Hwang Geun Hye, Jeon Yu Jin, Han Ho Jae, Park Soo Hyun, Baek Kyoung Min, Chang Woochul, Kim Joong Sun, Kim Lark Kyun, Lee You-Mie, Lee Sangkyu, Bae Jong-Sup, Jee Jun-Goo, Lee Min Young
College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 702-701, Korea.
Department of Veterinary Physiology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
J Vet Sci. 2015;16(1):17-23. doi: 10.4142/jvs.2015.16.1.17. Epub 2015 Mar 18.
Butylated hydroxyanisole (BHA) is a synthetic phenolic compound consisting of a mixture of two isomeric organic compounds: 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole. We examined the effect of BHA against hydrogen peroxide (H2O2)-induced apoptosis in primary cultured mouse hepatocytes. Cell viability was significantly decreased by H2O2 in a dose-dependent manner. Additionally, H2O2 treatment increased Bax, decreased Bcl-2, and promoted PARP-1 cleavage in a dose-dependent manner. Pretreatment with BHA before exposure to H2O2 significantly attenuated the H2O2-induced decrease of cell viability. H2O2 exposure resulted in an increase of intracellular reactive oxygen species (ROS) generation that was significantly inhibited by pretreatment with BHA or N-acetyl-cysteine (NAC, an ROS scavenger). H2O2-induced decrease of cell viability was also attenuated by pretreatment with BHA and NAC. Furthermore, H2O2-induced increase of Bax, decrease of Bcl-2, and PARP-1 cleavage was also inhibited by BHA. Taken together, results of this investigation demonstrated that BHA protects primary cultured mouse hepatocytes against H2O2-induced apoptosis by inhibiting ROS generation.
丁基羟基茴香醚(BHA)是一种合成酚类化合物,由两种异构有机化合物的混合物组成:2-叔丁基-4-羟基茴香醚和3-叔丁基-4-羟基茴香醚。我们研究了BHA对原代培养的小鼠肝细胞中过氧化氢(H2O2)诱导的细胞凋亡的影响。H2O2以剂量依赖性方式显著降低细胞活力。此外,H2O2处理以剂量依赖性方式增加Bax、降低Bcl-2并促进PARP-1裂解。在暴露于H2O2之前用BHA预处理可显著减轻H2O2诱导的细胞活力下降。H2O2暴露导致细胞内活性氧(ROS)生成增加,而用BHA或N-乙酰半胱氨酸(NAC,一种ROS清除剂)预处理可显著抑制这种增加。用BHA和NAC预处理也可减轻H2O2诱导的细胞活力下降。此外,BHA还抑制H2O2诱导的Bax增加、Bcl-2降低和PARP-1裂解。综上所述,本研究结果表明,BHA通过抑制ROS生成来保护原代培养的小鼠肝细胞免受H2O2诱导的细胞凋亡。