(Duarte et al., 2011). Among aflatoxins, aflatoxin B1 (AFB1) and among ochratoxins, ochratoxin A (OTA) occur with greatest frequencies and are the most toxic. 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. The European Food Safety Authority (EFSA) derived a PTWI for ochatoxin A of 120 ng/kg bw/week, based on the 8 g/kg bw/day LOAEL used in the JECFA evaluation (European Food Safety Authority, 2006). Ochratoxin, Citrinin, and Penicillic Acid (Nephrotoxins) Poisoning Male Sprague-Dawley rats (<200 g, n=6) were treated with OTA (0.5 mg/kg/day) and/or lycopene (5 mg/kg/day) by gavage for 14 days. Mycotoxins - PMC - National Center for Biotechnology Information This means they would be helpful in the digestive tract, but to know if they would be helpful systemically, we need invivo testing. Several limitations exist with our analysis of epidemiological studies on OTA. Ochratoxin A is partially absorbed from the gastrointestinal tract in monogastrics mammels. [28] For USA, the FDA considers a TDI of 5ng/kg. 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. in antiperspirants), antibiotics (vancomycin, aminosides), tenofovir (for AIDS), and cisplatin[citation needed]. Ochratoxin A is nephrotoxic to several species and is a renal carcinogen in rodents. kg-1 there was decreased feed efficiency, decreased daily gain of weight and final body weight. The most recent assessment of OTA at the 68th meeting in 2008 resulted in retaining the PTWI previously found. google.com, pub-8271161903931696, DIRECT, f08c47fec0942fa0 . Enzymes are being studied, both natural and synthetic in their ability to biotransform and biodetoxify OTA. Additionally, Health Canada derived a negligible cancer risk intake (NCRI) for OTA: the exposure associated with an increased cancer risk of 1:100,000 and equivalent in units to the TDI. Relation between endemic (Balkan) nephropathy and urinary-tract tumours. Abrunhosa et al. Besides glutathione conjugates, other phase 2 metabolites of OTA such as glucuronides have only been detected by indirect methods, so glucuronidation may be partly reasonable for biotransformation of OTA. Ochratoxin A serum levels in patients with Balkan nephropathy. Catalase and SOD (20 mg/kg body weight each) were given to rats by subcutaneous injection, every 48 h, 1 h before gavage by OTA (289 micrograms/kg b.w. All studies measured urinary OTA levels and associated these levels with several different adverse health effects. Fruit (except raisins and dried fruit) are very poor in ochratoxin, and processed meat can be rich in ochratoxin. 2002; Calcutt et al. Antioxidants, have been shown to decrease OTA toxicity in several species of animals. In plasma, no significant correlation was found between the two (R2 = 0.29). Monitoring of ochratoxin A exposure of the Portuguese population through a nationwide urine survey--Winter 2007. Joint FAO/WHO Committee On Food Additivies (JECFA) Evaluation of certain food additives and contaminants (Sixty-eighth report) of the Joint FAO/WHO Expert Committee on Food Additives). Ochratoxin A - an overview | ScienceDirect Topics OTA can lead to kidney disease and adverse neurological effects. 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. [10] Khalef A, Zidane C, Charef A, Gharbi A, Tadjerouna M, Betbeder AM, Creppy EE. (Duarte et al., 2011) and more recent studies. around 10 ppb or 10ng/ml). Malir F, Roubal T, Brndiar M, Osterreicher J, Severa J, Knizek H, Kacerovsky J, Tmejova M, Bebeder AM, Baudrimont I, Creppy EE. Melatonin demonstrated a protective effect in rats exposed to OTA for 28 days and alleviated most of the biochemical abnormalities associated with the exposure. Each study also had at least one corresponding control group. Other adverse effects of OTA include immunotoxicity (Bondy and Pestka, 2000; Pestka and Bondy, 1994), inhibition of macromolecular synthesis, increased lipid peroxidation, and inhibition of mitochondrial respiration (Kuiper-Goodman and Scott, 1989; Marquardt and Frohlich, 1992). official website and that any information you provide is encrypted Rodents have also shown increase TNF-alpha release, increase in IL-1 synthesis, IL-6 and IL-8 release and increased cyclooxygenase-2https://www.researchgate.net/figure/Continued_tbl2_273511420. Elimination of OTA in urine and feces is felt to be relatively slow and has been shown to vary by species and sex, as well as specific genotype that may affect the biotransformation of OTA. Ochratoxins - You Are The Healer After spending a lot of money on research they may simply prove the old methods of souring grains are a necessity for good health. OTA has been shown to be toxic and carcinogenic in animals. The laboratory reported "positive" concentrations of two mycotoxins: ochratoxin at 2.8 . Women tend to have high serum albumin levels, although they decrease and come closer to men's levels at age 60. Careers, Unable to load your collection due to an error. Mycotoxin-induced immunomodulation. metabolism of toxins occurs via intestinal biotransformation. Language links are at the top of the page across from the title. Based on the data needed to calculate ORs, three studies were included. Duarte SC, Pena A, Lino CM. This composite uncertainty factor was based on an intra-species factor of 10, interspecies factor of 15, and a factor of 3 for use of a LOAEL instead of a no observed adverse effect level (NOAEL). However, because this extremely high level of OTA exposure is not expected in most other parts of the world as evidenced by urinary OTA levels collected in multiple other world regions, the risk of OTA-related nephritic syndrome on a global scale is not expected to be significant. Baseline samples were taken at the beginning of the study. Toxicity from ochratoxin is considered serious enough that it is among approximately 20 mycotoxins monitored in food. Maaroufi K, Achour A, Betbeder AM, Hammami M, Ellouz F, Creppy EE, Bacha H. Foodstuffs and human blood contamination by the mycotoxin ochratoxin A: Correlation with chronic interstitial nephropathy in Tunisia. With one exception, there appears to be no statistically significant evidence for human health risks associated with OTA exposure. A study with rats given OTA showed damage such as testicular degeneration, seminiferous tubule atrophy, dissociation of germinative epithelium, vasodilatation with vascular thrombosis, perivascular immune cell infiltration, hypertrophied leydic cells, giant cell formation, and negative tubular differentiation index (TDI) . OTA causes nephrotoxicity and renal tumors in a variety of animal species; however, human health effects are less well-characterized. 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. Ochratoxin A is considered a carcinogen and immunotoxic, nephrotoxic, and neurotoxic mycotoxin. Ochratoxin A: What It Is, Symptoms, Testing & Treatment (2002) and Wafa et al. The rats had significant reduction in damage from OTA in this study. 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 ]. Saccharomyces cerevisiae Syrena LOCK 0201 and S. cerevisiae Malaga LOCK 0173 removed 85.1 and 82.8% of OTA (1 g/mL) in white grape juice as well as 65.2 and 10.7% of OTA (1 g/mL) in blackcurrant juice after 10 days incubation, respectively. I would point out that this binding is often partially reversible and is not studied much. (2006) Commercially purified enzymes have not worked as well. In: Dean JH, Luster MI, Munson AE, Kimber I, editors. The Crowdfunding I receive through regular patrons allows me to continue this website. Green Coffee Powder was shown to be protective of albino wistar rats. (Gilbert et al., 2001) and the urinary OTA studies summarized in Table 3. Contamination generally occurs as a result of poor storage of commodities and suboptimal agricultural practices during the drying of foods (Moss, 1996). Studer-Rohr I, Schlatter J, Dietrich DR. It is thought that these bacteria may also be beneficial to use as a probiotic to remove ochratoxin in the gut from food or during enterohepatic circulation of ochratoxin with the bile. Both authors contributed to the writing of the manuscript. (1998) study used healthy human controls. Decreased 5-oxoproline is seen with Mild glutathione synthetase deficiency. Personally, the idea of giving someone A. niger or other fungi that I perceive as being problematic bothers me. They are also using some different methods with yeast to remove OTA from liquids such as grape juice and wine. Duarte SC, Pena A, Lino CM. Fifteen studies were selected based on information in the title and abstract, and seven more were added based on reference lists in those selected studies. Some of the bacteria and yeast they use have come from sourdough, fermented flour, sausage, and wine. Elling F, Krogh P. Fungal toxins and Balkan (endemic) nephropathy. Urine biomarkers are more relevant for day to day exposure. For the purposes of establishing appropriate regulatory policies regarding human exposure to ochratoxin A, it is critical to gain a better understanding of OTAs impacts on human health. It has a positive charge as does cholestyramine and has been shown to have equal if not better ability as cholestyramine in lowering cholesterol. The table includes the three studies used to calculate unadjusted ORs organized by location. Ochratoxin is identified as a renal carcinogen to particular animal species (Kuiper-Goodman and Scott, 1989) and can cause nephrotoxic, teratogenic, and immunosuppressive effects in multiple animal species (Kuiper-Goodman and Scott, 1989; O'Brien and Dietrich, 2005). 