF beta-activated kinase 1 (TAK1), nuclear transcription factor-κB p65 (NF-κB p65) and the inhibitor of NF-κB alpha (IκBα) mRNA, and the ratio of the phosphonated IκBα (p-IκBα) to IκBα protein were increased in the 200 μM DHA treatment, while the ratio of phosphonated extracellular regulated protein kinases (p-ERK) to ERK protein was decreased in the 200 μM DHA treatment. These results indicate that DHA-treated (50, 100 and 200 μM) BRL-3A cells for 24 h promotes cell apoptosis and inflammatory response, and the p38 MAPK, ERK and NF-κB signal pathways were involved in mediating the apoptosis and inflammatory response.