STUDIES ON THE ORAL TOXICITY OF<i>CLOSTRIDIUM BOTULINUM</i>TOXIN, TYPE A

Coleman, I. W.

doi:10.1139/o54-004

Cited by 12 publications

(6 citation statements)

References 1 publication

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“…Table 2 lists reports on the effect of proteolytic enzymes on botulinal neurotoxic activity. The older reports of no detoxification by proteolytic enzymes suffer from the fact that experimenta- Crystalline, type A None tion was limited to few titrations and few test animals, a criticism that cannot be made of the work of Coleman (1954) and Halliwell (1954). Our results are in essential agreement with the more recent findings except for the report by Coleman (1954) of extensive detoxification by pepsin.…”

Section: Resultssupporting

confidence: 89%

Activity of Type a Botulinal Toxin and Hemagglutinin Exposed to Proteolytic Enzyme

Meyer

Lamanna

1959

J Bacteriol

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Section: Resultssupporting

confidence: 89%

Activity of Type a Botulinal Toxin and Hemagglutinin Exposed to Proteolytic Enzyme

Meyer

Lamanna

1959

J Bacteriol

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“…4). DISCUSSION The orally ingested botulinum toxin is absorbed mostly from the upper intestine (3,7,9,15). The absorbed toxin is transported mostly into the lymphatic and only slightly into the blood stream (9,15).…”

Section: Resultsmentioning

confidence: 99%

Intestinal Absorption of Botulinum Toxins of Different Molecular Sizes in Rats

1977

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During a period of 10 to 12 h after injection of type B 16S (L) toxin into the ligated duodenum of rats, 0.01 to 0.1% of the total toxicity administered was found in the lymph drawn by cannulation of the thoracic duct. The recovery was 50 to 100 times higher than that of the rat given type B 12S (M) or 7S (S) toxin. During the same period, 0.6 to 1.5% of the specific antigens were recovered, regardless of the molecular size of the toxin that had been administered. In lymph of the B-L or B-M toxin recipient, the toxic and nontoxic components were detected in comparable quantities, indicating that the undissociated progenitor toxin molecule is absorbed through the intestinal wall. Although the toxic component had lost its toxic activity, the two components of B-M toxin appearing in lymph reassembled to reconstruct the 12S molecule, whereas those of B-L toxin did not, although the toxic component was still active. Type B-L, B-M, and B-S toxins showed similar stabilities to in vitro exposure to rat lymph (pH 8.2), but B-L toxin showed a considerably higher stability to intestinal juice (pH 7.0) than did B-M toxin. Thus, the toxicity of lymph of rats administered botulinum toxin intraduodenally depends not upon the rate of absorption, but largely upon the stability in the intestine.

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“…Although absorption of neurotoxin from the gut is essential to the onset of disease, surprisingly little is known about specific mechanisms that contribute to absorption (1). A series of early studies indicated that the upper small intestine is the primary site of absorption (4,5,10,16). This early work also established that neurotoxin which was administered orally or directly into the intestine appeared in lymph and blood.…”

mentioning

confidence: 99%

Pure Botulinum Neurotoxin Is Absorbed from the Stomach and Small Intestine and Produces Peripheral Neuromuscular Blockade

et al. 1999

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Clostridium botulinum serotype A produces a neurotoxin composed of a 100-kDa heavy chain and a 50-kDa light chain linked by a disulfide bond. This neurotoxin is part of a ca. 900-kDa complex, formed by noncovalent association with a single nontoxin, nonhemagglutinin subunit and a family of hemagglutinating proteins. Previous work has suggested, although never conclusively demonstrated, that neurotoxin alone cannot survive passage through the stomach and/or cannot be absorbed from the gut without the involvement of auxiliary proteins in the complex. Therefore, this study compared the relative absorption and toxicity of three preparations of neurotoxin in an in vivo mouse model. Equimolar amounts of serotype A complex with hemagglutinins, complex without hemagglutinins, and purified neurotoxin were surgically introduced into the stomach or into the small intestine. In some experiments, movement of neurotoxin from the site of administration was restricted by ligation of the pylorus. Comparison of relative toxicities demonstrated that at adequate doses, complex with hemagglutinins, complex without hemagglutinins, and pure neurotoxin can be absorbed from the stomach. The potency of neurotoxin in complex was greater than that of pure neurotoxin, but the magnitude of this difference diminished as the dosage of neurotoxin increased. Qualitatively similar results were obtained when complex with hemagglutinins, complex without hemagglutinins, and pure neurotoxin were placed directly into the intestine. This work establishes that pure botulinum neurotoxin serotype A is toxic when administered orally. This means that pure neurotoxin does not require hemagglutinins or other auxiliary proteins for absorption from the gastrointestinal system into the general circulation.

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STUDIES ON THE ORAL TOXICITY OFCLOSTRIDIUM BOTULINUMTOXIN, TYPE A

Cited by 12 publications

References 1 publication

Activity of Type a Botulinal Toxin and Hemagglutinin Exposed to Proteolytic Enzyme

Activity of Type a Botulinal Toxin and Hemagglutinin Exposed to Proteolytic Enzyme

Intestinal Absorption of Botulinum Toxins of Different Molecular Sizes in Rats

Pure Botulinum Neurotoxin Is Absorbed from the Stomach and Small Intestine and Produces Peripheral Neuromuscular Blockade

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