PPAR-γ受体激活对百草枯中毒致大鼠急性肺损伤的保护作用

目的研究PPAR-γ受体激活对百草枯中毒致大鼠急性肺损伤的保护作用。方法 48只SD雄性大鼠随机平均分成3组,A组(百草枯中毒组):按照20 mg/kg剂量腹腔注射;B组(低剂量PPAR-γ受体激动剂罗格列酮预处理组):在给予百草枯腹腔注射前1 h腹腔注射3 mg/kg罗格列酮;C组(高剂量PPAR-γ受体激动剂罗格列酮预处理组):在给予百草枯腹腔注射前1 h腹腔注射10 mg/kg罗格列酮;D组(对照组):1 m L生理盐水腹腔注射。在注射百草枯后24 h和72 h时,每组取出6只,收集血清和肺组织标本。采用Elisa方法检测血清中IL-1β和TNF-α含量测定,行组织切片HE染色进行肺损伤评分,利用Western blot方法检测肺组织中caspase-3和AP-1蛋白表达水平,采用免疫组化方法检测caspase-3蛋白在肺组织中的表达。结果大鼠百草枯中毒后血清炎性细胞因子IL-1β和TNF-α含量明显增加。肺湿重/干重比以及肺损伤评分明显增加。罗格列酮预处理组可以减轻肺组织损伤程度,降低血清中IL-1β和TNF-α含量,减少肺组织中caspase-3和AP-1蛋白的表达。结论应用PPAR-γ激动剂罗格列酮可以抑制百草枯中毒大鼠肺组织中caspase-3和AP-1蛋白表达,抑制炎症反应和凋亡,对百草枯中毒导致急性肺损伤产生保护作用。     

肝X受体激活对全脑缺血/再灌注小鼠海马神经干细胞增殖及认知功能的影响

目的研究肝X受体激活对全脑缺血/再灌注(ischemia/reperfusion,I/R)小鼠的海马神经干细胞增殖及认知功能的影响,及其作用机制。方法将75只C57BL/6小鼠随机分为3组,即假手术组(Sham)、全脑缺血/再灌注组(I/R)、全脑缺血/再灌注+肝X受体激动剂TO901317干预组(I/R+TO90),每组25只。采用双侧颈总动脉夹闭方法建立全脑I/R小鼠模型;肝X受体激动剂TO901317(30 mg·kg^-1)在缺血后24 h腹腔注射(i.p,1次/天,连续14 d)。Morris水迷宫实验测定小鼠学习与记忆等认知功能的改变;HE染色观察小鼠海马CA1区病理形态学的改变;免疫组化观察小鼠海马齿状回区DCX阳性细胞的表达;免疫荧光观察海马齿状回区Brd U阳性细胞的表达;Western blot检测海马LXRα、LXRβ、ABCA1、p-ERK1/2、t-ERK1/2、p-CREB、tCREB、BDNF等蛋白的表达情况。结果LXR激动剂TO901317处理后,I/R小鼠的海马齿状回DCX与Brd U阳性细胞的表达数目均增加(P<0.01),认知功能得到了改善(P<0.01),同时,海马ABCA1、p-ERK1/2、p-CREB、BDNF等蛋白表达水平也上调(P<0.01)。结论肝X受体的激活促进了I/R小鼠海马齿状回颗粒下层神经干细胞的增殖和认知功能的改善,其机制可能与激活ERK1/2-CREB-BDNF信号通路,促进I/R小鼠海马DG区内源性神经发生有关。     

