A novel approach to medical countermeasures against organophosphorus compound toxicity

Wang,Tian; Wang,Yucun; Zhang,Leiming; Han,Bing; Wang,Hongbo; Li,Youxin; Fu,Fenghua

doi:10.3892/br.2013.172

November-December 2013 Volume 1 Issue 6

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November-December 2013 Volume 1 Issue 6

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Article

A novel approach to medical countermeasures against organophosphorus compound toxicity

Authors:
- Tian Wang
- Yucun Wang
- Leiming Zhang
- Bing Han
- Hongbo Wang
- Youxin Li
- Fenghua Fu
View Affiliations / Copyright

Affiliations: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China, Division of Gastroenterology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China
Pages: 901-906
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Published online on: September 25, 2013

https://doi.org/10.3892/br.2013.172
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Abstract

The toxicity of organophosphorus compounds (OPs) results primarily from the irreversible inhibition of acetylcholinesterase (AChE). Huperzine A (HupA) is a reversible inhibitor of AChE and HupA sustained‑release microspheres (HSMs) steadily release HupA, resulting in the continual inhibition of AChE activity for 14 days in mice. The present study aimed to investigate the preventive effects of HSMs on the toxicity of methyl parathion (MP). The mice were pretreated with HSMs followed by MP exposure. Subsequently, the median lethal dose (LD50) and survival of the mice were determined. a histopathological examination of the brain, liver, lungs, heart, kidneys and intercostal muscles was also performed. The results revealed that the LD50 was 51.4 mg/kg in the control group and 70.0, 67.5, 63.4 and 53.5 mg/kg at 2 h, 5, 10 and 15 days after pretreatment with HSMs, respectively. pretreatment with HSMs at 2 h, 5 days and 10 days prior to an acute challenge with 1.2 x LD50 MP was sufficient to counteract the lethality and acute toxicity of MP. HSM pretreatment also attenuated the pulmonary edema induced by MP. The results demonstrated that pretreatment with HSMs may be an effective method to counteract MP poisoning. To the best of our knowledge, the present study was the first to demonstrate that pretreatment with an AChE reversible inhibitor sustained‑release agent may be a novel approach to effective protection against OP toxicity.

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1	Soltaninejad K and Abdollahi M: Current opinion on the science of organophosphate pesticides and toxic stress: a systematic review. Med Sci Monit. 15:RA75–RA90. 2009.PubMed/NCBI
2	Bajgar J: Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv Clin Chem. 38:151–216. 2004. View Article : Google Scholar : PubMed/NCBI
3	Jia P, Wang Y, Yu M, et al: An organophosphorus hapten used in the preparation of monoclonal antibody and as an active immunization vaccine in the detoxication of soman poisoning. Toxicol Lett. 187:45–51. 2009. View Article : Google Scholar : PubMed/NCBI
4	Muggleton NG, Bowditch AP, Crofts HS, Scott EA and Pearce PC: Assessment of a combination of physostigmine and scopolamine as pretreatment against the behavioural effects of organophosphates in the common marmoset (Callithrix jacchus). Psychopharmacology (Berl). 166:212–220. 2003.PubMed/NCBI
5	Albuquerque EX, Pereira EF, Aracava Y, et al: Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents. Proc Natl Acad Sci USA. 103:13220–13225. 2006. View Article : Google Scholar : PubMed/NCBI
6	Ashani Y, Peggins JO III and Doctor BP: Mechanism of inhibition of cholinesterases by huperzine A. Biochem Biophys Res Commun. 184:719–726. 1992. View Article : Google Scholar : PubMed/NCBI
7	Wang C, Zhang T, Ma H, Liu J, Fu F and Liu K: Prolonged effects of poly(lactic-co-glycolic acid) microsphere-containing huperzine A on mouse memory dysfunction induced by scopolamine. Basic Clin Pharmacol Toxicol. 100:190–195. 2007. View Article : Google Scholar : PubMed/NCBI
8	Choi SC: Interval estimation of the LD₅₀based on an up-and-down experiment. Biometrics. 46:485–492. 1990. View Article : Google Scholar : PubMed/NCBI
9	Aracava Y, Pereira EF, Akkerman M, Adler M and Albuquerque EX: Effectiveness of donepezil, rivastigmine, and (+/−)huperzine A in counteracting the acute toxicity of organophosphorus nerve agents: comparison with galantamine. J Pharmacol Exp Ther. 331:1014–1024. 2009.
10	Lu L, Wang X, Lang L and Fu F: Protective effect of reduced glutathione on the liver injury induced by acute omethoate poisoning. Environ Toxicol Pharmacol. 30:279–283. 2010. View Article : Google Scholar : PubMed/NCBI
11	Munidasa UA, Gawarammana IB, Kularatne SA, Kumarasiri PV and Goonasekera CD: Survival pattern in patients with acute organophosphate poisoning receiving intensive care. J Toxicol Clin Toxicol. 42:343–347. 2004. View Article : Google Scholar : PubMed/NCBI
12	Tafuri J and Roberts J: Organophosphate poisoning. Ann Emerg Med. 16:193–202. 1987. View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

A novel approach to medical countermeasures against organophosphorus compound toxicity

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