ochratoxin a toxicity symptomsochratoxin a toxicity symptoms

Elling F. Ochratoxin A-induced mycotoxic porcine nephropathy: Alterations in enzyme activity in tubular cells. OTA has a similar structure to the amino acid phenylalanine, therefore it may impair protein synthesis. OTA causes decreased 5-oxoproline. In Hungary, Fazekas et al. Nikolov IG, Chernozemsky IN, Petkova-Bocharova T, Vrabcheva T, Stojchev I, Bankov B, Castegnaro M, Pfohl-Leszkowicz A, Dragacci S, Day N, Gill C, Useleber E, Dietrich R, Martlbauer E. Review of the cooperative studies of the national oncological centre in Bulgaria on Balkan endemic nephropathy and associated urinary tract tumors. The current state of exposure assessment for OTA is discussed as well. InChI=1S/C20H18ClNO6/c1-10-7-12-14(21)9-13(17(23)16(12)20(27)28-10)18(24)22-15(19(25)26)8-11-5-3-2-4-6-11/h2-6,9-10,15,23H,7-8H2,1H3,(H,22,24)(H,25,26)/t10-,15+/m1/s1, InChI=1/C20H18ClNO6/c1-10-7-12-14(21)9-13(17(23)16(12)20(27)28-10)18(24)22-15(19(25)26)8-11-5-3-2-4-6-11/h2-6,9-10,15,23H,7-8H2,1H3,(H,22,24)(H,25,26)/t10-,15+/m1/s1, O=C(O)[C@@H](NC(=O)c1c(O)c2c(c(Cl)c1)C[C@H](OC2=O)C)Cc3ccccc3, Except where otherwise noted, data are given for materials in their, Toggle Impact on human and animal health subsection, Toggle Immunosuppression and immunotoxicity subsection, "Ochratoxin A-Induced Mutagenesis in Mammalian Cells Is Consistent with the Production of Oxidative Stress", "REduction in antioxidant defences may contribute to ochratoxin A toxicity and carcinogenicity", "Ochratoxin A induces apoptosis in neuronal cells", "Mechanisms of Mycotoxin-Induced Neurotoxicity through Oxidative Stress-Associated Pathways", "Glomerular filtration rate in examined population of Bosnian Posavina region of Balkan Endemic Nephropathy", "Investigation of Balkan endemic nephropathy in Serbia: how to proceed? It also appears that the protozoans will decrease in number if the ruminant is fed grains. Baker RJ, Pusey CD. Ruminant animals are not as sensitive to ochratoxin A as are non-ruminants. (When I use to have organic dairy goats, all of us raising goats organically knew that grains were not healthy to feed the animal and we kept them to a minimum. Lycopene in a rat study proteted rats from OTA toxcity. Oxidative DNA damage has been seen in vitro with OTA and in the kidney and liver of rats. Men tend to have 27% more positive urine samples than women when groups of people are studied. (Ochratoxin alpha has been shown to be non harmful to pig kidneys.). Studer-Rohr I, Schlatter J, Dietrich DR. Green Tea - Camellia sinensis catechins, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) are antioxidants, and have been shown in vitro to be protective against OCTA. In pigs immunosuppression and delayed response to immunization against Salmonella Cholera-suis was seen. Antioxidants, have been shown to decrease OTA toxicity in several species of animals. [21] Ochratoxin possibly is not the cause of this nephropathy, and many authors are in favor of aristolochic acid, that is contained in a plant: birthwort (Aristolochia clematitis). A reassessment of risk associated with dietary intake of ochratoxin A based on a lifetime exposure model. Health evaluation of ochratoxin A in food products. Ochratoxin Aa toxin produced by different Aspergillus and Penicillium species is one of the most-abundant food-contaminating mycotoxins. Odds ratios were estimated for these different studies where the data permitted these calculations. How to recover from toxic mold syndrome - Easy Health Options The interspecies factor of 15 was based on the longer OTA half-life in humans and monkeys rather than pigs as determined by Hagelberg et al. Fruit (except raisins and dried fruit) are very poor in ochratoxin, and processed meat can be rich in ochratoxin. Mycotoxin Poisoning & Toxic Mold: Symptoms & Solutions ", "Balkan endemic nephropathy: role of ochratoxins A through biomarkers", "Role of exposure analysis in solving the mystery of Balkan endemic nephropathy", "A Review of the Diagnosis and Treatment of Ochratoxin A Inhalational Exposure Associated with Human Illness and Kidney Disease including Focal Segmental Glomerulosclerosis", "The effect of Ochratoxin A on egg quality development of embryos and the level of toxin in egg and tissue of hens and chicks", "Effects of Ochratoxin A on Livestock Production", "Opinion of the Scientific Panel on Contaminants in the Food Chain on a request from the Commission related to Ochratoxin A in Food, Question N EFSA-Q-2005-154, Adopted on 4 April 2006", "Codex