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An effective antidotal combination of polymyxin B and methylprednisolone for α-amanitin intoxication.
- Source :
-
Archives of Toxicology . May2019, Vol. 93 Issue 5, p1449-1463. 15p. 1 Color Photograph, 1 Diagram, 4 Charts, 5 Graphs. - Publication Year :
- 2019
-
Abstract
- Amanita phalloides is one of the most toxic mushrooms worldwide, and it is involved in the majority of human fatal cases of mushroom poisoning. α-Amanitin, the most deleterious toxin of A. phalloides to humans, inhibits RNA polymerase II (RNAPII), causing hepatic and renal failure. Previously, we have shown that polymyxin B (polB) reverts α-amanitin inhibition of RNAPII, although it was not able to guarantee the full survival of α-amanitin-intoxicated mice or prevent α-amanitin pro-inflammatory effects. α-Amanitin is also a substrate of the organic-anion-transporting polypeptide 1B3 (OATP1B3) and Na(+)-taurocholate cotransporter polypeptide (NTCP) transporters. Therefore, in the present work, we used a combination of polB [(2.5 mg/kg intraperitoneal (i.p.)] with the anti-inflammatory and NTCP inhibitor drug, methylprednisolone (MP) (10 mg/kg i.p.), as an attempt to fully revert α-amanitin-induced toxicity (0.33 mg/kg i.p.) in CD-1 mice. Results showed that the administration of the polB + MP combination, 4 h after α-amanitin, led to the full survival of the intoxicated animals, with a significant attenuation of α-amanitin-induced renal and hepatic necrosis. Also, the combination polB + MP led to a decrease of aminotransferase plasma levels, of the renal myeloperoxidase activity and of renal inflammatory cell infiltrate promoted by α-amanitin, although not preventing any of the hepatic pro-inflammatory effect of the toxin. The obtained results indicate that this combination may represent an important and valuable therapeutic approach to be used against α-amanitin intoxication. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03405761
- Volume :
- 93
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Archives of Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 136731666
- Full Text :
- https://doi.org/10.1007/s00204-019-02426-5