Ochratoxin A has been found to be nephrotoxic in all mammalian species treated [6], although differences in toxicity have been found among species and sex. This could interfere with the DNA repair systems and cell cycle controls systems and serve as an initiating point of carcinogenesis. In addition, ochratoxin A increased cytosolic and mitochondrial calcium levels, resulting in an increase in MMP2 and PLAUR mRNA expression in NHA-SV40LT cells. WebNeurological symptoms, such as headaches, memory loss, brain fog, and difficulty concentrating Fatigue and weakness Joint and muscle pain Digestive problems, such as nausea, abdominal pain, and diarrhea Immune system dysfunction, leading to frequent infections or autoimmune disorders In vitro experiments have shown decreased proliferation of neural progenitor stem cells in the hippocampal region of mice after exposure to OTA leading the authors to speculate that problems impairing hippocampal neurogenesis in vivo could contribute to the memory problems and depression commonly seen in humans exposed to mycotoxins [68]. In addition, lipid peroxidation and enzymes involved in arachidonic acid metabolism affect the biotransformation of OTA [23]. and transmitted securely. - OTA has been linked to kidney disease and cancer, but recent studies suggest it may also play a role in neurodegenerative diseases. Hyperlipidemia is a common complication of her type of renal disease or nephrotic syndrome. Hassan AM, Sheashaa HA, Fattah MFA, Ibrahim AZ, Gaber OA, Sobh MA. Gekle M, Silbernagl S. The role of the proximal tubule in ochratoxin A nephrotoxicity in vivo: toxodynamic and toxokinetic aspects. HHS Vulnerability Disclosure, Help doi: 10.1371/journal.pone.0119912. National Library of Medicine Kuiper-Goodman T, Scott PM. It can also affect the development of the brain in children and lead to cognitive impairment. Hazard characterisation for significant mycotoxins in food. Early detection and treatment can improve outcomes. Bookshelf Pretreatment of rats with retinol (vitamin A), ascorbic acid (vitamin C), or alpha tocopherol (vitamin E) before OTA administration significantly decreased the number of DNA adducts formed in the kidney by 70 percent, 90 percent, and 80 percent, respectively [22]. 8600 Rockville Pike Micco C, Ambruzzi A, Miraglia M, et al. At the time of presentation to this office, the patient was also reporting symptoms of night sweats, heat intolerance, frequent episodes of otitis media and conjunctivitis, dizziness, hair loss, fungal skin rashes, episodes of excessive thirst, and the recent onset of reversing letters when she writes. One such toxin is Ochratoxin A (OTA), a mycotoxin produced by certain fungi. PMID: 31154016 DOI: 10.1016/j.toxlet.2019.05.021 Abstract Astrocytes are the major glial cell type in the central nervous system (CNS), and the distal part of the It is found in contaminated food and can lead to serious health issues if consumed in large amounts. In this study, we studied the specific working mechanism of ochratoxin A in the human astrocyte cell line, NHA-SV40LT. have reported elevated concentrations of OTA in the urine of individuals exposed to water-damaged buildings versus unexposed controls [40]. The annual incidence of end-stage renal disease from FSGS has increased 11-fold from 0.2 percent to 2.3 percent between 1980 and 2000, and FSGS is now the most common cause of end-stage renal disease resulting from primary glomerular disease [72]. , 1. 2023 Feb 28. doi: 10.1007/s10123-023-00341-5. - OTA can cross the blood-brain barrier and accumulate in the brain. Oxibendazole induces apoptotic cell death in proliferating porcine trophectoderm and uterine luminal epithelial cells via mitochondria-mediated calcium disruption and breakdown of mitochondrial membrane potential. Implement good agricultural practices to reduce fungal contamination. sharing sensitive information, make sure youre on a federal As such, it is important to be aware of the potential risks associated with consuming these products and to take steps to minimize exposure. Here are some strategies: Early detection and treatment of ochratoxin A exposure can prevent neurological symptoms. It is produced by several different fungi including Neurological symptoms can be caused by a variety of factors, including exposure to toxins. Skaug MA, Helland I, Solvoll K, Saugstad OD. Web Neurological symptoms can