Committee on Food Additives and Contaminants, Position paper on ochratoxin A, Thirty-first Session, The Hague, The Netherlands, 22-26 March 1999", "Meat intake, mate drinking and renal cell cancer in Uruguay: a case-control study", "Major dietary patterns and risk of Renal Cell Carcinoma in a prospective cohort of Swedish women", "Genetic diseases conferring resistance to infectious diseases", https://en.wikipedia.org/w/index.php?title=Ochratoxin_A&oldid=1153399634, Pages using collapsible list with both background and text-align in titlestyle, Articles containing unverified chemical infoboxes, Articles with unsourced statements from January 2019, Articles with unsourced statements from November 2013, Articles with unsourced statements from November 2012, Creative Commons Attribution-ShareAlike License 4.0, This page was last edited on 6 May 2023, at 02:58. This means in those individuals exposed for a longer period of time, there is more liklihood of loss of a healthy gut microbiota and more chance the mycotoxins will end up getting into the blood stream from the gut. 1. Although not well known in Africa and the world at large compared to aflatoxins, ochratoxins are described as one of the most commonly occurring, mycotoxins in the world due to their presence in a. The role and risk assessment of OTA in animal and human disease has been reviewed. However, the incidence of transitional cell (urothelial) urinary cancers seems abnormally high in Balkan endemic nephropathy patients, especially for the upper urinary tract. Duarte SC, Pena A, Lino CM. In the case of OTA, diverse regulatory and advisory bodies have assessed dose-response data on OTA and have set exposure metrics for tolerable exposure to OTA in humans. A statistically significant correlation between urine OTA levels (R2 = 0.52) and dietary OTA consumption was found. OTA was shown to increase the formation of oxidative products of lipids, with increased production of malondialdehyde, increased reactive oxygen species levels, as well as 8-oxoguanine formation and deplted cellular glutathione levels. Despite being associated with a range of adverse health effects, a comprehensive systems-level . Chickens, turkeys, and ducklings are susceptible to this toxin. The disappearance rate of OTA from blood was slower than from kidney, liver and other tissues in the pig (Hult et al., 1979). And we know that animals exposed to ochratoxin A have the greatest concentration of it in their kidneys, liver, muscle, body fat, adrenal gland, skin, heart, stomach lining and even bones. This is not well studied but has been found to change with species. A full-text review of all 22 articles resulted in 19 being excluded because they did not measure urinary OTA or dietary OTA, or did not include both diseased and healthy individuals. The molecular mechanism of ochratoxin A carcinogenicity has been under debate due to conflicting literature, however this mycotoxin has been proposed to play a major role in reducing antioxidant defenses. Ingestion is the main source of exposure to OTA, through the foods and beverages listed in Table 1. The cyanidin 3-O--D-glucoside (C3G), an anthocyanin found in beans, fruits, vegetables and red wine, might counteract damage induced by chronic exposure to OTA in rats. Starving people will tend to eat rotten food rather than discard it. Surveillance data on OTA concentrations in different regions of the world is limited. Ochratoxin A is partially absorbed from the gastrointestinal tract in monogastrics mammels. (2001) when studying 16 human participants (Castegnaro et al., 2006). These fungi vary in their optimal growing temperatures and water activity, and contaminate various commodities as summarized in Table 1. These can be deadly if not addressed. Eating foods with high levels of DON can cause vomiting, nausea, and other symptoms. Many Nrf2-regulated enzymes are involved in the antioxidant defence and expression of most of them is inhibited by OTA treatment in the kidney of chickens. DNA adducts also occur in animals exposed to OTA in all available studies. Kuiper-Goodman T, Scott PM. Jrgensen K, Rasmussen G, Thorup I. Ochratoxin A in Danish cereals 19861992. Thus far, risk assessments on OTA, including those that have guided Health Canadas recently proposed MLs, have largely been based on animal and cell culture assay studies, with relatively less focus on human studies. This study reviews the epidemiological literature on OTA exposure and adverse health effects in different populations worldwide, and