JOURNAL ARTICLE

Effectiveness of a substituted β-cyclodextrin to prevent cyclosarin toxicity in vivo

Franz Worek, Thomas Seeger, Michael Zengerle, Stefan Kubik, Horst Thiermann, Timo Wille
Toxicology Letters 2014 April 21, 226 (2): 222-7
24561299
Standard treatment of poisoning by organophosphorus (OP) nerve agents with atropine and an oxime has a limited efficacy. An alternative approach is the development of stoichiometric or catalytic (bio-)scavengers which should be able to prevent systemic toxicity. Recently, a β-cyclodextrin derivative, 6-OxP-CD, bearing a pyridinium oximate in 6-position of one glucose unit was synthetized and shown to possess a promising detoxification potential against a variety of alkyl methylfluorophosphonates in vitro. In order to investigate the suitability of 6-OxP-CD as a small molecule scavenger an in vivo guinea pig model was established to determine the protective effect of 6-OxP-CD against the highly toxic nerve agent cyclosarin. Prophylactic i.v. injection of 6-OxP-CD (100mg/kg) prevented systemic toxicity in cyclosarin (∼2LD50) poisoned guinea pigs, preserved brain acetylcholinesterase (AChE) activity but did not protect erythrocyte AChE activity. A lower 6-OxP-CD dose (50mg/kg) reduced systemic toxicity and prevented mortality in all animals. Thus, the results of this proof of concept study indicate that 6-OxP-CD may be considered as a potential small molecule scavenger to protect against the toxic effects of a range of highly toxic OP nerve agents.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
24561299
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"