The Long-Acting Glucagon-Like Peptide-2 Analog Apraglutide Enhances Intestinal Protection and Survival After Chemotherapy and Allogeneic Transplantation in Mice.

IF 1.1 4区 医学 Q3 SURGERY Annals of Transplantation Pub Date : 2024-11-05 DOI:10.12659/AOT.945249
Mark D Minden, Cindy Audiger, Geneviève Chabot-Roy, Sylvie Lesage, Jean-Sébastien Delisle, Barbara Biemans, Violetta Dimitriadou
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Abstract

BACKGROUND The gastrointestinal (GI) barrier can be damaged by chemotherapy or radiation therapy, causing fatigue, malnutrition, sepsis, dose-limiting toxicity, and, occasionally, death. Glucagon-like peptide-2 (GLP-2) promotes mucosal epithelium growth and repair in the GI tract. Here, we examined the GI-protective effects of apraglutide, a long-acting peptide GLP-2 analog, in murine models of chemotherapy, and total body irradiation followed by allogeneic transplantation. MATERIAL AND METHODS The impact of apraglutide on cytarabine or melphalan chemotherapy-induced intestinal damage was assessed in BALB/c mice, and the effect on allogeneic transplantation in BALB/cJ and C57BL/6J mice. Outcomes included survival, and changes in body weight, intestinal function and morphology, including colon length and bacterial composition of the intestinal microbiota. RESULTS Adding apraglutide to chemotherapy significantly improved survival rates and reduced weight loss, with no impact on leukocyte counts (and, therefore, no effect on chemotherapy-induced immunosuppression), compared with chemotherapy alone in mice. These benefits were associated with preservation of the morphological integrity of the GI mucosa, attenuation of the negative impact of cytarabine on the intestinal microbiota, and significant improvement in plasma levels of citrulline. In addition, in a model of irradiation followed by allogeneic transplantation, mice in groups receiving apraglutide had improved survival, reduced weight loss, and increased colon length compared with those that did not. CONCLUSIONS Apraglutide protects intestinal function and improves survival in mice following allogeneic transplantation or chemotherapy with cytarabine or melphalan. The potential effect of apraglutide on chemotherapy efficacy and on engraftment following allogeneic transplantation has been investigated in a parallel manuscript.

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长效胰高血糖素样肽-2类似物阿普拉鲁肽能增强小鼠化疗和同种异体移植后的肠道保护和存活能力
背景 胃肠道(GI)屏障可因化疗或放疗而受损,导致疲劳、营养不良、败血症、剂量限制性毒性,有时甚至死亡。胰高血糖素样肽-2(GLP-2)可促进消化道粘膜上皮的生长和修复。在此,我们研究了阿普鲁肽(一种长效多肽 GLP-2 类似物)在小鼠化疗模型和全身照射后异体移植模型中的胃肠道保护作用。材料与方法 在 BALB/c 小鼠中评估阿普拉鲁肽对阿糖胞苷或美法仑化疗引起的肠道损伤的影响,以及对 BALB/cJ 和 C57BL/6J 小鼠异体移植的影响。结果包括存活率、体重变化、肠道功能和形态,包括结肠长度和肠道微生物群的细菌组成。结果 与单独化疗相比,在化疗中加入阿普鲁肽可显著提高小鼠的存活率并减少体重下降,但对白细胞计数没有影响(因此对化疗引起的免疫抑制也没有影响)。这些益处与保护胃肠道粘膜形态完整性、减轻阿糖胞苷对肠道微生物群的负面影响以及显著改善血浆瓜氨酸水平有关。此外,在辐照后进行同种异体移植的模型中,与未接受阿普拉鲁肽治疗的小鼠相比,接受阿普拉鲁肽治疗组的小鼠存活率提高,体重减轻,结肠长度增加。结论 阿普拉鲁肽能保护小鼠的肠道功能,并提高小鼠异体移植或接受阿糖胞苷或美法仑化疗后的存活率。阿普拉鲁肽对化疗疗效和异体移植后移植的潜在影响已在一份平行稿件中进行了研究。
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来源期刊
CiteScore
2.50
自引率
0.00%
发文量
79
审稿时长
>12 weeks
期刊介绍: Annals of Transplantation is one of the fast-developing journals open to all scientists and fields of transplant medicine and related research. The journal is published quarterly and provides extensive coverage of the most important advances in transplantation. Using an electronic on-line submission and peer review tracking system, Annals of Transplantation is committed to rapid review and publication. The average time to first decision is around 3-4 weeks. Time to publication of accepted manuscripts continues to be shortened, with the Editorial team committed to a goal of 3 months from acceptance to publication. Expert reseachers and clinicians from around the world contribute original Articles, Review Papers, Case Reports and Special Reports in every pertinent specialty, providing a lot of arguments for discussion of exciting developments and controversies in the field.
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The Long-Acting Glucagon-Like Peptide-2 Analog Apraglutide Enhances Intestinal Protection and Survival After Chemotherapy and Allogeneic Transplantation in Mice. Predictive Model for Post-Transplant Renal Fibrosis Using Ultrasound Shear Wave Elastography. Early Post-Transplant Serum Ferritin Levels as Predictive Biomarkers for Severe Acute Graft-Versus-Host Disease in Pediatric Umbilical Cord Blood Transplantation for Acute Leukemia. One-Year Mortality After Lung Transplantation: Experience of a Single French Center Between 2012 and 2021. Kidney After Lung Transplants or Combined Kidney-Lung Transplantation: A Single-Center Retrospective Cohort Study.
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