assesses the potential human health risks of OTA exposure. In a discussion of risk assessments conducted on OTA in the past, we compare the state of known data with what is still missing in terms of assessing human health effects. N-acetyl Cysteine has been shown to combine directly with OTA or metabolites and is removed in the urine. OTA induced intestinal barrier dysfunction indicated by the reduction in transepithelial electrical resistance and elevation in paracellular permeability to 4kDa dextran. While these ORs were unadjusted, demographics including age, sex, socio-economic status, and other lifestyle factors, were similar across both cases and controls in each accepted study. An official website of the United States government. Is it possible that people who are eating ochratoxin contaminated food on a regular basis, (too many of these folks) and have blastocystis in their intestine might be getting assistance from the blastocystis in removing the ochratoxin? The toxin's immunosuppressant activity in animals may include depressed antibody responses, reduced size of immune organs (such as the thymus, spleen, and lymph nodes), changes in immune cell number and function, and altered cytokine production. A recent risk assessment on OTA (Haighton et al., 2012) states that OTA was negative in genotoxicity assays with high specificity, and that OTA-DNA adduct levels were low and not typical of genotoxic carcinogens. Olsen M, Thorup I, Knudsen I, Larsen JJ, Hald B, Olsen J. Cancer Epidemiology, Biomarkers, Prevention. The International Agency for Research on Cancer (IARC) has classified OTA as a Group 2B possible human carcinogen, based on demonstrated carcinogenicity in animal studies (Fazekas et al., 2005; IARC, 1993), although OTA-related carcinogenicity has not been conclusively determined in humans. Rubert J, Soriano JM, Manes J, Soler C. Rapid mycotoxin analysis in human urine: a pilot study. Treatment of Ochratoxin A alone (group 2 rats) significantly increased malondialdehyde content, catalase, and glutathione reductase activities with a decrease in the activity of superoxide dismutase enzyme and reduced glutathione level in brain, kidney and liver. The foods more commonly assumed may have these mycotoxins and therefore more likely to be tested are grains, dried vine fruits, wine, grapes, coffee, cocoa and cheese. (Duarte et al., 2011). Mycotoxins are small toxic molecules produced by a great variety of microorganism, which encompass several classes of secondary metabolites with no common chemical structure or mode of action [].These harmful natural products of molds contaminate food and feed worldwide with appalling economic consequences, since they affect most of the staple food crops such as maize, wheat . Ochratoxin AAn Important Mycotoxin. All binders can do this. Vitamin C has been shown to be beneficial in laying hens exposed to ochratoxin. Liu Y, Wu F. Global burden of aflatoxin-induced hepatocellular carcinoma: a risk assessment. CIN does not appear to have the familial pattern of BEN, and may be acute or chronic with cases presenting anywhere from a few days up to 5 months. How much OTA is excreted by these different routes in various species is influenced by the extent of enterohepatic recirculation of ochratoxinA and its binding to serum macromolecules. Radic B, Fuchs R, Peraica M, Lucic A. Ochratoxin A in human sera in the area with endemic nephropathy in Croatia. Melatonin exhibits a preventive effect against OTA-induced oxidative stress, and structural damage in the kidney through its role in the scavenging of free radicals and/or the prevention of lipid peroxidation. Their symptoms are well known to nephrologists: glycosuria without hyperglycemia, microalbuminuria, poor urine concentration capacity, impaired urine acidification, and yet long-lasting normal creatinine clearance. Ochratoxin A competitively inhibits the coupling of phenylalanine to its cognate tRNA by the corresponding aminoacyl transferase and thereby disrupts protein synthesis. Increases of OTA intake resulted in an increase of OTA elimination a week after ingestion, not immediately (Castegnaro et al., 2006). The relative contribution of each excretory route is influenced by the degree of serum macromolecular binding, as well as differences in the enterohepatic recirculation of OTA. How To Spot Symptoms of Mold Toxicity (It's More Common Than You Think) Coronel MB, Marin S, Tarrago M, Cano-Sancho G, Ramos AJ, Sanchis V. Ochratoxin A and its metabolite ochratoxin alpha in urine and assessment