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Updated: Oct 30, 2025
Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors
Published on: February 7, 2018
A Novel Fluorogenic Assay for the Detection of Nephrotoxin-Induced Oxidative Stress in Live Cells and Renal Tissue
Kamalika Mukherjee1, Tak Ian Chio2, Han Gu2
1Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States.
Abstract:
Drug-induced kidney injury frequently leads to aborted clinical trials and drug withdrawals. Sufficiently sensitive sensors capable of detecting mild signs of chemical insult in cell-based screening assays are critical to identifying and eliminating potential toxins in the preclinical stage. Oxidative stress is a common early manifestation of chemical toxicity, and biomolecule carbonylation is an irreversible repercussion of oxidative stress. Here, we present a novel fluorogenic assay using a sensor, TFCH, that responds to biomolecule carbonylation and efficiently detects modest forms of renal injury with much greater sensitivity than standard assays for nephrotoxins. We demonstrate that this sensor can be deployed in live kidney cells and in renal tissue. Our robust assay may help inform preclinical decisions to recall unsafe drug candidates. The application of this sensor in identifying and analyzing diverse pathologies is envisioned.
Insights
A new sensor assay detects early kidney injury from drug toxicity by measuring biomolecule carbonylation. This sensitive tool aids in identifying harmful drug candidates during preclinical stages, preventing trial failures.
Area of Science:
- Biochemistry
- Toxicology
- Biomedical Engineering
Background:
- Drug-induced kidney injury is a major cause of clinical trial failures and drug withdrawals.
- Early detection of chemical insult in kidney cells is crucial for preclinical safety assessments.
- Oxidative stress and subsequent biomolecule carbonylation are early indicators of chemical toxicity.
Purpose of the Study:
- To develop a novel, highly sensitive fluorogenic assay for detecting early signs of drug-induced kidney injury.
- To utilize a sensor that specifically responds to biomolecule carbonylation, an indicator of oxidative stress.
- To improve the identification and elimination of potential nephrotoxins in the preclinical drug development pipeline.
Main Methods:
- Development of a novel fluorogenic sensor, TFCH, designed to detect biomolecule carbonylation.
- Deployment of the TFCH sensor in live kidney cells and renal tissue for toxicity screening.
- Comparison of the sensor's sensitivity against standard assays for nephrotoxins.
Main Results:
- The TFCH sensor demonstrated high sensitivity in detecting modest forms of renal injury.
- The assay successfully identified chemical insults in both cell-based assays and live renal tissue.
- The developed assay is significantly more sensitive than existing standard assays for nephrotoxins.
Conclusions:
- The novel fluorogenic assay using TFCH provides a sensitive method for detecting drug-induced kidney injury.
- This assay can aid in preclinical decision-making, potentially preventing the progression of unsafe drug candidates.
- The sensor holds promise for identifying and analyzing diverse pathologies involving oxidative stress and carbonylation.
