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BCH00025- BIOCHEMICAL EFFECTS OF MYCOTOXIN USING AFLATOXIN AS A CASE STUDY


ABSTRACT

Mycotoxins are ubiquitous, mold-produced toxins that contaminate a wide variety of foods and feeds. Ingestion of mycotoxins cause a range of toxic responses, from acute toxicity to long-term or chronic health disorders. Some mycotoxins have caused outbreaks of human toxicoses, and at least one mycotoxin, aflatoxin B1, is a presumed human hepatocarcingen. As part of a comprehensive effort to curtail the adverse health effects posed by mycotoxins, substantial research has been conducted to determine the mechanism of action of mycotoxins in animals. This review presents some of the current knowledge on the biological action of four diverse classes of mycotoxins-aflatoxin B1, tricothecenes, zearalenone, and fumonism B1-with particular emphasis on mechanisms of action.

CHAPTER ONE

  • INTRODUCTION

Mycotoxins are secondary metabolites of molds that have adverse effects on humans, animals, and crops and result in illnesses and economic losses (Krogh, 1987). The worldwide contamination of foods and feeds with mycotoxins is a significant problem (Fink-Gremmels, 199)Aflatoxins, ochratoxins, trichothecenes, zearalenone, fumonisins, tremorgenic toxins, and ergot alkaloids are the mycotoxins of greatest agro-economic importance. Some molds are capable of producing more than one mycotoxin and some mycotoxins are produced by more than one fungal species. Often more than one mycotoxin is found on a contaminated substrate. Mycotoxins occur more frequently in areas with a hot and humid climate, favourable for the growth of molds, they can also be found in temperate zone (Kpodo, 1996) Exposure to mycotoxins is mostly by ingestion, but also occurs by the dermal and inhalation routes. The diseases caused by exposure to mycotoxins are known as mycotoxicoses. However, mycotoxicoses often remain unrecognized by medical professionals, except when large numbers of people are involved (Lopez et al., 2002). Factors influencing the presence of mycotoxins in foods or feeds include environmental conditions related to storage that can be controlled (Klich, 2003). Other extrinsic factors such as climate or intrinsic factors such as fungal strain specificity, strain variation, and instability of toxigenic properties are more difficult to control. Mycotoxins have various acute and chronic effects on humans and animals (especially monogastrics) depending on species and susceptibility of an animal within a species (Bennett, 1987). Ruminants have, however, generally been more resistant to the adverse effects of mycotoxins. This is because the rumen microbiota is capable of degrading mycotoxins. The economic impact of mycotoxins include loss of human and animal life, increased health care and veterinary care costs, reduced livestock production, disposal of contaminated foods and feeds, and investment in research and applications to reduce severity of the mycotoxin problem (Jarvis 2002).

This study focus on the biochemical effects of four desses of mycotoxicoses with emphasis on their mechanism of action.

1.1       Mycotoxin

It is difficult to define mycotoxin in a few words. All mycotoxins are low-molecular-weight natural products (i.e., small molecules) (Bennett, 1987). produced as secondary metabolites by filamentous fungi. These metabolites constitute a toxigenically and chemically heterogeneous assemblage that are grouped together only because the members can cause disease and death in human beings and other vertebrates (Bennett, 1987). Not surprisingly, many mycotoxins display overlapping toxicities to invertebrates, plants, and microorganisms (Bennett, 1987). The term mycotoxin was coined in 1962 in the aftermath of an unusual veterinary crisis near London, England, during which approximately 100,000 turkey poults died. When this mysterious turkey X disease was linked to a peanut(groundnut) meal contaminated with secondary metabolites from Aspergillus flavus (aflatoxins), it sensitized scientists to the possibility that other occult mold metabolites might be deadly (Bennett and Klich, 2003). While all mycotoxins are of fungal origin, not all toxic  compounds produced by fungi are called mycotoxins. The target and the concentration of the metabolite are both important. Fungal products that are mainly toxic to bacteria (such as penicillin) are usually called antibiotics. Fungal products that are toxic to plants are called phytotoxins by plant pathologists (Klich, 2003). Mycotoxins are made by fungi and are toxic to vertebrates and other animal groups in low concentrations. Other low-molecular-weight fungal metabolites such as ethanol that are toxic only in high concentrations are not considered mycotoxins (Bennett, 1987).

Currently, more than 300 mycotoxins are known, scientific attention is focused mainly on those that have proven to be carcinogenic and/or toxic. Human exposure to mycotoxins may result from consumption of plant-derived foods that are contaminated with toxins, the carry-over of mycotoxins and their metabolites in animal products such as meat and eggs (CAST, 2003) or exposure to air and dust containing toxins (Jarvis, 2002).

Examples of mycotoxins of greatest public health and agro-economic significance include aflatoxins (AF), ochratoxins (OT), trichothecenes, zearalenone (ZEN),fumonisins (F), tremorgenic toxins, and ergot alkaloids.. Factors contributing to the presence or production of mycotoxins in foods or feeds include storage, environmental, and ecological conditions. Often times most factors are beyond human control (Hussein and Brasel, 2001).

