丹参对大鼠肝硬化门脉高压缺血再灌注胃粘膜损伤的实验研究

实验制成大鼠肝硬化门脉高压（ＰＨＴ）缺血再灌注模型，用电子自旋共振技术测定缺血再注前后及丹参治疗后胃粘膜中氧自由基（ＯＦＲ）以及脂质过化物（ＬＰＯ）和超氧化物歧化酶（ＳＯＤ）的变化，同时光镜、电镜观察其病理改变，探讨丹参对胃粘膜再注损伤的防治作用。实验结果提示，ＰＨＴ胃粘膜较正常胃膜更易受缺血再灌注损伤，粘膜损伤的严重程度与ＯＦＲ、ＬＰＯ及ＳＯＤ密切相关；早期使用丹参可显著降低胃粘膜中ＯＦＲ及ＬＰ     

苯妥英对局灶性脑缺血——再灌注后脑组织自由基含量的影响

目的观察大鼠局灶性脑缺血-再灌注后脑组织自由基的变化及苯妥英（PHT）对其改善的影响．并探讨其保护作用机制。方法将雄性成年Wistar大鼠随机分为4组：即假手术组、缺血-再灌注组、PHT低剂量治疗组和PHT高剂量治疗组。采用线栓法制成大脑中动脉闭塞模型，每组均于手术后6h、12h、24h三个时间点测定脑组织超氧化物歧化酶（SOD）活力和丙二醛（MDA）水平的改变。结果缺血-再灌注组各时点SOD活力显著低于假手术组相应时点SOD活力（P〈0．05），PHT低剂量治疗组和高剂量治疗组SOD活力明显高于缺血-再灌注组各时点SOD活力（P〈0.05），PHT高剂量治疗组各时点SOD活力又明显高于低剂量治疗组，且具有显著性差异（P〈0．05）；缺血-再灌注组MDA水平显著高于假手术组相应时点MDA水平（P〈0.05），PHT低剂量治疗组和高剂量治疗组MDA水平与缺血-再灌注组各相应时间点比较明显降低（P〈0．05），PHT高剂量治疗组MDA水平与PHT低剂量治疗组各相应时间点比较明显降低（P〈0.05）。结论脑缺血-再灌注后，缺血大鼠脑组织内的MDA的水平升高，SOD活力降低，说明自由基参与了脑缺血-再灌注损伤的病理生理过程。PHT可降低MDA的水平，增加SOD的活性，从而对脑缺血-再灌注损伤具有保护作用。     

西洋参茎叶三醇组皂苷对缺血再灌注损伤心肌的保护作用

目的　探讨西洋参茎叶三醇组皂苷 (PQTS)对缺血再灌注损伤心肌的保护作用及机制。方法　采用大鼠离体心脏Langendorff灌流模型 ,观察PQTS对缺血再灌注心肌组织中SOD活性、LPO水平及再灌注性心律失常的影响。结果　PQTS(30、1 0 0、30 0 μg/ml)可以不同程度地降低心肌组织中LPO含量、提高心肌SOD活性水平 ,并抑制再灌注性心律失常的发生。结论　PQTS对缺血再灌注损伤心肌的保护作用与抑制心肌脂质过氧化反应有关     

电子顺磁共振检测心肌缺血再灌产生的氧自由基及其保护的实验研究

为了更直接地证明心肌缺血再灌过程中活性氧自由基的产生 ,并找出较好的心肌保护药物。本实验采用电子顺磁共振 (ESR)波谱仪直接检测家兔在体心肌缺血再灌时产生的活性氧自由基 ,同时观察丹参注射液在心肌缺血再灌中的作用。结果再灌组氧自由基的含量显著高于缺血及保护组。缺血区心肌中的LPO的含量明显增加 ,内源性抗氧化系统SOD、GSH -Px及CAT的活性呈普遍下降趋势。SOD和丹参对缺血心肌组织中氧自由基的产生、LPO生成呈抑制作用 ,而对SOD、CAT及GSH -Px的活性却有提高作用。缺血心肌再灌可产生大量的氧自由基 ,加重心肌缺血的损伤 ,丹参对心肌再灌产生的氧自由基有清除作用 ,使缺血心肌得到保护 ,其作用与SOD相似。     

