Journal article
The role of systemic handling in the pathophysiologic actions of botulinum toxin
The Journal of pharmacology and experimental therapeutics, v 326(3), pp 856-863
01 Sep 2008
PMID: 18539649
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The ability of botulinum toxin to poison cholinergic nerve transmission is a dynamic phenomenon that involves not only the actions of the toxin on the body but also the actions of the body on the toxin. The former has been the subject of intense research, whereas the latter has received almost no attention. Therefore, a series of studies were performed to characterize systemic handling of botulinum toxin. The results indicated that the toxin reaches the general circulation (transcytosis across epithelial cells) without obvious changes in structure or biological activity. The general circulation acts as a holding compartment until there is adequate fractional distribution to neuromuscular junctions to produce blockade of transmission. During its transit through this compartment, the toxin 1) undergoes little biotransformation, 2) does not accumulate significantly in circulating cells, and 3) remains largely in the free state. In naive animals, the t(1/2) for toxin in the general circulation is approximately 10 h, and at any given point in time, there is little uptake in nontarget organs (liver, kidney, heart, and lung). In immunized animals, toxin clearance from the general circulation is rapid, and there is substantial accumulation of antibody-antigen complexes in liver. Thus, enhanced clearance from the circulation is a major mechanism by which active immunization can protect against poisoning.
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Details
- Title
- The role of systemic handling in the pathophysiologic actions of botulinum toxin
- Creators
- Fetweh H. Al-Saleem - Jefferson CollegeDenise M. Ancharski - Thomas Jefferson UniversityEaswaran Ravichandran - Thomas Jefferson UniversitySuresh G. Joshi - Thomas Jefferson UniversityAjay K. Singh - Thomas Jefferson UniversityYujing Gong - Thomas Jefferson UniversityLance L. Simpson - Thomas Jefferson University
- Publication Details
- The Journal of pharmacology and experimental therapeutics, v 326(3), pp 856-863
- Publisher
- Amer Soc Pharmacology Experimental Therapeutics
- Number of pages
- 8
- Grant note
- Contract N01-AI30028 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Contract 1-07-0032 / Defense Threat Reduction Agency; United States Department of Defense N01AI030028 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000258524400020
- Scopus ID
- 2-s2.0-53849114704
- Other Identifier
- 991021448060504721
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- Web of Science research areas
- Pharmacology & Pharmacy