MetaboLights MTBLS728 - GNPS Rabbit plasma metabolomic analysis of Nitroproston: a multi target natural prostaglandin based-drug (Targeted study)

INTRODUCTION: Nitroproston® is a novel multi-target drug bearing natural prostaglandin E2 (PGE2) and nitric oxide (NO)-donating fragments for treatment of inflammatory and obstructive diseases (i.e. asthma and obstructive bronchitis). OBJECTIVES: To investigate the effects of Nitroproston® administration on plasma metabolomics in vivo. METHODS: 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 minutes after administration. RESULTS: PGE2, 13,14-dihydro-15-keto-PGE2, PGB2, 1,3-GDN and 15-keto-PGE2 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, aminoadypic 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. CONCLUSION: Nitroproston®, a multi action novel drug based on natural prostaglandins, altered metabolites previously implicated as having anti inflammatory or anti-asthma properties (i.e. guanine, adenine, cortisol, cortisone and aspartate). Steroids, purine, urea and ammonia biological cycles were impacted. Mechanisms of action, metabolic pathway interconnections and useful information to further understand the metabolic effects of prostaglandin administration are presented. The targeted study data is reported in the current study MTBLS728. The untargeted study data associated with this study is reported in MTBLS727.
Linked Studies: MTBLS727