Title: Dual functional antioxidant and butyrylcholinesterase inhibitors for the treatment of Alzheimer's disease: Design, synthesis and evaluation of novel melatonin-alkylbenzylamine hybrids Liu P, Cheng M, Guo J, Cao D, Luo J, Wan Y, Fang Y, Jin Y, Xie SS, Liu J Ref: Bioorganic & Medicinal Chemistry, 78:117146, 2023 : PubMed
Here, we have designed and synthesized a series of melatonin-alkylbenzylamine hybrids as multitarget agents for the treatment of Alzheimer's disease (AD). Most of them exhibited a potent multifunctional profile involving cholinesterase inhibition and antioxidant effects. Among these compounds, compound 5 was most the potent antioxidant (ORAC =5.13) and also an excellent selective inhibitor of BuChE (huBuChE IC(50)=1.20 microM, huAChE IC(50) = 177.49 microM, SIs= 147.91). Moreover, kinetic study indicated compound 5 was a mixed-type inhibitor for huBuChE. Furthermore, it could induce expression of the Nrf2 as well as its downstream markers at the protein level in cells. More importantly, compound 5 display no acute toxicity in mice at doses up to 2500 mg/kg. And we found compound 5 could improve memory function of scopolamine-induced amnesia mice. These results highlighted compound 5 as a possible hit molecule for further investigation of new anti-AD drugs.
Title: Design, Synthesis and Biological Evaluation of New 3,4-Dihydro-2(1H)-Quinolinone-Dithiocarbamate Derivatives as Multifunctional Agents for the Treatment of Alzheimer's Disease Guo J, Xu A, Cheng M, Wan Y, Wang R, Fang Y, Jin Y, Xie SS, Liu J Ref: Drug Des Devel Ther, 16:1495, 2022 : PubMed
BACKGROUND: Alzheimer's disease (AD) belongs to neurodegenerative disease, and the increasing number of AD patients has placed a heavy burden on society, which needs to be addressed urgently. ChEs/MAOs dual-target inhibitor has potential to treat AD according to reports. PURPOSE: To obtain effective multi-targeted agents for the treatment of AD, a novel series of hybrid compounds were designed and synthesized by fusing the pharmacophoric features of 3,4-dihydro-2 (1H)-quinolinone and dithiocarbamate. METHODS: All compounds were evaluated for their inhibitory abilities of ChEs and MAOs. Then, further biological activities of the most promising candidate 3e were determined, including the ability to cross the blood-brain barrier (BBB), kinetics and molecular model analysis, cytotoxicity in vitro and acute toxicity studies in vivo. RESULTS: Most compounds showed potent and clear inhibition to AChE and MAOs. Among them, compound 3e was considered to be the most effective and balanced inhibitor to both AChE and MAOs (IC(50)=0.28 microM to eeAChE; IC(50)=0.34 microM to hAChE; IC(50)=2.81 microM to hMAO-B; IC(50)=0.91 microM to hMAO-A). In addition, 3e showed mixed inhibition of hAChE and competitive inhibition of hMAO-B in the enzyme kinetic studies. Further studies indicated that 3e could penetrate the BBB and showed no toxicity on PC12 cells and HT-22 cells when the concentration of 3e was lower than 12.5 microM. More importantly, 3e lacked acute toxicity in mice even at high dose (2500 mg/kg, P.O.). CONCLUSION: This work indicated that compound 3e with a six-carbon atom linker and a piperidine moiety at terminal position was a promising candidate and was worthy of further study.
