Intratracheally Administered Liposomal α-Tocopherol Protects the Lung against Long-Term Toxic Effects of Paraquat

Paraquat is a broad-spectrum herbicide known to produce lung injury via oxidative stress-mediated mechanisms. Different pharmacological strategies have been explored to reduce the formation of these reactive oxygen species and/or prevent their toxic effects in the treatment of paraquat poisoning. The present study was carried out to investigate whether the antioxidant (L-tocopherol, incorporated into liposomes and delivered directly to the lungs of rats, could protect the organ against the long-term toxic effects of paraquat.Plain liposomes (composed of dipalmitoylphosphatidylcholine, DPPC) or α-tocopherol liposomes (8 mg α-tocopherol/kg body weight) were administered intratracheally to animals 24 h prior to an intraperitoneal injection of paraquat dichloride (20 mg/kg) and rats wefe killed 0, 1, 4, 6, 8, 10, 12, 16, 19 or 24 days after paraquat treatment. Results of this study showed that lungs of animals treated with paraquat were extensively damaged,as evidenced by significant increases in lung weight and decreases in lung angiotensin converting enzyme (ACE) and alkaline phosphatase enzyme (AKP) activities. Moreover,paraquat treatme; resulted in a significant reduction in the number of neutrophils in the blood of rats with a concurrent increase in the pulmonary myeloperoxidase activity,suggestive of neutrophil infiltration in the lungs of treated animals. Pretreatment of rats with liposomes alone did not significantly alter the paraquat-induced changes of all parameters examined. On the other hand, pretreatment of rats with (t-tocopherol liposomes,24 h prior to paraquat challenge, attenuated paraquat-induced changes in ACE, AKP and myeloperoxidase activities but failed to prevent increases in lung weight. Thus, pretreatment of rats with liposome-associated α-tocopherol appears to protect the lung against some of the toxic effects of paraquat

The relationship between platelet endothelial cell adhesion molecule-1 and paraquat-induced lung injury in rabbits

BACKGROUND:Platelet endothelial cell adhesion molecule-1(PECAM-1),also known as CD31,is mainly distributed in vascular endothelial cells.Studies have shown that PECAM-1 is a very significant indicator of angiogenesis,and has been used as an indicator for vascular endothelial cells.The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury(ALI) and fibrosis in paraquat(PQ) induced lung injury in rabbits.METHODS:Thirty-six adult New Zealand rabbits were randomly divided into three groups(12rabbits in each group) according to PQ dosage:8 mg/kg(group A),16 mg/kg(group B),and 32 mg/kg(group C).After PQ infusion,the rabbits were monitored for 7 days and then euthanized.The lungs were removed for histological evaluation.Masson staining was used to determine the degree of lung fibrosis(LF),and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1.Pearson's product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF.RESULTS:Rabbits in the three groups showed apparent poisoning.The rabbits survived longer in group A than in groups B and C(6.47±0.99 days vs.6.09±1.04 days vs.4.77±2.04 days)(P<0.05).ALI score was lower in group A than in groups B and C(8.33±1.03 vs.9.83±1.17 vs.11.50±1.38)(P<0.05),and there was statistically significant difference between group B and group C(P=0.03).LF was slighter in group A than in groups B and C(31.09%±2.05%vs.34.37%±1.62%vs.36.54%±0.44%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.026).The PEACAM-1 expression was higher in group A than in groups B and C(20.31%±0.70%vs.19.34%±0.68%vs.18.37%±0.46%)(P<0.05),and there was statistically significant difference between group B and group C(P=0.017).Pearson's correlation analysis showed that the expression of PECAM-1 was negatively correlated to both ALI score(Coe=-0.732,P=0.001)and degree of LF(Coe=-0.779,P<0.001).CONCLUSIONS:The PECAM-1 expression significantly decreases in New Zealand rabbits after PQ poisoning,and the decrease is dose-dependent.The PECAM-1 expression is negatively correlated with ALI score and LF,showing a significant role in the development of lung injuries induced by PQ.

