A potential protective effect of 5-aminolevulinic acid against anticancer drug-induced damage to intestinal mucosa
A potential protective effect of 5-aminolevulinic acid against anticancer drug-induced damage to intestinal mucosa
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5-氨基乙酰丙酸对抗癌药物引起的肠粘膜损伤的潜在保护作用
DOI：
10.11482/kmj-e202147047
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
and Tomoki Yamatsuji
中科院分区：
文献类型：
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作者：
Munenori Takaoka;Naomasa Ishida;Miki Iwai;Yoshiko Tatsuta;Rie Kosaka;Etsuko Yokota;Noriko Miyake;Takuya Fukazawa;Masaki Matsubara;Tohru Tanaka;Motowo Nakajima;Naoto Ikemoto;Yoko Ochiai;and Tomoki Yamatsuji
有效的抗癌化疗方案可导致不良事件，如组织中的抗肿瘤药物诱导的氧化应激。当血红素加氧酶-1（HO-1）在氧化应激下的组织中被诱导时，观察到组织保护作用。非蛋白原性氨基酸5-氨基乙酰丙酸（5-ALA）在正常组织中诱导HO-1，并且被假设提供肠上皮保护作用以对抗药物诱导的胃肠道粘膜病症，例如腹泻和口腔炎。为了验证这一假设，我们引入了小鼠肠上皮细胞的类器官培养。使用这种类器官培养系统，SN-38（已知可诱导胃肠道粘膜疾病的药物伊立替康的活性代谢产物）与5-ALA一起和不与5-ALA一起给药，以研究HO-1抑制和表达的细胞毒性和保护作用。在正常肠上皮细胞中，观察到5-ALA诱导HO-1。在不存在5-ALA的情况下，通过施用SN-38抑制HO-1表达，但通过共同施用5-ALA维持HO-1表达。在小鼠肠类器官中，相同的5-ALA给药诱导HO-1表达。当向类器官施用SN-38时，细胞死亡信号随着氧化应激反应而表达，但5-ALA的共施用诱导HO-1表达和细胞死亡减少。通过5-ALA诱导HO-1表达抑制由抗肿瘤药物引起的氧化应激介导的肠上皮细胞死亡，是一种潜在的新的肠上皮保护治疗药物诱导的胃肠道粘膜损伤的方法。doi：10.11482/KMJ-E202147047（2021年2月15日受理）
An effective anti-cancer chemotherapy regimen can cause adverse events such as antineoplastic drug-induced oxidative stress in tissues. When hemeoxygenase-1 (HO-1) is induced in tissues under oxidative stress, a tissue protective effect is observed. The non-proteinogenic amino acid 5-aminolevulinic acid (5-ALA) induces HO-1 in normal tissue and is hypothesized to provide an intestinal epithelial protective effect against drug-induced gastrointestinal mucosal disorders such as diarrhea and stomatitis. To validate this hypothesis, we introduced organoid culture from mouse intestinal epithelium. Using this organoid culture system, SN-38, the active metabolite of the antineoplastic drug irinotecan which is known to induce gastrointestinal mucosal disorders, was administered with and without 5-ALA to investigate the cytotoxic and protective effects of HO-1 suppression and expression. In normal intestinal epithelial cells, HO-1 induction by 5-ALA was observed. HO-1 expression was suppressed by the administration of SN-38 in the absence of 5-ALA, but was maintained by the co-administration of 5-ALA. In the mouse intestinal organoids, the same administration of 5-ALA induced HO-1 expression. When SN-38 was administered to the organoids, a cell death signal was expressed with an oxidative stress response, but the co-administration of 5-ALA induced HO-1 expression and cell death was decreased. The induction of HO-1 expression by 5-ALA administration suppresses intestinal epithelial cell death mediated by oxidative stress caused by antineoplastic drugs and is a potential new intestinal epithelial protective therapy against drug-induced gastrointestinal mucosal injury. doi: 10.11482/KMJ-E202147047 (Accepted on February 15, 2021)