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A Method for the Evaluation of Site-Specific Nephrotoxic Injury in the Intact Rat Kidney

1
Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA
2
Department of Emergency Medicine, Captain James A. Lovell Federal Health Care Center, Department of Veteran Affairs, Chicago, IL 60064, USA
3
Radiology Department, Marshfield Medical Center, Marshfield, WI 54449, USA
*
Author to whom correspondence should be addressed.
Received: 19 December 2019 / Accepted: 16 January 2020 / Published: 20 January 2020
(This article belongs to the Section Toxicology and Public Health)
In a previously published report we detailed an in situ method to quantify cell death in the renal cortex by perfusing the cell membrane impermeable fluorochrome, ethidium homodimer in situ. The objective of the present study was to use this in situ viability assay to examine cell death following the administration of nephrotoxic drugs known to produce cell death and/or injury in specific segments of the nephron. Male Sprague/Dawley rats were treated with the following nephrotoxicants: Gentamicin, amphotericin-B, and indomethacin. Results of the in situ viability assay indicated that gentamicin and amphotericin-B treatment caused cell death localized in the kidney cortex and medulla, respectively. The urinary biomarker kidney injury molecule—1 (Kim-1) showed significant increases in both gentamicin (20 fold increase) and amphotericin-B-treated (9.2 fold increase) animals. Urinary alpha glutathione-S-transferase (GST) showed significant increases for gentamicin (6.2 fold increase) only and mu GST for amphotericin-B-treated (19.1 fold increase) animals only. These results show that this in situ viability assay provides a sensitive method to identify cell death in different regions of the kidney. Furthermore, urinary alpha GST and mu GST are specific for proximal and distal tubule injury, respectively; urinary Kim-1 demonstrated greater sensitivity to both proximal and distal tubule injury. View Full-Text
Keywords: drug toxicity; nephrotoxicity; cell viability; amphotericin; gentamicin; indomethacin drug toxicity; nephrotoxicity; cell viability; amphotericin; gentamicin; indomethacin
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Edwards, J.; Kowal, M.; VanDreel, A.; Lamar, P.; Prozialeck, W. A Method for the Evaluation of Site-Specific Nephrotoxic Injury in the Intact Rat Kidney. Toxics 2020, 8, 4.

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