Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University, 2-4 Bolshaya Pirogovskaya St., Moscow, Russia, 119991.
PhD Program in Nanoscience and Advanced Technology, Department of Diagnostics and Public Health, University of Verona, Policlinico G.B. Rossi - P.le L.A. Scuro 10, 37134, Verona, Italy.
Metabolomics. 2018 Aug 20;14(9):112. doi: 10.1007/s11306-018-1413-1.
Nitroproston® is a novel multi-target drug bearing natural prostaglandin E (PGE) and nitric oxide (NO)-donating fragments for treatment of inflammatory and obstructive diseases (i.e., asthma and obstructive bronchitis).
To investigate the effects of Nitroproston® administration on plasma metabolomics in vivo.
Experimental in vivo study randomly assigning the target drug (treatment group) or a saline solution without the drug (vehicle control group) to 12 rabbits (n = 6 in each group). Untargeted (5880 initial features; 1869 negative-4011 positive ion peaks; UPLC-IT-TOF/MS) and 84 targeted moieties (Nitroproston® related metabolites, prostaglandins, steroids, purines, pyrimidines and amino acids; HPLC-QQQ-MS/MS) were measured from plasma at 0, 2, 4, 6, 8, 12, 18, 24, 32 and 60 min after administration.
PGE, 13,14-dihydro-15-keto-PGE, PGB, 1,3-GDN and 15-keto-PGE increased in the treatment group. Steroids (i.e., cortisone, progesterone), organic acids, 3-oxododecanoic acid, nicotinate D-ribonucleoside, thymidine, the amino acids serine and aspartate, and derivatives pyridinoline, aminoadipic acid and uric acid increased (p < 0.05 AUCROC curve > 0.75) after treatment. Purines (i.e., xanthine, guanine, guanosine), bile acids, acylcarnitines and the amino acids L-tryptophan and L-phenylalanine were decreased. Nitroproston® impacted steroidogenesis, purine metabolism and ammonia recycling pathways, among others.
Nitroproston®, a multi action novel drug based on natural prostaglandins, altered metabolites (i.e., guanine, adenine, cortisol, cortisone and aspartate) involved in purine metabolism, urea and ammonia biological cycles, steroidogenesis, among other pathways. Suggested mechanisms of action, metabolic pathway interconnections and useful information to further understand the metabolic effects of prostaglandin administration are presented.
Nitroproston®是一种新型多靶标药物，含有天然前列腺素 E（PGE）和一氧化氮（NO）供体片段，用于治疗炎症和阻塞性疾病（如哮喘和阻塞性支气管炎）。
研究 Nitroproston®给药对体内血浆代谢组学的影响。
实验性体内研究将靶标药物（治疗组）或不含药物的生理盐水（载体对照组）随机分配给 12 只兔子（每组 6 只）。从给药后 0、2、4、6、8、12、18、24、32 和 60 分钟的血浆中测量非靶向（5880 个初始特征；1869 个负离子峰；4011 个正离子峰；UPLC-IT-TOF/MS）和 84 个靶向成分（Nitroproston®相关代谢物、前列腺素、类固醇、嘌呤、嘧啶和氨基酸；HPLC-QQQ-MS/MS）。
治疗组中 PGE、13,14-二氢-15-酮-PGE、PGB、1,3-GDN 和 15-酮-PGE 增加。类固醇（如皮质酮、孕酮）、有机酸、3-氧代十二烷酸、烟碱 D-核昔、胸昔、氨基酸丝氨酸和天冬氨酸以及吡啶酮酸、氨基己二酸和尿酸衍生物增加（p<0.05 AUCROC 曲线>0.75）。嘌呤（如黄嘌呤、鸟嘌呤、鸟苷）、胆汁酸、酰基辅酶 A 和氨基酸 L-色氨酸和 L-苯丙氨酸减少。Nitroproston®影响类固醇生成、嘌呤代谢和氨循环途径等。
Nitroproston®是一种基于天然前列腺素的新型多作用药物，改变了参与嘌呤代谢、尿素和氨生物循环、类固醇生成等途径的代谢物（如鸟嘌呤、腺嘌呤、皮质醇、皮质酮和天冬氨酸）。提出了作用机制、代谢途径相互关系以及进一步了解前列腺素给药代谢影响的有用信息。