麦角甾醇对LPS诱导的肺损伤小鼠的抗炎作用研究

目的研究麦角甾醇对LPS诱导的小鼠急性肺损伤的抗炎作用研究。方法取50只雄性BABL/c小鼠随机分为5组:空白对照组、模型组、地塞米松组(2 mg/kg)、麦角甾醇低剂量组(20 mg/kg)、麦角甾醇高剂量组(40 mg/kg)。空白对照组和模型组按体积给予生理盐水,地塞米松组(2 mg/kg)、麦角甾醇组(20、40mg/kg)灌胃给予相应药物。给药1 h后,除空白对照组,其余各组小鼠气管滴注20μg LPS。检测小鼠肺干湿重比(W/D),肺泡灌洗液(BALF)中超氧化物歧化酶(SOD)水平、丙二醛(MDA)含量,血清与肺泡灌洗液炎性细胞因子(TNF-α、IL-1β、IL-6)水平。取各组小鼠肺组织做HE染色,并检测肺组织Rho、ROCK1、ROCK2、p-NF-κBP65、NF-κBP65、p-IκBα、IκBα蛋白表达。结果麦角甾醇20、40 mg/kg能显著提升LPS诱导的急性肺损伤小鼠血清SOD水平,降低MDA含量;改善血清及肺泡灌洗液炎症因子水平和肺组织病理学改变;降低肺组织Rho、ROCK1、ROCK2、p-NF-κBP65、p-IκBα蛋白表达。结论麦角甾醇对LPS诱导的急性肺损伤小鼠有保护作用,其作用可能与Rho/ROCK/NF-κB信号通路有关。     

罗格列酮对百草枯致大鼠肺损伤的炎症抑制作用

目的：研究罗格列酮对百草枯致大鼠肺损伤过程中的炎症抑制作用机制。方法将72只SD雄性大鼠随机分成3组,每组24只。模型对照组：腹腔注射百草枯20 mg·kg-1;罗格列酮组：腹腔注射百草枯前1 h,腹腔注射罗格列酮10 mg·kg-1;空白对照组：腹腔注射0.9％氯化钠溶液1 mL。注射百草枯后4,8 h及1,3 d,收集各组大鼠血清和肺组织标本,组织切片苏木精-伊红( HE)染色进行肺损伤评分,采用酶联免疫吸附法( ELISA)检测血清白细胞介素-1β( IL-1β)和肿瘤坏死因子-α( TNF-α)含量,采用免疫组化方法检测NF-κB蛋白在肺组织的表达,利用Western blot法检测肺组织核因子-κB (NF-κB)和激活蛋白(AP-1)蛋白表达水平。结果模型对照组大鼠血清炎性细胞因子IL-1β和TNF-α含量明显增加。罗格列酮组肺组织损伤程度明显降低,血清IL-1β和TNF-α含量减少,肺组织NF-κB和AP-1蛋白的表达降低。结论罗格列酮可以抑制百草枯中毒大鼠肺组织NF-κB和AP-1蛋白表达,减少IL-1β和TNF-α分泌,对百草枯所致大鼠肺损伤炎症有抑制作用。     

百草枯中毒致小鼠肺纤维化模型的建立

目的探究百草枯中毒致小鼠肺纤维化模型的建立。方法无特定病原体级别(SPF)的BALB/c小鼠(6~8周龄,雄性,18~22 g)40只,分为A组(空白对照组)、B组(10 mg/kg百草枯单次染毒组)、C组(20 mg/kg百草枯单次染毒组)和D组(隔日1次百草枯染毒组,共3次),采用腹腔注射方式染毒观察至第21天取材,建立小鼠肺纤维化中毒模型。镜下观察组织HE染色变化和马松染色等纤维化改变和不同浓度的生存分析。结果20 mg/kg单次染毒组的小鼠HE染色和马松染色均显示纤维化改变,Ashcroft评分最高,肺组织上皮标志物和间质标志物的蛋白检测均显示有上皮间质改变。结论20 mg/kg腹腔注射单次给药至染毒后21 d的方法建立纤维化模型最好。     

辅助性T细胞17活化在百草枯致小鼠肺纤维化模型中的作用

目的 观察辅助性T细胞17(Th17)活化在百草枯致小鼠肺纤维化模型中的作用.方法 将30只C57BL/6小鼠随机分为对照组(10只)和百草枯中毒组(20只).百草枯中毒组经腹腔注射百草枯35 mg/kg建立小鼠中毒模型;对照组经腹腔注入等体积生理盐水.观察2组小鼠肺脏组织病理变化情况及肺纤维化评分,检测外周血Th17细胞、肺组织中维甲酸相关核孤儿受体γt(RORγt)基因及蛋白的表达情况.结果 百草枯中毒组肺平均内衬间隔、肺泡腔与肺总面积比高于对照组,平均肺泡数低于对照组,外周血Th17细胞阳性率高于对照组,肺组织中ROR-γtmRNA和蛋白表达水平高于对照组(P＜0.01).结论 百草枯致小鼠肺纤维化模型外周血及肺组织中Th17细胞明显活化,提示Th17细胞活化在百草枯致肺纤维化过程中起着重要作用.     

