高血压（HTN）是一种流行的慢性疾病。高血压与肝病的关联已被广泛关注。因此，找到一种可以减轻高血压及其伴随的肝脏损伤的药物将是有希望的。本研究调查了卡格列净“钠-葡萄糖协同转运蛋白 2 抑制剂”对 Nω-硝基-L-精氨酸甲酯 (L-NAME) 诱导的 HTN 大鼠模型肝脏的潜在影响。将二十四只成年雄性大鼠分为四组；阴性对照组、卡格列净组、L-NAME组：每天注射50mg/kg L-NAME，持续5周；L-NAME卡格列净组：注射L-NAME后1周，均注射L-NAME卡格列净（40mg/kg） ）每天同时给予，持续 4 周。测量了肝功能、血清脂质谱、肝脏氧化/硝化应激生物标志物、脂肪生成酶的基因表达、B细胞淋巴瘤2 (Bcl2)和DNA片段化。此外，还评估了核因子κB（NF-κB）和内皮一氧化氮合酶（eNOS）的肝组织学和免疫组织化学。 Canagliflozin 通过下调脂肪酸合酶 (FAS) 和转录调节元件结合蛋白 1c (SREBP1c) 基因来改善肝脏脂肪生成，从而改善血清脂质状况。此外，卡格列净除了恢复氧化剂-抗氧化剂平衡外，还改变了 eNOS/诱导型一氧化氮合酶 (iNOS) 途径并降低了 NF-κB 免疫反应性；还原型谷胱甘肽增加，同时丙二醛减少。肝脏结构的显着恢复反映了肝脏的这种改善，并通过保留的肝脏 DNA 含量和抗凋亡 Bcl2 mRNA 水平的上调以及丙氨酸转氨酶、天冬氨酸转氨酶的减弱得到证实。总之，卡格列净是一种有前途的抗高血压和保肝药物。研究亮点：卡格列净的抗氧化、抗炎、抗脂肪生成和抗细胞凋亡特性可减轻高血压引起的远程肝脏损害。卡格列净可用作保肝和抗高血压药物。© 2024 Wiley periodicals LLC。

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.© 2024 Wiley Periodicals LLC.