Metformin alleviates doxorubicin-induced hepatic damage by modulating oxidative stress: a molecular, biochemical, and histopathological approach in a rat model

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Язык: Английский

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Exploring the Effects of Metformin on the Body via the Urine Proteome

Biomolecules, Год журнала: 2025, Номер 15(2), С. 241 - 241

Опубликована: Фев. 7, 2025

Metformin is the first-line medication for treating type 2 diabetes mellitus, with more than 200 million patients taking it daily. Its effects are extensive and play a positive role in multiple areas. Can its potential mechanisms be explored through urine proteome? In this study, 166 differential proteins were identified following administration of 150 mg/(kg·d) metformin to rats five consecutive days. These included complement component C6, pyruvate kinase, coagulation factor X, growth differentiation 15, carboxypeptidase A4, chymotrypsin-like elastase family member 1, L-lactate dehydrogenase C chain. Several these have been reported directly affected by or associated effects. Multiple biological pathways enriched proteins, containing differentially modified peptides, metformin, such as glutathione metabolic process, negative regulation gluconeogenesis, renin-angiotensin system. Additionally, some significantly changed pathways, not yet metformin's effects, may provide clues exploring mechanisms. conclusion, application proteome offers comprehensive systematic approach drugs, providing new perspective on study

Язык: Английский

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Mechanistic insights into the P-coumaric acid protection against bisphenol A-induced hepatotoxicity in in vivo and in silico models

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Март 31, 2025

Bisphenol A (BPA), commonly found in plastic containers and epoxy resins used for food products, presents substantial health risks, particularly relation to hepatic toxicity. This study investigates BPA-induced liver damage explores the mechanistic dose-dependent protective effects of P-coumaric acid (PCA). 50 male rats were divided into control, BPA-treated, BPA + PCA50, PCA100, PCA100 groups. exposure 14 days induced oxidative stress, evidenced by elevated malondialdehyde levels decreased activities antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase). Higher doses PCA effectively mitigated these restoring redox balance enhancing enzyme activities. Additionally, disrupted inflammation apoptosis pathways, inhibiting anti-inflammatory markers interfering with nuclear factor erythroid 2-related 2/heme oxygenase-1 (Nrf2/HO-1) pathway. exhibited protection against disruptions. Computational analyses revealed that inhibits cyclooxygenase-1 through stable hydrogen bonding threonine at position 322. PCA's dual effect was confirmed attenuating inflammatory including TNF-α inhibition suppression Kelch-like ECH-associated protein 1 (KEAP1) Nrf2 signaling Histopathological assessments alleviated significant BPA. Immunohistochemical immunofluorescence further supported role cellular hepatotoxicity. These findings underscore potential hepatotoxicity highlight novel interactions warrant investigation applied nutritional biochemistry.

Язык: Английский

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1, 8-Cineole Ameliorated Staphylococcus aureus-Induced Pneumonia through Modulation of TRP-KYN and Arginine-NO Reprogramming

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Май 2, 2025

1, 8-Cineole (Cin), a cyclic monoterpenoid derived from tea trees and eucalyptus species, exhibits diverse pharmacological properties. Yet, its therapeutic impact underlying mechanism against Staphylococcus aureus (S. aureus) pneumonia remain to be elucidated. In this study, metabolomics based on UPLC-MS/MS was integrated with network pharmacology, molecular biology, docking investigate the effects of Cin. The findings demonstrated that Cin markedly reduced mortality lung bacterial load, lessened pulmonary damage while suppressing levels proinflammatory factors, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) infected mice. Additionally, 19 metabolites, primarily involved tryptophan metabolism arginine biosynthesis, were notably modified by via enzymatic activity indoleamine 2, 3-dioxygenase 1 (IDO1) inducible nitric oxide synthase (iNOS), thereby attenuating inflammatory response. Notably, knockdown IDO1 or iNOS significantly diminished anti-inflammation effect conclusion, our study validates potential S. downregulating iNOS. Our results provide theoretical basis natural substances applied treatment.

Язык: Английский

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Metformin alleviates sodium arsenite‐induced hepatotoxicity and glucose intolerance in mice by suppressing oxidative stress, inflammation, and apoptosis

Journal of Trace Elements in Medicine and Biology, Год журнала: 2023, Номер 80, С. 127299 - 127299

Опубликована: Сен. 6, 2023

Язык: Английский

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