The Role Of5-lipoxgenase On Oxidative Stress Induced By4-aminobiphenyl In Human Bronchial Epithelial Cell

[Objective]The role of5-lipoxygenase and other oxidative met-abolism enzymes involved in oxidative stress and oxidative damage in human bronchial epithelial cell induced by4-aminobiphenyl exposure were studied to provide novel clues for exploring the metabolic activat ion and injury mechanism of4-aminobiphenyl in extrahepatic tissues.[Method]The human bronchial epithelial cell used as target cells were treated with different co-ncentrations of4-aminobiphenyl(0、50、100、200μM) for24h, which the exposure dose was chosen by MTT assay. After the exposure the ROS、SOD、CAT、GSH、T-AOC. MDA and Nrf2protein level were measured in HBE cells.[Result] With the incr eased concentration of4-aminobiphenyl, the level of ROS was signific antly increased in human bronchial epithelial cells(p<0.05). The activit y of antioxidant emzyme SOD and CAT were increased first and then decreased gragually. Compared with DMSO solvent control, exposure to100、200μM of4-aminobiphenyl caused a significant decrease of S OD activity (p<0.05).The activity of CAT was significantlyincreased aft er50、100μM4-aminobiphenyl treatment. After exposure to different c oncentrations of4-aminobiphenyl, GSH and T-AOC level were reduced significantly (p<0.05), while the levels of lip id peroxidation and Nrf2protein expression were dramatically increased (p<0.05). However, the oxidative stress and oxidative damage induced by4-aminobiphenyl ca n be controled by5-LOXsiRNA and AA861. But5-LOXsiRNA and A A861have no effect on Nrf2protein expression. The inhibitor of CY P4501A (a-naphthoflavone) has a protective effect on oxidative damag e induced by4-aminobiphenyl, it also can control the expression Nrf2protein. But naproxen has no protective effect on oxidative stress and oxidative damage cuased by4-aminobiphenyl exposure.[Conclusions]4-aminobiphenyl can increase the ROS level in HBE cells, it also can affect cellular antioxidant system status and cause oxidative damage in a concentration-depend manner. The oxidative stress and oxidative da mage caused by4-aminobiphenyl can be protected by inhibiting the ac tivity of5-lipoxygenase and by the inhibitor of CYP450lA(α-naphtho flavone).