4-氨基水杨酸口服结肠定位包衣片的体内药效学研究(英文)

目的：评价自制的4-氨基水杨酸口服结肠定位包衣片在大鼠体内的药效学。方法：以2,4,6-三硝基苯磺酸(TNBS)的乙醇溶液灌肠,制作溃疡性结肠炎大鼠模型。将大鼠随机分为7组：健康对照组,TNBS对照组,TNBS+低剂量(包衣片)组,TNBS+中剂量(包衣片)组,TNBS+高剂量(包衣片)组,TNBS+柳氮磺吡啶(SASP)组,TNBS+中剂量非包衣片组。大鼠连续给药5 d后,对结肠部位的大体形态学改变、组织学损伤以及组织髓过氧化物酶(MPO)活性进行评分或测定,评价4-氨基水杨酸(4-ASA)结肠定位包衣片在大鼠体内的药效学。结果：以TNBS灌肠可一次性制作大鼠溃疡性结肠炎模型。与4-ASA非包衣片组相比,包衣片组或SASP组显示,给药后动物结肠的大体形态改变评分、组织损伤评分及MPO活性均有所降低；高剂量组对各指标的影响与SASP无显著差异(P>0．05)。结论：与非包衣片比较,自制的4-氨基水杨酸口服结肠定位包衣片在治疗大鼠溃疡性结肠炎方面有更好的疗效。     

肠泻停胶囊对实验性结肠炎大鼠的影响

目的:探讨肠泻停胶囊对三硝基苯磺酸(TNBS)诱导大鼠实验性结肠炎的影响.方法:120只SD大鼠随机分为6组,每组20只:正常组、模型组、阳性对照组、肠泻停胶囊高、中、低组.除正常对照组未行造模外,其余五组大鼠均采用TNBS造模.肠泻停胶囊高、中、低组分别灌胃给药(1.80,0.90,0.45 g /kg体质量)、阳性对照组灌胃给予地塞米松剂量(0.2 mg/kg体质量)、其余组灌胃给予0.5%羧甲基纤维素钠溶液连续3 周、4周;观察肠泻停胶囊对大鼠腹泻率、死亡率、血白细胞计数、淋巴细胞百分率、脾脏及胸腺重量、组织形态学评分、组织MPO活性的影响.结果:经肠泻停胶囊干预后各剂量组动物腹泻明显缓解,腹泻率降低,动物死亡率降低,外周血WBC、LYM值及组织MPO值降低,剖检可见结肠组织溃疡面积明显缩小,水肿缓解,坏死减轻,未见肠壁增厚.结论:肠泻停胶囊连续给药,对实验性结肠炎治疗作用显著.     

石榴皮水提物治疗溃疡性结肠炎模型大鼠的实验研究

目的：观察石榴皮水提物对慢性溃疡性结肠炎模型大鼠的治疗作用。方法：将80只SD大鼠随机分为正常对照组、模型组、柳氮磺吡啶（SASP）组、石榴皮水提物低、中、高剂量组（200、400、800 mg/kg）。用2,4-二硝基氯苯（DNCB）复合乙酸法建立大鼠溃疡性结肠炎模型。连续给药4周后麻醉处死动物,观察大鼠结肠大体形态的变化并进行结肠黏膜损伤指数（CMDI）评分,并测定大鼠结肠重量、肠重指数、组织髓过氧化物酶（MPO）活力、白介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）及丙二醛（MDA）含量。结果：与模型组比较,石榴皮水提物中、高剂量组及SASP组大鼠腹泻症状明显缓解。IL-1β、TNF-α、MDA含量和MPO活力显著降低（P〈0.05）;病理学检查或尸检可见结肠组织溃疡面积明显缩小,水肿缓解,组织坏死减轻,未见肠壁增厚。石榴皮水提物高、中剂量组治疗效果明显优于SASP组（P〈0.05）。结论：石榴皮水提物能显著缓解DNCB复合乙酸法所致慢性溃疡性结肠炎的症状,治疗作用明显。     

