灵芝孢子粉多糖对APAP肝损伤的保护作用研究

目的:探讨灵芝孢子粉多糖(Ganoderma lucidum spore polysaccharide,GLSP)在对乙酰氨基酚(Aceta-minophen,APAP)肝损伤中的保护作用。方法:将50只小鼠随机分为五组,分别为空白组、模型组、阳性药物组、GLSP低剂量组和GLSP高剂量组,每组10只,各组按相应剂量连续14 d预给药后,使用APAP造模、取材,测定肝脏指数、血清指标(谷草转氨酶(glutamic oxalacetic transaminase,AST)、谷丙转氨酶(glutamic-pyruvic transaminase,ALT))及肝组织匀浆指标(谷胱甘肽(glutathione,GSH)、丙二醛(malonaldehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、Caspase-3、Bax和Bcl-xl)。结果:与空白组相比,模型组中ALT、AST、MDA及促凋亡基因Caspase-3、Bax均极显著升高(P<0.01),SOD、GSH含量极显著降低(P<0.01),HE染色结果显示APAP处理的小鼠肝脏出现典型的小叶中心性坏死;多糖剂量组与模型组相比ALT、AST极显著降低(P<0.01),多糖低剂量组SOD、GSH显著升高(P<0.05),MDA显著降低(P<0.05),在多糖高剂量组中,SOD、GSH极显著升高(P<0.01),MDA极显著降低(P<0.01),多糖组促凋亡基因Caspase-3、Bax极显著降低(P<0.01),且肝组织病理学观察中可见肝组织坏死面积减小。结论:灵芝孢子粉多糖对APAP肝损伤能够起到预保护作用,其作用机制可能与提高肝脏的抗氧化能力和抑制凋亡的发生有关。

波棱瓜子总木脂素对APAP诱导肉鸡急性肝损伤的保护作用

为探究波棱瓜子总木脂素提取物对对乙酰氨基酚(acetaminophen,APAP)所致鸡肝损伤的保护作用,将50只白羽肉鸡分为溶媒对照组(0.5%羧甲基纤维素钠)、APAP模型对照组、波棱瓜子总木脂素低(50 mg/kg)、中(100 mg/kg)、高(200 mg/kg)剂量组。各组受试鸡均灌胃相应溶媒或药物,连续7 d,于末次给药后2 h,除溶媒对照组外,其余各组受试鸡腹腔注射400 mg/kg APAP进行急性肝损伤造模。APAP造模16 h后对受试动物进行肝脏系数和血清的生化指标测定,HE组织病理切片观察肝组织损伤情况。结果显示,与APAP模型对照组比较,波棱瓜子总木脂素各剂量组的肝脏系数显著降低(P<0.01),血清谷草转氨酶(AST)含量明显下降(P<0.01),血清谷丙转氨酶(ALT)含量明显下降(低、高剂量组P<0.05,中剂量组P<0.01)。组织病理学检查结果显示,波棱瓜子总木脂素各剂量组肝细胞坏死的程度和范围比APAP模型对照组减轻。表明波棱瓜子总木脂素对APAP诱导的白羽肉鸡急性肝损伤具有一定的保护作用。

APAP诱导的肝损伤中的线粒体自噬

药物性肝损伤是我国非感染性肝病中的第二大类别,也是美国肝衰竭和肝移植的主要原因。从机理上讲,药物性肝损伤可分为直接型(即剂量依赖型、内在型和可预测型)、特异型(大多数与剂量无关、特异型和不可预测型)两种主要类型。在临床前研究中,大多数药物引发的非特异性肝毒性通常会被及时发现,因此不会进一步用于临床应用,然而,有一个例外情况,那就是对乙酰氨基酚(扑热息痛,APAP)在正常治疗剂量下,这种药物是安全可靠的,但一旦超过建议用量,可能会对肝脏造成严重的危害,甚至有可能引发急性肝衰竭。在正确使用下,它对患者的健康有积极的影响,但滥用或过量使用则可能带来可怕的后果,特别是对肝脏健康的影响。在发达国家如欧美,过量服用APAP是引发急性肝衰竭的主要因素。氧化应激是APAP诱导的肝脏致病性中一个关键的起始事件,线粒体自噬已被证明可促进生存并在抗氧化反应中发挥关键作用。因此,深入探讨APAP所引发的肝损害机制,以及线粒体自噬在对乙酰氨基酚诱导的肝损害中的保护机制,有助于有针对性地开发用于干预肝损伤进程的治疗目标和计划。

