International Journal of Molecular Sciences

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18 pages, 3127 KiB

Open AccessArticle

The Influence of Prenatal Fumonisin Exposure on Bone Properties, as well as OPG and RANKL Expression and Immunolocalization, in Newborn Offspring Is Sex and Dose Dependent

by Ewa Tomaszewska, Halyna Rudyk, Izabela Świetlicka, Monika Hułas-Stasiak, Janine Donaldson, Marta Arczewska, Siemowit Muszyński, Piotr Dobrowolski, Iwona Puzio, Volodymyr Kushnir, Oksana Brezvyn, Viktor Muzyka and Ihor Kotsyumbas

Int. J. Mol. Sci. 2021, 22(24), 13234; https://doi.org/10.3390/ijms222413234 - 8 Dec 2021

Cited by 7 | Viewed by 2362

Abstract

The current study examined the effects of exposure of pregnant dams to fumonisins (FBs; FB1 and FB2), from the seventh day of pregnancy to parturition, on offspring bone metabolism and properties. The rats were randomly divided into three groups intoxicated with FBs at [...] Read more.

The current study examined the effects of exposure of pregnant dams to fumonisins (FBs; FB1 and FB2), from the seventh day of pregnancy to parturition, on offspring bone metabolism and properties. The rats were randomly divided into three groups intoxicated with FBs at either 0, 60, or 90 mg/kg b.w. Body weight and bone length were affected by fumonisin exposure, irrespective of sex or dose, while the negative and harmful effects of maternal FBs’ exposure on bone mechanical resistance were sex and dose dependent. The immunolocalization of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL), in bone and articular cartilage, indicated that the observed bone effects resulted from the FB-induced alterations in bone metabolism, which were confirmed by the changes observed in the Western blot expression of OPG and RANKL. It was concluded that the negative effects of prenatal FB exposure on the general growth and morphometry of the offspring bones, as a result of the altered expression of proteins responsible for bone metabolism, were dose and sex dependent. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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21 pages, 8615 KiB

Open AccessArticle

Trabecular Bone Parameters, TIMP-2, MMP-8, MMP-13, VEGF Expression and Immunolocalization in Bone and Cartilage in Newborn Offspring Prenatally Exposed to Fumonisins

by Ewa Tomaszewska, Halyna Rudyk, Izabela Świetlicka, Monika Hułas-Stasiak, Janine Donaldson, Marta Arczewska, Siemowit Muszyński, Piotr Dobrowolski, Maria Mielnik-Błaszczak, Marcin Bartłomiej Arciszewski, Volodymyr Kushnir, Oksana Brezvyn, Viktor Muzyka and Ihor Kotsyumbas

Int. J. Mol. Sci. 2021, 22(22), 12528; https://doi.org/10.3390/ijms222212528 - 20 Nov 2021

Cited by 9 | Viewed by 2059

Abstract

Fumonisins are protein serine/threonine phosphatase inhibitors and potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) disrupting de novo sphingolipid biosynthesis. The experiment was conducted to evaluate the effects of fumonisins (FB) exposure from the 7th day of pregnancy to parturition on offspring bone development. [...] Read more.

Fumonisins are protein serine/threonine phosphatase inhibitors and potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) disrupting de novo sphingolipid biosynthesis. The experiment was conducted to evaluate the effects of fumonisins (FB) exposure from the 7th day of pregnancy to parturition on offspring bone development. The rats were randomly allocated to either a control group (n = 6), not treated with FBs, or to one of the two groups intoxicated with FBs (either at 60 mg FB/kg b.w. or at 90 mg FB/kg b.w. Numerous negative, offspring sex-dependent effects of maternal FB exposure were observed with regards to the histomorphometry of trabecular bone. These effects were due to FB-inducted alterations in bone metabolism, as indicated by changes in the expression of selected proteins involved in bone development: tissue inhibitor of metalloproteinases 2 (TIMP-2), matrix metalloproteinase 8 (MMP-8), matrix metalloproteinase 13 (MMP-13), and vascular endothelial growth factor (VEGF). The immunolocalization of MMPs and TIMP-2 was performed in trabecular and compact bone, as well as articular and growth plate cartilages. Based on the results, it can be concluded that the exposure of pregnant dams to FB negatively affected the expression of certain proteins responsible for bone matrix degradation in newborns prenatally exposed to FB in a dose- and sex-dependent manner. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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18 pages, 5811 KiB

