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达格列净可减轻小鼠氧化应激、炎症和衰老的组织病理学标志物。

Dapagliflozin mitigates oxidative stress, inflammatory, and histopathological markers of aging in mice.

机构信息

Department of Pharmacology, College of Pharmacy, Al-Esraa University, Baghdad, Iraq.

Department of Clinical Pharmacy, College of Pharmacy, Al-Nahrain University, Baghdad, Iraq.

出版信息

J Med Life. 2024 Feb;17(2):157-163. doi: 10.25122/jml-2023-0343.


DOI:10.25122/jml-2023-0343
PMID:38813367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11131629/
Abstract

Aging, a complex physiological process affecting all living things, is a major area of research, particularly focused on interventions to slow its progression. This study assessed the antiaging efficacy of dapagliflozin (DAPA) on various aging-related parameters in a mouse model artificially induced to age. Forty male Swiss albino mice were randomly divided into four groups of ten animals each. The control group (Group I) received normal saline. The aging model group (Group II) was administered D-galactose orally at 500mg/kg to induce aging. Following the aging induction, the positive control group received Vitamin C supplementation (Group III), while the DAPA group (Group IV) was treated with dapagliflozin. The inflammatory mediators (TNF-α and IL-1β) showed similar patterns of change. No statistically significant difference was observed between groups III and IV. Both groups had significantly lower values compared to GII, while it was significantly higher compared to GI. Glutathione peroxidase (GSH-Px) showed no statistically significant difference between groups GIII and GIV, but it was higher in GIII compared to GII and significantly lower in GIII compared to GI. The study demonstrated that dapagliflozin exerts a beneficial impact on many indicators of aging in mice. The intervention resulted in a reduction in hypertrophy in cardiomyocytes, an enhancement in skin vitality, a decrease in the presence of inflammatory mediators, and an improvement in the efficacy of antioxidants.

摘要

衰老,一种影响所有生物的复杂生理过程,是一个主要的研究领域,特别是集中在干预措施以减缓其进展。本研究评估了达格列净(DAPA)对人工诱导衰老的小鼠模型中各种与衰老相关参数的抗衰老疗效。40 只雄性瑞士白化病小鼠被随机分为四组,每组 10 只动物。对照组(I 组)给予生理盐水。衰老模型组(II 组)给予 500mg/kg 的 D-半乳糖口服以诱导衰老。衰老诱导后,阳性对照组给予维生素 C 补充(III 组),而 DAPA 组(IV 组)给予达格列净治疗。炎症介质(TNF-α和 IL-1β)表现出相似的变化模式。III 组和 IV 组之间没有统计学差异。与 GII 相比,两组的数值均显著降低,而与 GI 相比,两组的数值均显著升高。谷胱甘肽过氧化物酶(GSH-Px)在 GIII 和 GIV 组之间没有统计学差异,但与 GII 相比,GIII 组的数值更高,与 GI 相比,GIII 组的数值显著更低。研究表明,达格列净对小鼠的许多衰老指标都有有益的影响。该干预措施导致心肌细胞肥大减少,皮肤活力增强,炎症介质的存在减少,抗氧化剂的功效改善。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/28b5f2e6aeab/JMedLife-17-157-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/31d219b6f0d1/JMedLife-17-157-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/48e65797528e/JMedLife-17-157-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/e01161b4bda1/JMedLife-17-157-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/8c525e580be2/JMedLife-17-157-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/28b5f2e6aeab/JMedLife-17-157-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/31d219b6f0d1/JMedLife-17-157-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/48e65797528e/JMedLife-17-157-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/e01161b4bda1/JMedLife-17-157-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/8c525e580be2/JMedLife-17-157-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/11131629/28b5f2e6aeab/JMedLife-17-157-g005.jpg

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[4]
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[5]
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[7]
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本文引用的文献

[1]
Dapagliflozin attenuates myocardial hypertrophy via activating the SIRT1/HIF-1α signaling pathway.

Biomed Pharmacother. 2023-9

[2]
Dapagliflozin Guards Against Cadmium-Induced Cardiotoxicity via Modulation of IL6/STAT3 and TLR2/TNFα Signaling Pathways.

Cardiovasc Toxicol. 2022-11

[3]
Skin Dryness Induced in the KK-Ay/TaJcl Type 2 Diabetes Mouse Model Deteriorates Following Dapagliflozin Administration.

Biol Pharm Bull. 2022-7-1

[4]
Role of Dapagliflozin and Liraglutide on Diabetes-Induced Cardiomyopathy in Rats: Implication of Oxidative Stress, Inflammation, and Apoptosis.

Front Endocrinol (Lausanne). 2022

[5]
SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes.

PLoS One. 2022

[6]
Dapagliflozin exerts anti-inflammatory effects via inhibition of LPS-induced TLR-4 overexpression and NF-κB activation in human endothelial cells and differentiated macrophages.

Eur J Pharmacol. 2022-3-5

[7]
Dapagliflozin: a sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced cardiac fibrotic remodeling by regulating TGFβ1/Smad signaling.

Cardiovasc Diabetol. 2021-6-11

[8]
Exploration of the optimal strategy for dietary calcium intervention against the toxicity of liver and kidney induced by cadmium in mice: An in vivo diet intervention study.

PLoS One. 2021

[9]
Potential anti-inflammatory effect of dapagliflozin in HCHF diet- induced fatty liver degeneration through inhibition of TNF-α, IL-1β, and IL-18 in rat liver.

Int Immunopharmacol. 2020-9

[10]
Dapagliflozin and Ticagrelor Have Additive Effects on the Attenuation of the Activation of the NLRP3 Inflammasome and the Progression of Diabetic Cardiomyopathy: an AMPK-mTOR Interplay.

Cardiovasc Drugs Ther. 2020-8

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