Department of Biomedical and Pharmaceutical Sciences, Chapman University, 9401 Jeronimo Road, Irvine, CA, 92618-1908, USA.
Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, 54000, Pakistan.
Sci Rep. 2023 Oct 16;13(1):17516. doi: 10.1038/s41598-023-44629-y.
Chronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP-UPLC-MS/MS) and hydrophilic interaction liquid chromatography (HILIC)-UPLC-MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-L-aspartic acid, thyroxine, and 3-beta-Hydroxy-5-cholestenoate were found to be significantly downregulated. 3-beta-Hydroxy-5-cholestenoate was downregulated more significantly in male than female kidneys. Trichome Staining also showed remarkable kidney fibrosis in mice subjected to chronic hypoxia. Our study offers potential intracellular metabolite signatures for hypoxic kidneys.
慢性缺氧可能对心血管和肾脏系统产生巨大影响。显微镜技术、代谢组学和生物信息学的进步为识别新的生物标志物提供了机会。在这项研究中，我们旨在使用非靶向代谢组学分析来阐明慢性缺氧引起的肾脏组织中的代谢变化。采用正离子和负离子模式电喷雾电离的反相超高效液相色谱-质谱/质谱（RP-UPLC-MS/MS）和亲水相互作用液相色谱（HILIC）-UPLC-MS/MS 方法进行代谢物谱分析。代谢组学分析显示与肉碱合成和嘌呤代谢相关的代谢物增加。此外，胆红素显著增加。血红素、N-乙酰-L-天冬氨酸、甲状腺素和 3-β-羟基-5-胆甾烯酸明显下调。3-β-羟基-5-胆甾烯酸在雄性肾脏中的下调更为显著。毛囊染色也显示慢性缺氧小鼠的肾脏纤维化明显。我们的研究为缺氧肾脏提供了潜在的细胞内代谢特征。
