title: NMR-based metabolomics approach to study the chronic toxicity of crude ricin from castor bean kernels on rats.
abstract: Ricin, a large, water soluble toxic glycoprotein, is distributed majorly in the kernels of castor beans (the seeds of Ricinus communis L.) and has been used in traditional Chinese medicine (TCM) or other folk remedies throughout the world. The toxicity of crude ricin (CR) from castor bean kernels was investigated for the first time using an NMR-based metabolomic approach complemented with histopathological inspection and clinical chemistry. The chronic administration of CR could cause kidney and lung impairment, spleen and thymus dysfunction and diminished nutrient intake in rats. An orthogonal signal correction partial least-squares discriminant analysis (OSC-PLSDA) of metabolomic profiles of rat biofluids highlighted a number of metabolic disturbances induced by CR. Long-term CR treatment produced perturbations on energy metabolism, nitrogen metabolism, amino acid metabolism and kynurenine pathway, and evoked oxidative stress. These findings could explain well the CR induced nephrotoxicity and pulmonary toxicity, and provided several potential biomarkers for diagnostics of these toxicities. Such a (1)H NMR based metabolomics approach showed its ability to give a systematic and holistic view of the response of an organism to drugs and is suitable for dynamic studies on the toxicological effects of TCM.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China. cpu_lykong@126.com.
authors.forename: Pingping
authors.initials: P
authors.lastname: Guo
authors.forename: Junsong
authors.initials: J
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Dong
authors.forename: Dandan
authors.initials: D
authors.lastname: Wei
authors.forename: Minghui
authors.initials: M
authors.lastname: Li
authors.forename: Minghua
authors.initials: M
authors.lastname: Yang
authors.forename: Lingyi
authors.initials: L
authors.lastname: Kong
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002367:Ricinus communis / Q000009:adverse effects*; D004734:Energy Metabolism / Q000187:drug effects; D007737:Kynurenine / Q000378:metabolism; D016018:Least-Squares Analysis; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008516:Medicine, Chinese Traditional / Q000009:adverse effects; D055432:Metabolomics / Q000379:methods; D009584:Nitrogen / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012276:Ricin / Q000009:adverse effects*; D012639:Seeds / Q000009:adverse effects*
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D007737:Kynurenine; D012276:Ricin; D009584:Nitrogen