Kolgazi Meltem, Jahovic Nermina, Yüksel Meral, Ercan Feriha, Alican Inci
Department of Physiology, School of Medicine, Marmara Unviersity, Haydarpasa, Istanbul, Turkey.
J Gastroenterol Hepatol. 2007 Nov;22(11):1859-65. doi: 10.1111/j.1440-1746.2006.04504.x.
Alpha-lipoic acid (ALA) has been shown to combat oxidative stress by quenching a variety of reactive oxygen species. It is involved in the regeneration of exogenous and endogenous antioxidants, chelation of metal ions, and repair of oxidized proteins. This study aimed to evaluate the potential beneficial effect of ALA on trinitrobenzenesulfonic acid (TNBS)-induced gut ileitis and colitis in rats.
After 48 h of fasting, Sprague-Dawley rats underwent a laparotomy under ether anesthesia. TNBS solution 30 mg/mL in 40% ethanol (1 mL) was injected into the lumen, 10 cm proximal to the ileocolonic junction to induce ileitis or intrarectally 8 cm proximal to the anal sphincter to induce colitis. ALA (25 mg/kg intraperitoneally, twice a day) was given after induction of inflammation and continued for 3 days. All animals were decapitated 3 days after induction of the inflammation. The mucosal lesions of the ileum and colon were scored macroscopically and microscopically. Samples were taken for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, tissue-associated myeloperoxidase (MPO) activity and luminol- or lucigenin-enhanced chemiluminescence (CL).
Macroscopic scores, morphological changes and increased tissue lipid peroxidation with a concomitant reduction in GSH of the ileitis or colitis groups were all reversed by treatment with ALA. ALA treatment was also effective in improving tissue MPO activity and CL values, which were elevated in untreated ileitis or colitis groups.
ALA is beneficial in TNBS-induced gut inflammation in rats via suppression of neutrophil accumulation, preservation of endogenous glutathione and inhibition of reactive oxidant generation.
α-硫辛酸(ALA)已被证明可通过淬灭多种活性氧来对抗氧化应激。它参与外源性和内源性抗氧化剂的再生、金属离子的螯合以及氧化蛋白质的修复。本研究旨在评估ALA对三硝基苯磺酸(TNBS)诱导的大鼠肠道回肠炎和结肠炎的潜在有益作用。
禁食48小时后,将Sprague-Dawley大鼠在乙醚麻醉下进行剖腹手术。将40%乙醇(1 mL)中30 mg/mL的TNBS溶液注入回结肠交界处近端10 cm的肠腔内以诱导回肠炎,或经直肠注入肛门括约肌近端8 cm处以诱导结肠炎。在炎症诱导后给予ALA(25 mg/kg腹腔注射,每天两次),并持续3天。在炎症诱导3天后将所有动物断头。对回肠和结肠的黏膜损伤进行宏观和微观评分。采集样本用于测量丙二醛(MDA)和谷胱甘肽(GSH)水平、组织相关髓过氧化物酶(MPO)活性以及鲁米诺或光泽精增强的化学发光(CL)。
回肠炎或结肠炎组的宏观评分、形态学变化以及组织脂质过氧化增加并伴有GSH降低的情况,均通过ALA治疗得到逆转。ALA治疗在改善组织MPO活性和CL值方面也有效,这些指标在未治疗的回肠炎或结肠炎组中升高。
ALA通过抑制中性粒细胞聚集、保留内源性谷胱甘肽以及抑制活性氧化剂生成,对TNBS诱导的大鼠肠道炎症有益。