Title: A multi-target directed ligands strategy for the treatment of Alzheimer's disease: Dimethyl fumarate plus Tranilast modified Dithiocarbate as AChE inhibitor and Nrf2 activator Guo J, Cheng M, Liu P, Cao D, Luo J, Wan Y, Fang Y, Jin Y, Xie SS, Liu J Ref: Eur Journal of Medicinal Chemistry, 242:114630, 2022 : PubMed
Alzheimer's disease (AD) possessed intricate pathogenesis. Currently, multi-targeted drugs were considered to have the potential to against AD by simultaneously triggering molecules in functionally complementary pathways. Hence, a series of molecules based on the pharmacophoric features of Dimethyl fumarate, Tranilast, and Dithiocarbate were designed and synthesized. These compounds showed significant AChE inhibitory activity in vitro. Among them, compound 4c(2) displayed the mighty inhibitory activity to hAChE (IC(50) = 0.053 microM) and held the ability to cross the BBB. Kinetic study and molecular docking pointed out that 4c(2) bound well into the active sites of hAChE, forming steady and sturdy interactions with key residues in hAChE. Additionally, 4c(2) as an Nrf2 activator could promote the nuclear translocation of Nrf2 protein and induce the expressions of Nrf2-dependent enzymes HO-1, NQO1, and GPX4. Moreover, 4c(2) rescued BV-2 cells from H(2)O(2)-induced injury and inhibited ROS accumulation. For the anti-neuroinflammatory potential of 4c(2), we observed that 4c(2) could lower the levels of pro-inflammatory cytokines (NO, IL-6 and TNF-alpha) and suppressed the expressions of iNOS and COX-2. In particular, 4c(2) was well tolerated in mice (2500 mg/kg, p.o.) and efficaciously recovered the memory impairment in a Scopolamine-induced mouse model. Overall, these results highlighted that 4c(2) was a promising multi-targeted agent for treating AD.
Title: Preventive Effect of Limosilactobacillus fermentum SCHY34 on Lead Acetate-Induced Neurological Damage in SD Rats Long X, Wu H, Zhou Y, Wan Y, Kan X, Gong J, Zhao X Ref: Front Nutr, 9:852012, 2022 : PubMed
Lead poisoning caused by lead pollution seriously affects people's health. Lactic acid bacteria has been shown to be useful for biological scavenging of lead. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral Limosilactobacillus fermentum (L. fermentum) SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity. The L. fermentum SCHY34 showed competent results on in vitro survival rate and the lead ion adsorption rate. Animal experiments showed that L. fermentum SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue. Further, L. fermentum SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats, such as glutamate (Glu), monoamine oxidase (MAO), acetylcholinesterase (AchE), cyclic adenosine monophosphate (cAMP), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity, antioxidation, and anti-apoptotic in rat brain tissues were increased L. fermentum SCHY34 treatment, such as brain-derived neurotrophic factor (BDNF), c-fos, c-jun, superoxide dismutase (SOD)1/2, Nuclear factor erythroid 2-related factor 2 (Nrf2), and B-cell lymphoma 2 (Bcl-2), and so on. L. fermentum SCHY34 showed a great biological scavenging and potential effect on alleviating the toxicity of lead ions.
Title: Highly stable acetylcholinesterase electrochemical biosensor based on polymerized ionic liquids microgel for pesticides detection Wan Y, Wang H, Zhang L, Chen Y, Li S, Zhou J, Zhang Q, Xia L Ref: Mikrochim Acta, 189:300, 2022 : PubMed
A highly stable electrochemical biosensor for pesticide detection was developed. For the first time polymeric ionic liquids (PILs) were introduced to construct an acetylcholinesterase (AChE) biosensor . AChE was entrapped in PILs microspheres through an emulsion polymerization reaction, where negatively charged Au nanoparticles (Au NPs) can be immobilized by the positively charged PILs, leading to improved catalytic performance. The results suggest that the positively charged PILs not only provide a biocompatible microenvironment around the enzyme molecule, stabilizing its biological activity and preventing its leakage, but also act as a modifiable interface allowing other components with electron transport properties to be loaded onto the polymer substrate, thus providing an efficient electron transport channel for the entrapped enzyme. More notably, when AChE was immobilized in a positively charged environment, the active site is closer to the electrode, promoting faster electron transfer. The detection limits of the constructed electrochemical biosensor AChE@PILs@Au NPs/GCE toward carbaryl and dichlorvos (DDVP) were 5.0 x 10(-2) ng ml(-1) and 3.9 x 10(-2) ng ml(-1), in a wide linear range of 6.3 x 10(-2)-8.8 x 10(2) ng ml(-1) and 1.3 x 10(-1)-1.4 x 10(3) ng ml(-1), respectively. More importantly, the biosensor has high thermal and storage stability, which facilitates rapid field analysis of fruits and vegetables in a variety of climates. In addition, the biosensor reported has good repeatability and selectivity and has high accuracy in the analysis of peaches, tap water, and other types of samples.
