Bax and CD68 Expression in Response to Liver Injury Induced by Acetaminophen: The Hepatoprotective Role of Thymoquinone and Curcumin
Bax and CD68 Expression in Response to Liver Injury Induced by Acetaminophen: The Hepatoprotective Role of Thymoquinone and Curcumin
Laila M. Fadda1, Nouf M. Al-Rasheed1, Iman H. Hasan1, Hanaa M. Ali2,3*, Nawal M. Al-Rasheed1,4, Musaed Al-Fayez5, Aly M. Ahmed5, Nada Almutlaq1, Nehal Qasem1 and Reem Khalaf1
ABSTRACT
Acetaminophen (APAP) overdose depleted glutathione (GSH) which lead to liver dysfunction and hence hepatotoxicity. N-acetylcysteine (NAC) is the best antidote for APAP but may induce a variety of side effects. This study was designed to compare the potential impact of NAC with that of Thymoquinone (THQ), and/or Curcumin (CUR) either alone or in combination on liver injury induced by inflammation, oxidative stress in response to APAP toxicity in rats. Serum aminotransferases (ALT and AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total protein, total bilirubin, hepatic glutathione (GSH), nitric oxide (NO), superoxide dismutase (SOD) and lipid peroxides (LP) levels were estimated. Moreover these biochemical parameters were confirmed by histopathological examination using hemotoxylin and eosin (H&E) and Mason trichrome stains (MTC). Immunohistochemical investigations for the expression of the proapoptotic protein (Bax) and the expression of macrosialin cluster of differentiation (CD68). APAP elevated of most of the previously measured parameters and decreased GSH, SOD, and total protein levels. Liver sections of H&E demonstrated liver injury characterized by centrilobular hepatocellular necrosis, CD68, and Bax expressions were also increased. Treatment with all the aforementioned antioxidants downregulated most of the elevated parameters compared to the APAP-treated group. Treatment with the combination of CUR and THQ was the most effective therapies in the attenuation of liver injury assessed by a decrease in ALT and ALP activities down-regulation of Bax and CD68 expressions. It was concluded that the combination strategy of THQ and/or CUR may be considered as a potential antidote in combating liver injury induced by APAP due to their antioxidant effects with fewer side effects compared to NAC.
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