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. The individual and combined effects of ochratoxin A with citrinin and their metabolites (ochratoxin B, ochratoxin C, and dihydrocitrinone) on 2D/3D cell cultures, and zebrafish embryo models - ScienceDirect Volume 158, December 2021, 112674 Levels of serum OTA have been noted to vary up to tenfold in one subject when tested over a ten-year period (Radic et al., 1997) and in repeatedly tested subjects over one year in Tuscany (Palli et al., 1999). Balkan (endemic) nephropathy and a toxin-producing strain of Penicillium verrucosum var cyclopium: An experimental model in rats. The cause of nephritic syndrome is multifactorial, and the term nephritic syndrome itself describes a condition with multiple symptoms. Purchasing my paperback books from this website or e-books from Amazon is another way to support this website. National Toxicology Program (NTP), Toxicology and carcinogenesis studies of ochratoxin A (CAS No. Ochratoxin A (OTA) is a mycotoxin produced by several fungal species including Aspergillus ochraceus, A. carbonarius, A. niger and Penicillium verrucosum. 2009), OTA presence was determined and analyzed by HPLC. Wide species differences in the serum half life of OTA have been reported. Ochratoxin A exposure assessment of the inhabitants of Lisbon during winter 2007/2008 through bread and urine analysis. 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. The highest recorded levels of OTA in urine, 367 ng/ml and 1801 ng/ml, were found in two French siblings with renal failure (Godin et al., 1996). It can increase risk for a vareity of infectious diseases. Dead Lactobacillus plantarum LOCK 0862, L. brevis LOCK 0845, and L. sanfranciscensis LOCK 0866 could reduce 46.2959.82% of OTA (1 g/mL) within 30 min in PBS buffer, but the alive L. plantarum LOCK 0862, L. brevis LOCK 0845, and L. sanfranciscensis LOCK 0866 needed 24 h to remove 14.8026.42% of OTA (1 g/mL) in PBS buffer. Hazard identification, determining whether exposure to an agent can increase the incidence of a particular health condition, has been carried out for OTA in assessments conducted by multiple institutions; including the International Agency for Research on Cancer (IARC), Health Canada, the Joint Food and Agriculture Organization / World Health Organization Expert Committee on Food Additives (JECFA), and the European Food Safety Authority (EFSA) (European Food Safety Authority (EFSA), 2006; Health Canada, 2009; IARC, 1993; Joint FAO/WHO Committee On Food Additivies (JECFA), 1991). Additionally, selenium was shown to block the increases of DNMT1, DNMT3a and HDAC1 mRNA and protein expression, reversed the decreases of glutathione peroxidase 1 (GPx1) mRNA and protein expression, and promoted the increases of SOCS3 mRNA and protein expression induced by OTA. Both viable and dead S. cervisiae Lalvin rone 2056 has been shown to be able to remove OTA. The phenylalanine moiety of OTA has been discussed as the responsible substructure for competitive inhibition of enzymes needed for protein biosynthesis. It appears that besides the biotransformation of the mycotoxin there is also a binding affinity of the bacteria cell walls to the ochratoxin. JECFA re-evaluated OTA at its 44th meeting, taking into account new toxicological data. These can be deadly if not addressed. Despite some previous studies about the effects of ochratoxin A in glial cells, the intracellular working mechanism in astrocytes is not fully understood. Ochratoxin A - Wikipedia A literature search was performed on PubMed until October 4th, 2011. 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. You must consult your practitioner before acting on any material on this website. Ochratoxicose humaine en Algerie. Ochratoxin-producing fungi, optimal growth conditions, and commodities affected. Licorice alleviated most of the biochemical abnormalities associated with the exposure. Chemical reaction products of these compounds such as glutathione conjugates have been detected in cell culture and in rodents. OTA was detected in all but four urine samples, with levels ranging from <0.01-0.058 ng/ml. Hagelberg S, Hult K, Fuchs R. Toxicokinetics of ochratoxin A in several species and its plasma-binding properties. The https:// ensures that you are connecting to the Oxidative metabolism of OTA resulting in OTA metabolites such as reactive quinone structures has also been observed (Dai et al. Ochratoxin damage to the kidneys of swine is characteristic enough to be called "porcine nephropathy," which is recognizable and recognizable in commercial slaughtering. 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. If you have any questions, please feel free to contact us. Sattler TA, Dimitrov T, Hall PW. For those of you who want to see the science behind this, here it is: In ruminant animals such as cows, OTA goes through hydrolysis to a non-toxic ochratoxin alpha that takes place in their digestive system in the presence of the ruminant protozoa. 8600 Rockville Pike The role and risk assessment of OTA in animal and human disease has been reviewed. Pfohl-Leszkowicz A, Petkova-Bocharova T, Chernozemsky IN, Castegnaro M. Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins. [9] and produced renal adenomas and carcinomas in male mice and in rats (carcinomas in 46% of males and 5% of females). This dose was determined to be 19.6 g/kg bw/day. Lycopene is found in red, pink and orange colored foods, including tomatoes, watermelon, pink grapefruit, apsaragus, red cabbage, guava, papapya, red bell pepper, persimmon, and mango. Ochratoxin A is the most common and, along with ochratoxin C, is among the most toxic homologues. Mycotoxins | FDA - U.S. Food and Drug Administration 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. Unfortunately, mycotoxins have also demonstrated an ability to modulate the gut microbiota too and usually it is not beneficial to the host and eventually leaves the host without the protective microbiota to remove mycotoxins. Various studies have linked OTA exposure with the human diseases Balkan endemic nephropathy (BEN) and chronic interstitial nephropathy (CIN), as well as other renal diseases. Data on the following were extracted from each study: authors, publication year, study design and sample size, study location, study period, participants gender and age, range of ochratoxin exposure, health effect under investigation, and data necessary to calculate ORs for each health effect if the OR was not already calculated. Summary of calculated tolerable human intakes of ochratoxin A (OTA) by international organization. Yet, little is known about population health impacts of dietary OTA exposure. A more accurate method to estimate exposure, when possible, is through measuring human biomarkers of OTA exposure, as reviewed in Duarte et al. Despite being associated with a range of adverse health effects, a comprehensive systems-level . Nephritic syndrome, also known as glomerulonephritis, is a disorder of the glomeruli characterized by body tissue swelling (edema), high blood pressure, and the presence of red blood cells in the urine. Patients with end stage renal disease or nephritic syndrome in Egypt had significantly higher levels of urinary OTA than two reference groups (Wafa et al., 1998). Ochratoxin A is excreted in the urine and feces. Petkova-Bocharova et al. As no other risk factors were controlled for in Wafa et al. [4][5][6] The toxin has been found in the tissues and organs of animals, including human blood and breast milk. Be sure to talk with your doctor for a complete discussion around any condition you have as well as the benefits and risks of any options you read about on this website. Malir F, Brndiar M, Roubal T, Severa J, Fixa P, Kacerovsky J, Zahradnik J, Osterreicher J, Knizek H, Cerna M. A study of the accumulation of ochratoxin A (OTA) in patients with chronic renal insufficiency (CHRI) in the Czech Republic. Others have come from pig feces, and soil. Ochratoxin poisoning is thought to be the cause of a chronic kidney disease in humans known as Balkan endemic nephropathy. Ochratoxin A. I have a long long story that's spanned over the last year and a half. High-performance liquid chromatographic determination of ochratoxin A and its 4R-4-hydroxy metabolite in human urine. All binders can slow down the digestive tract, so make sure the digestion is supported as needed. The extremely high end of this range comes from a study in Sierra Leone (Jonson-Ellis 2001). In rodents that mTOR/AKT pathways are significantly deregulated after exposure to OTA, possibly contributing to carcinogenicity in kidney cells. The disappearance rate of OTA from blood was slower than from kidney, liver and other tissues in the pig (Hult et al., 1979). However, it was noted that OTA occurs in coffee in countries including Brazil, Canada, Dubai, Europe, Japan, and the USA (Joint FAO/WHO Committee On Food Additivies (JECFA), 2001). Some researchers believe OTA in humans may have a long serum half life, based on the strong binding of OTA to human serum macromolecules. I have found one research article showing chitosan binds with anionic carboxyl groups of fatty acids and bile acids, making it extremely likely it will remove ochratoxin similar to cholestyramine, but I can't find in vivo clinical studies on it so far. The amount excreted in the urine is thought to be dependent of the free OTA concerntration. Domijan AM, Peraica M, Markov K, Fuchs R. Urine ochratoxin A and sphinganine/sphingosine ratio in residents of the endemic nephropathy area in Croatia. 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 authors declare no conflicts of interest. Abstract Ochratoxin A (OTA) is a mycotoxin produced by several fungal species including Aspergillus ochraceus, A. carbonarius, A. niger, and Penicillium verrucosum. Analysis of ochratoxin A in serum and urine of inhabitants from an area with Balkan endemic nephropathy: a one-month follow-up study. Purified protease A and Pancreatin degraded 87.3 and 43.4% of OTA after 25 h incubation at pH 7.5 and 37C, respectively. It serves as a mobile reserve of mycotoxin that can be available for release to the tissues for a long time. One of the clinical studies identified OTA in 83% of over 100 individuals tested with chronic illness and a history of water-damaged building exposure.