异钩藤碱对哮喘小鼠气道炎症的影响

目的 探讨异钩藤碱（IRN）调节单核细胞趋化蛋白1(MCP-1)/CC趋化因子受体2(CCR2)信号通路对哮喘小鼠气道炎症的影响。方法 通过注射和吸入卵清蛋白的方法建立哮喘小鼠模型，将造模成功后的小鼠随机分为哮喘组、IRN低剂量组（IRN-L组，灌胃10 mg/kg IRN）、IRN高剂量组（IRN-H组，灌胃20 mg/kg IRN）、IRN-H+CCL2组[灌胃20 mg/kg IRN+腹腔注射7.5 ng CC趋化因子配体（CCL2）]、阳性对照组（腹腔注射2 mg/kg地塞米松），并以注射和吸入无菌磷酸盐缓冲液的小鼠为空白对照组，每组10只。各药物组小鼠每天给予相应药物1次，连续给药2周。检测各组小鼠气道高反应指标——呼吸间歇（Penh）值，血清中肿瘤坏死因子α(TNF-α)、白细胞介素13(IL-13)、IL-4水平，支气管肺泡灌洗液中嗜酸性粒细胞（EOS）、淋巴细胞（LYM）和中性粒细胞（NEU）数量，肺组织中MCP-1、CCR2蛋白表达水平；观察肺组织病理学变化并进行炎症细胞浸润评分。结果 与空白对照组比较，哮喘组小鼠肺组织炎症细胞浸润较明显，并有细胞肿胀、脱落现象发生；...     

大容量全肺灌洗术对肺组织内百草枯清除作用的探讨

目的应用表面增强拉曼光谱法检测相关样品内百草枯含量,探究大容量全肺灌洗术对肺组织内百草枯清除效能。方法选用SPF级Wistar大鼠,60 mg/kg为染毒剂量,经口一次灌胃染毒制备动物模型,于染毒后相应时间点采血,行大容量全肺灌洗术留取肺泡灌洗液,留取肺组织。应用表面增强拉曼光谱法检测血浆、肺泡灌洗液及肺组织中百草枯含量,并进行统计分析。结果各时间点(1~168 h)血浆、肺泡灌洗液、肺组织匀浆中均检测到百草枯;染毒后1 h血浆、肺泡灌洗液中百草枯含量达峰值(分别是8 926.3±1 586.47和1 573.9±310.13 ng/ml),12 h肺组织中百草枯达峰值(13 642.2±1 242.66 ng/g),15h时肺泡灌洗液中百草枯含量出现第二高峰;各组灌洗侧(左侧)肺组织内百草枯浓度低于未灌洗侧(右侧),清除率为40%±12%。结论大容量全肺灌洗术对肺组织内百草枯有较高的清除效能,可作为清除肺组织内百草枯一项救治措施。     

百草枯中毒急性肺损伤的作用机制及丙酮酸乙酯干预研究

目的 探讨高迁移组蛋白B1(HMGB1)/Toll样受体4(TLR-4)在百草枯(PQ)中毒导致急性肺损伤作用机制及丙酮酸乙酯(EP)干预研究.方法 将90只SD大鼠均分为对照组、百草枯中毒组、丙酮酸乙酯治疗组,建立大鼠急性百草枯中毒动物模型后,分别于实验后的6、12、24、48 h、3 d每组随机处死6只大鼠,检测三组大鼠肺组织中肿瘤坏死因子-α(TNF-α)、HMGB1、白细胞介素-1(IL-1)和TLR-4mRNA变化;并测定三组大鼠血清中丙二醛(MDA)、超氧化物歧化酶(SOD)活性变化.结果 与对照组相比,PQ中毒组和EP治疗组染毒后6、12、24、48 h、3 d各时间点,肺组织TNF-α mRNA、HMGB1 mRNA、IL-1 mRNA、TLR-4 mRNA的表达量和丙二醛含量明显升高(均P<0.05),SOD 活力降低(均P<0.05);与PQ中毒组相比,EP治疗组在染毒后12、48 h时间点大鼠肺组织HMGB1 mRNA、TLR-4 mRNA、IL-1 mRNA、TNF-α mRNA表达量及血清MDA含量均降低(均P<0.05),血清SOD 活力均升高(均P<0.05).结论 百草枯中毒急性肺损伤的机制主要与氧化应激、细胞膜脂质过氧化及免疫系统炎症级联放大效应有关,丙酮酸乙酯可通过抑制该过程从而减轻急性肺损伤程度.     