间断性阻断肝血流对肝细胞和线粒体的保护作用

本实验观察并评价间断性和持续性肝缺血再灌注对大鼠肝细胞和线粒体结构功能、肝组织内钙和脂质过氧化物(LPO)含量．以及超氧化物歧化酶(SOD)活性改变的影响。实验大鼠分为持续阻断组、间断阻断和假处理组。结果表明；持续性缺血再灌注后大鼠肝线粒体呼吸控制比率，磷氧比值和氧化磷酸化效率均显著降低，肝组织内钙和LPO含量均增高，SOD活性下降，细胞损伤较重。间断性缺血再灌注后，上述指标无明显异常改变，细胞损伤较轻。说明间断性肝缺血有利于保护肝细胞和线粒体功能，该效应与细胞内钙稳定和SOD活性增高有关。     

蝙蝠葛碱对兔心肌缺血再灌注时血清MDA浓度和SOD活性的影响

目的探讨蝙蝠葛碱（Dau）对兔心肌缺血再灌注（IR）时血清丙二醛（MDA）浓度和超氧化物歧化酶（SOD）活性的影响。方法24只家兔随机分为假手术对照组、缺血再灌注组、缺血再灌注＋蝙蝠葛碱（Dau）干预组各8例。结扎兔左冠状动脉前降支40min造成心肌缺血再灌注模型，观察缺血前后及再灌注不同时相点血清MDA含量和SOD活性的变化。结果家兔心肌缺血40min时血清MDA含量开始明显升高（P〈0．05），SOD活性开始明显下降（P〈0．05）。Dau（剂量3．5mg／kg）能明显降低心肌缺血40min及缺血再灌注后兔血清MDA含量，升高血清SOD活性。结论Dau通过减轻兔心肌脂质过氧化作用所造成的损伤，增强SOD活性，提高氧自由基清除能力，对兔心肌缺血再灌注损伤具有一定保护作用。     

温阳通脉方预处理对心肌缺血再灌注大鼠MDA及SOD的影响

目的 观察温阳通脉方预处理对大鼠心肌缺血再灌注损伤（IR）模型丙二醛（MDA）、超氧化物歧化酶（SOD）含量的影响，探讨温阳通脉方对大鼠再灌注心肌的保护机制。方法 采用结扎大鼠冠状动脉左前降支，缺血30min，再灌注120min的方法建立心肌缺血再灌注损伤模型；缺血5min，再灌注5min，反复3次后缺血30min，再灌注120min建立心肌缺血预适应（IP）模型。检测大鼠灌胃14d后温阳通脉方组、心肌缺血预适应组（IP组）、再灌注损伤纽（IR组）、假性处理组血清MDA、SOD含量。结果 温阳通脉方组、IP组MDA含量低于IR组，SOD高于IR组，差异有统计学意义（P〈0．05）。结论 温阳通脉方预处理后，能降低大鼠心肌缺血再灌注损伤模型MDA含量，升高SOD含量，减轻大鼠急性心肌缺血所致心肌损伤，其机制可能是通过模拟心肌缺血预适应参与心肌保护作用。     

灯盏花在肢体缺血再灌注致远隔多器官损伤的预防作用

目的：观察肢体缺血再灌注致远隔多器官损伤及灯盏花的预防作用。方法：实验共分3组：（1）再灌注组：夹闭大鼠双侧股动脉，阻断循环2h再灌注5h，建立双下肢缺血再灌注模型；（2）灯盏花组：每日腹腔注射云南灯盏花注射液1ml，共7d，后按再灌注组方法制作模型；（3）对照组：行假手术处理。观察大鼠下肢骨骼肌、远隔器官胃、肾、肺、肝及脑组织超微病理改变、测定心肌酶、肝酶改变、红细胞超氧化物歧化酶（SOD）含量、组织丙二醛（MDA）含量、血清谷胱甘肽（GSH）含量，观察灯盏花对远隔器官损伤的预防作用和对以上指标的影响。结果：再灌注组骨骼肌病变较其单纯缺血时严重，远隔器官肝、肺、肾、胃及脑有弥漫性损伤；心肌酶、肝酶较对照组显增高（P＜0．05）；红细胞SOD及血清GSH较对照组显下降（P＜0．05）；肝、肺组织匀浆MDA含量则显增多（P＜0．05）；灯盏花组病变较对照组明显改善。结论：肢体缺血再灌注不但使再灌注器官本身损伤加重，还可引起远隔多器官损伤，灯盏花作为强抗氧化剂，可明显减轻肢体缺血再灌注所引起的远隔多器官损伤。     

