O O

Figure 12. Formation of conjugate between aflatoxin and DNA: (1) AFB!-8,9-oxide, (2) AFBr Guanine-DNA. Source: Ref. 85.

Figure 12. Formation of conjugate between aflatoxin and DNA: (1) AFB!-8,9-oxide, (2) AFBr Guanine-DNA. Source: Ref. 85.

in the peripheral nervous system, resulting in paralysis. The lethal dose is in the range of 1 to 5 ng/kg body weight. Botulinum toxins are synthesized as an inactive precursor, which is a single polypeptide with a molecular weight of —150,000 Da. The protein is cleaved by an endogenous protease into an active molecule consisting of a heavy chain and a light chain linked by a disulfide bond. The toxin initially binds to gangliosides (sialic acid-containing glyco-lipids) on the plasma membrane of cholinergic nerve. The toxin-ganglioside complex undergoes endocytosis, and the low pH in the vesicle activates the insertion of the toxin into the membrane (85).

Mycotoxins are toxic fungal metabolites that often contaminate peanuts, cereals, and dairy products. The most extensively studied mycotoxins are the aflatoxins produced by Aspergillus and Pénicillium. The toxicity of aflatoxin Bj is caused by their metabolism to the reactive AFBj-8,9-oxide, which forms covalently linked conjugates with DNA and proteins (86) (Fig. 12), or undergoes hydrolysis to AFBr8,9-dihydrodiol. The latter product is a dialdehyde phenolate ion stabilized by resonance and forms Schiff base with proteins.

Polycyclic aromatic hydrocarbons are known carcinogens found in grilled meat products. These compounds include benzo[a]pyrene, benzo[a]fluroanthene, benzo[a]-anthracene, and chrysene. They are metabolized by enzymatic activation to form a dihydrodiolepoxide that binds DNA. Heterocyclic amines found in high temperature cooking are enzymatically converted to O-acyl derivative, which covalently binds DNA, resulting in mispairing in replication and transcription (87).

Many JV-nitrosamines are found in cured meat and fish, including Af-nitrosodimethylamine, JV-nitrosodieth-ylamine, Af-nitrosopyrrolidine, and Af-nitrosopiperidine. Metabolically, nitrosamines undergo enzymatic a-hydrox-ylation, followed by C-N bond cleavage to yield alkydiazo-hydroxide, which further breaks down to alkyldiazonium ion. Both alkydiazohydroxide and alkyldiazonium ion react with DNA to form covalent conjugates (88).

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