Evaluating the potential impact of sodium-glucose cotransporter-2 inhibitor "canagliflozin" on the hepatic damage triggered by hypertension in rats.

IF 2 3区 工程技术 Q2 ANATOMY & MORPHOLOGY
Fatma E Hassan, Aliaa E M K El-Mosallamy, Mohamed Mansour Khalifa, Samira H Aljuaydi, Merhan E Ali, Sara Adel Hosny, Nermeen Bastawy
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引用次数: 0

Abstract

Hypertension (HTN) is a prevalent chronic disease. HTN and liver disease association is extensively noted. Thus, finding a medication that can alleviate HTN and its accompanying liver insult would be promising. This study investigated the potential impacts of canagliflozin "sodium-glucose cotransporter-2 inhibitor" on the liver of the Nω-nitro-L-arginine methyl ester (L-NAME)-induced HTN rat model. Twenty-four adult male rats were divided into four groups; negative control group, canagliflozin group, L-NAME group: 50 mg/kg of L-NAME was injected daily for 5 weeks and L-NAME + canagliflozin group: 1 week after L-NAME injection both L-NAME + canagliflozin (40 mg/kg) were given concomitantly daily for further 4 weeks. Liver functions, serum lipid profile, hepatic oxidative/nitrative stress biomarkers, gene expression of lipogenic enzymes, B-cell lymphoma 2 (Bcl2), and DNA fragmentation, were measured. Besides, hepatic histology and immunohistochemistry of nuclear factor kappa B (NF-κB) and endothelial nitric oxide synthase (eNOS) were assessed. Canagliflozin improved hepatic lipogenesis via the downregulation of fatty acid synthase (FAS) and transcriptional regulatory element binding protein 1c (SREBP1c) genes leading to an improved serum lipid profile. Further, canagliflozin modified the eNOS/inducible nitric oxide synthase (iNOS) pathway and decreased the NF-κB immunoreactivity besides restoring the oxidants-antioxidants balance; increased reduced glutathione concomitant with declined malondialdehyde. This improvement of the liver was mirrored by the significant restoration of liver architecture and confirmed by the preserved liver DNA content and upregulation of the antiapoptotic Bcl2 mRNA level and attenuation of the alanine transaminase, aspartate aminotransferase. In conclusion, canagliflozin is a promising anti-hypertensive and hepatic-supportive medication. RESEARCH HIGHLIGHTS: Canagliflozin's antioxidant, anti-inflammatory, anti-lipogenic, and antiapoptotic characteristics mitigate remote liver compromise caused by hypertension. Canagliflozin can be exploited as a hepatoprotective and antihypertensive medication.

评估钠-葡萄糖共转运体-2抑制剂 "卡格列净 "对高血压引发大鼠肝损伤的潜在影响
高血压(HTN)是一种普遍存在的慢性疾病。高血压与肝脏疾病的关系已被广泛关注。因此,找到一种能缓解高血压及其伴随的肝脏损伤的药物将大有可为。本研究探讨了 "钠-葡萄糖共转运体-2抑制剂 "卡格列净对ω-硝基-L-精氨酸甲酯(L-NAME)诱导的高血压大鼠模型肝脏的潜在影响。24只成年雄性大鼠分为四组:阴性对照组、卡格列净组、L-NAME组:L-NAME组:每天注射50毫克/千克L-NAME,连续5周;L-NAME+卡格列净组:注射 L-NAME 1 周后,每天同时注射 L-NAME 和 canagliflozin(40 毫克/千克),持续 4 周。测定肝功能、血清脂质概况、肝脏氧化/硝化应激生物标志物、脂肪生成酶基因表达、B细胞淋巴瘤2(Bcl2)和DNA片段。此外,还评估了肝组织学以及核因子卡巴B(NF-κB)和内皮一氧化氮合酶(eNOS)的免疫组化。卡格列净通过下调脂肪酸合成酶(FAS)和转录调节元件结合蛋白1c(SREBP1c)基因改善了肝脏脂肪生成,从而改善了血清脂质状况。此外,卡格列净还改变了 eNOS/诱导型一氧化氮合酶(iNOS)通路,降低了 NF-κB 免疫反应,恢复了氧化剂与抗氧化剂之间的平衡;增加了还原型谷胱甘肽,同时降低了丙二醛。肝脏结构的显著恢复反映了肝脏状况的改善,肝脏 DNA 含量的保留、抗凋亡 Bcl2 mRNA 水平的上调以及丙氨酸转氨酶和天门冬氨酸氨基转移酶的降低也证实了这一点。总之,卡格列净是一种很有前景的抗高血压和肝支持药物。研究亮点卡格列净的抗氧化、抗炎、抗生脂和抗细胞凋亡特性可减轻高血压引起的远期肝损害。Canagliflozin可作为保肝降压药物加以利用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Microscopy Research and Technique
Microscopy Research and Technique 医学-解剖学与形态学
CiteScore
5.30
自引率
20.00%
发文量
233
审稿时长
4.7 months
期刊介绍: Microscopy Research and Technique (MRT) publishes articles on all aspects of advanced microscopy original architecture and methodologies with applications in the biological, clinical, chemical, and materials sciences. Original basic and applied research as well as technical papers dealing with the various subsets of microscopy are encouraged. MRT is the right form for those developing new microscopy methods or using the microscope to answer key questions in basic and applied research.
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