Determination of Paraquat in Human Serum by HPLC

目的：建立HPLC法测定人血清中百草枯含量。方法：色谱柱：Kromasil C18柱（200mm×4．6mm，5μm），流动相：乙腈-水（含0．03mol·L-1庚烷磺酸钠，0．24mol·L-1磷酸）=3：97（用三乙胺调pH至2．0）；检测波长258nm；柱温25℃；进样体积20μl；流速0．8ml·min-1。结果：百草枯在0．106—10．6mg·L-1浓度范围内线性关系良好（r=0．9993），最低检出浓度为0．065mg·L-1。高、中、低3种浓度样品绝对回收率〉89．4％，方法回收率〉94．4％，日内精密度RSD在0．12％～1．74％之间，日间精密度RSD在0．44％～2．89％之间。结论：该方法操作简便易行、灵敏度高、专属性强，适用于百草枯的人体血清浓度测定。

Acute lung injury mechanism and therapy induced by paraquat poisoning

Paraquat (PQ, methyl viologen) was widely used in agricultural production throughout the world in 1962 for its efficient herbicidal activity. PQ was also highly toxic drug. About 5 mL medicine including 20% paraquat was life-threatening that can cause poisoning. In 1966, some people died because of PQ poisoning. Most patients had acute respiratory distress syndrome after 2 wk, and 70% of them died due to the lack of effective detoxification drugs. Thus, it was particularly important to understand the pathogenesis of PQ poisoning and give some effective treatments. This article will review the toxicological mechanism and treatment on PQ poisoning of acute lung injury.

Advances in molecular mechanism of lung injury induced by paraquat poisoning

Paraquat is a bipyridine dichloride non-selective herbicide,which was widely used in the world in the last century.Now,paraquat is banned in most countries because of the extremely high lethality and the lack of specific detoxification drugs.However,death due to paraquat poisoning still occurs frequently,thus it is of great clinical significance to explore the molecular mechanism of paraquat poisoning and the detoxification drugs.Paraquat poisoning causes multiple dysfunction of the lung,liver,kidney,heart,and brain through complex molecular mechanisms.About the mechanism there are excessive inflammatory reaction theory,REDOX reaction imbalance theory,oxidative stress free radical damage theory,calcium overload theory,NO molecular damage and cell apoptosis theory,etc.For the treatment of paraquat poisoning,paraquat antibody,pathway target blocker and related factor antibody have been developed in recent years.Although certain effects have been achieved,the treatment efficiency has not been significantly improved.This paper summarized the mechanism of signal transduction pathways involved in lung injury induced by paraquat poisoning in order to provide a theoretical basis for further research.

离子对SPE-HPLC法检测生物检材中的百草枯

目的建立生物检材中百草枯的简便、快速、灵敏、可靠的高效液相色谱分析方法。方法生物检材酶解后,用以十二烷基三甲基溴化铵和十二烷基硫酸钠预处理过的C18固相柱萃取,HPLC/DAD进行分析。结果回收率81%～94%,检出限为1ng·mL-1,线性范围50ng·mL-1～1mg·mL-1,结论此方法适用于中毒生物检材中百草枯的检测。

HPLC荧光检测法测定SO_2吸入后小鼠脑、心和肺亚硫酸盐水平

为了探讨二氧化硫 (SO2 )吸入后是否可进入小鼠不同组织器官 ,运用高效液相色谱 (HPLC)荧光检测 (FD)法测定了SO2 动式吸入后雄性小鼠脑、心和肺组织中SO2 在体内的衍生物———亚硫酸盐含量 .组织匀浆液经还原、衍生和沉淀蛋白 ,取上清液进入色谱仪检测 .亚硫酸盐测定标准曲线在 0 12 6μg·mL- 1 ～ 12 6μg·mL- 1 有良好的线性关系 ,检测限为 0 0 4μg·mL- 1 (S N =3 ) ,测定方法的回收率在 97%～ 10 1%之间 ,日内和日间的精密度RSD低于 9% .分析结果表明 ,SO2 吸入后小鼠 3种器官组织中亚硫酸盐含量比对照组显著增加 (P <0 0 5 ) ,且与SO2 浓度呈明确的剂量效应关系 (r>0 92 ) .这说明SO2 被小鼠吸入后转化为亚硫酸盐并可分布到肺和其它器官如脑和心等 ,从而为SO2 是一种全身性毒物的观点提供支持 .此外 ,本文对HPLC荧光检测亚硫酸盐的方法作了改进 ,为研究SO2

