Abstract：
Cyclophosphamide is an anti-neoplastic drug that has shown competence in the management of a broad range of malignant tumors. In addition, it represents a keystone agent for management of immunological conditions. Despite these unique properties, induction of lung toxicity may limit its clinical use. Omarigliptin is one of the dipeptidyl peptidase-4 inhibitors that has proven efficacy in management of diabetes mellitus. Rosinidin is an anthocyanidin flavonoid that exhibited promising results in management of diseases characterized by oxidative stress, inflammation, and apoptosis. The present work investigated the possible effects of omarigliptin with or without rosinidin on cyclophosphamide-induced lung toxicity with an exploration of the molecular mechanisms that contribute to these effects. In a rodent model of cyclophosphamide elicited lung toxicity, the potential efficacy of omarigliptin with or without rosinidin was investigated at both the biochemical and the histopathological levels. Both omarigliptin and rosinidin exhibited a synergistic ability to augment the tissue antioxidant defenses, mitigate the inflammatory pathways, restore glucagon-like peptide-1 levels, modulate high mobility group box 1 (HMGB1)/receptors of advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) axis, downregulate the fibrogenic mediators, and create a balance between the pathways involved in apoptosis and the autophagy signals in the pulmonary tissues. In conclusion, omarigliptin/rosinidin combination may be introduced as a novel therapeutic modality that attenuates the different forms of lung toxicities induced by cyclophosphamide.
摘要：
环磷酰胺是一种抗肿瘤药物，已显示出在广泛的恶性肿瘤的管理能力。此外,它代表了免疫疾病管理的关键试剂。尽管这些独特的属性，诱导肺毒性可能限制其临床使用。奥马格列汀是二肽基肽酶-4抑制剂之一，已被证明在治疗糖尿病方面有效。Rosinidin是一种花青素类黄酮，在以氧化应激为特征的疾病的管理中表现出有希望的结果，炎症,和凋亡。本工作研究了奥马列汀与或不与松香苷对环磷酰胺诱导的肺毒性的可能影响，并探索了导致这些影响的分子机制。在环磷酰胺引起肺毒性的啮齿动物模型中，在生化和组织病理学水平上研究了奥马列汀联合或不联合松香苷的潜在疗效.omarigliptin和松香苷都表现出协同增强组织抗氧化防御的能力，减轻炎症途径，恢复胰高血糖素样肽-1水平，调节高迁移率族蛋白1（HMGB1）/糖基化终产物受体（RAGE）/核因子κB（NF-κB）轴，下调纤维化介质，并在肺组织中参与细胞凋亡的途径和自噬信号之间建立平衡。总之,omarigliptin/松香素组合可以作为一种新的治疗方式引入，可以减轻环磷酰胺诱导的不同形式的肺毒性。