缺血后处理对大鼠肝脏缺血再灌注损伤的保护作用

目的探讨缺血后处理对大鼠肝脏缺血再灌注损伤的保护作用。方法将75只SD大鼠随机分为假手术组、缺血再灌注组和缺血后处理组,建立大鼠肝脏局部缺血再灌注模型。检测大鼠血清、肝组织丙二醛（MDA）、超氧化物歧化酶（SOD）水平,并行肝组织病理学和超微结构检查及免疫组化法检测内源性一氧化氮合成酶（eNOS）的表达。结果与缺血再灌注组相比,缺血后处理组血清ALT和AST水平及肝组织MDA明显降低（P＜0．01）,而SOD水平则显著升高（P〈0．01）;肝组织病理损伤减轻,在再灌注7min时IPO组肝组织eNOS蛋白表达比IR组增强。结论缺血后处理可通过抑制再灌注后氧自由基的过量生成和再灌注损伤保护激酶通路,从而减轻肝细胞损伤。     

刺五加对胃缺血再灌注损伤防护作用的实验研究

采用家兔胃缺血再灌注模型，观察刺五加对胃缺血再灌注损伤的防护作用。结果提示．刺五加能维持缺血及再灌注期超氧化物歧化酶活力．减少丙二醇含量．减轻缺血再灌注后胃粘膜病理损伤。刺五加通过消除和抑制胃缺血再灌注时氧自由基的产生，提高组织抗氧化能力，对胃缺血灌注损伤起到保护作用。     

休克／再灌注肝损伤中氧自由基的作用

采用电子自旋共振（ｅｌｅｃｔｒｏｎｓｐｉｎｒｅｓｏｎａｎｃｅ，ＥＳＲ）及自旋捕捉技术直接测定兔休克／再灌注不同时限肝组织内氧自由基（ｏｘｙｇｅｎｆｒｅｅｒａｄｉｃａｌｓ，ＯＦＲ）含量的变化，同时观察肝组织内脂质过氧化物（ｌｉｐｉｄｐｅｒｏｘｉｄｅ，ＬＰＯ）含量，超氧化物岐化酶（ｓｕｐｅｒｏｘｉｄｅｄｉｓｍｕｔａｓｅ，ＳＯＤ）及血清ＡＬＴ活性的变化。结果示，ＯＦＲ易被自由基捕捉剂ＰＢＮ（α－ｐｈｅｎｙｌ－ｔｅｒｔ－ｂｕｔｙｌｎｉｔｒｏｅｎｅ）捕捉，并可通过ＥＳＲ而检测。ＯＦＲ在休克１．５小时后即有明显增高，再灌注１５和３０分钟后增高更为显著，ＬＰＯ、ＳＯＤ于再灌注后才分别有显著增高和降低，ＡＬＴ休克１．５小时后即有大幅度增高。ＬＰＯ、ＡＬＴ与ＯＦＲ有良好的线性正相关，ＳＯＤ与ＯＦＲ有良好的线性负相关，提示兔休克／再灌注肝损伤可能由ＯＦＲ介导。     

