Minati Marie-Albane, Libert Maxime, Dahou Hajar, Jacquemin Patrick, Assi Mohamad
Liver and Pancreas Differentiation (LPAD) Group, de Duve Institute, Université Catholique de Louvain, 1200 Brussels, Belgium.
Antioxidants (Basel). 2021 Jul 11;10(7):1107. doi: 10.3390/antiox10071107.
Pancreatitis, an inflammation of the pancreas, appears to be a main driver of pancreatic cancer when combined with mutations. In this context, the exact redox mechanisms are not clearly elucidated. Herein, we treated mice expressing a mutation in pancreatic acinar cells with cerulein to induce acute pancreatitis. In the presence of , pancreatitis triggered significantly greater redox unbalance and oxidative damages compared to control mice expressing alleles. Further analyses identified the disruption in glutathione metabolism as the main redox event occurring during pancreatitis. Compared to the background, -bearing mice showed a greater responsiveness to treatment with a thiol-containing compound, N-acetylcysteine (NAC). Notably, NAC treatment increased the pancreatic glutathione pool, reduced systemic markers related to pancreatic and liver damages, limited the extent of pancreatic edema and fibrosis as well as reduced systemic and pancreatic oxidative damages. The protective effects of NAC were, at least, partly due to a decrease in the production of tumor necrosis factor-α (TNF-α) by acinar cells, which was concomitant with the inhibition of NF-κB(p65) nuclear translocation. Our data provide a rationale to use thiol-containing compounds as an adjuvant therapy to alleviate the severity of inflammation during pancreatitis and pancreatic tumorigenesis.
胰腺炎是胰腺的一种炎症，当与基因突变同时存在时，似乎是胰腺癌的主要驱动因素。在这种情况下，确切的氧化还原机制尚未完全阐明。在此，我们用雨蛙肽处理在胰腺腺泡细胞中表达一种突变的小鼠，以诱导急性胰腺炎。与表达野生型等位基因的对照小鼠相比，在存在该突变的情况下，胰腺炎引发了更显著的氧化还原失衡和氧化损伤。进一步分析确定，谷胱甘肽代谢紊乱是胰腺炎期间发生的主要氧化还原事件。与野生型背景相比，携带该突变的小鼠对含硫醇化合物N - 乙酰半胱氨酸（NAC）的治疗反应更大。值得注意的是，NAC治疗增加了胰腺谷胱甘肽池，降低了与胰腺和肝脏损伤相关的全身标志物水平，限制了胰腺水肿和纤维化的程度，并减少了全身和胰腺的氧化损伤。NAC的保护作用至少部分归因于腺泡细胞肿瘤坏死因子 - α（TNF - α）产生的减少，这与NF - κB（p65）核转位的抑制同时发生。我们的数据为使用含硫醇化合物作为辅助治疗以减轻胰腺炎和胰腺肿瘤发生过程中炎症的严重程度提供了理论依据。
