Toxicity of ricin toxin A chain in rats

Abstract

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.

Keywords::

• Inflammation
• liver
• lung
• neutrophils
• Kupffer cells
• oxidative stress