Bagchi D, Carryl O R, Tran M X, Bagchi M, Vuchetich P J, Krohn R L, Ray S D, Mitra S, Stohs S J
Department of Pharmaceutical and Administrative Sciences, Creighton University School of Pharmacy and Allied Health Professions, Omaha, Nebraska 68178, USA.
Dig Dis Sci. 1997 Sep;42(9):1890-900. doi: 10.1023/a:1018811210175.
Oxygen free radicals (OFR) are implicated in the pathogenesis of stress, chemically induced gastric lesions, and gastrointestinal injury. The concentration-dependent scavenging abilities of bismuth subsalicylate (SBS), colloidal bismuth subcitrate (CBS), and selected OFR scavengers, including superoxide dismutase (SOD), catalase, mannitol, and allopurinol were examined against biochemically or chemically generated superoxide anion, hydroxyl radical, and hypochlorite radical plus hypochlorous acid based on a chemiluminescence assay. Furthermore, both gastric (GM) and intestinal mucosa (IM) were individually exposed in vitro to these free radical generating systems, and the concentration-dependent protective abilities of SBS and CBS against lipid peroxidation (LP) were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with the necrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol, and aspirin (200 mg/kg). The extent of tissue injury in the GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity. Dose- and time-dependent in vivo protective abilities of CBS (100 mg/kg) and SBS (15 mg/kg) were also assessed. Following incubations with superoxide anion and hydroxyl radical generating systems in the presence of 125 mg SBS/liter, approximately 47% and 61% inhibitions were observed in the chemiluminescence response, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS and CBS exerted similar abilities towards hypochlorite radical plus hypochlorous acid. Approx. 3.1- and 3.7-fold increases in LP were observed in the GM and IM of rats following oral administration of 0.6 M HCl. Pretreatment of the rats with SBS and CBS decreased 0.6 M HCl-induced LP in the GM by approx. 39% and 27%, respectively, with similar decreases in LP in the IM. SBS exhibited better protective abilities towards 0.6 M HCl and 0.2 m NaOH-induced GM and IM injury as compared to CBS. SBS and CBS provided similar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protective ability towards aspirin-induced gastric injury. The results demonstrate that both SBS and CBS can scavenge reactive oxygen species and prevent tissue damage produced by OFR.
氧自由基（OFR）与应激、化学诱导的胃损伤及胃肠道损伤的发病机制有关。基于化学发光分析法，检测了次水杨酸铋（SBS）、枸橼酸铋钾（CBS）以及包括超氧化物歧化酶（SOD）、过氧化氢酶、甘露醇和别嘌呤醇在内的特定OFR清除剂对生化或化学产生的超氧阴离子、羟基自由基、次氯酸根自由基及次氯酸的浓度依赖性清除能力。此外，将胃黏膜（GM）和肠黏膜（IM）分别在体外暴露于这些自由基生成系统，并将SBS和CBS对脂质过氧化（LP）的浓度依赖性保护能力与特定OFR清除剂进行比较。另外，对禁食24小时的大鼠口服坏死剂0.6 M盐酸、0.2 M氢氧化钠、80%乙醇和阿司匹林（200 mg/kg）。通过评估LP、DNA片段化和膜微粘度来确定GM和IM中的组织损伤程度。还评估了CBS（100 mg/kg）和SBS（15 mg/kg）在体内的剂量和时间依赖性保护能力。在125 mg SBS/升存在的情况下，与超氧阴离子和羟基自由基生成系统孵育后，化学发光反应分别约有47%和61%的抑制，而125 mg CBS/升时观察到48%和46%的抑制。SBS和CBS对次氯酸根自由基及次氯酸具有相似的清除能力。口服0.6 M盐酸后，大鼠GM和IM中的LP分别约增加3.1倍和3.7倍。用SBS和CBS对大鼠进行预处理后，GM中0.6 M盐酸诱导的LP分别降低约39%和27%，IM中的LP也有类似程度的降低。与CBS相比，SBS对0.6 M盐酸和0.2 M氢氧化钠诱导的GM和IM损伤表现出更好的保护能力。SBS和CBS对80%乙醇诱导的胃损伤提供相似的保护，而CBS对阿司匹林诱导的胃损伤具有更强的保护能力。结果表明，SBS和CBS均可清除活性氧并预防OFR产生的组织损伤。