Open AccessArticle

Bacillus subtilis ANSB168 Producing d-alanyl-d-alanine Carboxypeptidase Could Alleviate the Immune Injury and Inflammation Induced by Ochratoxin A

by Hanrui Qing, Xueting Huo, Shimeng Huang, Lihong Zhao, Jianyun Zhang, Cheng Ji and Qiugang Ma

Int. J. Mol. Sci. 2021, 22(21), 12059; https://doi.org/10.3390/ijms222112059 - 8 Nov 2021

Cited by 9 | Viewed by 2652

Abstract

Ochratoxin A (OTA) is toxic to animals and threatens food safety through residues in animal tissues. A novel degrading strain Bacillus subtilis ANSB168 was isolated and further investigated. We cloned d-alanyl-d-alanine carboxypeptidase DacA and DacB from ANSB168 and over-expressed them [...] Read more.

Ochratoxin A (OTA) is toxic to animals and threatens food safety through residues in animal tissues. A novel degrading strain Bacillus subtilis ANSB168 was isolated and further investigated. We cloned d-alanyl-d-alanine carboxypeptidase DacA and DacB from ANSB168 and over-expressed them in Escherichia coli Rosetta (DE3). Then, we characterized the OTA degradation mechanism of DacA and DacB, which was degrading OTA into OTα. A total of 45 laying hens were divided into three equal groups. The control group was fed basal feed, and other groups were administered with OTA (250 μg/kg of feed). A freeze-dried culture powder of ANSB168 (3 × 10⁷ CFU/g, 2 kg/T of feed) was added to one of the OTA-fed groups for 28 days from day one of the experiment. We found that OTA significantly damaged the kidney and liver, inducing inflammation and activating the humoral immune system, causing oxidative stress in the layers. The ANSB168 bioproduct was able to alleviate OTA-induced kidney and liver damage, relieving OTA-induced inflammation and oxidative stress. Overall, DacA and DacB derived from ANSB168 degraded OTA into OTα, while the ANSB168 bioproduct was able to alleviate damages induced by OTA in laying hens. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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11 pages, 2160 KiB

Open AccessArticle

Selective Activation of Endoplasmic Reticulum Stress by Reactive-Oxygen-Species-Mediated Ochratoxin A-Induced Apoptosis in Tubular Epithelial Cells

by Chong-Sun Khoi, Yu-Wen Lin, Jia-Huang Chen, Biing-Hui Liu, Tzu-Yu Lin, Kuan-Yu Hung and Chih-Kang Chiang

Int. J. Mol. Sci. 2021, 22(20), 10951; https://doi.org/10.3390/ijms222010951 - 11 Oct 2021

Cited by 8 | Viewed by 2050

Abstract

Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress [...] Read more.

Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress activation in human renal proximal tubular cells (HK-2). OTA increased ER-stress-related JNK and precursor caspase-4 cleavage apoptotic pathways. Further study revealed that OTA increased reactive oxygen species (ROS) levels, and N-acetyl cysteine (NAC) could reduce OTA-induced JNK-related apoptosis and ROS levels in HK-2 cells. Our results demonstrate that OTA induced ER stress-related apoptosis through an ROS-mediated pathway. This study provides new evidence to clarify the mechanism of OTA-induced nephrotoxicity. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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14 pages, 2412 KiB

Open AccessArticle

T-2 Toxin Induces Oxidative Stress at Low Doses via Atf3ΔZip2a/2b-Mediated Ubiquitination and Degradation of Nrf2

by Xiaoxuan Chen, Peiqiang Mu, Lang Zhu, Xiaoxiao Mao, Shuang Chen, Huali Zhong and Yiqun Deng

Int. J. Mol. Sci. 2021, 22(15), 7936; https://doi.org/10.3390/ijms22157936 - 25 Jul 2021

Cited by 9 | Viewed by 2379

Abstract

T-2 toxin is mainly produced by Fusarium species, which is an extremely toxic mycotoxin to humans and animals. It is well known that T-2 toxin induces oxidative stress, but the molecular mechanism is still unknown. In this study, we found that T-2 toxin [...] Read more.

