Mono-(2-ethylhexyl) phthalate induces injury in human umbilical vein endothelial cells.
Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a widespread environmental contaminant and has been proved to have potential adverse effects on the reproductive system, carcinogenicity, liver, kidney and developmental toxicities. However, the effect of MEHP on vascular system remains unclear. The main purpose of this study was to evaluate the cytotoxic effects of MEHP on human umbilical endothelial cells (HUVEC) and its possible molecular mechanism. HUVEC cells were treated with MEHP (0, 6.25, 12.5, 25,50 and 100 µM), and the cellular apoptosis and mitochondrial membrane potential as well as intracellular reactive oxygen species were determined. In present study, MEHP induced a dose-dependent cell injury in HUVEC cell via an apoptosis pathway as characterized by increased percentage of sub-G1, activation of caspase-3, -8 and -9, and increased ratio of Bax/bcl-2 mRNA and protein expression as well as cytochrome C releasing. In addition, there was obvious oxidative stress, represented by decreased glutathione level, increased malondialdehyde level and superoxide dismutase activity. N-Acetylcysteine, as an antioxidant that is a direct reactive oxygen species scavenger, could effectively block MEHP-induced reactive oxygen species generation, mitochondrial membrane potential loss and cell apoptosis. These data indicated that MEHP induced apoptosis in HUVEC cells through a reactive oxygen species-mediated mitochondria-dependent pathway.
Department of General Thoracic Surgery, Tongji Hospital Attached to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Jin-Bao
JB
Ban
Department of General Thoracic Surgery, Tongji Hospital Attached to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Xiao-Wu
XW
Fan
Department of General Thoracic Surgery, Tongji Hospital Attached to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Qi
Q
Huang
Department of General Thoracic Surgery, Tongji Hospital Attached to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Bin-Feng
BF
Li
Department of General Thoracic Surgery, Tongji Hospital Attached to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Chen
C
Chen
Department of General Thoracic Surgery, Tongji Hospital Attached to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
Hua-Chuan
HC
Zhang
Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shun-Qing
SQ
Xu
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D045304:Cytochromes c / Q000096:biosynthesis; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D045304:Cytochromes c; D004051:Diethylhexyl Phthalate; D013482:Superoxide Dismutase; D020169:Caspases; C016599:mono-(2-ethylhexyl)phthalate; D005978:Glutathione; D000111:Acetylcysteine