The Protective Effect of Moringa oleifera Leaves Extract on Paracetamol Hepatotoxicity in Male Rats

In recent years, there has been an increase in concern regarding the effects of paracetamol poisoning on liver tissues, particularly when consumed in large amounts. Some studies have estimated that paracetamol is involved in 56% of acute liver diseases, whereas 0.4% of paracetamol overdose cases result in fatal-ity. In this study, the effects of Moringa oleifera on paracetamol toxicity in the liver were explored. It has been demonstrated that Moringa oleifera is highly nu-tritious, contains bioactive molecules, and is therapeutically beneficial. Many studies have shown that Moringa oleifera leaves possess a wide range of biologi-cal properties, including antioxidant, tissue protection, analgesic, antihyperten-sive, and immunomodulatory activities. This study highlights the protective role of Moringa oleifera on handling possible paracetamol hepatotoxicity in male rats. .

一种改进的APAP影像匹配算法

针对无人机影像匹配时易出现影像重影、透视失真和耗时较长等问题,本文提出了一种改进的APAP算法。该算法首先利用SIFT算法选取特征点,通过改进RANSAC算法去除误匹配点;然后根据APAP算法对影像进行网格划分,求每个网格的单应性矩阵,并对单应性矩阵进行线性化;最后根据线性化的单应性矩阵进行影像匹配,单应性矩阵的线性化不仅对影像匹配时产生的重影现象有较好的削弱作用,而且能减少非重叠区域的透视失真。试验结果表明,本文方法在匹配效率和匹配效果方面效果显著。

民族药马蹄金石油醚提取物对CCl_4、APAP致小鼠急性肝损伤的保护作用

目的:探讨马蹄金石油醚提取物对四氯化碳(CCl4)、扑热息痛(APAP)致小鼠急性肝损伤的保护作用。方法:用CCl4、APAP造成小鼠急性肝损伤,连续灌胃马蹄金石油醚提取物8 d后,测定小鼠血清酶学、甘胆酸等相关指标,并观察肝脏病理切片变化。结果:马蹄金石油醚提取物各剂量对CCl4、APAP引起小鼠血清转氨酶(ALT、AST)、碱性磷酸酶(ALP)升高呈不同程度降低作用,亦降低升高的血清甘胆酸(CG)含量,病理检查显示用药组肝损伤较模型组明显减轻。结论:马蹄金石油醚提取物对急性肝损伤小鼠具有一定的保护作用。

垂盆草总黄酮对APAP诱导小鼠肝损伤的保护作用

目的研究垂盆草总黄酮对对乙酰氨基酚(acetaminophen,APAP)所致小鼠肝损伤的保护作用及其可能的作用机制。方法将48只ICR雄性小鼠随机分为6组(n=8),正常对照组,模型组,阳性药物组(联苯双酯,300 mg/kg),垂盆草总黄酮低(150 mg/kg)、中(300 mg/kg)、高剂量组(600 mg/kg)。各组小鼠均灌胃相应药物或生理盐水,连续灌胃7 d,于第7天灌胃后1 h,除正常组外(腹腔注射生理盐水),其余各组均腹腔注射APAP 300 mg/kg进行肝损伤造模。APAP造模24 h后,采用相应的试剂盒测定肝组织和血清的生化指标,HE染色观察小鼠肝脏损伤情况,实时荧光定量PCR法检测Nrf2、HO⁃1 mRNA变化;Western blot法检测小鼠肝脏Nrf2、HO⁃1蛋白表达。结果垂盆草总黄酮降低了APAP诱导的ALT、AST、ALP、TBIL、LDH水平,降低肝脏指数和MDA水平,增加肝组织CAT、GSH水平以及SOD、GSH⁃PX活性;降低TNF⁃α、IL⁃1β、IL⁃6水平;明显改善肝脏组织病变;增加Nrf2、HO⁃1 mRNA和蛋白表达。结论垂盆草总黄酮对APAP诱导的肝损伤有一定的保护作用,其可能的作用机制是减少氧化应激和炎症反应。

