Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Egypt; Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Egypt.
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University, Egypt.
Int Immunopharmacol. 2021 Oct;99:107963. doi: 10.1016/j.intimp.2021.107963. Epub 2021 Jul 14.
Excessive consumption of alcohol may induce severe liver damage, in part via oxidative stress and inflammatory responses, which implicates these processes as potential therapeutic approaches. Prior literature has shown that Telmisartan (TEL) may provide protective effects, presumably mediated by its anti-oxidant and anti-inflammatory activities. The purpose of this study was to determine TEL's hepatoprotective effects and to identify its possible curative mechanisms in alcoholic liver disease. A mouse chronic alcohol plus binge feedings model was used in the current study for induction of alcoholic liver disease (ALD). Our results showed that TEL (10 mg/kg/day) has the ability to reduce serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). TEL also increased the activity of superoxide dismutase (SOD) and glutathione (GSH) with concomitant reduction of nitric oxide (NO) malonaldehyde (MDA) in the liver homogenate. Moreover, TEL downregulated nuclear factor kappa B (NF-κB) expression and decreased liver content of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). These anti-inflammatory and anti-oxidant activities were associated with a significant increase in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), peroxisome proliferator-activated receptors -γ (PPAR-γ), and heme oxygenase-1 (Hmox-1). In conclusion, TEL's hepatoprotective effects against ALD may be attributable to its anti-inflammatory and anti-oxidant activities which may be in part via the modulation of PPAR-γ/ Nrf-2/ NF-κB crosstalk.
过量饮酒可能会导致严重的肝损伤，部分原因是氧化应激和炎症反应，这表明这些过程可能是潜在的治疗方法。先前的文献表明，替米沙坦（TEL）可能通过其抗氧化和抗炎活性提供保护作用。本研究的目的是确定 TEL 在酒精性肝病中的保肝作用及其可能的治疗机制。本研究采用小鼠慢性酒精加 binge 喂养模型诱导酒精性肝病（ALD）。我们的结果表明，TEL（10mg/kg/天）能够降低血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）水平。TEL 还增加了肝匀浆中超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的活性，同时降低了一氧化氮（NO）、丙二醛（MDA）的含量。此外，TEL 下调了核因子 kappa B（NF-κB）的表达，并降低了肝组织中白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的含量。这些抗炎和抗氧化活性与核因子红细胞 2 相关因子 2（Nrf-2）、过氧化物酶体增殖物激活受体-γ（PPAR-γ）和血红素加氧酶-1（Hmox-1）的表达显著增加有关。总之，TEL 对 ALD 的保肝作用可能归因于其抗炎和抗氧化活性，部分原因可能是通过调节 PPAR-γ/Nrf-2/NF-κB 串扰。
