title: Use of precision-cut renal cortical slices in nephrotoxicity studies.
abstract: 1.Unlike cell lines and primary cells in culture, precision-cut tissue slices remain metabolically differentiated for at least 24-48 h and allow to study the effect of xenobiotics during short-term and long-term incubations. 2.In this article, we illustrate the use of such an experimental model to study the nephrotoxic effects of (i) chloroacetaldehyde, a metabolite of the anticancer drug ifosfamide, (ii) of cobalt chloride, a potential leakage product of the cobalt-containing nanoparticles, and (iii) of valproate, a widely used antiepileptic drug. 3.Since all the latter test compounds, like many toxic compounds, negatively interact with cellular metabolic pathways, we also illustrate our biochemical toxicology approach in which we used not only enzymatic but also carbon 13 NMR measurements and mathematical modelling of metabolic pathways. 4.This original approach, which can be applied to any tissue, allows to predict the nephrotoxic effects of milligram amounts of test compounds very early during the research and development processes of drugs and chemicals. This approach, combined with the use of cells that retain their in vivo metabolic properties and, therefore, are predictive, reduces the risk, the time and cost of such processes.
authors.affiliation: Metabolys Inc., Laennec Faculty of Medicine, 69372 Lyon Cedex 08, France. baverel@metabolys.com
authors.forename: Gabriel
authors.initials: G
authors.lastname: Baverel
authors.forename: Burhan
authors.initials: B
authors.lastname: Knouzy
authors.forename: Catherine
authors.initials: C
authors.lastname: Gauthier
authors.forename: Maha
authors.initials: M
authors.lastname: El Hage
authors.forename: Bernard
authors.initials: B
authors.lastname: Ferrier
authors.forename: Guy
authors.initials: G
authors.lastname: Martin
authors.forename: Agnès
authors.initials: A
authors.lastname: Duplany
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D003035:Cobalt / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism* / Q000473:pathology; D053768:Metal Nanoparticles / Q000009:adverse effects*; D042282:Microdissection / Q000379:methods; D009924:Organ Culture Techniques / Q000379:methods; D014635:Valproic Acid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D018906:Antineoplastic Agents, Alkylating; D003035:Cobalt; D014635:Valproic Acid; C004656:chloroacetaldehyde; D000079:Acetaldehyde; D007069:Ifosfamide