Bagchi M, Bagchi D, Balmoori J, Ye X, Stohs S J
Department of Pharmaceutical and Administrative Sciences, Creighton University Health Sciences Center, Omaha, NE 68178, USA.
Free Radic Biol Med. 1998 Jul 15;25(2):137-43. doi: 10.1016/s0891-5849(98)00063-x.
Naphthalene is a bicyclic aromatic compound that is widely used in various domestic and commercial applications including lavatory scent disks, soil fumigants and moth balls. However, little information is available regarding the mechanism of naphthalene toxicity. We have assessed the concentration-dependent in vitro effects of naphthalene on increased lipid peroxidation, cytochrome c reduction, hydroxyl radical production, modulation of intracellular oxidized states by laser scanning confocal microscopy, and DNA fragmentation in cultured macrophage J774A.1 cells. The cells were incubated with 0-500 microM concentrations of naphthalene for 0, 12 and 24 h at 37 degrees C. Concentration- and time-dependent changes were observed. No significant changes were observed with concentrations of naphthalene up to 100 microM. At 24 h, lipid peroxidation increased by 1.8-, 2.4- and 2.9-fold at 200, 300 and 500 microM concentrations of naphthalene. Approximately 2.0-, 3.1- and 4.6-fold increases in cytochrome c reduction were observed at 200, 300 and 500 microM concentrations of naphthalene, respectively, at this time point demonstrating the production of superoxide anion, while under the same conditions approximately 2.4-, 3.2- and 4.9-fold increases in hydroxyl radical production were observed, respectively. Following incubation of these cells with 200 and 500 microM concentrations of naphthalene 2.3- and 4.7-fold increases in fluorescence intensity were observed, respectively, as compared to the untreated cells. At 24 h, approximately 1.8-, 2.3- and 3.0-fold increases in DNA fragmentation were observed following incubation with 200, 300 and 500 microM concentrations of naphthalene, respectively. Naphthalene also produced concentration- dependent decreases in cell viability. At the 12 h time point, significant changes were observed only with 300 and 500 microM concentrations of naphthalene. These results demonstrate that naphthalene may induce toxic manifestations by enhanced production of oxygen free radicals, resulting in lipid peroxidation and DNA damage.
萘是一种双环芳香化合物，广泛应用于各种家庭和商业用途，包括厕所香薰盘、土壤熏蒸剂和樟脑丸。然而，关于萘毒性机制的信息却很少。我们评估了萘在体外对培养的巨噬细胞J774A.1中脂质过氧化增加、细胞色素c还原、羟基自由基产生、通过激光扫描共聚焦显微镜调节细胞内氧化状态以及DNA片段化的浓度依赖性影响。将细胞在37℃下用0 - 500微摩尔浓度的萘孵育0、12和24小时。观察到浓度和时间依赖性变化。萘浓度高达100微摩尔时未观察到显著变化。在24小时时，200、300和500微摩尔浓度的萘使脂质过氧化分别增加了1.8倍、2.4倍和2.9倍。在这个时间点，200、300和500微摩尔浓度的萘分别使细胞色素c还原增加了约2.0倍、3.1倍和4.6倍，表明产生了超氧阴离子，而在相同条件下，羟基自由基产生分别增加了约2.4倍、3.2倍和4.9倍。用200和500微摩尔浓度的萘孵育这些细胞后，与未处理的细胞相比，荧光强度分别增加了2.3倍和4.7倍。在24小时时，用200、300和500微摩尔浓度的萘孵育后，DNA片段化分别增加了约1.8倍、2.3倍和3.0倍。萘还导致细胞活力呈浓度依赖性下降。在12小时时间点，仅在300和500微摩尔浓度的萘时观察到显著变化。这些结果表明，萘可能通过增强氧自由基的产生诱导毒性表现，导致脂质过氧化和DNA损伤。
