Toxicity of ricin toxin A chain in rats.

07:47 EDT 26th May 2015 | BioPortfolio

Summary of "Toxicity of ricin toxin A chain in rats."

Ricin toxin A chain (RTA) is the cytotoxic component of the dimeric protein, ricin, one of the most potent and deadly plant toxins extracted from the seeds of Ricinus communis. RTA has been investigated as a potential candidate for cancer chemotherapy, in the form of immunotoxins, and as a method for depleting macrophages in vivo. The toxicity of RTA immunotoxins is mostly characterized by inflammation and necrosis and has been attributed to the RTA moiety of the conjugate. The present study was carried out to investigate the toxicity of intravenously (i.v.) administered RTA alone and to assess whether the observed tissue injuries are associated with increases in oxidative stress (OS) and inflammation. RTA (10 or 90 µg/kg body weight) was administered to animals i.v., and 5 or 24 hours later, liver, lungs, kidneys, and hearts were examined. RTA, at a dose of 90 µg/kg (i.v.), resulted in significant increases (P < 0.05) in an inflammatory response (i.e., increases in hepatic and lung myeloperoxidase activity) and increases in oxidant response (increases in lipid peroxidation and decreases in glutathione levels in hepatic and lung homogenates). These data suggest that i.v. administration of RTA resulted in organ injuries that were associated with inflammation and OS.

Affiliation

Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University , Ontario , Canada.

Journal Details

This article was published in the following journal.

Name: Drug and chemical toxicology
ISSN: 1525-6014
Pages:

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Medical and Biotech [MESH] Definitions

Protein synthesized by CLOSTRIDIUM TETANI as a single chain of ~150 kDa with 35% sequence identity to BOTULINUM TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal CONVULSIONS.

An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.

A toxin produced by certain pathogenic strains of ESCHERICHIA COLI such as ESCHERICHIA COLI O157. It shares 50-60% homology with SHIGA TOXIN and SHIGA TOXIN 1.

Mutant strains of rats that produce little or no hair. Several different homozygous recessive mutations can cause hairlessness in rats including rnu/rnu (Rowett nude), fz/fz (fuzzy), shn/shn (shorn), and nznu/nznu (New Zealand nude). Note that while NUDE RATS are often hairless, they are most characteristically athymic.

Proteins synthesized as a single chain of ~150 kDa with 35% sequence identity to TETANUS TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. They have neuro-, entero-, and hemotoxic properties, are immunogenic, and include the most potent poisons known. The most commonly used apparently blocks release of ACETYLCHOLINE at cholinergic SYNAPSES.

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