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Evaluation of KIM-1 and NGAL as Early Indicators for Assessment of Gentamycin-Induced Nephrotoxicity In Vivo and In Vitro.
Abstract: The aminolycoside Gentamicin is a widely used antibiotic, applied in equine medicine. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity. Early detection of renal damage is critical in preclinical drug development. This study was aimed to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be early indicators in the assessment of Gentamycin-induced nephrotoxicity. Methods: In our study, a model of Gentamicin-induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days at 50 or 100mg/kg/day was used to monitor the expressions of novel biomarkers of renal toxicity during the progression of acute kidney injury (AKI). Additionally, biomarkers were assessed in human kidney proximal epithelial cells (HK-2) treated with Gentamicin for 2, 6, 12, 24, 36 or 48h in vitro. Results: Repeated administration of Gentamicin to rats for 1, 3, or 7 days resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL. The expressions of the two biomarkers changed prior to renal tubule damage and increases in serum creatinine (SCr) and blood urea nitrogen (BUN) levels, suggesting their usefulness for predicting Gentamicin-induced acute kidney injury (AKI) in vivo. Conclusions: In contrast, no significant increase in the expression of the biomarker genes and proteins were evident in HK-2 cells after treated by Gentamycin for up to 48h, suggesting that they may not be suitable endpoints for sensitive detection of nephrotoxic effects in vitro.
© 2016 The Author(s) Published by S. Karger AG, Basel.
Publication Date: 2016-11-28 PubMed ID: 27889773DOI: 10.1159/000452592Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Evaluation Study
- Journal Article
Summary
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The research focuses on examining if kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) could be early indicators of kidney damage caused by the antibiotic, Gentamicin. The study found that in the Gentamycin-induced nephrotoxicity model using rats, the expression of these markers increased even before recognisable kidney damage, suggesting their potential as predictors for such kidney injuries. However, in in-vitro studies using human kidney cells, these markers did not show significant changes, indicating they may not be suitable for detecting nephrotoxic effects at the cellular level.
Methods
- The study used a model of Gentamicin-induced nephrotoxicity in male Sprague Dawley rats treated for up to 7 days with two different dosages of the antibiotic. This model was used to monitor changes in the expression of KIM-1 and NGAL during the progression of acute kidney injury.
- In addition, the biomarkers were also studied in human kidney proximal epithelial cells (HK-2 cells) treated with Gentamicin for various time intervals in order to assess their reaction to the antibiotic in vitro.
Results
- Repeated administration of Gentamicin to rats resulted in a dose- and time-dependent increase in the expression of KIM-1 and NGAL, suggesting these biomarkers reacted to the induced nephrotoxicity.
- The changes in the expression of these biomarkers were recorded before any observable damage in kidney tubules and increases in traditional markers of kidney damage such as serum creatinine (SCr) and blood urea nitrogen (BUN) levels, indicating their potential for predicting Gentamicin-induced kidney injury.
- However, in the in-vitro study, no significant changes were noticed in the expression of these biomarker genes and proteins in HK-2 cells after treatment with Gentamicin for up to 48 hours. This indicates that these biomarkers may not be suitable for detecting nephrotoxic effects at the cellular level.
Conclusions
- Based on the study’s results, KIM-1 and NGAL could serve as early indicators of Gentamicin-induced nephrotoxicity in an in-vivo model.
- However, they may not be adequate for sensitive detection of nephrotoxic effects in an in-vitro model based on the study’s observations on HK-2 cells.
Cite This Article
APA
Luo QH, Chen ML, Chen ZL, Huang C, Cheng AC, Fang J, Tang L, Geng Y.
(2016).
Evaluation of KIM-1 and NGAL as Early Indicators for Assessment of Gentamycin-Induced Nephrotoxicity In Vivo and In Vitro.
Kidney Blood Press Res, 41(6), 911-918.
https://doi.org/10.1159/000452592 Publication
Researcher Affiliations
- Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.
MeSH Terms
- Acute Kidney Injury / blood
- Acute Kidney Injury / chemically induced
- Acute Kidney Injury / diagnosis
- Acute-Phase Proteins
- Animals
- Biomarkers / blood
- Cell Adhesion Molecules / blood
- Cell Line
- Gene Expression Regulation / drug effects
- Gentamicins / toxicity
- Humans
- Lipocalin-2
- Lipocalins / blood
- Male
- Proto-Oncogene Proteins / blood
- Rats
- Rats, Sprague-Dawley
Citations
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