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Food Chem Toxicol. 2016 Jan;87:65-76. doi: 10.1016/j.fct.2015.11.018. Epub 2015 Dec 2.

Ochratoxin A-induced cytotoxicity, genotoxicity and reactive oxygen species in kidney cells: An integrative approach of complementary endpoints.

Author information

1
CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal; Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal; Department of Biomedical Sciences, University of Alcalá, Ctra. Madrid-Barcelona Km. 33.600, 28871 Alcalá de Henares, Madrid, Spain.
2
CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal.
3
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.
4
Department of Human Genetics, National Institute of Health Dr. Ricardo Jorge, I.P., Lisboa, Portugal; Center for Toxicogenomics and Human Health (ToxOmics), NMS, FCM - UNL, Lisboa, Portugal.
5
Department of Radiation Oncology, Duke University Medical School, Durham, NC, USA.
6
CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, 1749-024 Lisboa, Portugal. Electronic address: ana.fernandes@ulusofona.pt.

Abstract

Ochratoxin A (OTA) is a well-known nephrotoxic and potential carcinogenic agent but no consensus about the molecular mechanisms underlying its deleterious effects has been reached yet. The aim of this study is to integrate several endpoints concerning OTA-induced toxicological effects in Vero kidney cells in order to obtain additional mechanistic data, especially regarding the influence of reactive oxygen species (ROS). One innovative aspect of this work is the use of the superoxide dismutase mimic (SODm) MnTnHex-2-PyP as a mechanistic tool to clarify the involvement of oxidative stress in OTA toxicity. The results showed concentration and time-dependent cytotoxic effects of OTA (crystal violet, neutral red and LDH leakage assays). While the SODm mildly increased cell viability, trolox and ascorbic acid had no effect with regards to this endpoint. OTA induced micronuclei formation. Using the FPG modified comet assay, OTA modestly increased the % of DNA in tail, revealing the presence of oxidative DNA lesions. This mycotoxin increased apoptosis, which was attenuated by SODm. In addition, the SODm decreased the ROS accumulation observed in DHE assay. Taken together, our data suggest that ROS partially contribute to the cytotoxicity and genotoxicity of OTA, although other mechanisms may be relevant in OTA-induced deleterious effects.

KEYWORDS:

Antioxidants; Cytotoxicity; Genotoxicity; MnTnHex-2-PyP; Ochratoxin A; Reactive oxygen species

PMID:
26627377
DOI:
10.1016/j.fct.2015.11.018
[Indexed for MEDLINE]

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