Review of the inhibition of biological activities of food-related selected toxins by natural compounds

Abstract

There is a need to develop food-compatible conditions to alter the structures of fungal, bacterial, and plant toxins, thus transforming toxins to nontoxic molecules. The term 'chemical genetics' has been used to describe this approach. This overview attempts to survey and consolidate the widely scattered literature on the inhibition by natural compounds and plant extracts of the biological (toxicological) activity of the following food-related toxins: aflatoxin B1, fumonisins, and ochratoxin A produced by fungi; cholera toxin produced by Vibrio cholerae bacteria; Shiga toxins produced by E. coli bacteria; staphylococcal enterotoxins produced by Staphylococcus aureus bacteria; ricin produced by seeds of the castor plant Ricinus communis; and the glycoalkaloid α-chaconine synthesized in potato tubers and leaves. The reduction of biological activity has been achieved by one or more of the following approaches: inhibition of the release of the toxin into the environment, especially food; an alteration of the structural integrity of the toxin molecules; changes in the optimum microenvironment, especially pH, for toxin activity; and protection against adverse effects of the toxins in cells, animals, and humans (chemoprevention). The results show that food-compatible and safe compounds with anti-toxin properties can be used to reduce the toxic potential of these toxins. Practical applications and research needs are suggested that may further facilitate reducing the toxic burden of the diet. Researchers are challenged to (a) apply the available methods without adversely affecting the nutritional quality, safety, and sensory attributes of animal feed and human food and (b) educate food producers and processors and the public about available approaches to mitigating the undesirable effects of natural toxins that may present in the diet.

Figure 1

HPLC of AFB1 and AFB1-N-acetylcysteine (NAC) adduct. Adapted from [3,4].

Figure 2

Possible pathways for the inhibition of AFB1 mutagenicity/carcinogenicity of AFB1 by thiols such as cysteine, N-acetylcysteine, and reduced glutathione. See text. Adapted from [3,4].

Figure 3

Structure of botulinum neurotoxin showing three potential sites for inactivation: zinc-containing metalloproteinase susceptible to chelation by catechin phenolic OH groups; intramolecular disulfide bond of the heavy chain (disulfide site-1); intermolecular disulfide bond linking the light and heavy chains (disulfide site-2). The disulfide bonds are susceptible to reduction and/or sulfhydryl-disulfide interchange initiated by sulfhydryl compounds such as N-acetyl-l-cysteine. Adapted from [102].

Figure 4

Effect of plant compounds on protein synthesis levels in Stx-treated Vero-d2EGFP cells. Protein synthesis was measured in Vero-d2EGFP cells after a 2-hour co-incubation with plant polyphenolic compounds and Stx2. Cells were co-incubated with no plant compound, 1 mg caffeic acid/mL, 1 mg red wine concentrate/mL, 0.5 mg grape pomace extract/mL, or 0.1 mg grape seed extract/mL. Adapted from [129].

Figure 5

Comparison of inhibition of SEA by Red Delicious apple juice and apple polyphenols (Apple Poly). Splenocytes and SEA (1 ng/mL) were incubated for 48 h with Red Delicious juice or decreasing concentrations (0.3%, 0.06% and 0.012% w/v in PBS) of Apple Poly. The level of newly synthesized DNA was then determined, by measuring optical density at 450 nm. Adapted from [146].

Figure 6

Schematic representation of cellular events that lead to the inhibition of SEA induced cell proliferation by apple juice. The individual steps in this scheme involve (A) the formation of a bridge between antigen presenting cells (APC) and T cells that results in the induction of T-cell proliferation; and (B) the inhibition of T-cell proliferation by added pure apple juice that disrupt the connection between APC and T cells. The net beneficial result of these events is the prevention of release and the consequent adverse effects induced by cytokines. Abbreviations: MHC, major histocompatibility complex; TCR, T-cell receptor. Adapted from [146].

Figure 7

Effect of 4-hydroxytyrosol on splenocyte proliferation determined by two independent methods. Different concentrations of the toxin (0, 5, and 200 ng/mL) were exposed to 4-hydroxytyrosol or the control (media) and were then incubated for 48 h with splenocyte cells followed by determining (A) GF-AFC cleavage by live cell protease (a measure of cellular activity) or (B) BrdU incorporation into newly synthesized DNA (a measure of cellular proliferation). Conditions: (A) GF-AFC substrate in intact cells is cleaved by live cell protease releasing the fluorescent AFC, which is quantified at an excitation wavelength of 355 nm and an emission wavelength of 523 nm. (B) BrdU-labeled DNA was determined spectrophotometrically at absorbances of 620 nm and 450 nm. Both assays show that 4-hydroxytyrosol inhibited the biological activity of SEA. Adapted from [147].

Figure 8

ELISA method demonstrating that milk competitively inhibits in a concentration-dependent manner attachment of ricin to asialofetuin type II coated plates (reduces the number of toxin molecules on the plate). (A) Upper plot: time 0; (B) Lower plot: after 15 min. Absorbance is read at 450 nm. Adapted from [158].