HPLC法测定肺胀颗粒中橙皮苷和甘草苷的含量

建立同时测定肺胀颗粒中橙皮苷和甘草苷含量的方法。采用HPLC-UV法,Diamonsil C_（18）柱（4.6 mm×150 mm,5μm）,流动相为0.2%磷酸水溶液-乙腈,梯度洗脱,检测波长为283 nm,柱温为30℃,流速为1 mL/min。橙皮苷和甘草苷分别在3.812~114.36μg/mL和1.874~56.22μg/mL范围内线性关系良好,平均回收率分别为100.2%,98.87%,RSD分别为1.45%,1.15%。该法简便、准确、灵敏、重现性好,可用于肺胀颗粒中橙皮苷和甘草苷含量的同时测定。

HPLC在百草枯浓度检测中的应用研究

建立一种快速检测病人血清中百草枯浓度的方法。本文采用乙腈沉淀血液中蛋白,色谱柱为岛津vp-ODS柱,以乙腈-0.02 mol/L辛烷基磺酸钠(4∶6)为流动相,流速1.0 mL/min,PDA检测器,检测波长为258 nm,柱温25℃。结果是在0.1~100μg/mL范围内线性关系良好(r=0.999 3);回收率为94.87%~105.51%;精密度RSD值为3.08%,重复性RSD值为2.26%。以该色谱条件对某患者的血清进行检测,外标法计算得血清中百草枯浓度为5.91μg/mL。实验证明本方法蛋白沉淀完全,没有杂质峰干扰,出峰时间较早,灵敏度高,可快速检测病人血清中百草枯浓度,为临床治疗提供参考。

Effect of SP-A/B in lipoic acid on acute paraquat poisoning

BACKGROUND: This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poisoning after the treatment of metabolic antioxidant-lipoic acid and whether its influence was related to TNF-α.METHODS: Sixty-six male Sprage-Dawley rats were randomly divided into three groups: normal control group(NS group), 6 rats; paraquat poisoning group(PQ group), 30 rats; and paraquat+lipoic acid treatment group(LA group), 30 rats. The rats in the PQ and LA groups were subdivided into 3-, 6-, 12-, 24-, 48-hour subgroups, with 6 rats in each group. After the rats were sacrificed, lung tissue from the same part was taken from the rats. After HE staining, histological changes were observed in the tissue under a light microscope. Lung tissue was also taken to test the levels of superoxide dismutase(SOD) and malondialdehyde(MDA). Whole blood(0.8 mL) without anticoagulant was drawn from the tail vein of rats for the determination of the TNF-α level. The total RNA of the lung tissue was collected, and the Rt-PCR method was used to measure the levels of SP-A and SP-B mRNA.RESULTS: HE staining showed that histopathological changes were milder in the LA group than in the PQ group. There were significant differences in MDA and SOD levels between different intervals both in intergroups and intragroups except the 3-hour subgroup(P<0.01). Likewise, the significant differences in the levels of TNF-α were also present between the three groups and between different intervals(P<0.01). The significant differences in SP-A mRNA and SP-B mRNA amplification ratio were seen between the three groups at the same intervals(P<0.01), but the differences between different intervals in the PQ group were statistically significant(P<0.05). The differences between different intervals in the LA group were statistically significant(P<0.01).CONCLUSION: Lipoic acid in acute paraquat poisoning could diminish lung tissue damage by regulating directly tumor necrosis factor and indirectly the content of pulmonary surfactant so as to reduce pulmonary edema, improve lung compliance, and finally protect lung tissues.