Preparation of Cetyl-Chitosan Nanoparticles as Carriers for Paracetamol

Cetyl-chitosan, prepared by reacting chitosan with chlorocetane under alkaline condition, is soluble and spontaneously forms nanoparticles about 100 nm in diameter. Infrared spectra (IR) revealed that there was a substitution reaction mainly on the amine groups of chitosan (CS). By using paracetamol (PCTM) as a model drug, the balanced release concentration of PCTM in phosphate buffer solution (pH=7.4) can be decreased with the increase of degree of substitution alkyl and can be reduced effectively even under a lower PCTM loading.

人工远端肢体缺血再灌注对APAP诱导小鼠肝损伤的保护作用研究

目的研究人工远端肢体缺血再灌注预处理(R-IPC)和缺血再灌注后处理(R-IPOST)对对乙酰氨基酚(APAP)诱导小鼠肝损伤的保护作用。方法按随机数字表法将实验小鼠分为5组:正常对照组(不做任何处理)、假手术组(缺血再灌注处理前后腹腔注射1ml生理盐水)、APAP组(腹腔注射1ml APAP溶液)、R-IPC+APAP组(缺血再灌注预处理后腹腔注射1ml APAP溶液)、R-IPOST+APAP组(腹腔注射1ml APAP溶液后实施缺血再灌注后处理)。观察各组肝脏病理形态变化;检测各组血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性、肿瘤坏死因子-a(TNF-a)水平、白细胞介素-6(IL-6)水平;检测各组肝组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽酶(GSH)的水平和比较各指标组间差异。结果光镜下R-IPC+APAP组和R-IPOST+APAP组肝小叶结构破坏程度及炎性细胞浸润程度较APAP组均明显减轻。R-IPC+APAP组血清ALT,AST,TNF-a,IL-6和肝匀浆MDA含量均明显低于APAP组[(3742±519.7 U/L,3471±631.4U/L,264.8±70.4pg/ml,738.7±71.0 pg/ml,8.9±1.2nmol/mg.prot)vs(5564±621.7U/L,4647±813.9U/L,351.7±52.3pg/ml,929.7±140.6pg/ml,13.1±1.7nmol/mg.prot)],差异均有统计学意义(t=3.400~7.032,均P<0.05);R-IPC+APAP组肝匀浆SOD活性明显高于APAP组(11.0±1.9U/mg.prot vs 8.6±1.1U/mg.prot),差异有统计学意义(t=3.043,P<0.05);R-IPOST+APAP组血清ALT,AST,TNF-a,IL-6和肝匀浆MDA含量均明显低于APAP组[(3410±588.6 U/L,3546±499.5U/L,256.6±48.1pg/ml,775.4±98.4pg/ml,9.3±1.9nmol/mg.prot)vs(5564±621.7U/L,4647±813.9U/L,351.7±52.3pg/ml,929.7±140.6pg/ml,13.1±1.7nmol/mg.prot)],差异均有统计学意义(t=2.196~4.981,均P<0.05);R-IPOST+APAP组肝匀浆GSH活性明显高于APAP组(10.3±1.2U/mg.prot vs 7.9±0.6U/mg.prot),差异有统计学意义(t=3.702,P<0.05)。结论R-IPC和R-IPOST能降低APAP诱导的药物性肝损伤氧化应激和炎症反应程度,对肝功能具有保护作用。

