Metabolic profiling studies on the toxicological effects of realgar in rats by H NMR spectroscopy |
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Authors: | Lai Wei Fengkui Pei Weisheng Li Yijie Wu |
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Affiliation: | Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China |
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Abstract: | The toxicological effects of realgar after intragastrical administration (1 g/kg body weight) were investigated over a 21 day period in male Wistar rats using metabonomic analysis of 1H NMR spectra of urine, serum and liver tissue aqueous extracts. Liver and kidney histopathology examination and serum clinical chemistry analyses were also performed. 1H NMR spectra and pattern recognition analyses from realgar treated animals showed increased excretion of urinary Kreb's cycle intermediates, increased levels of ketone bodies in urine and serum, and decreased levels of hepatic glucose and glycogen, as well as hypoglycemia and hyperlipoidemia, suggesting the perturbation of energy metabolism. Elevated levels of choline containing metabolites and betaine in serum and liver tissue aqueous extracts and increased serum creatine indicated altered transmethylation. Decreased urinary levels of trimethylamine-N-oxide, phenylacetylglycine and hippurate suggested the effects on the gut microflora environment by realgar. Signs of impairment of amino acid metabolism were supported by increased hepatic glutamate levels, increased methionine and decreased alanine levels in serum, and hypertaurinuria. The observed increase in glutathione in liver tissue aqueous extracts could be a biomarker of realgar induced oxidative injury. Serum clinical chemistry analyses showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. The time-dependent biochemical variations induced by realgar were achieved using pattern recognition methods. This work illustrated the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by traditional Chinese medicine. |
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Keywords: | NMR, nuclear magnetic resonance TCM, traditional Chinese medicine i.g., intragastrically APL, acute promyelocytic leukemia PR, pattern recognition PCA, principal components analysis PC, principal component PLS-DA, partial least squares-discriminant analysis CV, cross validation LV, latent viable ANOVA, analysis of variance FIDs, free induction decays CPMG, Carr-Purcell-Meiboom-Gill TSP, 2,2&prime ,3,3&prime , -deuterotrimethylsilylproprionic acid CMC-Na, sodium carboxymethylcellulose LDH, lactate dehydrogenase ALT, alanine aminotransferase AST, aspartate aminotransferase ALP, alkaline phosphatase GGT, γ-glutamyltransferase CHE, choline esterase Glc, glucose ALB, albumin TP, total protein TG, triglyceride T-CHO, total cholesterol Crn, creatinine BUN, blood urea nitrogen Pyr, pyruvate Lac, lactate 3-D-HB, 3- smallcaps" >d-hydroxybutyrate Aco, acetone AcAc, acetoacetate Ace, acetate Cit, citrate 2-OG, 2-oxoglutarate Succ, succinate Ala, alanine Val, valine Leu, leucine Ile, isoleucine Glu, glutamine Gln, glutamine Met, methionine Gly, glycine Tau, taurine GSH, glutathione TMAO, trimethylamine-N-oxide DMG, dimethylglycine DMA, dimethylamine Bet, betaine Cr, creatine PAG, phenylacetylglycine Hipp, hippurate Cho, choline PCho, phosphocholine GPC, glycerophosphorylcholine NAC, N-acetyl signals from glycoproteins LDL, low-density lipoprotein VLDL, very low-density lipoprotein HBDH, 3-hydroxybutyrate dehydrogenase ACH, acetyl CoA hydrolase PC, pyruvate carboxylase FMOs, flavin-containing monooxygenases CMO, choline monooxygenase BADH, betaine-aldehyde dehydrogenase BHMT, betaine-homocysteine methyltransferase DMGDH, dimethylglycine dehydrogenase SDH, sarcosine dehydrogenase CTL, cystathionine γ-lyase CBS, cystathionine β-synthase SAHH, S-Adenosylhomocysteine hydrolase MAT, methionine adenosyltransferase CK, creatine kinase GAMT, guanidinoacetate methyltransferase AGAT, smallcaps" >l-arginine:glycine amidinotransferase N, nonenzymatic reaction |
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