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替米沙坦对乙酰氨基酚致小鼠肝毒性的治疗作用。

Therapeutic role of telmisartan against acetaminophen hepatotoxicity in mice.

机构信息

Department of Biomedical Sciences, Pharmacology Division, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia.

出版信息

Eur J Pharmacol. 2012 Oct 15;693(1-3):64-71. doi: 10.1016/j.ejphar.2012.07.049. Epub 2012 Aug 23.

Abstract

The therapeutic potential of telmisartan was investigated in mice exposed to acute hepatotoxicity induced by a single dose of acetaminophen (500 mg/kg, p.o.). Telmisartan treatment (two i.p. injections, 10mg/kg, each) was given at 1 and 12h following acetaminophen administration. Telmisartan significantly reduced the level of serum alanine aminotransferase, and suppressed lipid peroxidation, prevented the depletion of the antioxidant defenses (reduced glutathione level, and catalase and superoxide dismutase activities), and attenuated the elevation of nitric oxide resulted from acetaminophen administration. Also, telmisartan ameliorated the histopathological liver tissue damage induced by acetaminophen. Immunohistochemical analysis revealed that telmisartan significantly decreased the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in liver tissue of mice received acetaminophen overdose. In conclusion, telmisartan can be considered as a potential therapeutic option to protect against acute acetaminophen hepatotoxicity commonly encountered in clinical practice.

摘要

替米沙坦在单次给予乙酰氨基酚(500mg/kg,po)诱导的急性肝毒性的小鼠中进行了治疗潜力的研究。替米沙坦治疗(两次腹腔注射,每次 10mg/kg)在给予乙酰氨基酚后 1 小时和 12 小时进行。替米沙坦显著降低了血清丙氨酸氨基转移酶水平,并抑制了脂质过氧化,防止了抗氧化防御的耗竭(还原型谷胱甘肽水平以及过氧化氢酶和超氧化物歧化酶活性),并减弱了由乙酰氨基酚给药引起的一氧化氮升高。此外,替米沙坦改善了由乙酰氨基酚过量引起的肝组织损伤的组织病理学变化。免疫组化分析显示,替米沙坦显著降低了接受乙酰氨基酚过量的小鼠肝组织中诱导型一氧化氮合酶、肿瘤坏死因子-α、环加氧酶-2、核因子-κB 和半胱氨酸天冬氨酸蛋白酶-3 的表达。总之,替米沙坦可被认为是一种潜在的治疗选择,以防止在临床实践中常见的急性乙酰氨基酚肝毒性。

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