解毒护肝方防治APAP致药物性肝损伤作用与肠道微生态的相关性探讨

目的:探讨解毒护肝方防治药物性肝损伤(DILI)的作用与肠道微生态的相关性。方法:60只C57BL/6N小鼠随机分为正常组、模型组、水飞蓟宾组及解毒护肝方低、中、高剂量组。采用对乙酰氨基酚(APAP)药液灌胃复制DILI模型,造模同时给予相应药物治疗,连续14 d。半自动生化仪检测血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBIL)和直接胆红素(DBIL)的含量或活性,苏木素-伊红(HE)染色法观察肝脏病理形态,16SrRNA测序法分析粪便中肠道菌群组成结构。结果:与正常组比,模型组小鼠血清中ALT、AST、DBIL、TBIL的含量或活性均显著升高(P<0.01),肝细胞内可见大量的嗜酸性变和炎性细胞浸润,Chao1、Observed species、Simpson和Shannon指数均显著降低(P<0.01或P<0.05),厚壁菌门、变形菌门相对丰度以及厚壁菌门/拟杆菌门(F/B)值均明显升高(P<0.01或P<0.05),拟杆菌门相对丰度明显降低(P<0.05)。与模型组比,解毒护肝方能显著改善肝组织病理损伤,显著降低血清中ALT、AST、DBIL、TBIL的含量或活性(P<0.01或P<0.05),显著升高Chao1、Observed species、Simpson、Shannon指数以及拟杆菌门相对丰度(P<0.01或P<0.05),显著降低厚壁菌门、变形菌门相对丰度以及F/B值(P<0.01)。相关性分析结果表明,厚壁菌门、变形菌门相对丰度与肝损伤标志物成正相关,而拟杆菌门相对丰度与肝损伤标志物成负相关。结论:解毒护肝方防治DILI的机制可能与改善肠道菌群失衡有关。

异甘草酸镁对APAP诱导的大鼠药物性肝损伤的保护作用

目的:探讨异甘草酸镁对APAP诱导的大鼠药物性肝损伤的保护作用。方法:收集56只SD大鼠,随机分成正常组、模型组、不同剂量异甘草酸镁组(12.5 mg/kg,25 mg/kg,50 mg/kg)、NAC组(40 mg/kg)、Cs A组(15 mg/kg),比较各组的效果。结果:异甘草酸镁能明显改善APAP诱导的大鼠药物性肝损伤的肝功能,各项生化指标均明显改善。结论:异甘草酸镁能够明显改善APAP诱导的大鼠药物性肝损伤,对治疗APAP诱导的大鼠药物性肝损伤有较大的临床意义。

西咯他唑对APAP诱导的小鼠急性肝损伤的保护作用研究

目的研究西洛他唑能否减轻APAP诱导的小鼠急性肝损伤。方法通过腹腔注射APAP诱导小鼠发生急性肝损伤,观察西洛他唑对肝损伤的作用时,从APAP腹腔注射前2天起给予小鼠腹腔注射西洛他唑(20 mg/kg/天)。检测APAP腹腔注射后12 h小鼠血清转氨酶ALT和AST、血清MDA的活性以及小鼠肝组织中GSSG/GSH比值、H_2O_2水平,并通过实时定量PCR法检测肝组织中炎症因子IL-6mRNA的表达水平。结果西洛他唑能显著降低APAP引起的血清转氨酶升高,表明西洛他唑对APAP诱导的急性肝损伤有明确的保护作用。和APAP单独处理组相比,西洛他唑显著降低肝组织中H_2O_2水平、下调GSSG/GSH比值以及部分降低血清MDA水平。西洛他唑明显抑制APAP引起的IL-6等炎症因子的表达上调,表明西洛他唑对APAP诱导的急性肝损伤的保护作用与其抗炎、抗氧化活性有关。结论西洛他唑能够保护APAP诱导的小鼠急性肝损伤;其保护作用可能与其抗炎、抗氧化活性有关。

基于APAP模型的大视差图像拼接算法

针对待拼接图像具有大视差时,重叠区域会出现重影和拼接效率较低等问题,提出一种基于改进ORB算法的大视差图拼接模型。首先构建尺度空间,借助FAST算法提取特征点并建立主方向,再对特征采样区域建立MLDB描述符,然后采用向量场一致性算法筛选内点,最后通过APAP模型完成配准拼接。实验表明,与ORB算法相比,改进ORB算法的鲁棒性更好,与SIFT算法和AKAZE算法相比,匹配速度更快;本算法拼接与GlobalHomography算法、传统APAP模型和AANAP模型相比,效率更高、拼接效果更好,符合视觉审美。

