Premium
Comparison of brain protection in rats and guinea pigs by pro‐2‐pralidoxime (pro‐2‐PAM) to organophosphate exposure
Author(s) -
DeMar James C,
Somerville Shahza M,
Ratcliffe Ruthie H,
Logeman Laura M,
Ku Therese C,
Nur Nur M,
Ursic Benjamin M,
Gordon Richard K
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.749.2
Subject(s) - acetylcholinesterase , organophosphate , aché , soman , pharmacology , guinea pig , histopathology , chemistry , medicine , enzyme , biology , biochemistry , pathology , pesticide , agronomy
Organophosphates (OP) inhibit brain acetylcholinesterase (AChE), leading to seizures and neuronal apoptosis. Therapy includes pralidoxime chloride (2‐PAM), which restores only peripheral AChE since it is charged and excluded from the brain. We showed that pro‐2‐PAM, a non‐polar pro‐drug of 2‐PAM, protected guinea pig CNS to OP exposure. Guinea pigs, the preferred model since their repertoire of OP detoxifying enzymes matches humans, were then compared to rats; rodents received the OP diisopropylfluorophosphate (DFP) and were treated with pro‐2‐PAM or 2‐PAM. Seizures were monitored by EEG. Brains were removed at 24 h and AChE activity and histopathology determined. DFP‐induced seizures were blocked in both species by pro‐2‐PAM, but not 2‐PAM. Likewise, brain AChE activity was higher and histopathology showed neuronal protection only with pro‐2‐PAM. Guinea pigs, however, withstood longer time delays until pro‐2‐PAM therapy than rats. In conclusion, pro‐2‐PAM is a promising therapeutic for treating CNS OP poisoning in two animal species. (Supported by NIH Grant: 1 U01 NS058166‐01). The opinions or assertions are the private views of the authors, and are not official views of the US Army, DoD, or NIH.