Vildagliptin attenuates doxorubicin-induced hepatotoxicity via activating Nrf2/HO-1 and SIRT1 and suppressing NF-κB signals in rats

Immunopharmacology and Immunotoxicology, Год журнала: 2025, Номер unknown, С. 1 - 11

Опубликована: Март 27, 2025

Doxorubicin (DOX) is an anticancer commonly employed in cancer treatment. However, the clinical application of DOX associated with hepatotoxicity. Vildagliptin anti-hyperglycemic agent that inhibits dipeptidyl peptidase-4 enzyme. Besides being used managing type-2 diabetes, vildagliptin showed potential anti-inflammatory, antioxidant, and other activities. Our investigation targeted hepatoprotective effects against DOX-induced was given a dose 30 mg/kg, once daily; p.o. for 2 weeks while injected single i.p. effectively decreased serum alanine aminotransferase (ALT) aspartate (AST) activities, it elevated total protein (TP) level. Histologically, administration resulted significant efficacy abundant figures normal hepatocytes. Moreover, considerably lipid peroxidation biomarker malondialdehyde (MDA), cytokines interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX)-2, remarkably boosted antioxidative defenses glutathione (GSH) catalase (CAT). Dual antioxidant anti-inflammatory activities were mediated by upregulating nuclear factor (erythroid-derived 2)-like (Nrf2), silent information regulator 1 (SIRT1), heme oxygenase (HO-1) suppressing kappa B (NF-κB) signals. Finally, alleviated apoptosis downregulating hepatic p53 cytochrome (Cyt)-C. findings suggest improved hepatocellular architecture reduced oxidative injury, inflammation,

Язык: Английский

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Research progress on the role and mechanism of Sirtuin family in doxorubicin cardiotoxicity

Phytomedicine, Год журнала: 2024, Номер 129, С. 155673 - 155673

Опубликована: Апрель 22, 2024

Язык: Английский

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Pinocembrin's protective effect against acute pancreatitis in a rat model: The correlation between TLR4/NF-κB/NLRP3 and miR-34a-5p/SIRT1/Nrf2/HO-1 pathways

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 176, С. 116854 - 116854

Опубликована: Июнь 1, 2024

Acute pancreatitis (APS) is a prevalent acute pancreatic inflammation, where oxidative stress, inflammatory signaling pathways, and apoptosis activation contribute to injury. Pinocembrin, the predominant flavonoid in propolis, was explored for its likely shielding effect against APS provoked by two intraperitoneal doses of L-arginine (250 mg / 100 g) rat model. Pinocembrin ameliorated histological immunohistochemical changes tissues lowered activities amylase lipase that were markedly elevated with administration. Moreover, pinocembrin reinstated oxidant/antioxidant equilibrium, which perturbed L-arginine, boosted levels nuclear factor erythroid 2-related 2 (Nrf2) heme oxygenase-1 (HO-1). reduced elevation serum C-reactive protein (CRP) level induced L-arginine. Additionally, it decreased expression high motility group box 1 (HMGB1), toll-like receptor 4 (TLR4), kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), NOD-like (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome pancreas. Furthermore, also myeloperoxidase (MPO) activity. downregulated miR-34a-5p upregulated peroxisome proliferator-activated alpha (PPAR-α) Sirtuin (SIRT1) gene inhibitor NF-κB (IκB-α), along normalizing Bax/Bcl-2 ratio. notably improved L-arginine-induced antioxidant, anti-inflammatory, anti-apoptotic activities. exhibited protective role suppressing via TLR4/NF-κB/NLRP3 pathway enhancing cytoprotective miR-34a-5p/SIRT1/Nrf2/HO-1 pathway.

Язык: Английский

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Pathogenesis-directed therapy of methylphenidate-induced oxidative heart damage in rats

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 3, 2025

The current study aimed to investigate the protective effects of adenosine triphosphate (ATP), metyrosine, and melatonin on possible methylphenidate cardiotoxicity in rats using biochemical histopathological methods. Thirty were separated into five groups: healthy (HG), (MP), ATP + (ATMP), metyrosine (MSMP), (MLMP). (5 mg/kg) was given intraperitoneally once daily, (50 orally twice (10 daily. Methylphenidate administered daily for 1 h after ATP, melatonin. protocol repeated 30 days. Subsequently, blood samples taken from tail veins animals measure adrenaline, noradrenaline, dopamine, troponin I (TP I) creatine kinase MB (CK-MB) levels; then euthanized heart tissues extracted. Tissues analyzed malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT) histopathologically. In MP group, MDA, TP I, CK-MB levels increased (p < 0.001) tGSH, SOD, CAT decreased compared HG, histopathologic damage developed. Oxidant lower antioxidant higher ATMP, MSMP, MLMP groups group 0.001). Catecholamine measured MSMP 0.05), with lowest being melatonin, metirozin applications effective different degrees preventing changes. This may guide clinical trials prevent methylphenidate-induced myocardial injury.