of the exposure of inhabitants of Lleida, Spain. Several studies imply that the mode of action of ochratoxin is the formation of covalent DNA adducts and the increase of reactive oxygen species, which would explain the genotoxic and mutagenic activity of OTA. Mold toxicity illness is associated with various chronic health problems, including autoimmune disorders, liver and kidney disease, autism, chronic fatigue, and certain cancers. Ahn J, Kim D, Kim H, Jahng KY. Quantitative determination of mycotoxins in urine by LC-MS/MS. Furthermore, studies in Germany (Martlbauer et al., 1996), Switzerland (Studer-Rohr et al., 2000), Czech Republic (Ruprich and Ostry, 1993), Japan (Kawamura et al., 1993), and Bulgaria (Petkova-Bocharova et al., 2003) all showed high intra-subject variability in human subjects tested over time. 1999). Personally, the idea of giving someone A. niger or other fungi that I perceive as being problematic bothers me. Melatonin demonstrated a protective effect in rats exposed to OTA for 28 days and alleviated most of the biochemical abnormalities associated with the exposure. Ochratoxin, Citrinin, and Penicillic Acid (Nephrotoxins) Poisoning Whereas, low dose coffee (group 3) and high dose coffee (group 4) rats showed dose-dependent increase in antioxidant and less histopathological alterations. Sattler TA, Dimitrov T, Hall PW. You must consult your practitioner before acting on any material on this website. OTA was studied in pig intestinal epithelial cells to get an idea of how it might affect the intestinal barrier. sharing sensitive information, make sure youre on a federal Specifically, Maaroufi et al. Although the role of ochratoxin A in human disease is still speculative, its acute nephrotoxicity, immunosuppressive actions, and teratogenic effects in animal models . Ochratoxicose humaine en Algerie. Contamination generally occurs as a result of poor storage of commodities and suboptimal agricultural practices during the drying of foods (Moss, 1996). OTA was detected in all plasma samples with baseline sample levels ranging from 0.15-2.17 ng/ml and composited plasma samples ranging from 0.4-3.11 ng/ml. Studies using serum OTA as a marker for exposure were excluded because of the poor correlation between dietary OTA intake and serum OTA as measured in Gilbert et al. You Have Been Diagnosed With Mycotoxin Illness, Now What? Hazard characterization or dose-response assessment describes the relationship between different levels of exposure to a substance and associated incidence of disease in a population of animals or humans. The purpose of this systematic review was to attempt to reconcile the human and animal study results on OTA toxicity, or lack thereof. This Site will occasionally contain (paid) links to, and quotation of, material from other sites. Patients mean levels of urinary OTA were 3.093.4 ng/ml and 1.852.8 ng/ml respectively. Despite some previous studies about the effects of ochratoxin A in glial cells, the intracellular working mechanism in astrocytes is not fully understood. A literature search was performed on PubMed until October 4th, 2011. IARC Monographs on the evaluation of carcinogenic risks to humans: some naturally. The OTA binding ability of S. cerevisiae RC008 and RC009 was significantly stronger in simulated mammalian gastrointestinal conditions than that in YPD broth (pH 7), while the OTA binding ability of S. cerevisiae RC012 and RC016 was not significantly different between simulated mammalian gastrointestinal conditions and YPD broth (pH 7). Ochratoxin A has become an important topic in recent years, as Health Canada has proposed maximum limits (MLs) for OTA in a variety of foods and drinks that could have consequences for the marketability of these commodities in Canada, and could also affect nations that attempt to export food to Canada (Health Canada, 2009). There are two possible things that might be happening here. Sources of support: This work was funded by the National Cancer Institute (NCI) of the National Institutes of Health (NIH), Grant No. Limited information is available on the metabolic disposition of OTA in humans, although it has been suggested that it has a long serum half-life due to strong binding to human serum macromolecules. Three studies contained the relevant information needed to calculate unadjusted ORs for different OTA health effects. Ochratoxin A - Lab Results explained | HealthMatters.io The etiology of CIN has been postulated to include infections, toxins such as OTA, or reactions to medications (Baker