MMSL 2016, 85(2):63-68 | DOI: 10.31482/mmsl.2016.012

BLOOD-FETUS PENETRATION OF PRALIDOXIMEOriginal article

Shreesh Ojha1, Syed M. Nurulain1,2, S. Dhanasekaran1, Mohammad Shafiullah1, Abdu Adem1, Charu Sharma3, Kamil Kuča ORCID...4, Huba Kalasz1,5*
1 Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
2 COMSATS Institute of Information Technology, Islamabad, Pakistan
3 Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
4 Centre of Advanced Studies, Faculty of Military Health Science, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic
5 Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Budapest, Hungary

Pralidoxime (2-PAM) is a monopyridinium aldoxime-type compound of acetylcholinesterase reactivators. 2-PAM was introduced about five decades ago for the treatment of organophosphorus poisoning in order to reactivate inhibited acetylcholinesterase. The application of organophosphorus compounds is varied, including warfare agents, insecticides and pesticides in agriculture, the chemical industry, etc. The exposure is not limited to certain groups of humans: rather everyone can be affected, including pregnant women, and consequently fetuses as well.The present study was aimed to determine the 2-PAM concentration in the plasma of pregnant mice, assuming a different physiological condition than non-pregnant ones. Blood-placenta penetration of 2-PAM was also investigated. 2-PAM was intraperitoneally injected into mice on gestational day 18 and mother blood was collected following 5, 15, 30 and 90 minutes. Four fetuses along with their placentas were collected at every time point. HPLC-UV method was employed to determine the 2-PAM concentrations. The result showed higher levels of 2-PAM at 15 minutes (tmax) in the plasma of pregnant mice compared to non-pregnant ones.Moreover, 2-PAM copiously reached the placenta, which is a store house of nutrients for the fetus. A higher concentration of 2-PAM was found in the brain of fetuses in comparison to that of the mothers'.Our study concludes that 2-PAM crosses the placenta barrier and reaches the brain of the fetus in a more ample quantity than that in the mother's brain. The results provide an insight into a special condition of pregnancy when antidotal application of the acetylcholinesterase reactivator 2-PAM in organophosphorus poisoning results in 2-PAM exposure in the fetus.

Keywords: Blood-fetus penetration; Mice; Pralidoxime; CNS penetration; Blood-placenta transfer

Received: January 16, 2016; Revised: March 10, 2016; Published: June 14, 2016  Show citation

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Ojha, S., Nurulain, S.M., Dhanasekaran, S., Shafiullah, M., Adem, A., Sharma, C., Kuča, K., & Kalasz, H. (2016). BLOOD-FETUS PENETRATION OF PRALIDOXIME. MMSL, 85(2), 63-68. doi: 10.31482/mmsl.2016.012
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