Thymoquinone and curcumin modify inducible nitric oxide synthase, caspase 3, and thioredoxin immunohistochemical expression in acetaminophen hepatotoxicity

谷胱甘肽 肝损伤 天冬氨酸转氨酶 丙氨酸转氨酶 药理学 一氧化氮合酶 化学 脂质过氧化 砷毒性 超氧化物歧化酶 肝保护 毒性 氧化应激 丙二醛 对乙酰氨基酚 生物化学 生物 碱性磷酸酶 内分泌学 有机化学
作者
Muhammad Atteya,Ashraf M. Ahmed,Abdulrahman A. Al-Rabiah,Tahani Almatrafi,Maha Arafah,Samar Alsaggaf,S H Shereef,Anwar Ahmed,Hala Alqahtani,Raeesa A. Mohammad
出处
期刊:Folia Morphologica [VM Media Sp zo.o. - VMGroup SK]
卷期号:78 (4): 773-788 被引量:11
标识
DOI:10.5603/fm.a2019.0027
摘要

Acetaminophen (APAP) hepatotoxicity is characterised by an extensive oxidative stress due to depletion of glutathione (GSH), which results in massive lipid peroxidation and subsequent liver injury. The current paradigm suggests that mitochondria are the main source of reactive oxygen species (ROS), which impair mitochondrial function and are responsible for cell signalling resulting in cell death. This study was designed to compare the potential impact of thymoquinone (THQ), and/or curcumin (CURC) on liver injury induced by APAP toxicity in rats.Serum levels of alanine transaminase, aspartate transaminase, total bilirubin, and total protein were measured. In addition, liver nitric oxide (NO), malondialdehyde, reduced glutathione (GSH), and superoxide dismutase (SOD) were estimated. Moreover, these biochemical parameters were confirmed by histopathological and immunohistochemical investigations for the expression of thioredoxin, iNOS and caspase 3.Acetaminophen toxicity elevated most of the above-mentioned parameters but decreased GSH, SOD, and total protein levels. Histologically, liver sections demonstrated liver injury characterised by hepatocellular necrosis with nuclear pyknosis, karyorrhexis and karyolysis. Immunohistochemical study revealed increased expression of iNOS and caspase 3 proteins, while the thioredoxin protein expression was decreased.Treatment with the THQ and CURC regulated the biochemical and histopathological alterations induced by APAP toxicity. It was concluded that the combination strategy of THQ and CURC might be considered as a potential antidote in combating liver injury induced by APAP with minimal side effects.
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