NDLI: Discovery of early urinary biomarkers in preclinical study of gentamicin-induced kidney injury and recovery in rats

Content Provider	Springer Nature Link
Author	Sun, Jinchun Bhattacharyya, Sudeepa Schnackenberg, Laura K. Pence, Lisa Ando, Yosuke Zhang, Jun Stewart, Sharon Rosenzweig, Barry Rouse, Rodney Portilla, Didier Beger, Richard D.
Copyright Year	2012
Abstract	LC/MS- and NMR-based global metabolomics analyses were utilized to study the changes in rat urine in response to gentamicin treatment. Sprague–Dawley rats were dosed with gentamicin sulfate at 0, 75, 150 or 300 mg/kg/day for one, two or three consecutive days. Four animals from each group were sacrificed to harvest kidney tissue and to collect urine on days 1, 2, 3, 7, 10, 15, 18, 22, 29, 36 and 44 for a total of 11 different time points. Both uni- and multivariate statistical analyses were employed to identify the significantly changed metabolites in urine at the different dose levels and time points. Increases and decreases in amino acids including tyrosine, valine and hydroxyproline reflected histopathology changes of kidney injury development and/or kidney injury recovery. Glucosuria was noted much earlier than changes in the classic kidney function biomarkers, blood urea nitrogen and serum creatinine. Dopamine-related compounds, homovanillic acid sulfate (HVA-SO$_{4}$) and homoveratric acid sulfate (HVrA-SO$_{4}$) were significantly increased at early time points and could be early indicators of a renal adaptive response to gentamicin-induced renal injury. Furthermore, the drug efficacy of gentamicin was evaluated through the detection of changes in gut microflora-related compounds (e.g. indole-containing metabolites). Metabolomics was successful in identifying valine, hydroxyproline, HVA-SO$_{4}$ and HVrA-SO$_{4}$ that might serve as potential early injury biomarkers or adaptive markers of gentamicin-induced renal injury, and in assessing gentamicin efficacy through changes in compounds reported to be related to gut microflora. However, caution should be taken in direct translation of the biomarkers reported in clinical settings because a much higher dose of gentamicin than the normal therapeutic dose (~1–2 mg/kg) was used to cause kidney damaged.
Starting Page	1181
Ending Page	1193
Page Count	13
File Format	PDF
ISSN	15733882
Journal	Metabolomics
Volume Number	8
Issue Number	6
e-ISSN	15733890
Language	English
Publisher	Springer US
Publisher Date	2012-04-21
Publisher Institution	Metabolomics Society
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Nephrotoxicity Gentamicin Biomarker Efficacy Dopamine Metabolomics Molecular Medicine Biochemistry Developmental Biology Cell Biology Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Clinical Biochemistry Biochemistry

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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