Oral administration of Cr(VI) induced oxidative stress, DNA damage and apoptotic cell death in mice.
Potassium dichromate (Cr(VI)) was given orally to Swiss mice for 1 and 5 days with the dose of 25, 50 and 100 mg/kg body weight per day, respectively. Oxidative stress including the level of reactive oxygen species (ROS), the extent of lipid peroxidation and the activity of antioxidant enzymes in liver and kidney was determined. DNA damage in peripheral blood lymphocytes was determined by single-cell gel electrophoresis (comet assay). Apoptotic cell death in liver was detected using transmission electron microscopy and TUNEL assay. The results indicated that administration of Cr(VI) had caused a significant increase of ROS level in liver both after 1 and 5 days of exposure, accompanied with a dose-dependent decrease in superoxide dismutase (SOD) and catalase (CAT) activities. The malondialdehyde (MDA) content in liver was not changed as compared to the control animals. In contrast to the liver, no significant changes were observed in kidney on ROS, SOD, CAT and MDA as compared to the control animals. Dose- and time-dependent effects were observed on DNA damage after 1 and 5 days treatment. Significant difference was observed on the number of TUNEL positive liver cells between the control and Cr(VI) treatment groups. The apoptotic cells were also identified by characteristic ultrastructural features. The results obtained from the present study showed that Cr(VI) given orally to mice could induce dose- and time-dependent effects on DNA damage, hepatic oxidative stress and hepatocytes apoptosis. No significant oxidative stress observed in kidney in the study may suggest that the way of Cr(VI) exposure is an important factor affecting its toxicity.
Wang
Xiao-Feng
XF
Department of Biochemistry & Molecular Biology, School of Medicine, Zhejiang University, Hangzhou, China.
Xing
Ming-Luan
ML
Shen
Ying
Y
Zhu
Xin
X
Xu
Li-Hong
LH
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002452:Cell Count; D002857:Chromium / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D020287:In Situ Nick-End Labeling; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D002274:Carcinogens, Environmental; D017382:Reactive Oxygen Species; D002857:Chromium; C074702:chromium hexavalent ion; D013482:Superoxide Dismutase