Evaluation of SOD activity in gastric mucosa of hemorrhagic shock rats

Superoxide dismutase (SOD) exogenously administered has been documented to protect gastric mucosa against ischemia-reinfusion injury by scavenging oxygen radicals. However, the changes in levels of endogenous SOD in ischemic gastric mucosa are not known. To evaluate this, the present study was designed. METHODS: Fasted and anesthetized SD rats were given 0.1 N HCl i.g. and received the following procedures. Study 1: (1) Ischemia group--25 min after acid instillation, blood pressure was reduced to 20-30 mmHg for 20 min. (2) Ischemia-Reinfusion group--5 min after acid administration, rats received the same hypotension as above followed by reinfusion of shed blood for 20 min. (3) Control group-Rats were killed 45 min later without hypotension and reinfusion. Study 2: Three groups of rats treated with the same procedures as in Study 1 were given allopurinol (50 mg/kg/day) i.g. once daily for 2 days prior to the experiment. All rats were killed by exsanguination from the carotid artery to avoid as much as possible contamination of gastric mucosal samples with red blood cells rich in SOD. The supernatants of the corpus and antral mucosa homogenized were prepared for measuring their SOD activity using the nitrite method modified by Oyanagui. RESULTS: SOD activity in the gastric mucosa significantly increased in both the Ischemia (Ische.) and Ischemia-Reinfusion (I-R) groups compared to the control (Ische. vs. I-R vs. Cont'l: corpus-123.4 +/- 4.8 vs. 127.4 +/- 3.6 vs. 96.9 +/- 4.4 NU/Mg protein; antrum-71.6 +/- 2.8 vs. 81.4 +/- 6.8 vs. 62.1 +/- 3.1 NU/mg protein). No increase in SOD activity was observed in rats pretreated with allopurinol. CONCLUSION: SOD activity increases with oxyradicals generation in the rat stomach subjected to either hemorrhagic ischemia alone or hemorrhagic ischemia plus reinfusion. This also suggests that oxyradicals are generated even in the ischemic period.     

A selective cyclo-oxygenase-2 inhibitor, NS-398, may improve portal hypertension without inducing gastric mucosal injury

BACKGROUND AND AIMS: Prostacyclin has been shown to play a role in hyperdynamic circulation in portal hypertension. Recently, a new subtype of cyclo-oxygenase (COX), COX-2, which acts as an inducible synthase in response to various stimuli. The aim of this study was to investigate whether COX-2 contributes to portal hypertension and whether a COX-2 blockade induces the same sort of gastric mucosal injury as a COX-1 blockade. METHODS: Portal hypertension (PHT) in rats was induced by a two-step ligation of the portal vein. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), serum levels of 6-keto-prostaglandin F1alpha (PGF1alpha), thromboxane B2 (TXB2) and gastric mucosal injury induced by pure ethanol were all measured in PHT rats receiving different inhibitors (indomethacin, a highly selective COX-1 inhibitor; NS-398, a highly selective COX-2 inhibitor). Control rats treated by a sham operation were also studied. RESULTS: The NS-398 administration significantly decreased PP to the same extent as indomethacin at doses of 5 and 10 mg/kg in PHT rats after a 60 min administration, while neither inhibitor affected the control rats. Both inhibitors significantly increased PP after a 30 min administration in the PHT and control rats at a dose of 5 mg/kg while both inhibitors significantly decreased PP after 60 min administration only in the PHT rats. Portal vein ligation treatment induced a significant increase in PP and BFV of the portal vein, gastric mucosa, oesophageal mucosa and the serum levels of 6-keto-PGF1alpha and TXB2, while portal vein ligation treatment induced a significant decrease in BFV of the liver. Both blockades increased MAP and decreased PP and BFV in the splanchnic area and decreased the serum level of 6-keto-PGF1alpha and TXB2 in the PHT rats, while neither blockade modified any parameters in the control rats, except that indomethacin administration significantly decreased the BFV of the gastric mucosa. Indomethacin administration significantly increased the ulcer index (UI). The NS-398 had no effect on UI in either the PHT or control rats. Only indomethacin significantly increased the number of rats demonstrating gastric mucosal long lesions (> 2 cm) in the PHT rats. CONCLUSION: In the PHT rats, prostaglandin seemed to contribute to portal hypertension. Both COX blockades reduced PP and BFV of the portal vein and gastric mucosa. NS-398, a selective COX-2 inhibitor, may, therefore, improve portal hypertension without inducing gastric mucosal injury.     

Increased heat-shock protein 90 expression contributes to impaired adaptive cytoprotection in the gastric mucosa of portal hypertensive rats

