title: Metabonomic analysis reveals the CCl4-induced systems alterations for multiple rat organs.
abstract: CCl(4)-induced metabonomic changes have been extensively studied for mammalian liver, and such changes have not been reported for other organs. To investigate the CCl(4) effects on other organs, we analyzed the CCl(4)-induced metabonomic changes in rat kidney, lung, and spleen using (1)H NMR-based metabonomics approaches with complementary information on serum clinical chemistry and histopathology. We found that acute CCl(4) exposure caused significant level elevation for creatine and decline for glucose, taurine, trimethylamine, uridine, and adenosine in rat kidney. CCl(4)-treatment also induced elevation of amino acids (isoleucine, leucine, valine, threonine, alanine, lysine, ornithine, methionine, tyrosine, phenylalanine, and histidine), creatine, and betaine in rat lung together with depletion of glycogen, glucose, taurine, glycine, and hypoxanthine. Furthermore, CCl(4) caused elevation of lactate, alanine, betaine, and uracil in rat spleen accompanied with decline for glucose, choline, and hypoxanthine. These observations indicated that CCl(4) caused oxidative stresses to multiple rat organs and alterations of their functions including renal osmotic regulations, accelerated glycolysis, and protein and nucleotide catabolism. These findings provide essential information on CCl(4) toxicity to multiple rat organs and suggest that systems toxicological views are required for metabonomic studies of toxins by taking many other organs into consideration apart from so-called targeted ones.
authors.affiliation: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Centre for Biospectroscopy and Metabonomics, Wuhan Centre for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China.
authors.forename: Limiao
authors.initials: L
authors.lastname: Jiang
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003401:Creatine / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D015999:Multivariate Analysis; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D012997:Solvents; D014280:Triglycerides; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003401:Creatine