Combined effects of repeated administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyls on kidneys of male rats.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) are persistent environmental contaminants that exist as complex mixtures in the environment, but the possible interactions of TCDD and PCBs have not been systematically investigated. The main objective of this study was to investigate the combined nephrotoxic effects of TCDD and PCBs on rats and to reveal the potential interactions between TCDD and PCBs. Male Sprague-Dawley rats were intragastrically administered TCDD (10 microg/kg), PCBs (Aroclor 1254, 10 mg/kg), or the combination (10 microg/kg TCDD + 10 mg/kg Aroclor 1254). After 12 consecutive days of exposure, all treatments induced nephrotoxicity, as evidenced by significant increases in the levels of serum creatinine and blood urea nitrogen, changes of kidney histopathology, and significant renal oxidative stress. Most of these effects were more remarkable in the combined-exposure group. Furthermore, all treatments induced renal cytochrome P450 1A1 (CYP1A1) protein expression, and the induction was more conspicuous in the combined-exposure group. These findings suggested that the nephrotoxicity induced by TCDD and PCBs in the present study might be attributable to the high expression of CYP1A1. In addition, the result of the two-way analysis of variance revealed that the combined effects of TCDD and PCBs were complicated, being additive, synergistic, or antagonistic depending on the selection of toxicity end points under the present experimental condition. This study demonstrates that combined exposure to TCDD and PCBs induced significant nephrotoxicity in rats, and there were complicated interactions between the two pollutants on the nephrotoxicity.
Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention of PLA, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing, 100071, People's Republic of China.
Chun-Feng
CF
Lu
Yi-Mei
YM
Wang
Shuang-Qing
SQ
Peng
Li-Bo
LB
Zou
De-Hong
DH
Tan
Gang
G
Liu
Ze
Z
Fu
Qiao-Xu
QX
Wang
Jing
J
Zhao
D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D000072317:Polychlorinated Dibenzodioxins; D020111:Chlorodiphenyl (54% Chlorine); D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D019363:Cytochrome P-450 CYP1A1; D013482:Superoxide Dismutase; D005978:Glutathione