Background and Aims:  Portal hypertensive (PHT) gastropathy results in an increased susceptibility to damage. Adaptive cytoprotection against ethanol-induced damage is impaired in the gastric mucosa of rats with portal hypertension. Excessive nitric oxide (NO) production occurs in portal hypertension and is mediated in part via heat-shock protein (Hsp)90 production. The aim of this study was to investigate the relation between adaptive cytoprotection after exposure to ethanol and gastric expression of Hsp90 in PHT rats.
Methods:  Portal hypertension was induced in rats by staged portal vein occlusion. Adaptive cytoprotection to 70% ethanol was evaluated by assessing the injury index of the gastric mucosa with or without pretreatment with 10% ethanol. Expression of Hsp90 mRNA was evaluated by real-time polymerase chain reaction, and expression of Hsp90 protein was evaluated by western blotting. The effect of Hsp90 inhibition in PHT rats was evaluated by administration of geldanamycin.
Results:  Gastric Hsp90 mRNA expression in PHT rats was significantly less than that in sham-operated (SO) controls. However, after 10% ethanol pretreatment, Hsp90 mRNA expression was significantly greater in PHT rats than in SO controls. In PHT rats, gastric Hsp90 protein expression after 10% ethanol pretreatment was significantly greater than that without the pretreatment. However, the pretreatment had no effect on the injury index compared to SO rats. Administration of geldanamycin prior to 10% ethanol pretreatment significantly decreased the injury index in response to 70% ethanol in the PHT rats.
Conclusions:  These results show that 10% ethanol pretreatment markedly increases gastric Hsp90 expression in PHT rats. Excessive production of Hsp90 may contribute impaired adaptive cytoprotection.     

Overexpressed nitric oxide synthase in portal-hypertensive stomach of rat: A key to increased susceptibility to damage?

BACKGROUND & AIMS: Portal hypertension predisposes gastric mucosa to increased injury. The aim of this study was to determine whether overexpression of constitutive nitric oxide synthase (cNOS) is responsible for increased susceptibility of portal-hypertensive (PHT) gastric mucosa to damage. METHODS: In gastric specimens from PHT and sham-operated rats, cNOS messenger RNA expression was determined by Northern blotting and cNOS protein expression by Western blotting, immunohistochemistry, and enzyme activity assay. Extent of ethanol- induced gastric mucosal necrosis, mucosal blood flow, and gastric NOS activity in PHT and sham-operated rats was determined after administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) or saline. RESULTS: cNOS messenger RNA level, cNOS enzyme activity, and fluorescence signals for cNOS were increased significantly in PHT rats compared with controls. Inhibition of overexpressed cNOS by L-NAME (5 mg/kg) significantly reduced ethanol-induced mucosal necrosis and normalized blood flow in PHT gastric mucosa, whereas this dose of L- NAME significantly increased mucosal necrosis in sham-operated rats. CONCLUSIONS: Portal hypertension activates the cNOS gene with overexpression of cNOS protein in endothelia of gastric mucosal vessels. Excessive NO production by overexpressed cNOS may play an important role in the increased susceptibility of PHT gastric mucosa to damage. (Gastroenterology 1997 Jun;112(6):1920-30)     

五羟色胺含量在丹参改善颞叶缺血大鼠记忆障碍中的变化

目的 探讨五羟色胺(5-HT)含量在丹参改善单侧颞叶缺血性损害大鼠空间记忆障碍中的变化。方法采用立体定向光化学技术选择性地导致大鼠左侧颞叶皮层缺血,术前30min及术后第3天分别给丹参组大鼠腹腔注射丹参10g／kg体重,用Morris水迷宫及图像自动监视系统监测大鼠行为。然后取脑组织进行病理观察及5-HT免疫组化分析：结果经丹参治疗,颞叶缺血性损害大鼠的空间记忆障碍得到显改善,颞叶缺血性损害显减轻,缺血灶内5-HT表达明显减少。结论在丹参改善单侧颞叶缺血大鼠空间记忆障碍中,5-HT起一定作用。     

Effect of oxygen free radicals on cardiovascular function at organ and cellular levels

Oxygen free radicals (OFR) have been implicated as a causative factor of cell damage in several pathologic conditions. It is possible that OFR could have effects on cardiac function and contractility. The present investigation deals with the effects of OFR in the absence and in the presence of scavangers of OFR (superoxide dismutase and catalase) on cardiac function, index of cardiac contractility, serum creatine kinase (CK), and blood lactate, PO2 and pH in the anesthetized dogs. The hemodynamic measurements and collection of blood samples for measurement of CK, lactate, PO2 and pH were made before and at various intervals after administration of OFR for 1 hour. Xanthine and xanthine oxidase were used to generate OFR. OFR produced a decrease in cardiac function and indices of myocardial contractility and an increase in the serum CK. OFR produced an increase in the systemic and pulmonary vascular resistance. Although there was a tendency for an increase in the blood lactate, the increase was not significant. The blood PO2 and pH were not affected. Superoxide dismutase (SOD), alone or in combination with catalase, tended to protect cardiac function against the deleterious effects of OFR. Scavangers of OFR prevented the OFR-induced rise in serum CK. Although the protective effect of SOD plus catalase was slightly better than SOD alone, the results were not significantly different from each other. These results suggest that OFR are cardiac depressant and increase the peripheral vascular resistance besides causing cellular damage. Scavangers of OFR may be beneficial in counteracting the deleterious effects of OFR on hemodynamic parameters and cellular integrity.     