HPLC法测定复方止咳清肺胶囊中有效成分含量的研究

首次采用高效液相色谱法对中药复方止咳清肺胶囊中的有效成分—芥子碱硫氰酸盐进行了含量测定研究,由此建立了该复方的HPLC法质量分析方法。

HPLC法检测人血浆中百草枯的浓度

目的:建立检测人血浆百草枯浓度的高效液相色谱方法。方法:流动相为乙腈-3 mmol·L^(-1) SDS-0.2%TFA(35:28:37),流速为1.0 ml·min^(-1),检测波长258 nm,柱温35℃,内标为卡马西平。用乙腈沉淀血浆蛋白处理后,进行高效液相色谱分析。结果:血浆百草枯在0.5～100.0 mg·L^(-1)范围内线性关系良好(r=0.999 8)。高、中、低三个浓度(1.00,10.00,50.00 mg·L^(-1))的相对回收率分别为(103.06±4.04)%,(100.20±3.00)%和(99.33±2.26)%;日内RSD分别为4.85%,5.97%和4.91%;日间RSD分别为6.60%,5.98%和4.10%。结论:本方法准确可靠,简便快速,适用于百草枯中毒患者的血药浓度检测。

HPLC法测定洋参保肺丸中甘草酸的溶出度

采用HPLC测定洋参保肺丸中甘草酸的溶出度。方法:采用AgiLent TC-C18色谱柱(4.6 mm×150mm,5μm),流动相为乙腈-0.2磷酸水溶液(41∶59),流速为0.8 mL·min-1,柱温为室温,检测波长为:254 nm,按中国药典桨法,采用ZRS-8G智能溶出仪,以50%的甲醇溶液为溶出介质测定溶出度。结果:甘草酸进样量在0.034～1.02μg(r=0.9999)在范围内线性关系良好;平均加样回收率(n=6)为98.72%,RSD分别为0.65%。样品溶出度均一性好,在45 min时甘草酸溶出度均达到75%以上。结论:本方法准确、快速,结果良好,适用于洋参保肺丸中甘草酸溶出度测定。

Lysine acetylsalicylate ameliorates lung injury in rats acutely exposed to paraquat

Background Paraquat （PQ）, an effective and widely used herbicide, has been proven to be safe when appropriately applied to eliminate weeds. However, PQ poisoning is an extremely frustrating clinical condition with a high mortality and with a lack of effective treatments in humans. PQ mainly accumulates in the lung, and the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. The aim of this study was to evaluate whether lysine acetylsalicylate （LAS） could protect the lung from the damage of PQ poisoning and to study the mechanisms of protection. Methods A model of PQ poisoning was established in 75 Sprague-Dawley rats by intragastric administration of 50 mg/kg PQ, followed by treatment with 200 mg/kg of LAS. The rats were randomly divided into sham, PQ, and PQ＋LAS groups, with 25 in each group. We assessed and compared the malonaldehyde （MDA） content, superoxide dismutase activity （SOD）, glutathion peroxidase （GSH-Px）, and catalase （CAT） in serum and lung and the hydroxyproline （HYP） content, pathological changes, apoptosis and expression of Bcl-2/Bax protein in lung of rats on days 1, 3, 7, 14 and 21 after PQ poisoning and LAS treatment. Results Compared to the PQ group rats, early treatment with LAS reduced the MDA and HYP contents, and increased the SOD, GSH-Px, and CAT activities in the serum and lung on days 1, 3, 7, 14, and 21 after PQ poisoning （all P〈0.05）. After early LAS treatment, the apoptotic rate and Bax expression of lung decreased, the Bcl-2 expression increased, and the Bcl-2/Bax ratio increased, compared to the PQ group rats. Furthermore, the pathological results of lungs revealed that after LAS treatment, early manifestations of PQ poisoning, such as hemorrhage, edema and inflammatory-cell infiltration, were improved to some degree, and collagen fibers in the pulmonary interstitium were also obviously reduced. Conclusion In this rat model of PQ poisoning, LAS effectively ameliorated the lung injury induced by PQ, possibly through antioxidation, anti-fibrosis, anti-apoptosis, and anticoagulation.

