Lead induces oxidative stress, DNA damage and alteration of p53, Bax and Bcl-2 expressions in mice.
Oxidative stress is considered as a possible molecular mechanism involved in lead toxicity. This study was carried out to investigate whether lead acetate could induce oxidative stress in mice, and the following damages as well. Lead acetate was given orally to mice for 4 weeks at doses of 0, 10, 50, 100mg/kg body weight every other day, respectively. Production of reactive oxygen species (ROS) and malondialdehyde (MDA) were measured as indicators of oxidative stress. DNA damage in peripheral blood lymphocytes was determined by comet assay. Ultrastructure alteration was detected using transmission electron microscopy. The alterations of p53, Bax, and Bcl-2 expression were determined by western blotting. The results showed that lead acetate significantly increased the levels of ROS and MDA in mice. Meanwhile, severe DNA damage and ultrastructure alterations were obviously observed. In addition, p53 and Bax expressions increased and the imbalance of Bax/Bcl-2 occurred. Therefore, it strongly suggests that lead may induce oxidative stress and change the expressions of apoptosis-related proteins in mouse liver.
Xu
Jin
J
Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.
Lian
Ling-jun
LJ
Wu
Chen
C
Wang
Xiao-feng
XF
Fu
Wen-yu
WY
Xu
Li-hong
LH
D000818:Animals; D015153:Blotting, Western; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D007854:Lead / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D007854:Lead; D008315:Malondialdehyde; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases