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1.
Int J Mol Sci ; 23(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36232948

RESUMO

Patulin (PAT) is a common mycotoxin in the food industry, and is found in apple products in particular. Consumption of food or feed contaminated with PAT can cause acute or chronic toxicity in humans and animals. Lactiplantibacillus plantarum CCFM1287 is a probiotic strain that effectively degrades PAT in PBS and food systems. In this study, it was found that the concentration of PAT (50 mg/L) in MRS medium decreased by 85.09% during the first stages of CCFM1287 growth, and this change was consistent with the first-order degradation kinetic model. Meanwhile, the regulation of oxidative stress by L. plantarum CCFM1287 in response to PAT exposure and metabolic changes that occur during PAT degradation were investigated. The degree of intracellular damage was attenuated after 16 h of exposure compared to 8 h. Meanwhile, metabolomic data showed that 30 and 29 significantly different metabolites were screened intracellularly in the strain after 8 h and 16 h of PAT stress at 50 mg/L, respectively. The results of pathway enrichment analysis suggested that the purine metabolic pathway was significantly enriched at both 8 h and 16 h. However, as is consistent with the performance of the antioxidant system, the changes in Lactiplantibacillus diminished with increasing time of PAT exposure. Therefore, this study helps to further explain the mechanism of PAT degradation by L. plantarum CCFM1287.


Assuntos
Malus , Patulina , Probióticos , Animais , Antioxidantes , Humanos , Malus/metabolismo , Patulina/metabolismo , Patulina/toxicidade , Purinas
2.
Food Res Int ; 156: 111177, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35651038

RESUMO

Various studies have identified the kidney as a target organ for patulin (PAT)-induced toxicity. However, detailed mechanistic insights into PAT-induced nephrotoxicity had not yet been done. Therefore, along with classical toxicological parameters, liquid chromatography-high resolution massed spectrometry (LC-HRMS) based metabolomics has been carried out to delineate the mechanism(s) of PAT-induced nephrotoxicity.An in vivo study was conducted using male Wistar rats, divided into three groups. PAT (25 µg/kg b.wt and 100 µg/kg b.wt) and, control were given through oral gavage, 5 days/week for 28 days. At the end of the experiment, changes in the mean body/ organ weight, food and water intake, expression of marker proteins of kidney injury, and histopathological changes were investigated. Furthermore, using LC-HRMS based metabolomics was performed on the serum and urine of PAT-exposed rats. The histopathological and toxicological analysis revealed a significant increase in glomerular mesangial cells, vacuolar degeneration, and cast deposition in the proximal convoluted tubules. The metabolomics showed metabolic perturbations in amino and fatty acid-related metabolic pathways in serum and urine of PAT-treated rats. In conclusion this study expands our understanding of PAT-induced metabolic alterations and its effects on renal function.


Assuntos
Patulina , Animais , Masculino , Espectrometria de Massas , Metabolômica/métodos , Patulina/toxicidade , Ratos , Ratos Wistar , Urinálise
3.
Food Chem Toxicol ; 166: 113255, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35772596

RESUMO

Patulin (PAT) is a common food-borne mycotoxin with diverse toxic effects including nephrotoxicity. The induction of oxidative stress is suggested to be a key mechanism contributed to toxicities of PAT. Reduced glutathione (GSH), a sulfhydryl-containing tripeptide, is a key reason for PAT-mediated oxidative stress. Cystine/glutamate antiporter (system xc-)-mediated cystine uptake plays a critical role in maintaining redox balance via promoting GSH biosynthesis. In this study, we addressed if GSH reduction by PAT was associated with inhibition of system xc--mediated GSH biosynthesis. Results showed that PAT significantly decreased activity of SLC7A11, a core subunit of system xc-, through activating AMPK-mediated formation of beclin1-SLC7A11 complex. Furthermore, PAT promoted ferroptosis induced by a known ferroptosis inducer RSL3 in normal renal cells, and exacerbated folic acid-induced nephrotoxicity in a mouse model of acute kidney injury. The findings of the present study provide new insights into PAT-induced kidney toxicity, and implicate that patients with ferroptosis-associated diseases maybe more susceptible to PAT.


Assuntos
Ferroptose , Patulina , Sistema y+ de Transporte de Aminoácidos/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/farmacologia , Animais , Antioxidantes/farmacologia , Cisteína/farmacologia , Cistina/farmacologia , Glutationa/metabolismo , Rim , Camundongos , Patulina/toxicidade
4.
J Agric Food Chem ; 70(20): 6213-6223, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35543324

RESUMO

Patulin (PAT) is a common mycotoxin, widely found in cereals, seafood, nuts, and especially in fruits and their products. Exposure to this mycotoxin has been reported to induce kidney injury. However, the possible mechanism remains unclear. In our study, short-term high-dose intake of PAT caused acute kidney injury (AKI) in mice. We performed high-throughput transcriptional sequencing to identify differentially expressed genes (DEGs) between the treatment and control groups. The ferroptosis signaling pathway had the highest enrichment, suggesting ferroptosis is involved in PAT-induced AKI. Further, the existence of ferroptosis and autophagy was confirmed by observing the changes of mitochondria morphology and the formation of autophagosomes by electron microscopy. And the expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), p62, nuclear receptor coactivator 4 (NCOA4), and ferritin heavy chain 1 (FTH1) were downregulated, whereas acyl-CoA synthase long-chain family member 4 (ACSL4), transferrin (TF), LC3, and ferritin light chain (FTL) expression were upregulated in PAT-exposed mice. These results suggested autophagy-dependent ferroptosis occurred in the animal model. This view has also been confirmed in the human renal tubular epithelial cell (HKC) experiments. Autophagy inhibitor 3-methyladenine (3MA) attenuated PAT-induced ferroptosis and the iron contents in HKC cells. Simultaneous autophagy-dependent ferroptosis can be inhibited by ferroptosis inhibitors ferrostatin-1 (Fer-1) and desferrioxamine (DFO). In general, this study provides a new perspective for exploring the new mechanism of acute kidney injury caused by PAT.


Assuntos
Injúria Renal Aguda , Autofagia , Ferroptose , Patulina , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Animais , Camundongos , Patulina/toxicidade , Fosfolipídeo Hidroperóxido Glutationa Peroxidase
5.
J Agric Food Chem ; 70(15): 4755-4764, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35394776

RESUMO

Patulin (PAT) is a common mycotoxin. Oral ingestion of PAT could damage the intestinal mucosa. Both selenium and probiotics can alleviate intestinal damage, but there are few reports on selenium-enriched probiotics. Here, we studied the protective effects of a new selenium-enriched Pediococcus acidilactici MRS-7 (SeP) on PAT-induced jejunum injuries in mice. Results show that PAT induced jejunum injuries such as loss of crypts, ulceration of the mucosa, and intestinal epithelial barrier function impairment. However, SeP could protect against PAT-induced jejunum injuries and significantly inhibit the reduction of goblet cell numbers. SeP could not only alleviate PAT-induced oxidative stress by decreasing malondialdehyde (MDA) and increasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels in the jejunum tissues but also alleviate the inflammatory response caused by PAT by reducing the levels of inflammatory factors (interleukin (IL)-6 snd IL-1ß and tumor necrosis factor-α (TNF-α)) in the serum and jejunum tissues. In addition, SeP also inhibited the expression of nuclear factor-κB (NF-κB) and Toll-like receptor 4 (TLR-4), increased the expression of tight junction proteins (occludin, ZO-1, and claudin-1), and increased the selenium content in the jejunum, thereby antagonizing the jejunum injuries caused by PAT exposure. Finally, SeP rebalanced the intestinal microbiota and improved probiotic abundance such as Turicibacter, Bifidobacterium, Ileibacterium, and Pediococcus in PAT-treated mice. These results support the possibility of SeP as a novel protective agent to mitigate the toxicity of PAT.


Assuntos
Patulina , Pediococcus acidilactici , Selênio , Animais , Mucosa Intestinal/metabolismo , Jejuno/metabolismo , Camundongos , Estresse Oxidativo , Patulina/toxicidade , Pediococcus acidilactici/metabolismo , Selênio/metabolismo
6.
Mol Cell Biochem ; 477(5): 1405-1416, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35150386

RESUMO

Patulin (PAT) is a natural contaminant of fruits (primarily apples) and their products. Significantly, high levels of contamination have been found in fruit juices all over the world. Several in vitro studies have demonstrated PAT's ability to alter intestinal structure and function. However, in real life, the probability of low dose long-term exposure to PAT to humans is significantly higher through contaminated food items. Thus, in the present study, we have exposed normal intestinal cells to non-toxic levels of PAT for 16 weeks and observed that PAT had the ability to cause cancer-like properties in normal intestinal epithelial cells after chronic exposure. Here, our results showed that chronic exposure to low doses of PAT caused enhanced proliferation, migration and invasion ability, and the capability to grow in soft agar (anchorage independence). Moreover, an in vivo study showed the appearance of colonic aberrant crypt foci (ACFs) in PAT-exposed Wistar rats, which are well, establish markers for early colon cancer. Furthermore, as these neoplastic changes are consequences of alterations at the molecular level, here, we combined next-generation RNA sequencing with liquid chromatography mass spectrometry-based proteomic analysis to investigate the possible underlying mechanisms involved in PAT-induced neoplastic changes.


Assuntos
Neoplasias , Patulina , Animais , Células Epiteliais , Patulina/análise , Patulina/toxicidade , Fenótipo , Proteômica , Ratos , Ratos Wistar , Transcriptoma
7.
Toxicon ; 210: 58-65, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35217024

RESUMO

Patulin (PAT) is a mycotoxin produced by Penicillium and other fungi that contaminate fruit. PAT targets the kidney and is associated with nephrotoxicity. Micro-RNAs (miRNA) may offer new insights into PAT-induced nephrotoxicity. Cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1), involved in metabolism of dietary toxins is negatively regulated by miR-27b and linked with the nuclear factor kappa B (NF-κB) pathway and peroxisome proliferator activated receptor gamma (PPARÉ£) in renal fibrosis. This study investigated the effects of PAT on miR-27b, CYP1B1, PPARÉ£ and cytotoxicity in human kidney (HEK293) cells. HEK293 cells were exposed to PAT (2.5 µM, 24h). Protein expression of CYP1B1, PPARÉ£, NF-κB (p65), pNF-κB (p65) (phospho-Ser563) and cleaved PARP-1 was quantified using western blotting. QPCR evaluated mRNA levels of CYP1B1, IL-6, miR-27b, OGG1, mtDNA, TFAM and UCP2. Mitochondrial membrane potential and phosphatidylserine (PS) externalization was evaluated by flow cytometry while levels of ATP and caspase -9, -8, -3/7 activity was measured using luminometry. PAT significantly decreased miR-27b levels (p = 0.0014) and increased CYP1B1 mRNA (p = 0.0015) and protein (p = 0.0013) levels. PPARÉ£ protein expression was significantly increased (p = 0.0002) and associated with decreased NF-κB activation (p = 0.0273) and IL-6 mRNA levels (p = 0.0265). Finally, PAT significantly compromised mitochondrial repair mechanisms and increased apoptotic biomarkers. PAT altered miR-27b levels and PPARÉ£, with associated changes to NF-κB activation, downstream IL-6 and CYP1B1 expression. These results show that PAT impairs detoxification mechanisms leading to mitochondrial damage and apoptosis. In conclusion, PAT altered the epigenetic environment and impaired detoxification processes, supporting a mechanism for nephrotoxic outcomes.


Assuntos
MicroRNAs , Patulina , Células HEK293 , Humanos , MicroRNAs/genética , NF-kappa B/metabolismo , Patulina/toxicidade , RNA Mensageiro/metabolismo
8.
Crit Rev Food Sci Nutr ; 62(20): 5540-5568, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33624529

RESUMO

Patulin and Trichothecene as the main groups of mycotoxins in significant quantities can cause health risks from allergic reactions to death on both humans and animals. Accordingly, rapid and highly sensitive determination of these toxics agents is of great importance. This review starts with a comprehensive outlook regarding the characteristics, occurrence and toxic effects of Patulin and Trichothecene. In the following, numerous clinical and analytical approaches have been extensively discussed. The main emphasis of this review is placed on the utilization of novel nanomaterial based electrochemical sensing/biosensing tools for highly sensitive determination of Patulin and Trichothecene. Furthermore, a detailed and comprehensive comparison has been performed between clinical, analytical and sensing methods. Subsequently, the nanomaterial based electrochemical sensing platforms have been approved as reliable tools for on-site analysis of Patulin and Trichothecene in food processing and manufacturing industries. Different nanomaterials in improving the performance of detecting assays were investigated and have various benefits toward clinical and analytical methods. This paper would address the limitations in the current developments as well as the future challenges involved in the successful construction of sensing approaches with the functionalized nanomaterials and also allow exploring into core-research works regarding this area.[Formula: see text].


Assuntos
Técnicas Biossensoriais , Nanoestruturas , Patulina , Tricotecenos , Animais , Bioensaio , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Nanoestruturas/toxicidade , Patulina/toxicidade , Tricotecenos/análise , Tricotecenos/toxicidade
9.
Toxicon ; 207: 21-30, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34929212

RESUMO

Patulin (PAT) is a kind of mycotoxins that is universally found at rotten fruits, especially apples and apple products. Previous studies have shown that PAT has hepatotoxicity and nephrotoxicity. However, cardiotoxicity of PAT is rarely reported. Present study aimed at investigate the cardiotoxicity and relevant mechanisms of PAT on H9c2 cells. Cytotoxicity of PAT were evaluated by MTT assay and LDH. Hoechst 33258 staining was used to examine the nuclear morphology and AV/PI double staining was employed for apoptosis on H9c2 cells. Expression level of Caspase-3, Caspase-9, Bax, Bcl-2 were quantified to verify the potential mechanism of mitochondrial apoptosis pathway. The tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin 6 (IL-6) were quantified to determine the inflammatory response by using ELISA assay. ROS, SOD, MDA, GSH levels were measured to determine the oxidative stress status. Results demonstrated that PAT significantly induced cell injury, as evidenced by the down-regulated of cell viability, and the increase of LDH release. Hoesst33258 staining and flow cytometry showed that apoptosis rate was elevated by PAT. PAT treatment up-regulated the expression of Caspase-3, Caspase-9, Bax level and down-regulated the expression of Bcl-2 level. TNF-α, IL-1ß, IL-6 levels showed that PAT increased the pro-inflammatory response. As PAT concentration increased, intracellular MDA, ROS content were elevated, while GSH content and the activity of SOD were significantly decreased. Thus, it is concluded that PAT may induce apoptosis of H9c2 cells through oxidative stress.


Assuntos
Patulina , Apoptose , Cardiotoxicidade/metabolismo , Humanos , Mitocôndrias/metabolismo , Estresse Oxidativo , Patulina/toxicidade
10.
Toxicol Appl Pharmacol ; 434: 115819, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896196

RESUMO

Patulin (PAT) is a mycotoxin that contaminates a variety of food and foodstuffs. Earlier in vitro and in vivo findings have indicated that kidney is one of the target organs for PAT-induced toxicity. However, no study has evaluated the chronic effects of PAT exposure at environmentally relevant doses or elucidated the detailed mechanism(s) involved. Here, using in vitro and in vivo experimental approaches, we delineated the mechanism/s involved in pro-fibrotic changes in the kidney after low-dose chronic exposure to PAT. We found that non-toxic concentrations (50 nM and 100 nM) of PAT to normal rat kidney cells (NRK52E) caused a higher generation of reactive oxygen species (ROS) (mainly hydroxyl (•OH), peroxynitrite (ONOO-), and hypochlorite radical (ClO-). PAT exposure caused the activation of mitogen-activated protein kinases (MAPKs) and its downstream c-Jun/Fos signaling pathways. Moreover, our chromatin immunoprecipitation (ChIP) analysis suggested that c-Jun/Fos binds to the promoter region of Transforming growth factor beta (TGF-ß1) and possibly induces its expression. Results showed that PAT-induced TGF-ß1 further activates the TGF-ß1/smad signaling pathways. Higher activation of slug and snail transcription factors further modulates the regulation of pro-fibrotic molecules. Similarly, in vivo results showed that PAT exposure to rats through gavage at 25 and 100 µg/kg b. wt had higher levels of kidney injury/toxicity markers namely vascular endothelial growth factor (VEGF), kidney Injury Molecule-1 (Kim-1), tissue inhibitor of metalloproteinase-1 (Timp-1), and clusterin (CLU). Additionally, histopathological analysis indicated significant alterations in renal tubules and glomeruli along with collagen deposition in PAT-treated rat kidneys. Overall, our data provide evidence of the involvement of ROS mediated MAPKs and TGF-ß1/smad pathways in PAT-induced pro-fibrotic changes in the kidney via modulation of slug and snail expression.


Assuntos
Nefropatias/induzido quimicamente , Patulina/toxicidade , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/urina , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Mutagênicos/toxicidade , Ratos , Ratos Wistar , Proteínas Smad/genética , Fatores de Transcrição da Família Snail/genética , Fator de Crescimento Transformador beta/genética
11.
Toxicon ; 205: 31-37, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34822873

RESUMO

Patulin (PAT) is a toxic mycotoxin usually contaminated apple juices, which leads to a serious food safety issue in the world. Thiol-compounds are a class of compounds containing the thiol (-SH) group themselves or obtained the -SH group by physical or chemical modification. They have the ability to efficiently remove patulin in apple juices with manifested negligible effects on juice quality. This review investigates the latest development in the removal of patulin using thiol-compounds, including the removal efficiencies and mechanisms of patulin, the factors influencing the removal efficiency of patulin, as well as the toxicities of thiol-compounds and safety of juices after detoxification. This review shows that thiol-compounds are promising materials for the removal or degradation of patulin in the contaminated juices.


Assuntos
Patulina , Inocuidade dos Alimentos , Patulina/toxicidade , Compostos de Sulfidrila
12.
Toxicon ; 206: 64-73, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34968565

RESUMO

Patulin (PAT) a kind of mycotoxin, is a widely disseminated mycotoxin found in agricultural products and could cause liver damage. However, evidence on the underlying mechanisms of patulin is still lacking. In the present study, Human liver cancer cells (HepG2) together with a mouse model were used to explore the possible effect and mechanism. The results demonstrated that PAT treatment inhibited cell proliferation and caused liver toxicity in mice. In vitro, PAT inhibited the growth of HepG2 cells in a dose-dependent manner and a time-dependent manner; lipid peroxidation, malondialdehyde (MDA) production increased and the level of SOD and GSH in cells changed significantly. In vivo, Kunming mice were treated with PAT(2.5-15 µM), We indicated that liver damage are observed. The activity of serum alanine transaminase (ALT) and aspartate transaminase (AST) were increased significantly, the hepatocyte nucleus stained with Hematoxylin and Eosin (HE) was blurred and deformed. we also explored the lipid peroxidation and enzymes related to redox and found that the activities of SOD in animals do not change significantly, not like that in cells, while GSHpx played a major role. In addition, we measured the caspase activity of cells and the expression of caspase in mice. PAT-induced the caspase cascade was confirmed with the elevation of the activity and expression of caspase. These data suggest that PAT treatment altered both the redox systems in cells and animals. involvement of caspase in patulin-induced hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Patulina , Animais , Animais não Endogâmicos , Caspase 3 , Caspases , Peroxidação de Lipídeos , Camundongos , Patulina/toxicidade
13.
Toxicology ; 464: 153013, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34718031

RESUMO

Patulin is a secondary metabolite mainly secreted by fungi and is the most common mycotoxin found in apples and apple-based products. For the past few years, numerous studies suggested the wide distribution and toxicity of patulin. In this study, we investigated the toxic effect of patulin on mouse oocytes and its possible mechanisms. The results showed that patulin treatment did not affect meiotic resumption, but inhibited oocyte maturation as indicated by failure of first polar body extrusion. Further mechanistic study showed that patulin treatment disturbed normal spindle assembly, chromosome alignment and morphology. We also found increased oxidative stress by testing the level of ROS and decreased mitochondrial membrane potential, indicating mitochondria dysfunction. In summary, our results suggest that patulin treatment causes oocyte meiotic arrest by disturbing normal spindle assembly and chromosome alignment, which may be caused by dysfunctions of mitochondria.


Assuntos
Mitocôndrias/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Patulina/toxicidade , Animais , Feminino , Meiose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/patologia , Oócitos/patologia , Espécies Reativas de Oxigênio/metabolismo
14.
Toxins (Basel) ; 13(10)2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34679020

RESUMO

Patulin, a mycotoxin, is known to have cytotoxic effects, but few studies have focused on the involvement of the endoplasmic reticulum (ER) stress response in patulin toxicity and the natural compounds that attenuate it in HepG2 cells. This study tested the ability of patulin to induce ER stress, and that of four thiols and three thioethers to attenuate patulin-induced ER stress in HepG2 cells. Patulin dose-dependently inhibited cell proliferation (IC50, 8.43 µM). Additionally, patulin was found to increase the expression levels of ER stress-related genes and/or protein markers, including BiP, CHOP, and spliced XBP1, in HepG2 cells compared to the vehicle control, indicating its potential in ER stress induction. Patulin-induced cytotoxicity in HepG2 cells was reduced by naturally occurring thiol compounds (glutathione, L-acetyl-L-cysteine, cysteine, and captopril), but not by thioether compounds (sulforaphane, sulforaphene, and S-allyl-L-cysteine). Patulin-thiol co-treatment decreased CHOP expression and BiP and CHOP levels in HepG2 cells but did not alter BiP expression. Spliced XBP1 expression was decreased by patulin-thiol co-treatment. Thus, patulin induced ER stress in HepG2 cells and thiols, but not in thioethers, attenuated patulin-induced ER stress.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Patulina/toxicidade , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Compostos de Sulfidrila/farmacologia , Sulfetos/farmacologia
15.
J Agric Food Chem ; 69(26): 7313-7323, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34165302

RESUMO

A biocontrol method plays an important role in weed management. In this study, we aimed to clarify the phytotoxicity of the mycotoxin patulin (PAT) and reveal its mode of action as a new natural photosystem II (PSII) inhibitor. Phytotoxicity test showed that PAT has herbicidal activity and causes significant leaf lesions on Ageratina adenophora. Under a half-inhibition concentration I50 (2.24 µM), the observed significant decrease in oxygen evolution rate and the increase in the J-step of the chlorophyll fluorescence rise OJIP curve indicated that PAT strongly reduces photosynthetic efficiency by blocking electron transport from the primary to secondary plastoquinone acceptors (QA to QB) of PSII. Molecular modeling of PAT docking to the A. adenophora D1 protein suggested that PAT bounds to the QB site by forming hydrogen bonds to histidine 252 in the D1 protein. It is proposed that PAT is a new natural PSII inhibitor and has the potential to be developed into a bioherbicide or used as a template scaffold for discovering novel derivatives with more potent herbicidal activity.


Assuntos
Patulina , Complexo de Proteína do Fotossistema II , Clorofila , Transporte de Elétrons , Patulina/toxicidade , Fotossíntese , Complexo de Proteína do Fotossistema II/metabolismo
16.
Toxicon ; 198: 12-23, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33933519

RESUMO

The mycotoxin patulin is primarily produced as a secondary metabolite by numerous fungal species and predominantly by Aspergillus, Byssochlamys, and Penicillium species. It is generally associated with fungal infected food materials. Penicillium expansum is considered the only fungal species liable for patulin contamination in pome fruits, especially in apples and apple-based products. This toxin in food poses serious health concerns and economic threat, which has aroused the need to adopt effective detection and mitigation strategies. Understanding its origin sources and biosynthetic mechanism stands essential for efficiently designing a management strategy against this fungal contamination. This review aims to present an updated outline of the sources of patulin occurrence in different foods and their biosynthetic mechanisms. It further provides information regarding the detrimental effects of patulin on human and agriculture as well as its effective detection, management, and control strategies.


Assuntos
Malus , Patulina , Penicillium , Contaminação de Alimentos/análise , Frutas/química , Humanos , Patulina/toxicidade
17.
Toxins (Basel) ; 13(3)2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803748

RESUMO

Food can be contaminated by various types of contaminants such as mycotoxins and toxic heavy metals. Therefore, it is very likely that simultaneous intake of more than one type of food contaminant by consumers may take place, which provides a strong rationale for investigating the combined toxicities of these food contaminants. Patulin is one of the most common food-borne mycotoxins, whereas cadmium is a representative of toxic heavy metals found in food. The liver and kidneys are the main target organ sites for both patulin and cadmium. We hypothesized that simultaneous exposure to patulin and cadmium could produce synergistic hepatotoxicity and nephrotoxicity. Alpha mouse liver 12 (AML12) and Human embryonic kidney (HEK) 293 (HEK293) cell lines together with a mouse model were used to explore the combination effect and mechanism. The results demonstrated, for the first time, that the co-exposure of liver or renal cells to patulin and cadmium caused synergistic cytotoxicity in vitro and enhanced liver toxicity in vivo. The synergistic toxicity caused by the co-administration of patulin and cadmium was attributed to the boosted reactive oxygen species (ROS) generation. c-Jun N-terminal kinase 1 (JNK1) and p53 as downstream mediators of oxidative stress contributed to the synergistic toxicity by co-exposure of patulin and cadmium, while p53/JNK1 activation promoted the second-round ROS production through a positive feedback loop. The findings of the present study extend the toxicological knowledge about patulin and cadmium, which could be beneficial to more precisely perform risk assessments on these food contaminants.


Assuntos
Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Patulina/toxicidade , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Sinergismo Farmacológico , Contaminação de Alimentos , Células HEK293 , Humanos , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo
18.
Food Res Int ; 140: 110034, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33648261

RESUMO

Patulin-producing fungi pose an unavoidable problem for apple and its product quality, thereby threatening human and/or animal health. Studies on controlling the patulin-producing fungal growth and patulin contamination in apple and its products by physical methods, chemical fungicides, and biological methods have been performed for decades, but patulin contamination has not been addressed. Here, the important of studying regulation mechanism of patulin production in apple at the protein expression and metabolism levels is proposed, which will facilitate the development of controlling patulin production by using physical, chemical, and biological methods. Furthermore, the advantages or disadvantages and effects or mechanisms of using physical, chemical, biological methods to control the decay caused by Penicillium expansum and to remove patulin in food was discussed. The development of physical methods to remove patulin depends on the development of special equipment. Chemical methods are economical and efficient, if we have ensured that there are no unknown reactions or toxic by-products by using these chemicals. The biological method not only effectively controls the decay caused by Penicillium espansum, but also removes the toxins that already exist in the food. Degradation of patulin by microorganisms or biodegradation enzymes is an efficient and promising method to remove patulin in food if the microorganisms used and the degradation products are completely non-toxic.


Assuntos
Malus , Patulina , Penicillium , Animais , Humanos , Patulina/toxicidade
19.
Food Chem Toxicol ; 150: 112055, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33577942

RESUMO

Patulin (PAT) is a kind of mycotoxins that commonly found in decayed fruits and their products. Our previous studies have shown that PAT induced cell apoptosis and the overproduction of reactive oxygen species (ROS) in human embryonic kidney (HEK293) cells. The present study aimed to further investigate the functional role of NADPH oxidase, one of the main cellular sources of ROS, in PAT-induced apoptosis and oxidative damage in HEK293 cells. We demonstrated that the protein and mRNA expression levels of NADPH oxidase catalytic subunit NOX2 and regulatory subunit p47phox were up-regulated under PAT stress. Inhibiting of NADPH oxidase with the specific antagonist diphenyleneiodonium (DPI) suppressed cytotoxicity and apoptosis induced by PAT as evidenced by the increase of cell viability, the decrease of LDH release and the inhibition of caspase activities. Furthermore, DPI re-established mitochondrial membrane potential (MMP) and enhanced cellular ATP content. Importantly, DPI supplementation elevated endogenous GSH contents as well as the ratio of GSH/GSSG. Meanwhile, the antioxidant-enzyme activities of GPx, GR, CAT and SOD were significantly promoted. Collectively, our results suggested that NADPH oxidase played a critical role in PAT-induced nephrotoxicity, and inhibition of NADPH oxidase by DPI attenuated cell injury and apoptosis via regulation of oxidative damage.


Assuntos
Compostos de Bifenilo/farmacologia , Sobrevivência Celular/efeitos dos fármacos , NADPH Oxidases/metabolismo , Oniocompostos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Patulina/toxicidade , Trifosfato de Adenosina/metabolismo , Caspases/genética , Caspases/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Células HEK293 , Humanos , Lactato Desidrogenases/genética , Lactato Desidrogenases/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mutagênicos/toxicidade , NADPH Oxidases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Toxins (Basel) ; 13(9)2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34564600

RESUMO

Patulin (PAT) belongs to the family of food-borne mycotoxins. Our previous studies revealed that PAT caused cytotoxicity in human embryonic kidney cells (HEK293). In the present research, we systematically explored the detailed mechanism of ROS production and ROS clearance in PAT-induced HEK293 cell apoptosis. Results showed that PAT treatment (2.5, 5, 7.5, 10 µM) for 10 h could regulate the expression of genes and proteins involved in the mitochondrial respiratory chain complex, resulting in dysfunction of mitochondrial oxidative phosphorylation and induction of ROS overproduction. We further investigated the role of N-acetylcysteine (NAC), an ROS scavenger, in promoting the survival of PAT-treated HEK293 cells. NAC improves PAT-induced apoptosis of HEK293 cells by clearing excess ROS, modulating the expression of mitochondrial respiratory chain complex genes and proteins, and maintaining normal mitochondrial function. In addition, NAC protects the activity of antioxidant enzymes, maintains normal GSH content, and relieves oxidative damage. Additionally, 4 mM NAC alleviated 7.5 µM PAT-mediated apoptosis through the caspase pathway in HEK293 cells. In summary, our study demonstrated that ROS is significant in PAT-mediated cytotoxicity, which provides valuable insight into the management of PAT-associated health issues.


Assuntos
Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Apoptose/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Patulina/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas/efeitos dos fármacos , Células HEK293/efeitos dos fármacos , Humanos , Redes e Vias Metabólicas , Mitocôndrias/metabolismo , Micotoxinas/toxicidade
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