title: A novel approach to medical countermeasures against organophosphorus compound toxicity.
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 LD50was 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 × LD50MP 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.
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Division of Gastroenterology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
authors.forename: Yucun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Leiming
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China ; State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies, Luye Pharma Group Ltd., Yantai, Shandong 264003, P.R. China.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education of China, School of Pharmacy, Yantai University, Yantai, Shandong 264005, P.R. China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
keywords: huperzine A; methyl parathion; toxicity