Preclinical evaluation of the ribosome-inactivating proteins PAP-1, PAP-S and RTA in mice
| Autor: | Silvana Canevari, Fabio Benigni, Massimo Gadina, Elena Adobati, Elena Ferraris di Celle, Andrés JoséMaria Ferreri, Roberto Comolli, Maria I. Colnaghi |
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| Rok vydání: | 1995 |
| Předmět: |
Immunoconjugates
medicine.medical_treatment T-Lymphocytes Immunology Drug Evaluation Preclinical Pancreatitis-Associated Proteins Ricin Pharmacology Biology Kidney Median lethal dose Blood Urea Nitrogen Mice Immune system Pharmacokinetics In vivo medicine Animals Tissue Distribution Blood urea nitrogen N-Glycosyl Hydrolases Plant Proteins Mice Inbred BALB C Immunosuppression Alanine Transaminase female genital diseases and pregnancy complications medicine.anatomical_structure Liver Toxicity Ribosome Inactivating Proteins Type 1 Female Ribosomes |
| Zdroj: | International journal of immunopharmacology. 17(10) |
| ISSN: | 0192-0561 |
| Popis: | In a preclinical mouse model the plant ribosome-inactivating proteins (RIPs) pokeweed antiviral proteins PAP-1, and PAP-S and ricin A-chain (RTA) induced a pathological elevation of serum concentrations of glutamate pyruvate transaminase (GPT) and blood urea nitrogen (BUN) and had a significant immunosuppressive effect on B- and T-lymphocytes. The present analysis and comparison of the biodistribution and systemic/organ toxicity associated with RIP injection suggest a possible in vivo mechanism of action of PAP-1 and PAP-S and identify several limitations in the clinical use of these two toxins and RTA. When administered intravenously, PAP-1 and PAP-S consistently accumulated in kidneys and induced histologically documented damage to kidney and liver, with a ld 50 of 3.3 mg/kg and 1.6 mg/kg for PAP-1 and PAP-S, respectively. In mice injected with PAP-S after chlorpromazine (CPZ) administration, GPT levels returned to normal between 24 and 72 h after toxin injection, while the BUN levels remained elevated. Mortality of the animals was delayed but all mice eventually succumbed. All the three toxins inhibited the expansion of anti-sheep red blood cells (SRBC) antibody-forming cells and the production of anti-SRBC antibody levels, although PAP-S showed the most potent activity. Despite the immunosuppressive activity, all toxins were highly immunogenic. |
| Databáze: | OpenAIRE |
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