Aflatoxin inhibitor

Other naturally derived aflatoxin inhibitors obtained from the "neem" tree have been investigated in our laboratory (84), Azadirachta indica Juss. commonly known as "margosa" or "neem" is an ornamental tree of Asia and Africa that produces natural products having reputed value for their medicinal, antiviral, antibacterial, insecticidal, antifungal and antinematode properties (86, 87). Several active principles from different parts of the neem tree have been reported (88). Our investigation (84) examined the effects of these neem leaf components in neem leaves on aflatoxin biosynthesis by either Aspergillus parasiticus or A. flavus. 

In relation to the prevention of the occurrence of aflatoxins, inhibitors of their formation are often studied. In addition to compounds used in practice for their fungicidal effects, such as preservatives, inhibitory effects of zinc or caffeine have also been demonstrated. Aflatoxin production can be stimulated by long chain fatty acids and inhibited by oleic, linoleic and lauric acids. 

Pea.nuts, The proteins of peanuts are low in lysine, threonine, cystine plus methionine, and tryptophan when compared to the amino acid requirements for children but meet the requirements for adults (see Table 3). Peanut flour can be used to increase the nutritive value of cereals such as cornmeal but further improvement is noted by the addition of lysine (71). The trypsin inhibitor content of raw peanuts is about one-fifth that of raw soybeans, but this concentration is sufficient to cause hypertrophy (enlargement) of the pancreas in rats. The inhibitors of peanuts are largely inactivated by moist heat treatment (48). As for cottonseed, peanuts are prone to contamination by aflatoxin. FDA regulations limit aflatoxin levels of peanuts and meals to 100 ppb for breeding beef catde, breeding swine, or poultry 200 ppb for finishing swine 300 ppb for finishing beef catde 20 ppb for immature animals and dairy animals and 20 ppb for humans. 

Breinholt V, Hendricks J, Pereira C, Arbogast D and Bailey G. 1995. Dietary chlorophyllin is a potent inhibitor of aflatoxin Bi hepatocarcinogenesis in rainbow trout. Cancer Res 55(l) 57-62. 

The potent carcinogen aflatoxin B1 is activated by generation of an epoxide on a dihydrofuran moiety [43]. The potent MBIs contained in grapefruit juice and in the herbal medication St J ohn s Wort are furanocoumarin compounds [44—46]. A similar moiety is also incorporated in the HIV protease inhibitor L-754,394, a potent CYP3A4 MBI [47]. 

Inhibitors/Toxins Trypsin inhibitors, aflatoxins, exotoxins (botulinum), endotoxins, PCBs, vomitoxin... 

Two other examples of sigmoidal reactions that are made linear by an activator include a report by Johnson et al. (31), who showed that pregnenolone has a nonlinear double-reciprocal plot that was made linear by the presence of 5 pM 7,8-benzoflavone, and Ueng et al. (23), who showed that aflatoxin B1 has sigmoidal saturation curve that is made more hyperbolic by 7,8-benzoflavone. As with the effect of quinine on carbamazepine metabolism, 7,8-benzoflavone is an activator at low aflatoxin B1 concentrations and an inhibitor at high aflatoxin B1 concentrations. 

In the first part of this chapter, we deal with insecticides including miticides and nematocides, which include very useful compounds such as avermectins and milbemycins, produced by bacteria and fungi. We list out microbial insecticides of importance and review the works mainly on the mode of action and biosynthesis of each metabolite. In the next part, major mycotoxins are listed and recent topics on them, especially on their biosynthesis, are described. Since contamination of two major mycotoxin groups, aflatoxins (AFs) and trichothecenes, in food and feed is a worldwide problem, they are treated in detail in the last part of this chapter. Recent studies on their biosynthesis, regulatory mechanism for their production, and inhibitors of their production are described. 

Figure 26 Aflatoxin production inhibitors from pesticides and plants.

Figure 27 Aflatoxin production inhibitors from microorganisms.

Therefore, adding alkali to proteins may accomplish an increased solubilization of the protein while in the alkaline solution. However, upon adjustment to neutral or acid pH, the protein may be less soluble than originally because of denaturation. In texturization of proteins, this denaturation may be an advantage. However, in other cases such as alkali treatment to destroy aflatoxin or protease inhibitors it may be a disadvantage. 

A number of chemicals with demonstrable suppression of immune function produce this action via indirect effects. By and large, the approach that has been most frequently used to support an indirect mechanism of action is to show immune suppression after in vivo exposure but no immune suppression after in vitro exposure to relevant concentrations. One of the most often cited mechanisms for an indirect action is centered around the limited metabolic capabilities of immunocompetent cells and tissues. A number of chemicals have caused immune suppression when administered to animals but were essentially devoid of any potency when added directly to suspensions of lymphocytes and macrophages. Many of these chemicals are capable of being metabolized to reactive metabolites, including dime-thylnitrosamine, aflatoxin Bi, and carbon tetrachloride. Interestingly, a similar profile of activity (i.e., suppression after in vivo exposure but no activity after in vitro exposure) has been demonstrated with the potent immunosuppressive drug cyclophosphamide. With the exception of the PAHs, few chemicals have been demonstrated to be metabolized when added directly to immunocompetent cells in culture. A primary role for a reactive intermediate in the immune suppression by dimethylnitrosamine, aflatoxin Bi, carbon tetrachloride, and cyclophosphamide has been confirmed in studies in which these xenobiotics were incubated with suspensions of immunocompetent cells in the presence of metabolic activation systems (MASs). Examples of MASs include primary hepatocytes, liver microsomes, and liver homogenates. In most cases, confirmation of a primary role for a reactive metabolite has been provided by in vivo studies in which the metabolic capability was either enhanced or suppressed by the administration of an enzyme inducer or a metabolic inhibitor, respectively. 

A review of pharmaceutical and therapeutic potentials of essential oils, some of which are found in Kenya and their individual constituents has also been reported. At its sublethal doses, the oil of Cymbopogon citratus was found to completely inhibit aflatoxin Bi production from Aspergillus flavus. These findings show the potential of this oil as an effective inhibitor of biodegradation and storage contamination fungi and also in fruit juice preservation. The essential oil from Foeniculum vulgare has hepatoprotective activity due to the... 

Takahashi, N., C.L. Miranda, M.C. Henderson, D.R. Buhler, D.E. Williams and G.S. Bailey. Inhibition of in vitro aflatoxin B1 DNA binding in rainbow trout by CYP1A inhibitors - alpha-naphthoflavone, beta-naphthoflavone and trout CYP1A1 peptide antibody. Comp. Biochem. Physiol. 110C 273 -280, 1995. 

Other medically important polyketides include the antibiotics doxorubicin (14-hydroxydaunomycin Fig. 5-23), rifamycin (Box 28-and the antifimgal pimaricin, griseofulvin, and amphotericin (Fig. 21-10), the HMG-CoA reductase inhibitor lovastatin, the 2-butanyl-4-methylthreonine of cyclosporin A (Box 9-F), and other immunosuppressants such as rapamycin. Many characteristic plant products, including stilbenes and chalcones (Box 21-E), are polyketides. A variety of different polyketides serve as phytoalexins. Some such as aflatoxin are dangerous toxins. Ants and ladybird beetles make toxic polyamine alkaloids using a polyketide pathway. ... 

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