Inability of cytoprotection to occur during a period of gastric ischemia

Prostaglandin E₂ (PGE₂), colloidal bismuth subcitrate (CBS), and sucralfate (SUC) are known to protect the gastric mucosa from ethanol injury. The proposed central role for the microcirculation in gastric mucosal defense and as a site for the expression of the protective effects of these agents was investigated in the rat stomach. Animals were pretreated with either PGE₂, CBS, or SUC. Control rats were given normal saline. After allowing 15 min for expression of the pretreatment, ethanol was administered as a 10%, 25%, 50% or 100% solution to groups of rats with normally perfused stomach and to other groups of rats in whom the stomach was made ischemic by cross-clamping the supracoeliac aorta immediately prior to the instillation of ethanol. The extent of gastric mucosal damage was measured using quantitative histological techniques and expressed as a percentage of surface area and volume of mucosa damaged. In the presence of ischemia, the extent of damage by ethanol was markedly increased, with total destruction of the mucosa by the 50% and 100% solutions. With 25% ethanol, the volume of mucosal damage was increased from 0.5% in the normally perfused stomach to 53.5% with ischemia. When 10% ethanol was instilled into the ischemic stomach, only 0.8% of the volume of the mucosa was damaged, which was not different from the volume of mucosa damaged after the ischemic stomach was exposed to normal saline alone (1.0%). Pretreatment with PGE₂, CBS, or SUC did not significantly change the extent of damage seen with exposure of the ischemic stomach to 25% or 50% ethanol. These results show that the absence of normal mucosal microvascular perfusion markedly increases the extent of damage by ethanol and that, in the absence of microvascular flow, the protective effects of PGE₂, CBS, and SUC are not expressed. These findings support the proposal that a primary component of the protective action of these agents is the, maintenance of the integrity of the mucosal microvasculature.This study was supported by a grant from the National Health and Medical Research Council of Australia.     

Immunohistochemical localization of vascular endothelial growth factor in the rat portal hypertensive gastropathy

BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is now recognized to be a distinct entity. Recently, angiogenesis has been noticed as a key factor in clarifying the pathophysiology of various diseases. Angiogenesis in the PHT of explored gastric mucosa has yet to be explored. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. The aim of the present study was thus to investigate whether the hypoxic state exists in PHG, and whether VEGF appears more strongly in PHG than in normal gastric mucosa and, if so, what exactly is the role of the hypoxic state and VEGF in PHG. METHODS: At 1, 3, 7 and 14 days after either a portal ligation or sham operation, the portal venous pressure, the gastric mucosal blood flow volume and the blood gas were measured and, the expression of VEGF and antiproliferating cell nuclear antigen (PCNA) in gastric mucosal specimens was immunohistochemically assessed. RESULTS: The portal pressure (PP) and the gastric mucosal blood flow (GMBF) in the PHT rats were significantly greater than in the control (CTR). Both the SaO2 and PaO2 of the arterial blood gas were lower in the PHT rats than in the control rats. The percentage of VEGF expression in the PHG was found to be higher than that in the control gastric mucosa. The percentage of PCNA expression in the PHG was higher than that in the control gastric mucosa. CONCLUSION: The levels of SaO2 and PaO2 were lower in the PHT rats. There is a possibility that a kind of portal hypertensive gastric change may trigger an enhanced histochemical expression of VEGF. The increased activity of VEGF may have a possibility of the hypoxic gastric mucosal state caused by the presence of active congestion. This damaged mucosal state 'PHG' may thus facilitate the fragility in PHG and such lesions may be slow and insidious, which may therefore lead to sudden and severe anemia, thus causing massive and sometimes fatal hemorrhaging.     

Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts

Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR.