Metabonomic study of aristolochic acid-induced nephrotoxicity in rats.
This paper describes a metabonomic study characterizing the nephrotoxicity induced by aristolochic acid (AA), a suspected kidney toxicant. For these studies, we examined the biochemical compositions of AA-treated rat urine using LC-MS and pattern recognition methods. The biochemical and histological patterns of rat groups treated with different AA sources showed distinct differences from those of the control group. Certain metabolic pathways, such as homocysteine formation and the folate cycle were significantly accelerated, while others, including arachidonic acid biosynthesis, were decreased. A subset-validation procedure using linear discriminant analysis (LDA) and selected predictive variables indicated that approximately 95% of the treated and nontreated rat urine samples were classified correctly into their respective treatment groups. The results suggested that this metabonomic approach is a promising methodology for the rapid in vivo screening of nephrotoxicity associated with ingesting multi-ingredient medicinal herb supplements, and provides a valid method for comprehending the chemical-induced perturbations in the metabolic network and the networked lesions.
Chen
Minjun
M
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, China.
Su
Mingming
M
Zhao
Liping
L
Jiang
Jian
J
Liu
Ping
P
Cheng
Jiye
J
Lai
Yijiang
Y
Liu
Yumin
Y
Jia
Wei
W
D000818:Animals; D034341:Aristolochic Acids / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002853:Chromatography, Liquid; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D008516:Medicine, Chinese Traditional / Q000009:adverse effects*; D015999:Multivariate Analysis; D010449:Peptide Mapping; D011507:Proteinuria / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar; D014118:Toxins, Biological / Q000633:toxicity*; D014508:Urea / Q000097:blood
D034341:Aristolochic Acids; D014118:Toxins, Biological; D014508:Urea; C000228:aristolochic acid I; D003404:Creatinine