title: Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.
abstract: Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and β-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity.
authors.affiliation: NMR Research Centre, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Tyagi
authors.forename: Poonam
authors.initials: P
authors.lastname: Rana
authors.forename: Ahmad Raza
authors.initials: AR
authors.lastname: Khan
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatnagar
authors.forename: M Memita
authors.initials: MM
authors.lastname: Devi
authors.forename: Shubhra
authors.initials: S
authors.lastname: Chaturvedi
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Tripathi
authors.forename: Subash
authors.initials: S
authors.lastname: Khushu
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000032:analysis; D000818:Animals; D002794:Choline / Q000378:metabolism; D003404:Creatinine / Q000032:analysis; D000075322:Heavy Metal Poisoning; D006626:Hippurates / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics / Q000379:methods; D019216:Metals, Heavy / Q000633:toxicity / Q000652:urine; D008744:Methylamines / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D011041:Poisoning / Q000652:urine*; D025341:Principal Component Analysis; D013654:Taurine / Q000032:analysis; D013793:Thallium / Q000633:toxicity* / Q000652:urine*
chemical_list: D006626:Hippurates; D019216:Metals, Heavy; D008744:Methylamines; D013654:Taurine; D013793:Thallium; D003404:Creatinine; C023336:trimethylamine; D002794:Choline; C030514:hippuric acid; D020155:3-Hydroxybutyric Acid; C013707:thallium sulfate