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Rabbit plasma metabolomic analysis of Nitroproston®: a multi target natural prostaglandin based-drug

Shestakova K. M., Brito O. A. A., Mesonzhnik N. V., Moskaleva N. E., Kurynina K. O., Grestskaya N. M., Serkov I. V., Lyubimov I. I., Bezuglov V. V., Appolonova S. A.
Metabolomics
Vol.14, Issue9, Num.112
Опубликовано: 2018
Тип ресурса: Статья

DOI:10.1007/s11306-018-1413-1

Аннотация:
Introduction: Nitroproston® is a novel multi-target drug bearing natural prostaglandin E 2 (PGE 2 ) 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 min after administration. Results: PGE 2 , 13,14-dihydro-15-keto-PGE 2 , PGB 2 , 1,3-GDN and 15-keto-PGE 2 increased in the treatment group. Steroids (i.e., cortisone, proge
Ключевые слова:
LC–MS; Metabolomics; Multivariate statistical analysis; Nitroproston®; Pathway analysis; Prostaglandin; Time-resolved metabolomics
3 oxododecanoic acid; amino acid; aminoadipic acid; ammonia; aspartic acid; bronchodilating agent; carboxylic acid; nicotinic acid; nitroproston; phenylalanine; prostaglandin; prostaglandin B2; prostaglandin E2; purine derivative; pyridinoline; pyrimidine derivative; ribonucleoside; serine; thymidine; tryptophan; unclassified drug; uric acid; prostaglandin E2; animal experiment; area under the curve; Article; blood level; chinchilla rabbit; controlled study; in vivo study; liquid chromatography-mass spectrometry; metabolite; metabolomics; nonhuman; plasma; purine metabolism; receiver operating characteristic; steroidogenesis; time of flight mass spectrometry; animal; blood; chemistry; Leporidae; metabolism; metabolomics; Animals; Dinoprostone; Metabolomics; Rabbits
Язык текста: Английский
ISSN: 1573-3890
Shestakova K. M. Kseniya Mikhaylovna 1992-
Brito O. A. A. Olivares Aleks Al`berto 1982-
Mesonzhnik N. V. Natal`ya Vladimirovna 1983-
Moskaleva N. E. Natal`ya Evgenyevna 1971-
Kurynina K. O.
Grestskaya N. M.
Serkov I. V.
Lyubimov I. I.
Bezuglov V. V.
Appolonova S. A. Svetlana Aleksandrovna 1973-
Шестакова К. М. Ксения Михайловна 1992-
Брито О. А. А. Оливарес Алекс Альберто 1982-
Месонжник Н. В. Наталья Владимировна 1983-
Москалева Н. Е. Наталья Евгеньевна 1971-
Курyнина К. О.
Гресцкайа Н. М.
Серков И. В.
Любимов И. И.
Безуглов В. В.
Апполонова С. А. Светлана Александровна 1973-
Rabbit plasma metabolomic analysis of Nitroproston®: a multi target natural prostaglandin based-drug
Текст визуальный непосредственный
Metabolomics
Springer Science+Business Media Inc., Formerly Kluwer Boston Inc
Vol.14, Issue9 Num.112
2018
Статья
LC–MS Metabolomics Multivariate statistical analysis Nitroproston® Pathway analysis Prostaglandin Time-resolved metabolomics
3 oxododecanoic acid amino acid aminoadipic acid ammonia aspartic acid bronchodilating agent carboxylic acid nicotinic acid nitroproston phenylalanine prostaglandin prostaglandin B2 prostaglandin E2 purine derivative pyridinoline pyrimidine derivative ribonucleoside serine thymidine tryptophan unclassified drug uric acid prostaglandin E2 animal experiment area under the curve Article blood level chinchilla rabbit controlled study in vivo study liquid chromatography-mass spectrometry metabolite metabolomics nonhuman plasma purine metabolism receiver operating characteristic steroidogenesis time of flight mass spectrometry animal blood chemistry Leporidae metabolism metabolomics Animals Dinoprostone Metabolomics Rabbits
Introduction: Nitroproston® is a novel multi-target drug bearing natural prostaglandin E 2 (PGE 2 ) 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 min after administration. Results: PGE 2 , 13,14-dihydro-15-keto-PGE 2 , PGB 2 , 1,3-GDN and 15-keto-PGE 2 increased in the treatment group. Steroids (i.e., cortisone, proge