Язык: Английский

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Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling

International Journal of Molecular Medicine, Год журнала: 2025, Номер 55(3)

Опубликована: Янв. 23, 2025

Curcumin (Cur) effectively attenuates myocardial ischemia/reperfusion injury (MIRI). MIRI has a complex mechanism and is associated with autophagy‑dependent ferroptosis. Therefore, the present study aimed to determine whether ferroptosis occurs in assess of Cur attenuating MIRI. The was conducted on Sprague‑Dawley rat model H9c2 cell anoxia/reoxygenation (A/R) model. effect pretreatment A/R or induced its molecular were investigated. Protein expression, lysosomal, reactive oxygen species, Fe2+, oxidative systems, mitochondrial function, subcellular localization molecules, cardiac function assays will be employed. decreased MIRI; improved histopathology; increased cardiomyocyte viability; inhibited ferroptosis, apoptosis autophagy; reduced infarct size maintained function. silent information regulator 1 (Sirt1), AKT forkhead box O3A (FoxO3a) phosphorylation, leading FoxO3a entry into nucleus activate translation autophagy‑related genes inducing autophagy. However, activated phosphorylation via Sirt1, thereby transporting out nucleus, reducing gene MIRI‑induced Of note, silencing Sirt1 administration triciribine (an inhibitor) both eliminated protective Cur. Thus, by inhibiting Sirt1/AKT/FoxO3a signaling.

Язык: Английский

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Potential protective role of Lycium ruthenicum Murray polysaccharides against lipopolysaccharide-induced liver injury via mitochondrial biogenesis

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 141365 - 141365

Опубликована: Фев. 1, 2025

Язык: Английский

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The Application and Molecular Mechanisms of Mitochondria-Targeted Antioxidants in Chemotherapy-Induced Cardiac Injury

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(3), С. 176 - 176

Опубликована: Март 7, 2025

Chemotherapeutic agents play a crucial role in cancer treatment. However, their use is often associated with significant adverse effects, particularly cardiotoxicity. Drugs such as anthracyclines (e.g., doxorubicin) and platinum-based cisplatin) cause mitochondrial damage, which one of the main mechanisms underlying These drugs induce oxidative stress, leading to an increase reactive oxygen species (ROS), turn damage mitochondria cardiomyocytes, resulting impaired cardiac function heart failure. Mitochondria-targeted antioxidants (MTAs) have emerged promising cardioprotective strategy, offering potential solution. efficiently scavenge ROS within mitochondria, protecting cardiomyocytes from damage. Recent studies shown that MTAs, elamipretide, SkQ1, CoQ10, melatonin, significantly mitigate chemotherapy-induced not only reduce but also help maintain structure function, stabilize membrane potential, prevent excessive opening permeability transition pore, thus preventing apoptosis dysfunction. In this review, we integrate recent findings elucidate cardiotoxicity highlight substantial therapeutic MTAs reducing are expected offer safer more effective treatment options for patients clinical practice.

Язык: Английский

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Small Molecules Targeting Mitochondria: A Mechanistic Approach to Combating Doxorubicin-Induced Cardiotoxicity

Cardiovascular Toxicology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 4, 2024

Язык: Английский

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From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1

Pharmaceuticals, Год журнала: 2024, Номер 17(11), С. 1495 - 1495

Опубликована: Ноя. 7, 2024

Silent information regulator sirtuin 1 (SIRT1) is an NAD+-dependent deacetylase with potent anti-arterial aging activities. Its protective function in aging-related diseases has been extensively studied. In the microcirculation, SIRT1 plays a crucial role preventing microcirculatory endothelial senescence by suppressing inflammation and oxidative stress while promoting mitochondrial optimizing autophagy. It suppresses hypoxia-inducible factor-1α (HIF-1α)-mediated pathological angiogenesis healthy, physiological capillarization. As result, protects against microvascular dysfunction, such as diabetic microangiopathy, enhancing exercise-induced skeletal muscle capillarization energy metabolism. brain, upregulates tight junction proteins strengthens their interactions, thus maintaining integrity of blood-brain barrier. The present review summarizes recent findings on regulation SIRT1, underlying mechanisms, various approaches to modulate activity microcirculation. importance molecular target diseases, retinopathy stroke, underscored, along need for more clinical evidence support modulation

Язык: Английский

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Through regulation of the SIRT1 pathway plant sterol ester of α-linolenic acid inhibits pyroptosis thereby attenuating the development of NASH in mice

The Journal of Nutritional Biochemistry, Год журнала: 2023, Номер 119, С. 109408 - 109408

Опубликована: Июнь 17, 2023

Язык: Английский

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