Title: The Role of Cholinesterase in Differential Diagnosis between Gastric Cancer and Benign Gastric Diseases Gao H, Wan Y, Fan X, Dong Y, Ji X, Song W Ref: Clin Lab, 67:, 2021 : PubMed
BACKGROUND: Gastric cancer is the fifth most common malignancy worldwide. In early stages, no obvious symptoms are usually observed in gastric cancer patients, and it is especially hard to distinguish gastric cancer from benign gastric diseases, resulting in delayed diagnosis and poor prognosis. Common biomarkers of gastric cancer, such as CEA and CA19-9, are also elevated in benign diseases. There is an urgent need to develop a convenient and reliable biomarker for differentiating between gastric cancer and benign gastric diseases. METHODS: This study retrospectively analyzed the data of 126 patients, including 73 gastric cancer patients and 53 benign gastric disease patients. Patient characteristics collected for analysis included age, gender, laboratory data, and clinical staging. Unpaired t-test was used to check the difference of cholinesterase level between the gastric cancer group and the benign gastric disease group. Kruskal Wallis H test and Mann-Whitney U test were used to check the difference of cholinesterase level among different stage groups. Receiver operating characteristic (ROC) curve was used to assess whether cholinesterase level can be used as a biomarker for differentiating between gastric cancer and benign gastric diseases. RESULTS: Serum cholinesterase level was decreased significantly in the gastric cancer group in comparison to that of the benign gastric disease group (p < 0.001). In addition, cholinesterase level of stage IV patients was significantly lower than stage I patients. ROC curve analysis revealed that with a cutoff of 5,969.00 U/L, cholinesterase level showed an area under the curve of 0.819 (95% CI 0.732 - 0.905, p < 0.001) in differentiating between gastric cancer and benign gastric diseases. No significant difference in the levels of CEA and CA19-9 was observed between gastric cancer patients and benign gastric disease patients. CONCLUSIONS: This study indicated that serum cholinesterase level could be considered as a potential biomarker for differentiating between gastric cancer and benign gastric diseases.
Title: Inhibitory Effect of Lactococcus lactis subsp. lactis HFY14 on Diphenoxylate-Induced Constipation in Mice by Regulating the VIP-cAMP-PKA-AQP3 Signaling Pathway Tan Q, Hu J, Zhou Y, Wan Y, Zhang C, Liu X, Long X, Tan F, Zhao X Ref: Drug Des Devel Ther, 15:1971, 2021 : PubMed
AIM: The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special. Lactococcus lactis subsp. lactis HFY14 (LLSL-HFY14) is a new lactic acid bacterium isolated from naturally fermented yak yogurt. The purpose of this study was to study the inhibitory effect of the bacterium on constipation. METHODS: Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay. RESULTS: Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner. CONCLUSION: LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.
Title: Design, synthesis, and biological evaluation of novel xanthone-alkylbenzylamine hybrids as multifunctional agents for the treatment of Alzheimer's disease Zhang Z, Guo J, Cheng M, Zhou W, Wan Y, Wang R, Fang Y, Jin Y, Liu J, Xie SS Ref: Eur Journal of Medicinal Chemistry, 213:113154, 2021 : PubMed
In this study, a series of multifunctional hybrids against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of xanthone and alkylbenzylamine through the alkyl linker. Biological activity results demonstrated that compound 4j was the most potent and balanced dual ChEs inhibitor with IC(50) values 0.85 microM and 0.59 microM for eeAChE and eqBuChE, respectively. Kinetic analysis and docking study indicated that compound 4j was a mixed-type inhibitor for both AChE and BuChE. Additionally, it exhibited good abilities to penetrate BBB, scavenge free radicals (4.6 trolox equivalent) and selectively chelate with Cu(2+) and Al(3+) at a 1:1.4 ligand/metal molar ratio. Importantly, after assessments of cytotoxic and acute toxicity, we found compound 4j could improve memory function of scopolamine-induced amnesia mice. Hence, the compound 4j can be considered as a promising lead compound for further investigation in the treatment of AD.
Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy.
BACKGROUND: Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention. METHODS: Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised. RESULTS: A total of 44676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). INTERPRETATION: Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.
Title: Structural Basis of Fullerene Derivatives as Novel Potent Inhibitors of Protein Acetylcholinesterase without Catalytic Active Site Interaction: Insight into the Inhibitory Mechanism through Molecular Modeling Studies Wan Y, Guan S, Qian M, Huang H, Han F, Wang S, Zhang H Ref: J Biomol Struct Dyn, :1, 2019 : PubMed
Acetylcholinesterase (AChE) is an important kind of esterase that plays a key biological role in the central and peripheral nervous system. Recent research has demonstrated that some fullerene derivatives serve as a new nanoscale-class of potent inhibitors of AChE, but the specific inhibition mechanism remains unclear. In the present article, several molecular modeling methods, such as molecular docking, molecular dynamics simulations, and molecular mechanics/generalized Born surface area calculations, were used for the investigation of the binding mode and inhibition mechanism of fullerene inhibitions for AChE. Results revealed that fullerene inhibitors block the entrance of substrates by binding with the peripheral anionic site (PAS) region. Thus, fullerene derivatives might mainly serve as competitive inhibitors. The - interactions of a fullerene backbone with AChE are at the same level in different single side chain systems and seem to be related to the length or aromaticity of the side chain. The inhibitor with multi hydroxyl side chains shows an obviously large electrostatic interaction as it forms additional hydrogen bonds with AChE. Moreover, fullerene derivatives might exhibit noncompetitive inhibition partly by affecting some secondary structures around them. Thus, the destructions of these secondary structures can lead to conformational changes in some important regions, such as the catalytic triad and acyl pocket. The investigation is of great importance to the discovery of good fullerene inhibitors.
Title: Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant Liu Y, Wan Y, Zhu J, Yu Z, Tian X, Han J, Zhang Z, Han W Ref: Int J Mol Sci, 19:, 2018 : PubMed
Zearalenone hydrolase (ZHD) is the only reported alpha/beta-hydrolase that can detoxify zearalenone (ZEN). ZHD has demonstrated its potential as a treatment for ZEN contamination that will not result in damage to cereal crops. Recent researches have shown that the V153H mutant ZHD increased the specific activity against alpha-ZOL, but decreased its specific activity to beta-ZOL. To understand whyV153H mutation showed catalytic specificity for alpha-ZOL, four molecular dynamics simulations combining with protein network analysis for wild type ZHD alpha-ZOL, ZHD beta-ZOL, V153H alpha-ZOL, and V153H beta-ZOL complexes were performed using Gromacs software. Our theoretical results indicated that the V153H mutant could cause a conformational switch at the cap domain (residues Gly161(-)Thr190) to affect the relative position catalytic residue (H242). Protein network analysis illustrated that the V153H mutation enhanced the communication with the whole protein and residues with high betweenness in the four complexes, which were primarily assembled in the cap domain and residues Met241 to Tyr245 regions. In addition, the existence of alpha-ZOL binding to V153H mutation enlarged the distance from the OAE atom in alpha-ZOL to the NE2 atom in His242, which prompted the side chain of H242 to the position with catalytic activity, thereby increasing the activity of V153H on the alpha-ZOL. Furthermore, alpha-ZOL could easily form a right attack angle and attack distance in the ZHD and alpha-ZOL complex to guarantee catalytic reaction. The alanine scanning results indicated that modifications of the residues in the cap domain produced significant changes in the binding affinity for alpha-ZOL and beta-ZOL. Our results may provide useful theoretical evidence for the mechanism underlying the catalytic specificity of ZHD.
