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Metabolomics for the identification of early biomarkers of nephrotoxicity in a mouse model of cisplatin-induced acute kidney injury.
Lim, Yong Jin; Tonial, Nicholas C; Hartjes, Emily D; Haig, Aaron; Velenosi, Thomas J; Urquhart, Bradley L.
Afiliação
  • Lim YJ; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
  • Tonial NC; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
  • Hartjes ED; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
  • Haig A; Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
  • Velenosi TJ; Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Urquhart BL; Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada; Division of Nephrology, Department of Medicine, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada. Electronic address: Brad.Urquhart@schulic
Biomed Pharmacother ; 163: 114787, 2023 Jul.
Article em En | MEDLINE | ID: mdl-37126930
BACKGROUND AND PURPOSE: Cisplatin-induced nephrotoxicity manifests as acute kidney injury (AKI) in approximately one third of patients receiving cisplatin therapy. Current measures of AKI are inadequate in detecting AKI prior to significant renal injury, and better biomarkers are needed for early diagnosis of cisplatin-induced AKI. EXPERIMENTAL APPROACH: C57BL/6 and FVB/N mice were treated with a single intraperitoneal injection of cisplatin (15 mg kg-1) or saline. Plasma, urine, and kidney samples were collected prior to cisplatin injection and 24-, 48-, 72-, and 96-hours following cisplatin injection. Untargeted metabolomics was employed using liquid chromatography-mass spectrometry to identify early diagnostic biomarkers for cisplatin nephrotoxicity. PRINCIPAL RESULTS: There was clear metabolic discrimination between saline and cisplatin-treated mice at all timepoints (day 1 to day 4). In total, 26 plasma, urine, and kidney metabolites were identified as exhibiting early alterations following cisplatin treatment. Several of the metabolites showing early alterations were associated with mitochondrial function and energetics, including intermediates of the tricarboxylic acid cycle, regulators of mitochondrial function and indicators of fatty acid ß-oxidation dysfunction. Furthermore, several metabolites were derived from the gut microbiome. MAJOR CONCLUSIONS: Our results highlight the detrimental effects of cisplatin on mitochondrial function and demonstrate potential involvement of the gut microbiome in the pathophysiology of cisplatin-induced AKI. We provide a panel of metabolites to guide future clinical studies of cisplatin-induced AKI and provide insight into potential mechanisms behind cisplatin nephrotoxicity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cisplatino / Injúria Renal Aguda Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Animals Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cisplatino / Injúria Renal Aguda Tipo de estudo: Diagnostic_studies / Prognostic_studies / Screening_studies Limite: Animals Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Canadá