The role of oxidative stress in the ochratoxin A-mediated toxicity in proximal tubular cells
| Autor: | Gerben J. Schaaf, Roel F.M Maas, E.M. de Groene, Sandra M. Nijmeijer, Johanna Fink-Gremmels, Peggy Roestenberg |
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| Rok vydání: | 2002 |
| Předmět: |
Ochratoxin A
Guanine Time Factors Cell Survival Animal food 8-Oxoguanine Pharmacology Biology medicine.disease_cause Antioxidants Cell Line Nephrotoxicity Kidney Tubules Proximal chemistry.chemical_compound Oxidative damage medicine Animals Molecular Biology chemistry.chemical_classification Reactive oxygen species Kidney Dose-Response Relationship Drug Proteins Glutathione Mycotoxins Ochratoxins Rats Oxidative Stress medicine.anatomical_structure chemistry Biochemistry Protein Biosynthesis Proximal tubule cell Toxicity Molecular Medicine Reactive Oxygen Species Oxidative stress DNA Damage |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1588:149-158 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/s0925-4439(02)00159-x |
| Popis: | Balkan endemic nephropathy (BEN), a disease characterized by progressive renal fibrosis in human patients, has been associated with exposure to ochratoxin A (OTA). This mycotoxin is a frequent contaminant of human and animal food products, and is toxic to all animal species tested. OTA predominantly affects the kidney and is known to accumulate in the proximal tubule (PT). The induction of oxidative stress is implicated in the toxicity of this mycotoxin. In the present study, primary rat PT cells and LLC-PK(1) cells, which express characteristics of the PT, were used to investigate the OTA-mediated oxidative stress response. OTA exposure of these cells resulted in a concentration-dependent elevation of reactive oxygen species (ROS) levels, depletion of cellular glutathione (GSH) levels and an increase in the formation of 8-oxoguanine. The OTA-induced ROS response was significantly reduced following treatment with alpha-tocopherol (TOCO). However, this chain-braking anti-oxidant did not reduce the cytotoxicity of OTA and was unable to prevent the depletion of total GSH levels in OTA-exposed cells. In contrast, pre-incubation of the cell with N-acetyl-L-cysteine (NAC) completely prevented the OTA-induced increase in ROS levels as well as the formation of 8-oxoguanine and completely protected against the cytotoxicity of OTA. In addition, NAC treatment also limited the GSH depletion in OTA-exposed PT- and LLC-PK(1) cells. From these data, we conclude that oxidative stress contributes to the tubular toxicity of OTA. Subsequently, cellular GSH levels play a pivotal role in limiting the short-term toxicity of this mycotoxin in renal tubular cells. |
| Databáze: | OpenAIRE |
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