肠炎宁浸膏粉对大鼠溃疡性结肠炎模型实验研究

目的研究肠炎宁浸膏粉对三硝基苯磺酸致大鼠溃疡性结肠炎模型的治疗作用。方法采用三硝基苯磺酸建立大鼠溃疡性结肠炎模型,各组分别给予肠炎宁浸膏粉低、中、高(相当于2.52、5.05、10.1 g生药·kg-1)剂量,连续给药2周,采血检测血清TNF-α、IL-1、IL-6、IL-8水平及结肠组织病理学检查。结果肠炎宁浸膏粉高剂量能明显降低三硝基苯磺酸致大鼠溃疡性结肠炎模型血清TNF-α、IL-8含量(P<0.05或P<0.01),能明显减少三硝基苯磺酸致大鼠溃疡性结肠模型结肠病理改变。结论肠炎宁浸膏粉对溃疡性结肠炎模型具有明显的治疗作用。     

甘草甲醇提取物FM100对小鼠溃疡性结肠炎的药效学研究

目的观察甘草甲醇提取物FM100对小鼠溃疡性结肠炎的作用。方法用三硝基苯磺酸钠(TNBS)和乙醇制造小鼠溃疡性结肠炎模型,空白对照组和TNBS模型组灌胃等容量生理盐水,阳性对照组灌胃地塞米松0.2mg/kg,FM100大、中、小剂量组分别灌胃FM100300mg/kg、200mg/kg、100mg/kg,连续灌胃14d。观察小鼠体质量变化、腹泻、结肠黏膜组织形态学、脾脏指数及髓过氧化物酶(MPO)活力等指标。结果甘草甲醇提取物FM100可不同程度地改善TNBS/乙醇所致溃疡性结肠炎小鼠体质量下降和腹泻症状,明显降低结肠黏膜粘连及其溃疡分值和脾脏指数,但可增高MPO活力(P<0.05或P<0.01)。结论甘草甲醇提取物FM100对小鼠溃疡性结肠炎有较好的改善作用,能减轻结肠局部的病理性损伤。     

甘草酸二铵抗大鼠溃疡性结肠炎作用及相关机制研究

目的:研究甘草酸二铵(DG)对2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠溃疡性结肠炎的作用及可能作用途径。方法:以柳氮磺吡啶(SASP,225 mg.kg-1)为阳性对照,研究甘草酸二铵结肠给药(2,10,50 mg.kg-1,qd,共给药7 d)对TNBS性溃疡性结肠炎大鼠的结肠单位长度重量、结肠黏膜损伤评分、髓过氧化物酶(MPO)、结肠组织丙二醛(MDA)和超氧化物歧化酶(SOD)以及血清白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量的影响;由HE染色、扫描和透射电镜观察结肠组织病理学变化;由免疫组化观察结肠组织环氧酶-2(COX-2)和细胞间黏附分子-1(ICAM-Ⅰ)表达的变化。结果:模型动物结肠组织发生明显病理学变化,伴有充血、溃疡以及大量的炎性细胞浸润,DG组均不同程度改善结肠组织病理学变化,降低单位长度结肠重量,并呈剂量依赖关系。与正常组比较,模型组大鼠结肠组织中MPO活性和MDA含量显著升高,SOD活性明显下降;DG能显著逆转模型组MPO,MDA和SOD的变化。与模型组比较,DG组结肠组织COX-2和ICAM-Ⅰ表达下调,血清中IL-1β和TNF-α表达量也有不同程度下降。结论:甘草酸二铵能有效改善溃疡性结肠炎大鼠的结肠炎症反应,其作用机制与抗氧化、降低促炎性细胞因子水平等有关。     

三硝基苯磺酸诱导Balb/c小鼠结肠炎的实验研究

目的建立三硝基苯磺酸(TNBS)小鼠结肠炎模型。方法采用不同剂量的TNBS给♀Balb/c小鼠灌肠后制备结肠炎模型。观察动物的存活率、疾病活动度指数、结肠肉眼观和组织学变化,并检测结肠组织中髓过氧化物酶(MPO)的活力及小鼠脾T淋巴细胞增殖情况。结果随着TNBS剂量的提高,模型组小鼠存活率下降。存活的多数小鼠疾病活动度指数及MPO活力升高,病理切片显示结肠固有层及粘膜下层有大量淋巴细胞、单核巨噬细胞以及中性白细胞浸润,伴有肠腺扭曲、减少,杯状细胞丢失,隐窝脓肿,血管增生,肠壁增厚等病理改变,表明均建立了慢性结肠炎模型。结论每只小鼠给予1.5mgTNBS灌肠,动物死亡较少,并能够成功制备小鼠结肠炎模型。     

