Khodir Ahmed E, Atef Hoda, Said Eman, ElKashef Hassan A, Salem Hatem A
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Delta University, Mansoura, Egypt.
Department of Histology and Cytology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Inflammopharmacology. 2017 Feb;25(1):119-135. doi: 10.1007/s10787-016-0305-0. Epub 2017 Jan 3.
Given the increased incidence of ulcerative colitis worldwide, the current study was designed to investigate the coloprotective potential of CoQ10 against experimentally induced ulcerative colitis (UC) and specify the implicated mechanisms.
Ulcerative colitis was induced by intracolonic instillation of [2 ml, 3% v/v acetic acid (AA)]. Rats in the different experimental groups received CoQ10 (10 or 30 and 100 mg/kg, orally) for eight consecutive days, either in a protective or curative regimen.
Intracolonic AA instillation significantly increased colon/body weight index, colon weight/colon length ratio, clinical evaluation and macroscopic scoring of UC, serum LDH, C-reactive protein and decreased the serum total antioxidant capacity. Colon MDA, TNF-α and calcium content significantly increased as well, with concomitant reduction in colon GSH, SOD, CAT, Nrf2 and HO-1 contents. Moreover, immunohistochemical staining of colon specimen revealed increased expression of caspase-3 with significant histopathological changes. Coenzyme Q10 suppressed the release of inflammatory biomarkers and restored oxidants/antioxidants hemostasis. In a dose-dependent manner, CoQ10 significantly decreased colon/body weight index, colon weight/colon length ratio, clinical evaluation and macroscopic scoring of UC, serum LDH, C-reactive protein, colon MDA, TNF-α, caspase-3 expression and increased the serum total antioxidant capacity. Colon GSH, SOD, CAT, Nrf2 and HO-1 contents significantly increased. Moreover, coenzyme Q10 significantly preserved tissue histopathological architecture. It appears that the coloprotective effect of CoQ10 was calcium-independent.
Coenzyme Q10 dose-dependently protects against AA-induced UC mainly via modulation of Nrf2/HO-1 and caspase-3 pathways. Antioxidant, anti-inflammatory and anti-apoptotic properties of CoQ10 are implicated in its observed therapeutic benefit.
鉴于全球溃疡性结肠炎发病率上升，本研究旨在探讨辅酶Q10对实验性诱导的溃疡性结肠炎（UC）的结肠保护潜力，并明确其中涉及的机制。
通过结肠内注入[2毫升，3%（体积/体积）乙酸（AA）]诱导溃疡性结肠炎。不同实验组的大鼠连续八天接受辅酶Q10（10、30和100毫克/千克，口服），采用保护或治疗方案。
结肠内注入AA显著增加了结肠/体重指数、结肠重量/结肠长度比、UC的临床评估和宏观评分、血清乳酸脱氢酶、C反应蛋白，并降低了血清总抗氧化能力。结肠丙二醛、肿瘤坏死因子-α和钙含量也显著增加，同时结肠谷胱甘肽、超氧化物歧化酶、过氧化氢酶、核因子E2相关因子2和血红素加氧酶-1含量降低。此外，结肠标本的免疫组织化学染色显示半胱天冬酶-3表达增加，伴有明显的组织病理学变化。辅酶Q10抑制了炎症生物标志物的释放，并恢复了氧化剂/抗氧化剂的平衡。辅酶Q10以剂量依赖的方式显著降低了结肠/体重指数、结肠重量/结肠长度比、UC的临床评估和宏观评分、血清乳酸脱氢酶、C反应蛋白、结肠丙二醛、肿瘤坏死因子-α、半胱天冬酶-3表达，并增加了血清总抗氧化能力。结肠谷胱甘肽、超氧化物歧化酶、过氧化氢酶、核因子E2相关因子2和血红素加氧酶-1含量显著增加。此外，辅酶Q10显著保留了组织的组织病理学结构。辅酶Q10的结肠保护作用似乎与钙无关。
辅酶Q10主要通过调节核因子E2相关因子2/血红素加氧酶-1和半胱天冬酶-3途径，剂量依赖性地保护免受AA诱导的UC。辅酶Q10的抗氧化、抗炎和抗凋亡特性与其观察到的治疗益处有关。
