Developmental Toxicity of Ochratoxin A in Rat Embryo Midbrain Micromass Cultures

Wilk-Zasadna, Iwona; Minta, Maria

doi:10.3390/ijms10010037

Cited by 19 publications

(24 citation statements)

References 41 publications

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“…According to this finding, we found a decrease in the number of GFAP + cells starting from the second dose, consistent with the proliferation BrdU assay. proliferation and differentiation with OTA administration in a dose-dependent manner, which is coherent with previous observations (Sava et al, 2007;Wilk-Zasadna & Minta, 2009;Zhang et al, 2009). Ultrastructural characterization of mice SVZ after OTA treatment.…”

Section: Effect On Cell Differentiationsupporting

confidence: 93%

“…Previous works in vitro, determined a negative effect of OTA in terms of viability and proliferation on different cellular types of the CNS such as mesencephalic embryonic cells (Wilk-Zasadna & Minta, 2009), rat and human neurons (Zhang et al, 2009) and NSCs from the adult mouse hippocampus (Sava et al, 2007). We found that the exposure to increasing doses of OTA (0.01-100 μg ml À1 ) caused a progressive decrease in cell proliferation and viability, reflecting an accumulative effect.…”

Section: Negative Effect Of Ochratoxin a Exposure On Brain Developmentmentioning

confidence: 59%

“…The SVZ of control mice showed its characteristic organization in several cell layers. OTA toxicity has not been reported as selective between astrocytes and neurons (Wilk-Zasadna & Minta, 2009). Otherwise, the OTA-treated group presented a noticeable reduction in the number of cell layers in this structure (B).…”

Section: Effect On Cell Differentiationmentioning

confidence: 99%

“…It has been reported that the half-life of OTA in humans is approximately 35 days (Creppy et al, 1983;Hagelberg et al, 1989). In fact, OTA has been frequently found in human blood plasma (Bennett & Klich, 2003;Coronel et al, 2010;Medina et al, 2010), and its nephro-, hepato-, terato-and immunotoxic consequences have been reported (Arora et al, 1983;Harvey et al, 1992;Haubeck et al, 1981;Hope & Hope, 2012;Kuiper-Goodman, 1991;López de Cerain, 2007;Mortensen et al, 1983;Pfohl-Leszkowicz & Manderville, 2007;Wilk-Zasadna & Minta, 2009). In the last few years, OTA exposure studies have been developed on different cell lines of human and animal models, especially describing the mechanisms associated with increased levels of oxidative stress, DNA, lipid and protein damage (Bennett & Klich, 2003;Creppy et al, 1985b;Friedman & Rasooly, 2013;Gautier et al, 2001;Hibi et al, 2013;Hope & Hope, 2012;Kumar et al, 2012;Marin-Kuan et al, 2011;Sava et al, 2006aSava et al, ,2006b.…”

Section: Introductionmentioning

confidence: 99%

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Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain

Paradells

Rocamonde

Llinares

et al. 2014

J of Applied Toxicology

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Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner.

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Section: Effect On Cell Differentiationsupporting

confidence: 93%

Section: Negative Effect Of Ochratoxin a Exposure On Brain Developmentmentioning

confidence: 59%

Section: Effect On Cell Differentiationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain

Paradells

Rocamonde

Llinares

et al. 2014

J of Applied Toxicology

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“…Ochratoxin A (OTA) is a mycotoxin that is produced by several fungal species in the Aspergillus and Penicillium genera [1,2,3]. OTA displays nephrotoxicity [4], hepatotoxicity [1], carcinogenicity [5], and neurotoxicity [6] in mammals.…”

Section: Introductionmentioning

confidence: 99%

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: Developmental and Reproductive Toxicity—An Overview

Malíř

Ostrý

Pfohl‐Leszkowicz

et al. 2013

Birth Defects Research Pt B

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Ochratoxin A (OTA) is nephrotoxic, hepatotoxic, reprotoxic, embryotoxic, teratogenic, neurotoxic, immunotoxic, and carcinogenic for laboratory and farm animals. Male and female reproductive health has deteriorated in many countries during the last few decades. A number of toxins in environment are suspected to affect reproductive system in male and female. OTA is one of them. OTA has been found to be teratogenic in several animal models including rat, mouse, hamster, quail, and chick, with reduced birth weight and craniofacial abnormalities being the most common signs. The presence of OTA also results in congenital defects in the fetus. Neither the potential of OTA to cause malformations in human nor its teratogenic mode of action is known. Exposure to OTA leads to increased embryo lethality manifested as resorptions or dead fetuses. The mechanism of OTA transfer across human placenta (e.g., which transporters are involved in the transfer mechanism) is not fully understood. Some of the toxic effects of OTA are potentiated by other mycotoxins or other contaminants. Therefore, OTA exposure of pregnant women should be minimized. OTA has been shown to be an endocrine disruptor and a reproductive toxicant, with abilities of altering sperm quality. Other studies have shown that OTA is a testicular toxin in animals. Thus, OTA is a biologically plausible cause of testicular cancer in man.

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Developmental Toxicity of Ochratoxin A in Rat Embryo Midbrain Micromass Cultures

Cited by 19 publications

References 41 publications

Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain

Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain

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

Ochratoxin A: Developmental and Reproductive Toxicity—An Overview

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