葎草总黄酮对溃疡性结肠炎模型大鼠保护作用的研究

目的:研究葎草总黄酮(HTF)对三硝基苯磺酸(TNBS)诱发大鼠溃疡性结肠炎(UC)的保护作用。方法:采用TNBS灌肠制备UC大鼠模型。实验分为6组,即正常对照(等容生理盐水)、模型(等容生理盐水)、柳氮磺胺嘧啶(SASP,300mg.kg-1)和HTF高、中、低剂量(450、300、150mg.kg-1)组,ig给药,每天1次,连续3周。给药结束后观察各组大鼠的临床表现和结肠损伤的情况,测定结肠组织中超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)活性和丙二醛(MDA)含量,称定胸腺、脾脏的重量。结果:与模型组比较,HTF高、中、低剂量组大鼠的临床症状显著改善,结肠黏膜的损伤程度显著减轻,病变结肠组织中MDA含量显著减少,MPO活性显著降低,SOD活性显著增强,胸腺萎缩与脾脏肿大现象明显改善,尤以HTF高剂量组效果显著。结论:HTF对TNBS诱发的UC模型具有显著保护作用,其作用机制可能与抗炎和抗自由基氧化作用有关。     

肠包衣地塞米松脂质体壳聚糖胶囊对炎性结肠组织MPO活性的影响

目的评价肠包衣地塞米松(DSP)脂质体冻干剂壳聚糖胶囊对大鼠炎性结肠组织髓过氧化酶(MPO)活性的影响。方法用2,4,6-三硝基苯磺酸钠(TNBS)诱导大鼠结肠炎,建立反应结肠炎症程度的结肠组织MPO浓度的测定方法,观察口服各种DSP制剂对MPO的抑制程度。结果TNBS灌肠后d 5时MPO达到最高值;各种DSP制剂均有降低TNBS诱导的实验性大鼠结肠炎结肠组织MPO的效果,但DSP脂质体壳聚糖胶囊具有最好的抑制作用。结论肠包衣DSP脂质体冻干剂壳聚糖胶囊在治疗结肠炎中可能具有较大的应用前景,值得进一步开发研究。     

白术黄芪汤及其单药提取部位组方对溃疡性结肠炎的治疗作用

目的探讨白术黄芪汤(DAA)益气健脾作用的物质基础。方法DAA以原方配伍水提,煮沸浓缩至相当于药材1500g.L-1;DAA单药提取部位组方(PEAAG)以组成DAA的3个单药白术、黄芪和甘草提取部位白术糖复合物(AMPS-Ⅱ)、黄芪总皂苷(TSA)和甘草总黄酮(TFG)以4∶3∶3比例混合,加蒸馏水混匀研磨配成储存液,含提取物100g.L-1。用三硝基苯磺酸(TNBS)制备大鼠溃疡性结肠炎模型,造模d2分别灌胃给予DAA(相当于药材15g.kg-1)和PEAAG(含提取部位0.3g.kg-1)连续15d,肉眼观察大鼠结肠病变并进行组织病理学检查。用TNBS制备小鼠结肠炎模型,于d2分别灌胃给予PEAAG及其3个组成部位(剂量均为0.2g.kg-1)连续10d,观察结肠组织髓过氧化物酶(MPO)活性的变化。用一次最大耐受量实验观察DAA和PEAAG的小鼠急性毒性。结果与模型对照组比较,PEAAG组结肠的肉眼和组织病理学评分均降低,DAA组变化不明显。PEAAG和AMPS-Ⅱ可降低TNBS致小鼠结肠炎结肠组织MPO的活性,PEAAG作用更明显,TSA和TFG作用不明显。DAA和PEAAG一次最大耐受量分别为60g.kg-1和4g.kg-1,相当于临床用量的180倍和300～600倍。结论单药提取部位组方PEAAG对溃疡性结肠炎具有较好的治疗作用,在所观察的剂量条件下可能优于原方DAA和3个提取部位,且毒性未增加。     

The effect of sodium valproate on acetic acid-induced colitis in rats

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.     