Can kissing cause paraquat poisoning: A case report and review of literature

BACKGROUND Paraquat is an effective,broad-spectrum,highly toxic quaternary ammonium herbicide.Paraquat poisoning has been reported frequently in recent years.It has severe lung,kidney,liver,and nervous system toxicity,and there is currently no specific antidote.Paraquat poisoning may follow ingestion,inhalation,and skin contact.There have been no previous reports of paraquat poisoning that resulted from kissing.This rare case provides a new reference for the prevention of paraquat poisoning.CASE SUMMARY A 27-year-old man came to the emergency department complaining that he had come into contact with paraquat by kissing his girlfriend,who had taken 80-120 mL 20%paraquat.After admission,his lung computed tomography(CT)showed increased lung markings.Redness and a burning sensation developed on his tongue,which progressed to painful erosions and coalescent ulcers.The final diagnosis was mild paraquat poisoning.Anti-inflammatory,antioxidant,and symptomatic treatment were initiated and continued for 7 d.Dyspnea did not occur,subsequent lung CT showed no significant changes,and the tongue pain was slightly improved.One month after discharge,the tongue injury was resolved.CONCLUSION This case indicated that the tongue and lung tissues are particularly vulnerable to paraquat toxicity,even after a limited exposure.

HPLC法测定小儿肺热咳喘口服液中连翘苷的含量

采用C18色谱柱(4.6mm×250mm,5μm),以乙腈-水(25∶75)为流动相,流速1.0ml.min-1,检测波长277nm,建立反相高效液相色谱法(HPLC)测定小儿肺热咳喘口服液中的连翘苷含量。结果表明,连翘苷在0.4132～4.132μg范围内与峰面积呈良好线性关系,r=0.9999,平均加样回收率为98.02%,RSD为1.24%(n=6)。本方法分离度好,干扰小,并具有良好的重复性,适用于小儿肺热咳喘口服液中连翘苷的含量测定。

Effects of hemoperfusion combined with hemodialysis on target organ damage in patients with acute paraquat poisoning

Objective: To investigate the effects of hemoperfusion combined with hemodialysis on target organ damage in patients with acute paraquat poisoning. Methods: A total of 42 patients with acute paraquat poisoning who were admitted and treated in our hospital between December 2013 and October 2017 were selected as the research subjects, and their therapies were reviewed and used to divide them into the control group (n=20) who received hemoperfusion alone and the combined treatment group (n=22) who received hemoperfusion combined with hemodialysis. The differences in the levels of liver and kidney function indexes in peripheral blood as well as lung function indexes in arterial blood were compared between the two groups of patients immediately after admission, after 1 d of treatment and after 3 d of treatment. Results: Immediately after admission, the differences in the levels of liver and kidney function indexes in peripheral blood as well as lung function indexes in arterial blood were not statistically significant between the two groups. After 1d of treatment and after 3 d of treatment, kidney function indexes Scr, BUN and β2-MG levels in peripheral blood of combined treatment group were lower than those of control group at corresponding time points respectively;liver function indexes ALT, AST, TB and ALP levels in peripheral blood were lower than those of control group at corresponding time points respectively;lung function indexes PaO2, BE and PCO3- levels in arterial blood were higher than those of control group at corresponding time points respectively whereas PaCO2 levels were lower than those of control group at corresponding time points respectively. Conclusion: Compared with hemoperfusion alone, hemoperfusion combined with hemodialysis is more advantageous in protecting the functions of liver, kidney, lungs and other target organs of patients with acute paraquat poisoning.

Protective effect of ghrelin against paraquatinduced acute lung injury in mice

Objective To measure the levels of ghrelin-induced expression or activation of nuclear factor erythroid 2-re-lated factor 2(Nrf2),heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1)in the PQ-injured lungs of mice and to evaluate the protective effect of ghrelin against paraquat(PQ)-induced acute lung injury in mice.Methods According to the random number table method,50 ICR mice of clean grade