Farias-Silva Elisangela, Cola Maíra, Calvo Tamara R, Barbastefano Victor, Ferreira Anderson L, De Paula Michelatto Debora, Alves de Almeida Ana Cristina, Hiruma-Lima Clélia A, Vilegas Wagner, Brito Alba R M Souza
Departamento de Fisiologia e Biofísica, IB, UNICAMP, Campinas, SP, Brazil.
Planta Med. 2007 Oct;73(12):1241-6. doi: 10.1055/s-2007-981613.
Ethanol-induced oxidative damage is commonly associated with the generation of reactive oxygen molecules, leading to oxidative stress. Considering that antioxidant activity is an important mechanism of action involved in cytoprotection, the aim of this work was to evaluate the antioxidant properties of the alkaloid indigo (1) (2 mg/kg, P. O.), obtained from the leaves of Indigofera truxillensis Kunth (Fabaceae), on rat gastric mucosa submitted to ethanol-induced (100%, 1 mL, P. O.) gastric ulcer. Enzymatic assays and DNA fragmentation analysis were performed. When ethanol was administered to the control group, the sulfhydryl content (SH) and the glutathione peroxidase (GPx) activity decreased by 41% and 50%, respectively; in contrast, superoxide dismutase (SOD) and glutathione reductase (GR) activities increased by 56% and 67%, respectively. Additionally, myeloperoxidase (MPO) activity, a marker for free radical generation caused by polymorphonuclear neutrophil (PMN) tissue infiltration, also increased 4.5-fold after ethanol treatment. Rat gastric mucosa exposed to ethanol showed DNA fragmentation. Indigo alkaloid pretreatment protected rats from ethanol-induced gastric lesions. This effect was determined by the ulcerative lesion area (ULA), indicating an inhibition of around 80% at 2 mg/kg. This alkaloid also diminished GPx activity, which was higher than that observed with ethanol alone. However, this effect was counterbalanced by increased GR activity. Indigo was unable to restore alterations in SOD activity promoted by ethanol. After indigo pretreatment, SH levels and MPO activity remained normal and gastric mucosa DNA damage caused by ethanol was also partially prevented by indigo. These results suggest that the gastroprotective mechanisms of indigo include non-enzymatic antioxidant effects and the inhibition of PMN infiltration which, in combination, partially protect the gastric mucosa against ethanol-induced DNA damage.
乙醇诱导的氧化损伤通常与活性氧分子的产生有关，从而导致氧化应激。鉴于抗氧化活性是细胞保护作用的一个重要作用机制，本研究的目的是评估从特鲁希略木蓝（豆科）叶片中获得的生物碱靛蓝（1）（2毫克/千克，口服）对大鼠胃黏膜乙醇诱导（100%，1毫升，口服）胃溃疡的抗氧化特性。进行了酶活性测定和DNA片段化分析。当给对照组大鼠灌胃乙醇后，巯基含量（SH）和谷胱甘肽过氧化物酶（GPx）活性分别下降了41%和50%；相反，超氧化物歧化酶（SOD）和谷胱甘肽还原酶（GR）活性分别增加了56%和67%。此外，髓过氧化物酶（MPO）活性是多形核中性粒细胞（PMN）组织浸润引起的自由基生成的标志物，乙醇处理后也增加了4.5倍。暴露于乙醇的大鼠胃黏膜出现DNA片段化。靛蓝生物碱预处理可保护大鼠免受乙醇诱导的胃损伤。这种作用通过溃疡病变面积（ULA）来确定，在2毫克/千克时显示出约80%的抑制率。这种生物碱还降低了GPx活性，该活性高于单独使用乙醇时观察到的活性。然而，这种作用被GR活性的增加所抵消。靛蓝无法恢复乙醇促进的SOD活性变化。靛蓝预处理后，SH水平和MPO活性保持正常，并且靛蓝还部分预防了乙醇引起的胃黏膜DNA损伤。这些结果表明，靛蓝的胃保护机制包括非酶抗氧化作用和对PMN浸润的抑制，二者共同作用可部分保护胃黏膜免受乙醇诱导的DNA损伤。