心理应激对溃疡性结肠炎病情及疗效的影响

目的:通过观察心理应激对溃疡性结肠炎大鼠产生的影响并探讨其影响的机制;同时观察抗焦虑药物对处于应激状态下溃疡性结肠炎大鼠症状的干预作用及其作用机制。方法:80只Wistar大鼠随机分为UC对照组、UC应激组、UC+氯硝西泮组和UC应激+氯硝西泮组各20只,用免疫接种法建立溃疡性结肠炎大鼠模型后,用猫恐吓的方法建立心理应激模型。建立心理应激模型期间分别给予各组生理盐水、氯硝西泮(2 mg.kg-1)灌胃。15 d后处死大鼠,以组织损伤评分、结肠组织MPO和NO活性等指标来评价其炎症和损伤程度。结肠组织损伤评分通过显微镜观察得出。并用分光光度分析法测定结肠组织MPO、NO活性,放射免疫分析法(RIA)检测大鼠血清中皮质醇的含量。结果:应激模型组的血清皮质醇、肠组织MPO、NO含量及结肠组织损伤评分较UC对照组明显增高;UC应激+氯硝西泮组上述指标明显低于UC应激组;而UC+氯硝西泮组上述指标与UC对照组无明显区别。结论:心理应激可以明显加重溃疡性结肠炎的症状。苯二氮卓类药物本身无抗炎作用,但可通过影响边缘系统和网状结构,减轻了心理应激对内脏的影响,缓解炎性肠病症状的加重。     

芝麻素对2,4,6-三硝基苯磺酸诱导的大鼠溃疡性结肠炎的影响

目的研究芝麻素对2,4,6-三硝基苯磺酸（TNBS）诱导的大鼠溃疡性结肠炎（UC）的保护作用。方法 Wistar大鼠50只,随机分为空白对照组,模型组和芝麻素低、中、高剂量5组,每组10只。用TNBS/乙醇灌肠法复制大鼠UC模型,芝麻素组分别给与不同剂量芝麻素进行灌胃治疗,10 d后处死全部大鼠,收集血液和结肠标本,ELISA法检测血清中IL-6、IL-10和TNF-α含量以及生化法检测结肠组织中髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）活力以及一氧化氮（NO）、还原性谷胱甘肽（GSH）、丙二醛（MDA）含量。结果与模型组比较,芝麻素3个剂量组以及空白对照组血清TNF-α、IL-6含量显著降低,IL-10含量显著升高,差异有统计学意义（P〈0.01或P〈0.05）。与模型组相比,芝麻素3个剂量组以及空白对照组MPO活力及NO和MDA含量均降低,SOD活力与GSH含量升高,差异有统计学意义（P〈0.01）。结论芝麻素可通过提高结肠炎大鼠结肠组织抗氧化能力,调节结肠炎大鼠血清炎性细胞因子的平衡,抑制NO生成,发挥治疗作用。     

Anti-inflammatory activity of phycocyanin extract in acetic acid-induced colitis in rats.

The anti-inflammatory effect of c-phycocyanin extract was studied in acetic acid-induced colitis in rats. Phycocyanin (150, 200 and 300 mg kg(-1) p.o.) was administered 30 min gbefore induction of colitis with enema of 1 ml of 4% acetic acid per rat. Twenty-four hours later myeloperoxidase (MPO) activity was determined as well as histopathological and ultrastructural studies were carried out in colonic tissue. Phycocyanin substantially reduced MPO activity which was increase din the control colitis group. Also, histopathological and ultrastructural studies were carried out in colonic tissue. Phycocyanin substantially reduced MPO activity which was increased in the control colitis group. Also, histopathological and ultrastructural studies showed inhibition in inflammatory cell infiltration and reduction to some extent in colonic damage in rats treated with phycocyanin. The probable role of antioxidative and the scavenging properties of phycocyanin against reactive oxygen species in the anti-colitic effect is discussed in this paper. To our knowledge this is the first report on the anti-inflammatory effect of phycocyanin in an experimental model of colitis.     