            The most important genera of mycotoxigenic fungi are Aspergillus, Alternaria, Claviceps, Fusarium, Penicillium and Stachybotrys. The principal classes of mycotoxins include a metabolite of A. flavus and Aspergillus parasiticus, aflatoxin B1 (AFB1), the most potent hepatocarcinogenic substance known, which has been recently proven to also be genotoxic. In dairy cattle, another problem arises from the transformation of AFB1 andAFB2 into hydroxylated metabolites, aflatoxin M1 and M2 (AFM1 and AFM2), which are found in milk and milk products obtained from livestock that have ingested contaminated feed (Boudra et al., 2007). In 1993, the WHO-International Agency for Research on Cancer (WHO-IARC, 1993a,b) evaluated the carcinogenic potential of AF, OT, trichothecenes, ZEN, and F. Naturally occurring AF were classified as carcinogenic to humans (Group 1) while OT and F were classified as possible carcinogens (Group 2B). Trichothecenes and ZEN, however, were not classified as human carcinogens (Group 3). The health hazards of mycotoxins to humans or animals have been reviewed extensively in recent years (Yaling et al., 2008; Averkieva, 2009).

Mycotoxins can be classified as hepatotoxins, nephrotoxins, neurotoxins, immunotoxins, and so forth (Yaling et al., 2008). Cell biologists put them into generic groups such as teratogens, mutagens, carcinogens, and allergens. Organic chemists have attempted to classify them by their chemical structures (e.g., lactones, coumarins); biochemists according to their biosynthetic origins (polyketides, amino acid-derived, etc.); physicians by the illnesses they cause (e.g., St. Anthony’s fire, stachybotryotoxicosis), and mycologists by the fungi that produce them (e.g., Aspergillus toxins, Penicillium toxins). None of these classifications is entirely satisfactory (Bennett and Klich, 2003).

Occurrence and significance of mycotoxins in foods and feeds Mycotoxicoses in humans or animals are characterized as food or feed related, non-contagious, non-transferable, non-infec- tious, and non-traceable to microorganisms other than fungi. Clinical symptoms usually subside upon removal of contaminated food or feed. A wide range of commodities can be contaminated with mycotoxins both pre- and post-harvest ( CAST, 2003). Aflatoxins (AFTs) are found in maize and peanuts, as well as in tree nuts and dried fruits. OTA is found mainly in cereals, but significant levels of contamination may also occur in wines, coffee, spices and dried fruits. Other products of concern are beans, roasted coffee and cocoa, malt and beer, bread and bakery products, wines and grape juices, spices, poultry meat and kidneys, pig kidneys and pork sausages (Milicevic et al., 2008).

The aflatoxins were isolated and characterized after the death of more than 100,000 turkey poults (turkey X disease) was traced to the consumption of a mold-contaminated peanut meal. The major aflatoxins are called B1, B2, G1, and G2 (based on their fluorescence under UV light (blue or green) and relative chromatographic mobility during thin-layer chromatography)

M1 and M2 (produced in milk and dairy products) (D’Mello and MacDonald, 1997). Aflatoxin B1 is the most potent natural carcinogen known and is usually the major aflatoxin produced by toxigenic strains (Squire,1981). Aflatoxins are difluranocoumarin derivatives produced by polyketide pathway by many strains of A. flavus and A. parasiticus; in particular, A. flavus is a common contaminant in agriculture. Aspergillus bombycis, Aspergillus ochraceoroseus, Aspergillus nomius, and Aspergillus pseudotamari are also aflatoxin producing species, but they are encountered less frequently (Peterson et al., 2001).

Aflatoxin contamination has been linked to increased mortality in farm animals and thus significantly lowers the value of grains as an animal feed and as an export commodity. Milk products can also serve as an indirect source of aflatoxin. When cows consume aflatoxin-contaminated feeds, they metabolically biotransform aflatoxin B1 into a hydroxylated form called aflatoxinM1 (Van Egmond, 1989). Aflatoxin is associated with both toxicity and carcinogenicity in human and animal populations. The diseases caused by aflatoxin consumption are loosely called aflatoxicoses. Acute aflatoxicosis results in death; chronic aflatoxicosis results in cancer, immune suppression, and other ‘‘slow’’ pathological conditions. The liver is the primary target organ, with liver damage occurring when poultry, fish, rodents, and nonhuman primates are fed aflatoxin B1. There are substantial differences in species susceptibility. Moreover, within a given species, the magnitude of the response is influenced by age, sex, weight, diet, exposure to infectious agents, and the presence of other mycotoxins and pharmacologically active substances. Thousands of studies on aflatoxin toxicity have been conducted, mostly concerning laboratory models or agriculturally important species (Cullen and Newberne, 1994).

Finally, it should be mentioned that Aspergillus oryzae and Aspergillus sojae, species that are widely used in Asian food fermentations such as soy sauce, miso, and sake, are closely related to the aflatoxigenic species A. flavus and A. parasiticus.  Although these food fungi have never been shown to produce aflatoxin, they contain homologues of several aflatoxin biosynthesis pathway genes. Deletions and other genetic defects have led to silencing of the aflatoxin pathway in both A. oryzae and A. sojae (Takahashi et al., 2002).