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      Presence of Mycotoxins in Milk Thistle ( Silybum marianum) Food Supplements: A Review

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          Abstract

          The consumption of herbal-based supplements, which are believed to have beneficial effects on human health with no side effects, has become popular around the world and this trend is still increasing. Silybum marianum (L.) Gaertn, commonly known as milk thistle (MT), is the most commonly studied herb associated with the treatment of liver diseases. The hepatoprotective effects of active substances in silymarin, with silybin being the main compound, have been demonstrated in many studies. However, MT can be affected by toxigenic micro-fungi and contaminated by mycotoxins with adverse effects. The beneficial effect of silymarin can thus be reduced or totally antagonized by mycotoxins. MT has proven to be affected by micro-fungi of the Fusarium and Alternaria genera, in particular, and their mycotoxins. Alternariol-methyl-ether (AME), alternariol (AOH), beauvericin (BEA), deoxynivalenol (DON), enniatin A (ENNA), enniatin A 1 (ENNA 1), enniatin B (ENNB), enniatin B 1 (ENNB 1), HT-2 toxin (HT-2), T-2 toxin (T-2), tentoxin (TEN), and zearalenone (ZEA) seem to be most significant in MT-based dietary supplements. This review focuses on summarizing cases of mycotoxins in MT to emphasize the need for strict monitoring and regulation, as mycotoxins in relation with MT-based dietary supplements are not covered by European Union legislation.

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          Burden of liver diseases in the world

          Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.
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            Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin.

            Zearalenone (ZEA) is a mycotoxin produced mainly by fungi belonging to the genus Fusarium in foods and feeds. It is frequently implicated in reproductive disorders of farm animals and occasionally in hyperoestrogenic syndromes in humans. There is evidence that ZEA and its metabolites possess oestrogenic activity in pigs, cattle and sheep. However, ZEA is of a relatively low acute toxicity after oral or interperitoneal administration in mice, rat and pig. The biotransformation for ZEA in animals involves the formation of two metabolites alpha-zearalenol (alpha-ZEA) and beta-zearalenol (beta-ZEA) which are subsequently conjugated with glucuronic acid. Moreover, ZEA has also been shown to be hepatotoxic, haematotoxic, immunotoxic and genotoxic. The exact mechanism of ZEA toxicity is not completely established. This paper gives an overview about the acute, subacute and chronic toxicity, reproductive and developmental toxicity, carcinogenicity, genotoxicity and immunotoxicity of ZEA and its metabolites. ZEA is commonly found on several foods and feeds in the temperate regions of Europe, Africa, Asia, America and Oceania. Recent data about the worldwide contamination of foods and feeds by ZEA are considered in this review. Due to economic losses engendered by ZEA and its impact on human and animal health, several strategies for detoxifying contaminated foods and feeds have been described in the literature including physical, chemical and biological process. Dietary intakes of ZEA were reported from few countries from the world. The mean dietary intakes for ZEA have been estimated at 20 ng/kgb.w./day for Canada, Denmark and Norway and at 30 ng/kgb.w./day for the USA. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) established a provisional maximum tolerable daily intake (PMTDI) for ZEA of 0.5 microg/kg of body weight.
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              Emerging fusarium-mycotoxins fusaproliferin, beauvericin, enniatins, and moniliformin: a review.

              The contamination of foods and feed with mycotoxins is a commonly known problem. Intense investigations have been conducted to study the occurrence, toxicity, and recently also the prevention and detoxification strategies of mycotoxins in human and animal food chains. Most of the studies have emphasized on "traditional" mycotoxins, such as aflatoxins, ochratoxin A, and trichothecenes. However, one of the most common grain-contaminating genus of fungi, Fusarium spp., is also capable of producing other toxic secondary metabolites - the so-called emerging mycotoxins such as fusaproliferin, beauvericin, enniatins, and moniliformin. So far, only limited data is available on these metabolites. This is not only due to their late recognition but especially the late understanding of their role as mycotoxins. This paper summarizes the existing data on the chemistry, analytical techniques, biosynthesis, production, toxicity, and occurrence data on fusaproliferin, beauvericin, enniatins, and moniliformin. Based on the available studies, attention should be paid to the studies on the distinct significance of these compounds in the human and animal food chains.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                08 December 2020
                December 2020
                : 12
                : 12
                : 782
                Affiliations
                [1 ]Department of Biology, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, CZ-50003 Hradec Kralove, Czech Republic; ostry@ 123456chpr.szu.cz (V.O.); jakub.toman@ 123456uhk.cz (J.T.); frantisek.malir@ 123456uhk.cz (F.M.)
                [2 ]Center for Health, National Institute of Public Health in Prague, Nutrition and Food in Brno, Palackeho 3a, CZ-61242 Brno, Czech Republic
                Author notes
                [* ]Correspondence: darina.pickova@ 123456uhk.cz ; Tel.: +420-722-049-025
                Author information
                https://orcid.org/0000-0003-3665-624X
                https://orcid.org/0000-0002-7396-5503
                https://orcid.org/0000-0003-0232-9670
                Article
                toxins-12-00782
                10.3390/toxins12120782
                7763672
                33302488
                fcd4f311-b676-458b-9849-9f883aadef75
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 November 2020
                : 06 December 2020
                Categories
                Review

                Molecular medicine
                milk thistle,food supplements,liver diseases,silymarin,mycotoxins
                Molecular medicine
                milk thistle, food supplements, liver diseases, silymarin, mycotoxins

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