Antiinflammatory effects of various drugs on acetic acid induced colitis in the rat

The efficacy of various drugs used to treat ulcerative colitis, (sulfasalazine, 5-aminosalicylate, hydrocortisone) was investigated in a model of acetic acid-induced colitis in the rat. Subsequently, we tested the ability of antioxidant/5-lipoxygenase inhibitors (gossypol and nordihydroguiaretic acid [NDGA]) and a cyclooxygenase inhibitor (indomethacin) to attenuate the macroscopic colonic damage and/or neutrophil influx (myeloperoxidase activity [MPO]) associated with this model of colitis. Oral pretreatment with either sulfasalazine, gossypol, or NDGA significantly decreased colonic MPO activity induced by acetic acid. Intrarectal administration of such drugs resulted in an even larger reduction of the colonic inflammation, with gossypol being the most potent compound. Oral or intrarectal administration of corticosteroids (dexamethasone, hydrocortisone) also attenuated the parameters of acetic acid induced colitis. In contrast, pretreatment with indomethacin was ineffective, or when administered daily after colitis induction, indomethacin actually increased colonic neutrophil influx significantly. Our data suggest that both the route of drug administration and dosing regimen employed affect the antiinflammatory potency and/or efficacy of compounds on colitis induced by acetic acid in the rat. Drugs which were effective against this colitis may act by scavenging of oxygen derived free radicals.     

葡萄籽原花青素对复发性结肠炎大鼠血清抗氧化能力及NO含量的影响

目的：观察葡萄籽原花青素（GSPE）对复发性结肠炎大鼠血清抗氧化能力及NO含量的影响,初步探讨葡萄籽原花青素治疗复发性结肠炎的作用机制。方法：直肠给予雄性Wistar大鼠80mg/kg2,4,6-三硝基苯磺酸（TNBS）/50%乙醇溶液复制结肠炎模型,在第16天时,用30mg/kgTNBS/50%乙醇溶液诱导结肠炎复发的模型。大鼠第二次致炎24h后,分别应用GSPE低、中、高剂量（100、200、400mg/kg）灌胃对其进行治疗,并以柳氮磺吡啶（SASP,500mg/kg）作为阳性对照。连续给药7d后处死所有大鼠,取结肠标本评价结肠湿重指数,生化法检测血清中髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和一氧化氮合酶（iNOS）活力及丙二醛（MDA）、谷胱甘肽（GSH）和NO含量。结果：与模型对照组比较,GSPE各剂量组大鼠体重下降程度较轻（P〈0.05或P〈0.01）,结肠湿重指数明显降低（P〈0.05或P〈0.01） 大鼠血清中MPO和iNOS活力及MDA和NO含量均明显降低（P〈0.05或P〈0.01） 大鼠血清中SOD和GSH-Px活力及GSH含量明显升高（P〈0.05或P〈0.01）。结论：GSPE可能通过提高复发性结肠炎大鼠血清抗氧化能力,抑制NO生成,来减轻复发性结肠炎炎症反应。     

Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats

Ulcerative colitis is a common inflammatory bowel disease (IBD) of unknown etiology. Recent studies have revealed the role of some microorganisms in the initiation and perpetuation of IBD. The role of antibiotics in the possible modulation of colon inflammation is still uncertain. In this study, we evaluated the effects of two macrolides, namely azithromycin and erythromycin, at different doses on the extent and severity of ulcerative colitis caused by intracolonic administration of 3% acetic acid in rats. The lesions and the inflammatory response were assessed by histology and measurement of myeloperoxidase (MPO) activity, nitric oxide synthetase (NOS) and tumor necrosis factor alpha (TNFα) in colonic tissues. Inflammation following acetic acid instillation was characterized by oedema, diffuse inflammatory cell infiltration and necrosis. Increase in MPO, NOS and TNFα was detected in the colonic tissues. Administration of either azithromycin or erythromycin at different dosage (10, 20 and 40 mg/kg orally, daily for 5 consecutive days) significantly (P < 0.05) reduced the colonic damage, MPO and NOS activities as well as TNFα level. This reduction was highly significant with azithromycin when given at a dose of 40 mg/kg. It is concluded that azithromycin and erythromycin may have a beneficial therapeutic role in ulcerative colitis.     