and Pusey, 2004). AFB 1 primarily produces hepatic cancer, while OTA and citrinin produce nephropathy. In Irish women, lower rates of abortion were found in those who were heterozygous for PKU. Exposure to toxic mold might elicit zero symptoms in one person and a slew of symptoms in another, such as brain fog, mood changes, hair loss, insomnia, muscle weakness, tremors and joint pain. it would be prudent for the medical commu- nity to pay closer attention to the possibility of ochratoxin toxicity in patients with symptoms of . Urinary OTA levels in humans from several different world regions, summarized in Table 3, range from <0.01-148 ng/ml. The barrier dysfunction was accompanied with tight junction disruption including a down-regulation in ZO-1 expression and redistribution of Occludin and ZO-1. 2015 Nov 10; 55(13): 18601869. Nervous system toxicity including blood-brain barrier damage and CNS effects. Hassen W, Abid S, Achour A, Creppy E, Bacha H. Ochratoxin A and beta2-microglobulinuria in healthy individuals and in chronic interstitial nephrppathy patients in the centre of Tunisia: a hot spot of Ochratoxin A exposure. [8], The evidence in experimental animals is sufficient to indicate carcinogenicity of ochratoxin A. (1998). Figure 2 summarizes ORs and 95% confidence intervals for each of the adverse health outcomes associated with OTA exposure as measured by urinary OTA in the three study populations. Ochratoxin A was first described in a paper published in Nature by van der Merwe and co-workers (1965) after they isolated a new toxic metabolite from Aspergillus ochraceus [].Ochratoxins are produced by certain Aspergillus species such as A. ochraceus or A. niger and some Penicillium species, especially P. verrucosum. Ochratoxin A can be produced in peas and cereals grains such as corn, wheat, barley, rice, and sorghum . You Are The Healer exists due to the generosity of my readers. [12], Ochratoxin A has a strong affinity for the brain, especially the cerebellum (Purkinje cells), ventral mesencephalon, and hippocampal structures. The goal of this study was to systematically review the epidemiological literature linking OTA exposure with adverse health effects in diverse human populations worldwide. It is kind of like feeding candy to kids.) (Gilbert et al., 2001) and the urinary OTA studies summarized in Table 3. In humans, very little histology data are available, so a relationship between ochratoxin A and renal cell carcinoma has not been found. Ochratoxin can be measured in blood serum, in urine and in human kidneys (post-mortem of course). (2002) and Wafa et al. It is more toxic to fetuses than to adults. A more accurate method to estimate exposure, when possible, is through measuring human biomarkers of OTA exposure, as reviewed in Duarte et al. National Toxicology Program (NTP), Toxicology and carcinogenesis studies of ochratoxin A (CAS No. Ochratoxin A can permeate through the human skin. OTA in serum was first detected in 1977 and has been one of the most widely used biomonitoring approaches for human OTA exposure. 2019-2023 You Are The Healer/Wise Acres LLC. OTA is nephrotoxic and is suspected of being the main etiological agent responsible for human Balkan endemic nephropathy (BEN) and associated urinary tract tumours. We characterize the risk of OTA to human populations and describe limitations in the available data. Eligibility criteria for inclusion in the review were as follows: (1) epidemiological studies; (2) case-control or cohort study design; (3) ochratoxin A as the exposure of interest; (4) OTA exposure measured either in terms of dietary intake or urinary OTA levels; and (5) relative risk (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) reported, or data to calculate these. Central European Journal of Occupational and Environmental Medicine. Baseline samples were taken at the beginning of the study. Abrunhosa et al. Ochratoxin A and human health risk: a review of the evidence Dahlmann A, Dantzler WH, Silbernagl S, Gekle M. Detailed mapping of ochratoxin A reabsorption along the rat nephron in vivo: the nephrotoxin can be reabsorbed in all nephron segments by different mechanisms. Listlessness, huddling, diarrhea, tremors, and other neural abnormalities are often encountered in broiler poultry production in the southeastern United States. This appears to be due to the fetus having low levels of the enzymes that inactivate xenobiotics and toxins such as ochratoxin. A review of recent advances in understanding ochratoxicosis. Various dose-response