In vitro and in vivo effects of gliotoxin, a fungal metabolite:: Efficacy against dextran sodium sulfate-induced colitis in rats
In vitro and in vivo effects of gliotoxin, a fungal metabolite:: Efficacy against dextran sodium sulfate-induced colitis in rats
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DOI：
10.1023/a:1005630723111
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发表时间：
2000-12-01
影响因子：
3.1
通讯作者：
Le, T
中科院分区：
文献类型：
--
作者：
Fitzpatrick, LR;Wang, J;Le, T
胶霉毒素是一种真菌代谢产物，具有免疫抑制特性。首先，我们确定胶毒素是否可以抑制巨噬细胞和结肠上皮细胞系的细胞因子产生，以及它是否抑制这些相同细胞类型的核因子-κ B。其次，我们评估了胶霉毒素是否可以减少葡聚糖硫酸钠诱导的大鼠结肠炎。在第7天或第21天评价疾病活动指数、髓过氧化物酶活性和细胞因子水平。在这两种细胞系中，胶毒素剂量依赖性地抑制细胞因子的产生和核因子-κ B。在第21天，胶霉毒素显著降低了大鼠的疾病活动（腹泻和血便）。在第7天，胶霉毒素治疗显著改善了结肠炎的各种指数，包括结肠细胞因子水平。更大剂量的胶粘毒素明显降低了摄食量和体重增加。总之，胶粘毒素（一种核因子-κ B抑制剂）有效降低了葡聚糖硫酸钠诱导的大鼠结肠炎。然而，胶霉毒素在这些大鼠中表现出狭窄的治疗毒性比。
Gliotoxin is a fungal metabolite that has immunosuppressive properties. First, we determined if gliotoxin could inhibit cytokine production from macrophage and colonic epithelial cell lines, as well as whether it inhibited nuclear factor-kappa B in these same cell types. Second, we evaluated whether gliotoxin could reduce dextran sodium sulfate-induced colitis in rats. A disease activity index, myeloperoxidase activity, and cytokine levels were evaluated on either day 7 or 21. In both cell lines, gliotoxin dose dependently inhibited cytokine production and nuclear factor-kappa B. On day 21, gliotoxin significantly reduced disease activity (diarrhea and bloody stools) in rats. On day 7, gliotoxin treatment significantly improved various indices of colitis, including colonic cytokine levels. Decreased food consumption and weight gain was evident with a larger dose of gliotoxin, In summary, gliotoxin, a nuclear factor-kappa B inhibitor, effectively reduced dextran sodium sulfate-induced colitis in rats. However, gliotoxin exhibited a narrow therapeutic to toxicity ratio in these rats.