Protective effect of alpha‐lipoic acid,aerobic or resistance exercise from colitis in second hand smoke exposed young rats

The role of second hand smoke (SHS) exposure on ulcerative colitis is not known. Our aim was to examine the effects of α‐lipoic acid (ALA), chronic aerobic (AE) or resistance exercise (RE) on SHS exposed rats with colitis. Sprague‐Dawley male rats (150‐200 g, n=54) were selected for colitis induction. Among the colitis groups, one group was exposed to SHS (6 d/wk, 4 cigarettes/d) and the other was not. The SHS group was divided into subgroups as follows: sedentary; AE (swimming; 3 d/wk); and RE (climbing with weight; 3 d/wk). After 5 weeks, colitis was induced by intrarectal acetic acid. All groups had subgroups that were given subcutaneously ALA (50 mg/kg per day) or vehicle for 3 days. Following decapitation, colon tissues were sampled to examine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, luminol and lucigenin chemiluminenscence, macroscopic scoring and histologic examination. ANOVA and Student's t‐test were used for statistical analysis. The increased macroscopic and microscopic scores, MPO, MDA, luminol and lucigenin measurements in colitis and SHS‐colitis groups were decreased via ALA (P<.05‐.001). AE declined macroscopic and microscopic scores, MDA, lucigenin compared to colitis and SHS‐colitis groups (P<.01‐.001). RE reduced microscopic score, MPO, MDA, luminol, lucigenin (P<.05‐.001) that were increased with colitis. Decreased GSH levels (P<.01) in the SHS‐colitis group approached to control levels when given ALA. According to our results SHS and colitis induction increased inflammatory damage. SHS did not worsen it more than colitis. Our results suggest that ALA, AE or RE might be protective for SHS exposed ulcerative colitis conditions.     

PARP inhibition reduces acute colonic inflammation in rats

Poly(ADP-ribose) polymerases (PARP) comprise a family of enzymes which catalyse poly(ADP-ribosyl)ation of DNA-binding proteins. Multiple researches indicate the importance of PARP in promoting cell recruitment and thereby inducing organ injury in various forms of inflammation, such as colitis. We have evaluated the effects of two PARP inhibitors, nicotinamide and 1,5-dihydroxyisoquinoline, in acute colitis induced by trinitrobenzensulfonic acid (TNBS) in rats. Nicotinamide (20-40 mg/kg) and 1,5-dihydroxyisoquinoline (4-8 mg/kg) were administered 48, 24 and 1 h prior to the induction of colitis as well as 24 h later. 48 h after colitis induction the lesions were blindly scored and quantified as ulcer index. Histological study and colonic inflammation were assessed by gross appearance and myeloperoxidase (MPO) activity. Prostaglandin E2 (PGE2) synthesis and, cyclooxygenase-1 and cyclooxygenase-2 expressions by Western blotting and immunohistochemistry were also performed. Inflammation following TNBS induction was characterized by increased colonic wall thickness, oedema, diffuse inflammatory cells infiltration in the mucosa and necrosis. Furthermore, increased MPO activity, cyclooxygenase-2 expression and PGE2 synthesis were significantly augmented after TNBS instillation. On the contrary, treatment with 1,5-dihydroxyisoquinoline significantly reduced the degree of colon injury and also caused a substantial reduction in the rise in MPO activity, in the increase of staining for cyclooxygenase-2, as well as in the up-regulation of PGE2 caused by TNBS in the colon. Although nicotinamide significantly did not reduce macroscopic damage, it decreased both MPO activity and PGE2 colonic levels. In conclusion, we demonstrated that PARP inhibition can exert beneficial effects in experimental colitis and may, therefore, be useful in the treatment of ulcerative colitis.