be caused by a variety of factors, including exposure to toxins. Zeng Z, Leng T, Feng X, Sun H, Inoue K, Zhu L, Xiong ZG. Bendele AM, Carlton WW, Krogh P, Lillehoj EB. . The most important are the avoidance of further exposure and the use of the bile acid resin binding agent, cholestyramine, to decrease enterohepatic recirculation of OTA. Since testing for mycotoxins in urine and other tissues is now readily available [40], it is appropriate to obtain this testing on urine and renal biopsy tissue to help elucidate whether this is a potential contributor to illness. Clipboard, Search History, and several other advanced features are temporarily unavailable. Several studies have indicated that phenylalanine decreases the absorption and consequent toxicity of OTA, and this is also true of aspartame [34, 37, 38]. Its potential role in neurodegenerative diseases is a relatively new area of research. MeSH There has been increasing recognition of causes in primary FSGS including genetic, viral, drug toxicity, and others. A water damaged home and health occupants: a case study. Pfohl-Leszkowicz A, Pinelli E, Bartsch H, Mohr U, Castegnaro M. Sex- and strain-specific expression of cytochrome P450s in ochratoxin A- induced genotoxicity and carcinogenicity in rats. Hydrogen peroxide is another odorless option that can be used to kill black mold. She was born by NSVD at 39 weeks gestation. In addition, in cases where the disease has progressed to the state where kidney transplantation is indicated, knowing if the existing kidneys have a significant concentration of OTA might affect the decision about whether to leave the diseased kidneys in place at the time of transplantation. In early stages of the disease, the kidneys are typically normal or enlarged, while in the late stage of the illness, kidneys are typically shrunken [72]. Prevention is key, as there is no specific cure for Ochratoxin A toxicity. - OTA can cause neurodegenerative diseases such as Parkinson's and Alzheimer's. After initial exposure from any source, the urinary and fecal excretory routes of OTA are both important with the relative contribution of each dependent upon factors such as route of administration and dose [5]. WebOchratoxin A is a major concern to livestock producers, especially in Europe. and transmitted securely. Interestingly, aspartame has been found to decrease toxicity of OTA through a phenylalanine-mediated mechanism [38]; however, there may be some concerns about other potential toxicities associated with aspartame. Ochratoxin A. Hagelberg S, Hult K, Fuchs R. Toxicokinetics of ochratoxin A in several species and its plasma-binding properties. Comp Biochem Physiol C Toxicol Pharmacol. - The US FDA has established guidelines for OTA in coffee, dried vine fruits, and cereal grains. Would you like email updates of new search results? Given the important metabolism of OTA that occurs in the gut, and evidence of increased toxicity when gut flora is disturbed with an antibiotic, it would pay to direct attention toward achieving and maintaining healthy gastrointestinal functioning. Retinol, ascorbic acid and. Alzheimer's disease and dementia. Her mother reports she required some initial resuscitation, but improved quickly and did not require transfer to neonatal intensive care unit. Other potential sequestrant treatments include the use of charcoal which is included in the military textbook recommendations for exposure to trichothecene mycotoxins which has been associated with Yellow Rain exposure [77]. Ochratoxin A Regulations and Safety Measures for Protecting Public Health. OTA can lead to kidney disease and adverse neurological effects. OTA is commonly found in contaminated food, such as grains, coffee, and wine. In addition, the mother had OTA in her breast milk, urine, and nasal secretions [33]. How aspartame prevents the toxicity of ochratoxin A. Galtier P, Camguilhem R, Bodin G. Evidence for in vitro and in vivo interaction between ochratoxin A and three acidic drugs. - The European Union has set maximum limits for OTA in various food products. In this study, the transfer of OTA to breast milk was found to be very efficient with levels at 60 percent of blood concentrations. Ochratoxin A (OTA) exposure via ingestion and inhalation has been described in the literature to cause kidney disease in both animals and humans. Silencing TRPM7 in mouse cortical astrocytes