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Updated: May 12, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Programmed cell death by interaction of ochratoxin A with other nephrotoxins
F Weber1, G Schwerdt, R Freudinger
1Physiologisches Institut, Universität Würzburg, Röntgenring 9, D - 97070, Würzburg, Germany.
Abstract:
We determined the effects of co-exposure of OTA and other (potentially) nephrotoxic substances on renal tubule cells (IHKE, from the proximal tubule; MDCK-C7 cells, representing principal cells of the collecting duct) by measuring the activation of caspase-3, an enzyme with key roles in the process of programmed cell death or apoptosis.Substances used in combination with OTA included: cadmium, a known nephrotoxin with apoptotic effects, cisplatin (anticancer drug, also a known nephrotoxin), cyclosporin A (an immunosuppresive agent), H2O2 (generated during oxidative cell stress), amphotericin B (antifungal agent), and fumonisin B1. Because of the great number of possible combinations, a method based on the 96-well format was developed which allowed a fast and cost-efficient succesive measurement of caspase-3 activity and protein content in one well as well as necrotic effects in parallel.We found that cells responded differently to the various combinations: for example, 1 µM OTA combined with 100 µM cisplatin had an antagonizing effect on caspase-3 activation in IHKE cells but potentiating effects in MDCK-C7. DNA ladder formation confirmed the results. Necrotic effects were very small and additive. We conclude that the co-exposure of renal cells to OTA with other substances can enhance or reduce the apoptotic potential of one substance alone depending on the substance and on the cell line investigated. A "harmless" substance can thus convert to a potent cell toxic substance when combined with OTA or other mycotoxins.These first findings show the necessity to further investigate the combined effects of OTA or other mycotoxins with other substances or of mycotoxins with each other.
Insights
Co-exposure of ochratoxin A (OTA) with other substances can alter kidney cell apoptosis. The combined effects vary by substance and cell type, potentially turning harmless substances into potent toxins.
Area of Science:
- Toxicology
- Cell Biology
- Renal Physiology
Background:
- Ochratoxin A (OTA) is a mycotoxin with known nephrotoxic potential.
- The combined effects of OTA with other nephrotoxic substances on renal cells are not well understood.
- Apoptosis, or programmed cell death, is a critical cellular process implicated in kidney injury.
Purpose of the Study:
- To investigate the effects of co-exposure of OTA with various nephrotoxic substances on renal tubule cells.
- To measure the activation of caspase-3, a key enzyme in apoptosis, in response to these combinations.
- To assess whether combined exposures enhance or reduce the apoptotic potential of individual substances.
Main Methods:
- Utilized IHKE (proximal tubule) and MDCK-C7 (collecting duct) renal cell lines.
- Measured caspase-3 activation and protein content using a 96-well format assay.
- Assessed necrotic effects and confirmed apoptosis via DNA ladder formation.
Main Results:
- Co-exposure effects on caspase-3 activation were cell-type dependent; for instance, OTA and cisplatin showed antagonistic effects in IHKE cells but potentiating effects in MDCK-C7 cells.
- Necrotic effects were generally small and additive.
- The combination of OTA with other substances significantly altered the apoptotic potential compared to individual exposures.
Conclusions:
- Co-exposure of renal cells to OTA with other substances can modulate apoptotic responses, either enhancing or reducing toxicity.
- The outcome is dependent on the specific co-exposed substance and the renal cell type.
- These findings highlight the need for further research into the complex interactions of mycotoxins with other chemicals in renal toxicity.
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