肺灌洗对百草枯中毒家兔的治疗效果研究

目的探讨肺灌洗治疗百草枯(paraquat,PQ)中毒的效果。方法 18只家兔随机分为3个组:PQ染毒组,生理盐水(NS)对照组及PQ+肺灌洗组,每组6只。PQ染毒组给予50 mg/kg PQ一次性灌胃;NS对照组给予等体积0.9%NS一次性灌胃,24 h后给予5 ml 0.9%NS肺灌洗;PQ+肺灌洗治疗组给予50 mg/kg PQ一次性灌胃,24 h后给予等量0.9%NS肺灌洗。分别在染毒前及染毒后第1、3和7天取各组动物血标本并在染毒后7 d处死动物,进行血清中髓过氧化物酶(MPO)、羟脯氨酸(Hyp)、白介素1(IL-1)、肿瘤坏死因子α(TNF-α)的含量检测及肺组织病理学检查。结果PQ染毒组肺组织肉眼及光学显微镜检查表现为急性肺损伤;PQ+肺灌洗组肺组织病理改变表现为部分细支气管周围炎细胞浸润,小血管扩张充血。PQ染毒组MPO、IL-1、TNF-α含量染毒后1、3和7 d高于NS对照组,Hyp浓度染毒后3和7 d高于NS对照组;PQ+肺灌洗组血清MPO、TNF-α含量染毒后1、3和7 d均高于NS对照组,IL-1、Hyp染毒后3和7 d高于NS对照组;PQ+肺灌洗组MPO、Hyp、IL-1、TNF-α分别在染毒后1~7 d、7 d、3~7 d、1~3 d低于PQ染毒组,差异有统计学意义(P<0.05,P<0.01)。结论肺灌洗疗法可降低急性肺损伤的炎症反应,有利于改善家兔PQ中毒所致的肺损伤,延缓肺纤维化。     

The protective effect of C-phycocyanin on paraquat-induced acute lung injury in rats

To investigate the potential protective effect of C-phycocyanin (PC) on paraquat (PQ)-induced acute lung injury, rats were divided into control, PQ-treated and PQ + PC-treated groups. Rats in PQ-treated group were orally administered with 50 mg/kg PQ, and rats in PQ + PC-treated group were intraperitoneally injected with 50 mg/kg PC after administration of PQ. At 8, 24, 48 and 72 h after treatments, GSH-Px and SOD activities, MDA levels in plasma and BALF, HYP, NF-κB, IκB-α and TNF-α contents in lung tissues were measured. The pathological changes in lung were observed. After treatment with PC, the levels of MDA and the relative contents of NF-κB and TNF-α were significantly decreased, the activities of GSH-Px and SOD and the relative contents of IκB-α were significantly increased. The degree of rat lung damage was obviously reduced in PQ + PC-treated group. The results suggested that PC treatment significantly attenuated PQ-induced acute lung injury.     

不同剂量乌司他丁对急性百草枯中毒大鼠过氧化损伤的保护作用

目的：观察不同剂量乌司他丁（UTI）对急性百草枯（PQ）中毒大鼠过氧化损伤的保护作用。方法将50只SD大鼠随机分为5组,正常对照组（A）、PQ中毒组（B）、小剂量UTI治疗组（C）、中剂量UTI治疗组（D）、大剂量UTI治疗组（E）,每组10只。 B、C、D、E组大鼠采用PQ一次性灌胃染毒法（80mg/kg）复制PQ中毒肺损伤模型,A组采用等量生理盐水灌胃。灌胃30min后,C组腹腔注射UTI100KU/Kg,D组腹腔注射UTI300KU/Kg,E组腹腔注射UTI600KU/Kg,A、B组注射等量生理盐水。24h后检测血清丙二醛（MDA）、超氧化物歧化酶（SOD）浓度,观察各组大鼠的一般情况,蛋白含量变化。光镜下观察肺组织病理学变化,进行肺损伤评分。结果 C、D、E组和B组比较,大鼠血清MDA、SOD浓度,肺组织损伤病理评分存在显著差异（P〈0.05）,C、D、E组之间比较也有显著差异（P〈0.05）。结论大剂量UTI对急性PQ中毒大鼠过氧化损伤具有较强保护作用。     

