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Folia Morphol (Warsz). 2019 Mar 5. doi: 10.5603/FM.a2019.0027. [Epub ahead of print]

Thymoquinone and curcumin modify iNOS, caspase-3, and thioredoxin immunohistochemical expression in acetaminophen (APAP) hepatotoxicity.

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Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Department of Anatomy, Faculty of Medicine, King Abdul Aziz University, Jeddah, Saudi Arabia.


Acetaminophen (APAP) hepatotoxicity is characterized 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 signaling 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 (ALT), aspartate transaminase (AST), total bilirubin, and total protein were measured. In addition, liver nitric oxide (NO), malondialdehyde (MDA), 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 characterized 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.


acetaminophen; curcumin; hepatotoxicity; thymoquinone

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