studies in animals were the basis for advisory groups determinations of safe weekly or daily OTA intakes for humans. Monitoring of ochratoxin A exposure of the Portuguese population through a nationwide urine survey--Winter 2007. For example, Petkova-Bocharova et al. Notes from the Field: Use of Unvalidated Urine Mycotoxin Tests for the Yet, little is known about population health impacts of dietary OTA exposure. Resveratrol is used by grapes to control Aspergillus carbonarius growth and ochratoxin A biosynthesis, and has also been used in research to attenuate damage from OTA. Estimating human OTA exposure may be done using food surveys combined with OTA surveillance in commodities, or biomarkers of exposure. Instead, a systematic review was performed in this study, and unadjusted odds ratios (ORs) were calculated for various health effects associated with OTA exposure based on data from existing studies. Petkova-Bocharova T, Castegnaro M, Pfohl-Leskowicz A, Garren L, Grosso F, Nikolov I, Vrabcheva T, Dragacci S, Chernozemsky IN. In Nigeria, Ghana, and Burkina Faso, OTA was detected in sorghum, maize, and millet. 2009), OTA presence was determined and analyzed by HPLC. Biomarkers of human exposure to ochratoxin A. Solfrizzo M, Gambacorta L, Lattanzio VM, Powers S, Visconti A. However, the accuracy of this estimation is limited due to the large variability in OTA content in commodities, as well as variation in dietary habits (Fazekas et al., 2005). When this study and the Egyptian study are excluded, the urinary OTA levels measured in different world regions ranges from non-detectable to 0.860 ng/ml: much lower than the levels found in the study populations in Egypt and Sierra Leone. The degradation of OTA to OT (7-carboxy-5-chloro-8-hydroxy-3,4-dihydro-3-R-methylisocoumarin) is the most important mechanism of OTA biodegradation. The toxin also enhances lipid peroxidation both in vivo and in vitro, which is probably responsible for its adverse affects on mitochondrial function. Concomitant treatment of Yemeni green coffee powder and Ochratoxin A brought dose-dependent protective effects against oxidative stress which was induced using Ochratoxin A in rats and after death examining liver, brain, and kidney tissues of female rats. TheMilk thistle and Ashwagandha had a hepatoprotective effect and the Milk thistle had a kidney protective effect. [28] For USA, the FDA considers a TDI of 5ng/kg. Some researchers believe OTA in humans may have a long serum half life, based on the strong binding of OTA to human serum macromolecules. A study showed OTA could be decreased by maintaining glutathione production through pretreating the in vitro cell with the glutathione limiting amino acid, N-acetyl cysteine, which decreased reactive oxygen species and 8-oxoguanine formation. In the blood, OTA binds to albumin and the bound fraction constitutes a mobile reserve of OTA. All studies measured urinary OTA levels and associated these levels with several different adverse health effects. Jonsyn-Ellis FE. 2001; Gillman et al. Ochratoxin A (OTA) is a mycotoxin produced by several fungal species including Aspergillus ochraceus, A. carbonarius, A. niger and Penicillium verrucosum. Applying this composite uncertainty factor to the BD10 of 1.56 g/kg bw/day resulted in a TDI of 3.0 ng/kg bw/day after rounding (Kuiper-Goodman et al., 2010), which in practice is considerably stricter than the JECFA or EFSA tolerable limits. One Egyptian study showed a significantly higher risk of nephritic syndrome in those with very high urinary OTA levels compared with relatively unexposed individuals; however, other potential risk factors were not controlled for in the study. [10] Rats of Group 1 designated Vehicle Control (only water), Group2 (10mg/kg Ochratoxin A); Group 3 designated Low dose (2000mg/kg Coffee+10mg/kg Ochratoxin A); Group 4 designated High dose (4000mg/kg Coffee+10mg/kg Ochratoxin A); Group 5 designated Coffee Control (1000mg/kg Coffee) and orally administered with the above test materials repeatedly every day for 28 days. Joint FAO/WHO Committee On Food Additivies (JECFA) Safety Evaluations of Certain Mycotoxins in Food. Women tend to have high serum albumin levels, although they decrease and come closer to men's levels at age 60. Toxicity from ochratoxin is considered serious enough that it is among approximately 20 mycotoxins monitored in food. Ochratoxin A (OTA), a mycotoxin widely contaminating staple foods and beverages, has been classified as a "possible human carcinogen (Group 2B)" by the IARC.