title: Differential biochemical response of rat kidney towards low and high doses of NiCl2 as revealed by NMR spectroscopy.
abstract: Heavy metals are known for their associated nephrotoxicity and nickel is no exception. An integrated metabonomic approach, based on high-resolution (1) H NMR spectroscopy, was applied to determine the acute biochemical effects of NiCl(2) on the renal tissues of rats. Kidney homogenates from rats treated with NiCl(2) at two dose levels (4 and 20 mg kg(-1) b.w., i.p.) and those from controls were analysed using (1) H NMR spectroscopy and also assessed for antioxidant parameters at days 1, 3 and 5 post-dose. The major metabolite changes corresponding to nickel exposure were related to amino acids, osmolytes and energy metabolites. Differential responses were observed in (1) H NMR spectra with exposure to low and high doses of NiCl(2). For high doses, (1) H NMR spectral analysis revealed alterations in renal tissues, along with damage to the cortical and papillary region and depletion of renal osmolytes such as betaine, trimethyl amine oxide, myo-inositol and taurine, which persisted until day 5 post-dose. The metabolite profile of (1) H NMR spectra obtained from animals treated with lower dose of NiCl(2) initially increased as an immediate stress response and then showed signs of recovery with the passage of time. NMR spectral analysis was well corroborated with histopathological and oxidative stress results. Nickel-induced oxidative stress was observed in both groups of animals with increased levels of antioxidant parameters at initial time points, but continued to increase in the high-dose group. The present study shows a huge potential of metabonomics for mapping organ-based metabolic response during heavy metal 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: Mamta
authors.initials: M
authors.lastname: Gupta
authors.forename: Ahmad Raza
authors.initials: AR
authors.lastname: Khan
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatnagar
authors.forename: P J S
authors.initials: PJ
authors.lastname: Bhalla
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: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D009532:Nickel / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; C022838:nickel chloride; D009532:Nickel