Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

doi:10.1016/j.taap.2014.08.030

Cited by 36 publications

(30 citation statements)

References 47 publications

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“…Here we confirm that OTA is able to trigger an antioxidant response in yeast, however, ROS production is not the principle effect of OTA. This is in agreement with recent studies, which demonstrate in rats that renal carcinogenicity and cell cycle aberrations caused by OTA cannot be explained by oxidative damage [51,52]. Here we show that OTA treatment causes a general deregulation of developmental genes in yeast.…”

Section: Discussionsupporting

confidence: 94%

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Vanacloig-Pedros

Proft

Pascual-Ahuir

2016

Toxins

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Citrinin (CIT) and ochratoxin A (OTA) are important mycotoxins, which frequently co-contaminate foodstuff. In order to assess the toxicologic threat posed by the two mycotoxins separately or in combination, their biological effects were studied here using genomic transcription profiling and specific live cell gene expression reporters in yeast cells. Both CIT and OTA cause highly transient transcriptional activation of different stress genes, which is greatly enhanced by the disruption of the multidrug exporter Pdr5. Therefore, we performed genome-wide transcription profiling experiments with the pdr5 mutant in response to acute CIT, OTA, or combined CIT/OTA exposure. We found that CIT and OTA activate divergent and largely nonoverlapping gene sets in yeast. CIT mainly caused the rapid induction of antioxidant and drug extrusion-related gene functions, while OTA mainly deregulated developmental genes related with yeast sporulation and sexual reproduction, having only a minor effect on the antioxidant response. The simultaneous exposure to CIT and OTA gave rise to a genomic response, which combined the specific features of the separated mycotoxin treatments. The application of stress-specific mutants and reporter gene fusions further confirmed that both mycotoxins have divergent biological effects in cells. Our results indicate that CIT exposure causes a strong oxidative stress, which triggers a massive transcriptional antioxidant and drug extrusion response, while OTA mainly deregulates developmental genes and only marginally induces the antioxidant defense.

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Section: Discussionsupporting

confidence: 94%

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Vanacloig-Pedros

Proft

Pascual-Ahuir

2016

Toxins

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“…These results indicated that blood parameters and biomarkers suggest damage earlier than pathological observations. This result is also consistent with our long-term experiments [30]. …”

Section: Discussionsupporting

confidence: 94%

“…Also, Rached et al [44] stated that the early effects of OTA treatment consisted of cell loss accompanied by increased cell proliferation and prominent nuclear enlargement within the straight segment of the proximal tubule epithelium (P3) in the OSOM. Besides, proliferation also has been regarded as one of the indicators of OTA-induced tumor in Qi et al [30]. Based on this, the proliferation in the kidney may be the mode of action of early effects of OTA-induced toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…This also can explain the elevation of the level of albumin in serum. Pathological change always occurs with severe damage, and OTA treatment for longer than 4 weeks induced kidney and liver damage [30,44]. These results indicated that blood parameters and biomarkers suggest damage earlier than pathological observations.…”

Section: Discussionmentioning

confidence: 99%

“…We previously explored oxidative damage and DNA damage in rats treated with carcinogenic doses (0, 70 or 210 μg/kg b.w.) of OTA for 4 or 13 weeks [30], and showed a trend of rat renal carcinogenicity with limited induction of oxidative stress responses.…”

Section: Introductionmentioning

confidence: 99%

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Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

Zhu

et al. 2016

Toxins

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Ochratoxin A (OTA) displays nephrotoxicity and hepatotoxicity. However, in the acute toxicity rat model, there is no evidence on the relationship between OTA and nephrotoxicity and hepatotoxicity. Based on this, the integrated analysis of physiological status, damage biomarkers, oxidative stress, and DNA damage were performed. After OTA treatment, the body weight decreased and AST, ALP, TP, and BUN levels in serum increased. Hydropic degeneration, swelling, vacuolization, and partial drop occurred in proximal tubule epithelial cells. PCNA and Kim-1 were dose-dependently increased in the kidney, but Cox-2 expression and proliferation were not found in the liver. In OTA-treated kidneys, the mRNA expressions of Kim-1, Cox-2, Lcn2, and Clu were dose-dependently increased. The mRNA expressions of Vim and Cox-2 were decreased in OTA-treated livers. Some oxidative stress indicators were altered in the kidneys (ROS and SOD) and livers (SOD and GSH). DNA damage and oxidative DNA damage were not found. In conclusion, there is a limited link between oxidative stress and OTA-induced renal injury in an acute toxicity rat model.

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Ochratoxin A–induced genotoxic and epigenetic mechanisms lead to Alzheimer disease: its modulation with strategies

Niaz

Shah

Khan

et al. 2020

Environ Sci Pollut Res

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Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

Cited by 36 publications

References 47 publications

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Different Toxicity Mechanisms for Citrinin and Ochratoxin A Revealed by Transcriptomic Analysis in Yeast

Limited Link between Oxidative Stress and Ochratoxin A—Induced Renal Injury in an Acute Toxicity Rat Model

Ochratoxin A–induced genotoxic and epigenetic mechanisms lead to Alzheimer disease: its modulation with strategies

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