Project description: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 untargeted study data is reported in the current study MTBLS727. The targeted study data associated with this study is reported in MTBLS728. Linked Studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS728' target='_blank'>MTBLS728</a>

Project description: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: <a href='https://www.ebi.ac.uk/metabolights/MTBLS727' target='_blank'>MTBLS727</a>

Project description:Drug-induced alterations in transcriptional regulation play a central role in establishing the persistent neuroplasticities that occur during drug addiction. Additionally, changes in gene expression associated with drug administration provide valuable insight into the molecular basis of drug abuse. The molecular mechanisms that underlie susceptibility to psychostimulant addiction remain unknown. Identifying the common gene transcriptional responses to psychostimulants can provide a mechanistic insight to elucidate the molecular nature of drug dependence. Male Wistar rats (4 weeks old) were acclimatized for a week to their housing conditions prior to experiments. Thereafter, they were divided into two groups: (cohort 1) 4 groups of rats (n=12 rats per group) given saline only (i.p., "drug-naive" rats); and (cohort 2): 3 groups of rats given either methamphetamine, amphetamine or methylphenidate (5 mg/kg,i.p., M-CM-"M-bM-^BM-,M-EM-^Sdrug-pretreated") for 7 days (2x daily) prior to behavioral assays. Conditioned place preference (CPP) tests were conducted a day after the final drug administration. Rats which showed CPP were evaluated for self-administration of the psychostimulants. [Cohort 1] A day after the final self-administration test, brains of 2-3 rats from each subgroups (i.e. those which showed the most robust self-administration), as well as 5 rats from the control group were removed for microarray analysis. The striatum (rostral part of the caudate putamen and the nucleus accumbens [NAc]) and the prefrontal cortex were dissected and immediately frozen at -70M-CM-^BM-BM-0C. Total RNA was isolated and gene expression profiling was conducted on independent pools of total RNA from 2-5 animals per group. [Cohort 2] A day after the final self-administration test, brains of 3 rats from each subgroups (i.e. those which showed the most robust self-administration), as well as 3 rats from the control group were removed for microarray analysis. The striatum (rostral part of the caudate putamen and the nucleus accumbens [NAc]) and the prefrontal cortex were dissected and immediately frozen at -70M-BM-0C. Total RNA was isolated and gene expression profiling was conducted on independent pools of total RNA from three animals per group.

Project description:VAAM stands for an amino acid mixture simulating the composition of Vespa, a hornet larval saliva. We conducted a comparative study on metabolism-regulatory roles of VAAM, casein-simulating amino acid mixture (CAAM), and pure water on murine hepatic and adipose tissue transcriptomes. Mice were orally fed VAAM solution ( 0.675 g/ kg BW = 2% of food-derived amino acids = 0.38% of total food energy/ day), CAAM solution ( 0.675 g / kg BW/ day) or water under ad libitum for five days. Hepatic transcriptome comparison of VAAM, CAAM and water-treated groups revealed a VAAM-specific regulation of the metabolic pathway, i.e., the down-regulation of glycolysis and fatty acid oxidation, and up-regulation of poly unsaturated fatty acid synthesis and glycogenic amino acids utilization in TCA cycle. Similar transcriptomic analysis of white and brown adipose tissues (WAT and BAT) suggested the up-regulation of phospholipid synthesis in WAT and the negative regulation of cellular processes in BAT. Because these coordinated regulations of tissue transcriptomes implicated the presence of upstream signaling common to these tissues, we conducted Ingenuity Pathways Analysis of these transcriptomes with the results that estrogenic and glucagon signals seemed to be activated in liver and WAT as well as beta-adrenergic signaling did in the three tissues by administration of VAAM. Our data provide a clue to understanding the role of VAAM in metabolic regulation of multiple tissues. Mice were divided randomly into three groups, VAAM, CAAM or water administered group. VAAM, CAAM or water was orally administrated five times once a day using feeding tube. The dosage of 1.8%VAAM, 1.8%CAAM or water was 37.5 microliter per gram of body weight. On day of last administration, food was removed and mice were moved to clean cages at 8:00. The last administrations started at 10:00. At 4 hours later after last administration, mice were sacrificed by cervical dislocation to collect blood, liver, white adipose tissue (WAT) and brown adipose tissue (BAT). Small hepatic pieces were immersed into RNAlater. WAT and BAT were frozen immediately after extraction using liquid nitrogen. All samples were extracted total RNA and hybridized on Affymetrix microarrays.

Project description:Aim: To find the genes that related with the drug's(7-P) function. Design: 36 Rats were randomly divided into three group:control group(12), model group(12) and drug group(12). At last, randomly choosing 3 Rat from each group to do genechip analysis. In model group, the Porcine serum was given intraperitoneally (i.p.) to rats in a volume of 1.5 mL/kg every 3 days for a total of 20 treatments. Effect on model animals was confirmed by liver histology and biochemical assays . In drug group, 7-P was dissolved in balanced saline solution for administration subcutaneously at dosages of 174 μg/kg in a volume of 1 mL/kg. The doses were given 15 times, one day interval. In control group, the animals were not treated with porcine serum. but given an equal volume of vehicle alone. During 7-P and vehicle administration, porcine serum was given intraperitoneally (i.p.) to rats in a volume of 1.5 mL/ kg once weekly. All animals were fasted for 24 h before porcine serum treatment. Background: During investigation of hypervariable region 1 (HVR1) of hepatitis C virus (HCV), a seven amino acids mimic peptide named 7-P was identified within the N-terminal of HVR1 that could induce IFN-γ and IL-10 expression while decreasing the expression of TNF-α in vivo and in vitro. Further studies revealed that 7-P could not only decrease the serum levels of aminotransferases (ALT, AST), alkaline phosphatase (AKP), and billirubin, but were also effective in reversing histopathological evidence of inflammation-mediated hepatic injury in 3 rat models. The protective mechanism and gene expression profiles were investigated in detail in a rat chronic liver injury model using Affymetrix microarrays . Conclusion: We found that IL-1β, tumor necrosis factor receptor superfamily 14 (TNFRSF14), intercellular adhesion molecule 2 (ICAM2), sterol regulatory element-binding protein 1 (SREBP 1), Prohibitin (PHB), and inhibitor of DNA binding 2 (Id2) were the target genes that related with 7-P Keywords: comparative genomic hybridization 36 Rats were randomly divided into three group:control group(12), model group(12) and drug group(12). At last, randomly choosing 3 Rat from each group to do genechip analysis.

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

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