The effect of amifostine, a cytoprotective agent, on paraquat toxicity in mice

Background

Paraquat (PQ) is a highly poisonous herbicide with a variety of toxic effects, most notably pulmonary fibrosis. In alveolar epithelial cells, it is converted to a PQ radical and subsequently generates other reactive species resulting in lipid peroxidation and cell destruction. Amifostine is a thiophosphate prodrug approved by the FDA for the prevention of toxicities associated with cisplatin and therapeutic radiation. When amifostine is converted to an active metabolite (WR-1065), it functions as an oxygen and DNA radical scavenger that has been shown to protect against lipoperoxidation. The aim of this study was to determine whether amifostine improves survival or lung injury resulting from PQ toxicity.

Methods

Swiss mice (n = 23 per group) were given an approximate LD₇₅ dose of PQ intraperitoneal (60 mg/kg). Thirty minutes prior to PQ injection, group 1 was pretreated with 200 mg/kg of amifostine subcutaneously (s.c.). Subsequent doses of amifostine at 75 mg/kg were administered 4 hours after PQ injection, and injections continued every 8 hours for a total of 6 doses (cumulative dose: 575 mg/kg). Four hours after PQ injection, group 2 received 200 mg/kg of amifostine subcutaneously. Subsequent doses of amifostine at 75 mg/kg were administered every 8 hours (cumulative dose: 575 mg/kg). Four hours after PQ injection, group 3 received 100 mg/kg of amifostine subcutaneously. Subsequent doses of amifostine at 30 mg/kg were administered every 8 hours (cumulative dose: 250 mg/kg). Group 4 received equivolume injections of sterile 0.9% saline s.c. at the same time intervals. We removed lungs from all mice for histologic analysis and injury scoring.

Results

The number of surviving mice in groups 1, 2, 3, and 4 were 17, 18, 17, and 17 respectively. The Kaplan-Meier with log rank analysis showed no differences in survival. Lung injury scores did not differ between treatment groups and the control group for either dead or surviving mice.

Conclusion

Amifostine does not appear to improve survival or lung injury due to PQ toxicity at the doses administered.     

依布硒啉对大鼠脂多糖诱导的急性肺损伤的保护作用

目的探讨依布硒啉对内毒素性急性肺损伤大鼠肺功能的保护作用及对肺组织中相关细胞因子表达的影响。方法健康雄性SD大鼠随机分成6组：正常对照组,模型组,地塞米松对照组,依布硒啉30、15和7.5 mg/kg治疗组。通过大鼠尾静脉注射脂多糖（5 mg/kg）建立急性肺损伤模型,治疗大鼠组于造模前30 min腹腔注射给药,对照组和模型组分别注入等量溶剂。造模后6 h,麻醉抽取动脉血并放血处死动物,检测动脉血氧分压（PaO2）和二氧化碳分压（PaCO2）,取肺组织,测定肺湿/干质量比,收集支气管肺泡灌洗液,检测其中总蛋白水平。分别检测肺组织中丙二醛（MDA）、TNF-α含量及核因子E2相关因子（Nrf2）蛋白表达。结果与模型组相比,依布硒啉15和30 mg/kg剂量组大鼠动脉血中PaO2明显增高、PaCO2明显降低,肺湿/干质量比降低,肺组织MDA和TNF-α含量显著减少,而Nrf2表达明显增高。结论依布硒啉对内毒素性急性肺损伤有一定保护作用,其机制可能与诱导Nrf2表达有关。     

Activation of liver X receptor enhances the proliferation and migration of endothelial progenitor cells and promotes vascular repair through PI3K/Akt/eNOS signaling pathway activation