impairs cell proliferation and migration via ERK and JNK signaling pathways. Another study of OTA in human blood samples comparing persons with various types of chronic kidney disease to controls showed elevations in serum ochratoxin which were greatest in those diagnosed with chronic interstitial nephropathy at mean values of 2559ng/mL (ppb) compared to 0.77.8ng/mL (0.77.8 ppb) in the general population and 618ng/mL (ppb) in those with other types of kidney disease [58]. WebOchratoxin A has a strong affinity for the brain, especially the cerebellum (Purkinje cells), ventral mesencephalon, and hippocampal structures. In conclusion, Ochratoxin A is a harmful mycotoxin that can cause various neurological symptoms. Hypothesis: does ochratoxin A cause testicular cancer? Online ahead of print. WebPMID: 17195275 DOI: 10.1002/mnfr.200600137 Abstract Ochratoxin A (OTA) is a ubiquitous mycotoxin produced by fungi of improperly stored food products. Remember, prevention is the best defense against Ochratoxin A toxicity. - Exposure to OTA can lead to oxidative stress and inflammation in the brain. Collected conidia also contained OTA. Careers. 2023 Apr 18;7(5):34-45. doi: 10.15698/cst2023.05.279. Individual genetic differences affect the biotransformation and relative toxicity of OTA, with enzymatic hydrolysis and cytochrome p450 induction felt to play a role in toxicity. Additionally, consideration should be given to the testing of breast milk for OTA and other mycotoxins in mothers exposed to water-damaged environments as the data is strong that OTA can be excreted in breast milk and that the consequences of this exposure can be significant especially given the increased susceptibility of the neonate to toxins. At the time of presentation to this office she was taking vitamin D, folic acid, dialyvite, calcitriol, sevelamer carbonate (a phosphate binder), and rosuvastatin for hyperlipidemia. Carcinogenicity of ochratoxin A in experimental animals. The diagnosis of FSGS followed several kidney biopsies after it was initially undetected. Prevention of nephrotoxicity of ochratoxin A, a food contaminant. 2022 Oct 25;14(11):729. doi: 10.3390/toxins14110729. Mechanisms of Ochratoxin A Neurotoxicity in the Brain, 4. Ochratoxin A has a number of toxic effects in animals. The most significant elevations were found in the room she had used as a home office. Clipboard, Search History, and several other advanced features are temporarily unavailable. WebThis mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Epilepsy and seizures. It is also important to limit exposure to ochratoxin A through dietary choices and avoiding contaminated products. National Library of Medicine Epub 2007 Jun 5. Muoz K, Campos V, Blaszkewicz M, et al. Exposure level to OTA. Rarely intravenous albumin or mannitol has been used for intractable edema. WebModerate deficiency can cause hemolytic anemia, elevated acidity metabolic acidosis. Malir F, Pickova D, Toman J, Grosse Y, Ostry V. Mycotoxin Res. Thrasher J. Antioxidants and anti-inflammatory drugs may be used to reduce oxidative stress. Undoubtedly, like most human illnesses, it will involve a complex interaction of environmental exposures with underlying genetics. Throughout the literature, much of the study of ochratoxin exposure focuses on exposure through ingestion. 5. Careers. Ndiaye S, Zhang M, Fall M, Ayessou NM, Zhang Q, Li P. Toxins (Basel). One mechanism is by interfering with the production of neurotransmitters, which are chemicals that allow nerve cells to communicate with each other. Interestingly, the majority of the recurrence occurs in the first 6 months, with the recurrence of illness rare after two years posttransplantation. The patient worked as a marriage and family therapist from her home office until she was no longer able to work due to her illness. As has been discussed, a toxin as potent as OTA that is known to be found in the highest concentrations in kidney tissue could certainly play a role in the onset and progression of the disease. OTA is excreted in both the stool and urine. Naturally contaminated barley given for 6 weeks from 20kg compared with normal barley supplemented with crystalline ochratoxin A and/or citrinin. Urine mycotoxin testing was performed, and she was found to have significantly elevated level of ochratoxin A at 9.1ppb (limit of detection 2.0ppb). Microbial food toxicants: ochratoxins. Ochratoxin A (OTA) exposure via ingestion and inhalation has been described in the literature to cause kidney disease in both animals and humans. Unadjusted odds ratios and 95% confidence intervals for various health endpoints of OTA exposure identified through a systematic review. Concerns regarding exposure to ochratoxin have primarily centered on exposure to food contaminated with OTA such as wine, beer, coffee, dried vine fruit, grape juices, pork, poultry, dairy, spices, and chocolate [1]. Aspergillus fumigatus is responsible for a life-threatening systemic disease called invasive aspergillosis (IA) in immunocompromised individuals where mold actually grows inside the lungs but can invade other areas as well. The National Toxicology Program (NTP) has designated OTA as reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals [1]. DNA adducts consist of a chemical covalently bound to DNA. Prior to the dietary changes required by the onset of renal failure, the patient's diet was typical of the general population and did not include excessive consumption of foods known to contain OTA. - OTA can disrupt mitochondrial function and impair energy metabolism in the brain. 2023 Apr 12;13(4):551. doi: 10.3390/metabo13040551. In fact, there is evidence that some beneficial gastrointestinal flora can have positive effects on decreasing toxicity from OTA including specific strains of yeast [80]. Larsen TO, Svendsen A, Smedsgaard J. Biochemical characterization of ochratoxin A-producing strains of the genus penicillium. The family sought care from the authors due to chronic symptoms and illnesses in all family members and history of exposure to water-damaged environments in past and current homes. Pei X, Zhang W, Jiang H, Liu D, Liu X, Li L, Li C, Xiao X, Tang S, Li D. Oxid Med Cell Longev. - Ochratoxin A (OTA) is a mycotoxin produced by fungi that can contaminate food. Unauthorized use of these marks is strictly prohibited. - OTA can also disrupt the blood-brain barrier, leading to increased permeability and potential neurotoxicity. Sex- and strain-specific induction of renal tumors by ochratoxin A in rats correlates with DNA adduction. Neurological exams and imaging tests may be necessary. An Immunoenzymatic Method for the Determination of Ochratoxin A in Biological Liquids (Colostrum and Cow's Milk). - OTA can alter neurotransmitter levels and impair synaptic plasticity in the brain. Whitlow L. Evaluation of mycotoxin binders. Ochratoxin A can also disrupt the blood-brain barrier, which normally protects the brain from harmful substances. APGAR scores are not available. - Regular monitoring of food products for Ochratoxin A levels can help identify contaminated products and prevent their distribution. The recent investigations Ochratoxin A concentrations in food and feed from a region with Balkan Endemic Nephropathy. Metabolites. PMC OTA is nephrotoxic and is suspected of being the main etiological agent responsible for human Balkan endemic nephropathy (BEN) and associated urinary tract tumours. 2011 Nov;63(7-8):613-8. doi: 10.1016/j.etp.2010.05.001. Finally, ochratoxin A can cause changes in gene expression in the brain, which can lead to alterations in brain function and behavior. Her protein excretion in urine is followed regularly, and her mother reports an increased level of proteinuria upon moving to their most recent home. This exposure is believed to have resulted from inhalational exposure from water damaged indoor environments found to have elevated levels of mold including species of Aspergillus and Penicillium. Bethesda, MD 20894, Web Policies Administration of piperonyl butoxide was also shown to significantly decrease the LD50 of OTA [35] thus increasing toxicity. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Food Chem Toxicol. OTA lowers the level of phosphoenolpyruvate carboxykinase, a key enzyme in gluconeogenesis. Careers, Unable to load your collection due to an error. Untreated, this form of aspergillosis may be fatal. CRISPR-activation screen identified potassium channels for protection against mycotoxins through cell cycle progression and mitochondrial function. A study of rats exposed to OTA preconception, during gestation and during lactation showed that the exposed offspring had three to four times higher levels of OTA than the controls.
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