Investigation of hepatoprotective activity of Cyathea gigantea(Wall.ex.Hook.)leaves against paracetamol-induced hepatotoxicity in rats

Objective:To investigate the hepatoprotective activity of methanolic leaf extract of Cyathea gigantea(C.gigantea)against paracetamol induced liver damage in rats.Methods:The hepatoprotective activity for plant extract was investigated for paracetamol induced hepatoxicity in rats.Wislar albino rats of either sex were divided into five groups of 6 animals each and are given orally the following treatment for seven days.The normal control group was given 1%Na.CMC 1mL/kg bw,p.o.Paracetamol at dose of 1g/kg bw,p.o.was given as toxic dose for inducing hepatoloxicity.Silymarin(50mg/kg.p.o.) was given as reference standard.Two doses of C. gigantea extract i.e.,100 mg/kg.p.o.and 200 mg/kg,p.o.were tested for hepatoprotective activity. The treatment was given for seven days and after 24 h of last treatment blood was collected from retro-orbital plexus and analysed for various serum parameters like serum glutamic-oxaloacetic transaminase(SGOT),serum glutamic pyruvic transaminase(SGPT),alkaline phosphatase(ALP),total bilirubin(TB)and total protein(TP)in different groups.Results:The paracetamol intoxication lead to histological and biochemical deteriorations.The treatment with methanolic leaf extract of C.gigantea reduced the elevated levels of SCOT,SGPT,ALP,TB and also reversed the hepatic damage towards normal which further supports the hepatoprotective activity of leaf extract of C.gigantea.Conclusions:The methanolic extract of leaves of C.gigantea at doses of 100 mg/kg bw and 200 mg/kg bw have significant effect on liver of paracetamol induced hepatotoxicity model in rats.

Hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatocellular damage in Wistar albino rats

Objective:To evaluate the hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatic damage in rats.Methods:The plant material was shade dried, powdered and extracted with ethanol.Liv 52 and silymarin were used as standard drugs and 2%gum acacia as a control(vehicle).Alteration in the levels of biochemical markers of hepatic damage like AST,ALT,ALP and lipid peroxides were tested,and phytochemical tests were also performed.Results:Paracetamol(2 g/kg) increased the serum levels of alanine aminotransfer (ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP) and the lipid peroxides. Treatment of Liv 52,silymarin and ethanolic extract of Terminalia paniculata(200 mg/kg) altered levels of biochemical marker and showed significant hepatoprotective activity.Ethanolic extract revealed the presence of phenolic compound and flavanoids.Our findings suggested that ethanolic bark extract of Terminalia paniculata possessed hepatoprotective activity in a dose dependent manner.Conclusions:Terminalia paniculata possesses hepatoprotective activity.It could be an effective and promising preventive agent against PCT induced hepatotoxicity.

Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and dif erential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution proi les. The dissolution parameters of the 1:4 batch was faster with- m∞(90.5%), t50%(3.5 min), t70%(11.6 min) while that of ratio 1:1 was the least with- m∞(48.6%), m5min(23.8%). Their release kinetics followed a KorsmeyerPeppas model with a super case-II transport mechanism.Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specii cations. The t50% value of the 1:4 batch of tablets may i nd its usefulness in formulating drugs for which a fast onset of action is desired.

Simultaneous Quantification of Ibuprofen and Paracetamol in Tablet Formulations Using Transmission Fourier Transform Infrared Spectroscopy

A very simple, non-destructive, inexpensive and green strategy was applied for the simultaneous determination of ibu-profen (IBP) and paracetamol (PC) using transmission Fourier Transform Infrared (FTIR) spectroscopy in tablet formulations for routine quality control laboratories. For the determination of the active pharmaceutical ingredients (API), KBr pellets containing known amount of standards and samples were used for acquisition of the FTIR spectra. The partial least squares (PLS) calibration model was developed using the spectral region from 1781 - 1683 cm-1 for IBP and 1630 - 1530 cm-1 for PC. The excellent coefficients of determination (R2), 0.9999 and 0.9998 were achieved for IBP and PC, respectively. The accuracy of calibration model was also verified through root mean square error of cross validation (RMSECV) which was found to be 0.064. This work clearly shows the capability of transmission FTIR spectroscopy for assessment of exact quantity of API to control the quality of finished products as well as during processing in pharmaceutical industries without involvement of any solvent.

Development of a microcomposite with single-walled carbon nanotubes and Nd_2O_3 for determination of paracetamol in pharmaceutical dosage by adsorptive voltammetry

This study presents for the first time a new composite of carbon paste(CP), single-walled carbon nanotubes(SWCNTs) and Nd2 O3(NdOX). This versatile composite(NdOX-SWCNT/CPE) was applied to the oxidation of paracetamol(PCM). The newly formed surface was characterized by scanning electron microscopy(SEM), electrochemical impedance spectroscopy(EIS) and cyclic voltammetry(CV). The results showed greater conductivity and a higher surface area for the composite than those of the carbon paste alone. Moreover, the anodic peak currents for PCM increased from 1.6 to 3.6 m A with CPE and NdOXSWCNT/CPE, indicating an increase of nearly 51.0% for the anodic peak current. On the other hand, the anodic peak potentials shifted from 0.67 to 0.57 V. The detection limits were 0.05 mmol/L with NdOXSWCNT/CPE and 0.50 mmol/L with SWCNT/CPE. The relative standard deviations(RSDs) were 1.5%(n=7). The accuracy and interference of the methods were evaluated with a urine chemistry control spiked with known quantities of PCM, uric acid, dopamine, ascorbic acid, caffeine, acetylsalicylic acid,tartrazine, sunset yellow, allure red, rutin, morin and metal ions. Finally, the novelty and usefulness of the composite were evaluated to quantify PCM in pharmaceutical dosage forms such as tablets, powders and syrups for children.

Hepatoprotective effect of leaf extracts from Citrus hystrix and C.maxima against paracetamol induced liver injury in rats

The present investigation is aimed to evaluate the hepatoprotective effects of Citrus hystrix and Citrus maxima(Red and White variety)methanolic leaf extracts on paracetamol induced toxicity.Leaf extracts were given in the dose of 200 mg/kg body weight for 7 days and toxicity was induced by paracetamol(2 g/kg)on day 5.Silymarin(100 mg/kg body weight)was used as reference standard.On the 7th day animals were sacrificed and liver function markers(ALT,AST,ALP),total bilirubin and total protein in blood serums and hepatic antioxidants(SOD,CAT,GSH and GPx)in liver homogenate were estimated.The leaf extracts restored the liver function markers and hepatic antioxidants to the normal level than elevated levels noticed on paracetamol control at P<0.001.Reversal of hepatoarchitecture has also been registered.The present study shows that C.hystrix and C.maxima leaf extracts possess hepatoprotective action against paracetamol induced hepatotoxicity.©2015 Beijing Academy of Food Sciences.Production and hosting by Elsevier B.V.All rights reserved.

Long-term administration of large doses of paracetamol impairs the reproductive competence of male rats

Aim: To evaluate the antireproductive effect of paracetamol in male rats. Methods: Male rats were orally adminis-tered daily with 500 mg/kg or 1000 mg/kg of paracetamol for 30 consecutive days. Their sexual behaviour and fertilitywere evaluated using receptive females. Results: At 2 h after treratment, sexual behaviour was not inhibited but onday 30 both doses of paracetamol caused marked impairment of libido (assessed by % mounting, % intromission and% ejaculation), sexual vigour (number of mounts and intromissions and copulatory efficiency) or sexual performance(intercopulatory interval). In mating experiments, the fertility (in terms of quantal pregnancy, fertility index, implan-tation index and number of implants) was significantly reduced. All these effects were reversible. The antireproductiveeffect was not due to a general toxicity but due to an increase in pre-implantation losses resulting from oligozoospermia,impairments of normal and hyper-activated sperm motility, and reduction in the fertilizing potential of spermatozoa.Conclusion: Long-term use of high doses of paracetamol may be detrimental to male reproductive competence.( Asian J Andro12000 Dec; 2: 247-255 )