Vascular endothelial injury is a major cause of many cardiovascular diseases. The proliferation and migration of endothelial progenitor cells (EPCs) play a pivotal role in endothelial regeneration and repair after vascular injury. Recently, liver X receptor (LXR) activation has been suggested as a potential target for novel therapeutic interventions in the treatment of cardiovascular disease. However, the effects of LXR activation on endothelial regeneration and repair, as well as EPC function, have not been investigated. In the present study, we demonstrate that LXRs, including LXRα and LXRβ, are expressed and functional in rat bone marrow-derived EPCs. Treatment with an LXR agonist, TO901317 (TO) or GW3965 (GW), significantly increased the proliferation and migration of EPCs, as well as Akt and eNOS phosphorylation in EPCs. Moreover, LXR agonist treatment enhanced the expression and secretion of vascular endothelial growth factor in EPCs. LXR agonists accelerated re-endothelialization in injured mouse carotid arteries in vivo. These data confirm that LXR activation may improve EPC function and endothelial regeneration and repair after vascular injury by activating the PI3K/Akt/eNOS pathway. We conclude that LXRs may be attractive targets for drug development in the treatment of cardiovascular diseases associated with vascular injury.     

异莲心碱对百草枯诱导的小鼠急性肺损伤及肺纤维化的保护作用(英文)

目的探讨异莲心碱对百草枯(PQ)诱导的小鼠急性肺损伤及肺纤维化是否有保护作用。方法一次性给不同剂量PQ分别制备小鼠急性肺损伤模型(45mg·kg-1,ip)和肺纤维化模型(100mg·kg-1,ig)。异莲心碱在给PQ前1 d开始给予至实验结束。实验分空白对照组、模型组(PQ)、单用异莲心碱组及异莲心碱治疗组(异莲心碱+PQ)。急性肺损伤模型组给予PQ后第8,24及48 h观察异莲心碱(20 mg.kg-1,ig,每天3次)对血浆及支气管肺泡灌洗液(BALF)中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及碱性磷酸酶(ALP)活性的影响。肺纤维化组给予PQ后14 d观察异莲心碱(10,20, 40 mg·kg-1,ig,每天2次)对肺组织羟脯氨酸含量、肺组织中转化生长因子β1(TGF-β1)及基质金属蛋白酶2(MMP-2)表达的影响。同时采用HE染色方法观察两模型在上述各时间点的肺组织病理变化。结果在急性肺损伤模型中,与空白组比较,模型组的肺组织出现充血、出血、炎性渗出及水肿等病变,血浆和BALF中的SOD活性明显下降,MDA水平明显升高,而血浆中的ALP活性显著升高;与模型组比较,异莲心碱治疗组的肺组织炎症反应减轻,血浆和BALF中SOD活性明显升高,血浆中ALP活性以及血浆和BALF中MDA含量明显降低;单用异莲心碱以上指标无明显作用。在肺纤维化模型中,一次性给PQ14 d后,与空白组比较,模型组肺组织出现肺间质增厚和胶原纤维增生等病理变化,肺组织中羟脯氨酸含量明显升高(2.44±0.33 )vs(1.26±0.10 )mg·g-1湿组织;与模型组比较,异莲心碱10, 20和40mg·kg-1治疗组间质炎症及肺纤维化病变有所改善,肺组织中羟脯氨酸含量显著减少分别为(2.11±0.21), (1.94±0.24)和(1.89±0.26)mg·g-1湿组织;与模型组比较,异莲心碱40mg·kg-1治疗组肺组织中TGF-β1和MMP-2的表达明显降低。结论异莲心碱对PQ诱导的急性肺损伤及肺纤维化具有一定的保护作用。     

Protective effects of intranasal curcumin on paraquot induced acute lung injury (ALI) in mice

