Nephrotoxicity study of total rhubarb anthraquinones on Sprague Dawley rats using DNA microarrays.
Total rhubarb anthraquinones (TRAs) are the active therapeutic components from the rhizomes of Rheum palmatum L. (Polygonaceae), which are widely used in traditional Chinese medicines (TCMs) and have been reported to have cell toxicity recently. This study focuses on the toxicity of TRAs on Sprague Dawley (S.D.) rats. TRAs administrated per os for 13 weeks induced nephrotoxicity on S.D. rats as renal tubule epithelial cells swelled and denatured in tissue slice examination. After high-density oligonucleotide microarrays scanning, we have identified mitogen-activated protein kinase (MAPK) kinase 6 to be the target gene which causes cell cycle arrest and proliferation inhibition and contributes to nephrotoxicity on S.D. rats.
Yan
Ming
M
National Drug Screening Laboratory, China Pharmaceutical University, No. 1 ShenNong Road, E-04#, Nanjing City, 210038 Jiangsu Province, China.
Zhang
Lu-Yong
LY
Sun
Li-Xin
LX
Jiang
Zhen-Zhou
ZZ
Xiao
Xiao-He
XH
D000818:Animals; D000880:Anthraquinones / Q000302:isolation & purification / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D009153:Mutagens / Q000302:isolation & purification / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000737:chemistry / Q000633:toxicity*; D027343:Rhizome / Q000737:chemistry / Q000633:toxicity
D000880:Anthraquinones; D009153:Mutagens; D012313:RNA; D019363:Cytochrome P-450 CYP1A1; D020930:MAP Kinase Kinase Kinases; C116394:MAP kinase kinase kinase 6