Title: Characterization of a Lipase From the Silkworm Intestinal Bacterium Bacillus pumilus With Antiviral Activity Against Bombyx mori (Lepidoptera: Bombycidae) Nucleopolyhedrovirus In Vitro Liu R, Wang W, Liu X, Lu Y, Xiang T, Zhou W, Wan Y Ref: J Insect Sci, 18:, 2018 : PubMed
To investigate whether Bombyx mori Linnaeus (Lepidoptera: Bombycidae) intestinal microorganism play a role in the host defence system against viral pathogens, a lipase gene from the silkworm intestinal bacterium Bacillus pumilus SW41 was characterized, and antiviral activity of its protein against B. mori nucleopolyhedrovirus (BmNPV) was tested. The lipase gene has an open-reading frame of 648 bp, which encodes a 215-amino-acid enzyme with a 34-amino-acid signal peptide. The recombinant lipase (without signal peptide) was expressed and purified by using an Escherichia coli BL21 (DE3) expression system. The total enzyme activity of this recombinant lipase reached 277.40 U/mg at the optimum temperature of 25 degrees C and optimum pH value of 8.0. The antiviral test showed that a relative high concentration of the recombinant lipase reduced BmNPV infectivity in vitro, which resulted in decreased viral DNA abundance and viral occlusion bodies. Besides, the preincubation method also suggested that the lipase probably directly acting on the budded virions. The results suggest that the lipase from intestinal bacterium B. pumilus SW41 is a potential antiviral factor for silkworm against BmNPV.
The recently reported Middle East respiratory syndrome coronavirus (MERS-CoV) is phylogenetically closely related to the bat coronaviruses (BatCoVs) HKU4 and HKU5. However, the evolutionary pathway of MERS-CoV is still unclear. A receptor binding domain (RBD) in the MERS-CoV envelope-embedded spike protein specifically engages human CD26 (hCD26) to initiate viral entry. The high sequence identity in the viral spike protein prompted us to investigate if HKU4 and HKU5 can recognize hCD26 for cell entry. We found that HKU4-RBD, but not HKU5-RBD, binds to hCD26, and pseudotyped viruses embedding HKU4 spike can infect cells via hCD26 recognition. The structure of the HKU4-RBD/hCD26 complex revealed a hCD26-binding mode similar overall to that observed for MERS-RBD. HKU4-RBD, however, is less adapted to hCD26 than MERS-RBD, explaining its lower affinity for receptor binding. Our findings support a bat origin for MERS-CoV and indicate the need for surveillance of HKU4-related viruses in bats.
Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, a cause of considerable world wide economic losses in the swine industry. We sequenced the complete genome of A. pleuropneumoniae, JL03, an isolate of serotype 3 prevalent in China. Its genome is a single chromosome of 2,242,062 base pairs containing 2,097 predicted protein-coding sequences, six ribosomal rRNA operons, and 63 tRNA genes. Preliminary analysis of the genomic sequence and the functions of the encoded proteins not only confirmed the present physiological and pathological knowledge but also offered new insights into the metabolic and virulence characteristics of this important pathogen. We identified a full spectrum of genes related to its characteristic chemoheterotrophic catabolism of fermentation and respiration with an incomplete TCA system for anabolism. In addition to confirming the lack of ApxI toxin, identification of a nonsense mutation in apxIVA and a 5'-proximal truncation of the flp operon deleting both its promoter and the flp1flp2tadV genes have provided convincing scenarios for the low virulence property of JL03. Comparative genomic analysis using the available sequences of other serotypes, probable strain (serotype)-specific genomic islands related to capsular polysaccharides and lipopolysaccharide O-antigen biosyntheses were identified in JL03, which provides a foundation for future research into the mechanisms of serotypic diversity of A. pleuropneumoniae.
Sodium pentachlorophenate (Na-PCP) has been used in China for years as an molluscacide to kill oncomelania, which is an intermediate host of Schistosome. To evaluate the effects of its long-term successive usage on environment, human exposure and health, studies were carried out in Sichuan, Jiangxi, Jiangsu and Fujian provinces, with a time gap of more than one month between sample collection and last spray of Na-PCP. Results indicated that PCP contents in surface water, soil, sediment, animals and plants were significantly higher in studied areas than in control areas. The daily intake and the content in urine of PCP were also sigificantify higher in studied areas. But, there was no difference on physical and biochemical examinations except that a 22%-28% decrease of blood cholinesterase activity was found in studied areas. The health effect of impurities in Na-PCP, dioxins and furans, was assessed and discussed.
