Integrative analysis of toxicometabolomics and toxicoproteomics data: new molecular insights into thiazolidinedione-induced cardiotoxicity DOI Creative Commons
Abdullah S. Sultan, Zahra Rattray, Nicholas J. W. Rattray

et al.

Metabolomics, Journal Year: 2024, Volume and Issue: 21(1)

Published: Dec. 4, 2024

Abstract Introduction Despite the well-established efficacy of thiazolidinediones (TZDs), including pioglitazone and rosiglitazone, in type II diabetes management, their potential contribution to heart failure risk remains a significant area uncertainty. This incomplete understanding, which persists despite decades clinical use TZDs, has generated ongoing controversy unanswered questions regarding safety profiles, ultimately limiting broader application. Objective methods study presented multi-omics approach, integrating toxicoproteomics toxicometabolomics data with goal uncovering novel mechanistic insights into TZD cardiotoxicity identifying molecular signatures predictive side effect progression. Results Network analysis proteo-metabolomic revealed distinct fingerprint disrupted biochemical pathways, were primarily related energy metabolism. Downregulation oxidative phosphorylation fatty acid synthesis was coupled increased activity anaerobic glycolysis, pentose phosphate pathway, amino purine suggests metabolic shift AC16 cells from oxidation towards potentially contributing observed cardiotoxicity. Additionally, identified marked disruption glutathione system, indicating an imbalanced redox state triggered by exposure. Importantly, our key across omics datasets, prominent acids like L-ornithine, L-tyrosine glutamine, are evidently associated failure, supporting for early prediction Conclusion By explanation cardiotoxicity, this simultaneously illuminates therapeutic interventions, opening avenues future research improve profile agents. ( 250 words ) Graphical abstracts

Language: Английский

Innovative applications and future perspectives of chromatography-mass spectrometry in drug research DOI Creative Commons
Hong Cai,

Xue Xing,

Ying Su

et al.

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 26, 2025

Chromatography coupled with mass spectrometry (MS) has emerged as a cornerstone analytical technique in drug research. Over the years, advancements chromatography-MS have significantly enhanced its capabilities, leading to improved sensitivity, specificity, and throughput. This review explores innovative applications of research, particularly focusing on role absorption, distribution, metabolism, excretion (ADME), toxicity evaluation, personalized medicine. It also addresses future perspectives this powerful technique, including challenges potential solutions, highlights how emerging trends such high spatial resolution imaging multimodal integration could revolutionize discovery development. Through these innovations, promises contribute substantially development more effective, safer, therapeutic interventions.

Language: Английский

Citations

0
Integrative analysis of toxicometabolomics and toxicoproteomics data: new molecular insights into thiazolidinedione-induced cardiotoxicity DOI Creative Commons
Abdullah S. Sultan, Zahra Rattray, Nicholas J. W. Rattray

et al.

Metabolomics, Journal Year: 2024, Volume and Issue: 21(1)

Published: Dec. 4, 2024

Abstract Introduction Despite the well-established efficacy of thiazolidinediones (TZDs), including pioglitazone and rosiglitazone, in type II diabetes management, their potential contribution to heart failure risk remains a significant area uncertainty. This incomplete understanding, which persists despite decades clinical use TZDs, has generated ongoing controversy unanswered questions regarding safety profiles, ultimately limiting broader application. Objective methods study presented multi-omics approach, integrating toxicoproteomics toxicometabolomics data with goal uncovering novel mechanistic insights into TZD cardiotoxicity identifying molecular signatures predictive side effect progression. Results Network analysis proteo-metabolomic revealed distinct fingerprint disrupted biochemical pathways, were primarily related energy metabolism. Downregulation oxidative phosphorylation fatty acid synthesis was coupled increased activity anaerobic glycolysis, pentose phosphate pathway, amino purine suggests metabolic shift AC16 cells from oxidation towards potentially contributing observed cardiotoxicity. Additionally, identified marked disruption glutathione system, indicating an imbalanced redox state triggered by exposure. Importantly, our key across omics datasets, prominent acids like L-ornithine, L-tyrosine glutamine, are evidently associated failure, supporting for early prediction Conclusion By explanation cardiotoxicity, this simultaneously illuminates therapeutic interventions, opening avenues future research improve profile agents. ( 250 words ) Graphical abstracts

Language: Английский

Citations

2