Paraquot (PQ) is widely and commonly used as herbicide and has been reported to be hazardous as it causes lung injury. However, molecular mechanism underlying lung toxicity caused by PQ has not been elucidated. Curcumin, a known anti-inflammatory molecule derived from rhizomes of Curcuma longa has variety of pharmacological activities including free-radical scavenging properties but the protective effects of curcumin on PQ-induced acute lung injury (ALI) have not been studied. In this study, we aimed to study the effects of curcumin on ALI caused by PQ in male parke's strain mice which were challenged acutely by PQ (50 mg/kg, i.p.) with or without curcumin an hour before (5 mg/kg, i.n.) PQ intoxication. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for pathological and biochemical analysis after 48 h of PQ exposure. Curcumin administration has significantly enhanced superoxide dismutase (SOD) and catalase activities. Lung wet/dry weight ratio, malondialdehyde (MDA) and lactate dehydrogenase (LDH) content, total cell number and myeloperoxidase (MPO) levels in BALF as well as neutrophil infiltration were attenuated by curcumin. Pathological studies also revealed that intranasal curcumin alleviate PQ-induced pulmonary damage and pro-inflammatory cytokine levels like tumor necrosis factor-α (TNF-α) and nitric oxide (NO). These results suggest that intranasal curcumin may directly target lungs and curcumin inhalers may prove to be effective in PQ-induced ALI treatment in near future.     

Effect of paraquat on serum and lung angiotensin I converting enzyme (AICE) activity in beagle dogs

The purpose of this study was to examine the relationship between lung or serum angiotensin I converting enzyme (AICE) activity and lung damage due to the administration of paraquat (PQ) which develops into PQ toxicity. Our experimental animals consisted of 19 beagle dogs (1-1.5 years old) that were allocated, randomly, into 2 treatment group, consisting of 11 PQ-treated animals and a control group of 8 saline-treated animals. These canines were administered PQ dichloride sc at a dose of 1.0 mg/kg body weight (PQ group) or sc saline at a dose of 0.5 ml/kg body weight (control group) for 7 to 11 consecutive days; these are doses which had been shown to be toxic to lungs. If a decrease in the animal's body weight was detected, the administration of PQ to that dog was discontinued. Body weight loss was observed in 10 of the 11 dogs treated with PQ. Representative dogs were sacrificed on days 11, 25 and 180 for the determination of both serum and lung AICE activity. The PQ group experienced a reduction in lung AICE activity and an elevation in the serum AICE activity. These results suggest that PQ damaged the endothelial cells of the lung and releasing lung AICE into the circulating blood, which led to an elevated total AICE activity in the serum. This pattern suggested damage to endothelial cells, indicating that PQ produced either continuing or repeated reinjury to lungs. Only the lungs were injured; therefore AICE from the rest of the body would not be expected to contribute to our AICE measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

Docosahexaenoic acid (DHA) attenuated paraquat induced lung damage in mice

Context: Accumulating evidences have proposed the critical roles of oxidative stress in the etiology of lung injury caused by paraquat (PQ). Docosahexaenoic acid (DHA) is an essential n-3 polyunsaturated fatty acid (PUFA), which has been proved to possess prominent antioxidative and anti-inflammatory effects. Objective: The aim of this study was to evaluate effects of DHA against acute lung injury (ALI) induced by PQ in mice. Materials and methods: Male Kunming mice were randomly divided into three groups: control group, PQ group, and PQ+DHA group (n = 24). The mice of PQ+DHA group received 500 mg/kg bodyweight DHA by gavage daily for consecutive 14 days. On day 8, the mice in PQ and PQ+DHA groups received a single oral dose of 50 mg/kg bodyweight PQ. All the mice were sacrificed on day 15. The myeloperoxidase (MPO) activities, levels of the malondialdehyde (MDA) and glutathione (GSH), and the 4-hydroxynonenal (4-HNE) and MDA modified proteins of lung were investigated. Results: DHA treatment significantly increased the survival rate of mice treated with PQ. Pulmonary MPO activities and MDA contents were elevated in the mice of the PQ group, while the GSH level was reduced. Furthermore, levels of 4-HNE and MDA modified protein in lungs of the PQ group mice were significantly increased. All the above changes were significantly inhibited by DHA pretreatment. Morphological examination revealed that DHA effectively attenuated the hyperemia, edema of ALI induced by PQ. Conclusion: These results demonstrated that DHA could effectively attenuate PQ-induced ALI in mice probably via its antioxidant activity.     

The Role of Urotensin Receptors in the Paracetamol‐Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist

We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor‐alpha (TNF‐α) and IL‐1β and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre‐treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre‐treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti‐inflammatory effects on high‐dose PARA‐induced hepatotoxicity in mice.