T-2 toxin is mainly produced by Fusarium species, which is an extremely toxic mycotoxin to humans and animals. It is well known that T-2 toxin induces oxidative stress, but the molecular mechanism is still unknown. In this study, we found that T-2 toxin significantly promoted reactive oxygen species (ROS) accumulation in MCF-7 cells at low doses which maintains cell viability at least 80%. Further analysis showed that T-2 toxin downregulated the expression of the master regulator of antioxidant defense gene, nuclear factor erythroid 2-related factor (Nrf2), and its targeted antioxidant genes. Overexpression of Nrf2 or its target gene heme oxygenase 1 (HO1) significantly blocked the ROS accumulation in MCF-7 cells under T-2 toxin treatment. Moreover, we found that T-2 toxin downregulated the antioxidant genes via inducing the expression of ATF3ΔZip2a/2b. Importantly, overexpression of ATF3ΔZip2a/2b promoted the ubiquitination and degradation of Nrf2. Altogether, our results demonstrated that T-2 toxin-induced ROS accumulation via ATF3ΔZip2a/2b mediated ubiquitination and degradation of Nrf2, which provided a new insight into the mechanism of T-2 toxin-induced oxidative stress. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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Review

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19 pages, 4335 KiB

Open AccessReview

Biological Detoxification of Mycotoxins: Current Status and Future Advances

by Lu Liu, Mei Xie and Dong Wei

Int. J. Mol. Sci. 2022, 23(3), 1064; https://doi.org/10.3390/ijms23031064 - 19 Jan 2022

Cited by 63 | Viewed by 9861

Abstract

Mycotoxins are highly toxic metabolites produced by fungi that pose a huge threat to human and animal health. Contamination of food and feed with mycotoxins is a worldwide issue, which leads to huge financial losses, annually. Decades of research have developed various approaches [...] Read more.

Mycotoxins are highly toxic metabolites produced by fungi that pose a huge threat to human and animal health. Contamination of food and feed with mycotoxins is a worldwide issue, which leads to huge financial losses, annually. Decades of research have developed various approaches to degrade mycotoxins, among which the biological methods have been proved to have great potential and advantages. This review provides an overview on the important advances in the biological removal of mycotoxins over the last decade. Here, we provided further insight into the chemical structures and the toxicity of the main mycotoxins. The innovative strategies including mycotoxin degradation by novel probiotics are summarized in an in-depth discussion on potentialities and limitations. We prospected the promising future for the development of multifunctional approaches using recombinant enzymes and microbial consortia for the simultaneous removal of multiple mycotoxins. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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22 pages, 11994 KiB

Open AccessReview

The Toxic Mechanism of Gliotoxins and Biosynthetic Strategies for Toxicity Prevention

by Wei Ye, Taomei Liu, Weiyang Zhang and Weimin Zhang

Int. J. Mol. Sci. 2021, 22(24), 13510; https://doi.org/10.3390/ijms222413510 - 16 Dec 2021

Cited by 13 | Viewed by 4519

Abstract

Gliotoxin is a kind of epipolythiodioxopiperazine derived from different fungi that is characterized by a disulfide bridge. Gliotoxins can be biosynthesized by a gli gene cluster and regulated by a positive GliZ regulator. Gliotoxins show cytotoxic effects via the suppression the function of [...] Read more.

Gliotoxin is a kind of epipolythiodioxopiperazine derived from different fungi that is characterized by a disulfide bridge. Gliotoxins can be biosynthesized by a gli gene cluster and regulated by a positive GliZ regulator. Gliotoxins show cytotoxic effects via the suppression the function of macrophage immune function, inflammation, antiangiogenesis, DNA damage by ROS production, peroxide damage by the inhibition of various enzymes, and apoptosis through different signal pathways. In the other hand, gliotoxins can also be beneficial with different doses. Low doses of gliotoxin can be used as an antioxidant, in the diagnosis and treatment of HIV, and as an anti-tumor agent in the future. Gliotoxins have also been used in the control of plant pathogens, including Pythium ultimum and Sclerotinia sclerotiorum. Thus, it is important to elucidate the toxic mechanism of gliotoxins. The toxic mechanism of gliotoxins and biosynthetic strategies to reduce the toxicity of gliotoxins and their producing strains are summarized in this review. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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20 pages, 1652 KiB

Open AccessReview

Mold, Mycotoxins and a Dysregulated Immune System: A Combination of Concern?

by Stephanie Kraft, Lisa Buchenauer and Tobias Polte

Int. J. Mol. Sci. 2021, 22(22), 12269; https://doi.org/10.3390/ijms222212269 - 12 Nov 2021

Cited by 31 | Viewed by 12518

Abstract

Fungi represent one of the most diverse and abundant eukaryotes on earth. The interplay between mold exposure and the host immune system is still not fully elucidated. Literature research focusing on up-to-date publications is providing a heterogenous picture of evidence and opinions regarding [...] Read more.

Fungi represent one of the most diverse and abundant eukaryotes on earth. The interplay between mold exposure and the host immune system is still not fully elucidated. Literature research focusing on up-to-date publications is providing a heterogenous picture of evidence and opinions regarding the role of mold and mycotoxins in the development of immune diseases. While the induction of allergic immune responses by molds is generally acknowledged, other direct health effects like the toxic mold syndrome are controversially discussed. However, recent observations indicate a particular importance of mold/mycotoxin exposure in individuals with pre-existing dysregulation of the immune system, due to exacerbation of underlying pathophysiology including allergic and non-allergic chronic inflammatory diseases, autoimmune disorders, and even human immunodeficiency virus (HIV) disease progression. In this review, we focus on the impact of mycotoxins regarding their impact on disease progression in pre-existing immune dysregulation. This is complemented by experimental in vivo and in vitro findings to present cellular and molecular modes of action. Furthermore, we discuss hypothetical mechanisms of action, where evidence is missing since much remains to be discovered. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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20 pages, 4985 KiB

Open AccessReview

Ochratoxin A-Induced Nephrotoxicity: Up-to-Date Evidence

by Chong-Sun Khoi, Jia-Huang Chen, Tzu-Yu Lin, Chih-Kang Chiang and Kuan-Yu Hung

Int. J. Mol. Sci. 2021, 22(20), 11237; https://doi.org/10.3390/ijms222011237 - 18 Oct 2021

Cited by 44 | Viewed by 4716

Abstract

Ochratoxin A (OTA) is a mycotoxin widely found in various foods and feeds that have a deleterious effect on humans and animals. It has been shown that OTA causes multiorgan toxicity, and the kidney is the main target of OTA among them. This [...] Read more.

Ochratoxin A (OTA) is a mycotoxin widely found in various foods and feeds that have a deleterious effect on humans and animals. It has been shown that OTA causes multiorgan toxicity, and the kidney is the main target of OTA among them. This present article aims to review recent and latest intracellular molecular interactions and signaling pathways of OTA-induced nephrotoxicity. Pyroptosis, lipotoxicity, organic anionic membrane transporter, autophagy, the ubiquitin-proteasome system, and histone acetyltransferase have been involved in the renal toxicity caused by OTA. Meanwhile, the literature reviewed the alternative or method against OTA toxicity by reducing ROS production, oxidative stress, activating the Nrf2 pathway, through using nanoparticles, a natural flavonoid, and metal supplement. The present review discloses the molecular mechanism of OTA-induced nephrotoxicity, providing opinions and strategies against OTA toxicity. Full article

(This article belongs to the Special Issue Mycotoxins, Immunity, and Inflammation 2022)

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