Hepatoprotective Role of α-Lipoic acid and Thymoquinone in Acetaminophen- Induced Liver Injury: Down-Regulation of COX-2 and flt-1 Expression
| Autor: | Iman H. Hasan, Raeesa A. Mohamad, Musaed Alfayez, Nawal M. Al-Rasheed, Hanaa M. Ali, Nouf M. Al-Rasheed, Laila M. Fadda |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment lcsh:Biotechnology Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine lcsh:TP248.13-248.65 medicine Thymoquinone Antidote Acetaminophen Liver injury Multidisciplinary digestive oral and skin physiology α-Lipoic acid medicine.disease Vascular endothelial growth factor Lipoic acid 030104 developmental biology medicine.anatomical_structure chemistry cyclooxygenase-2 Hepatocyte Hepatocyte growth factor TP248.13-248.65 Biotechnology medicine.drug |
| Zdroj: | Brazilian Archives of Biology and Technology, Volume: 60, Article number: e17160703, Published: 17 AUG 2017 Brazilian Archives of Biology and Technology, Vol 60, Iss 0 (2017) Brazilian Archives of Biology and Technology v.60 2017 Brazilian Archives of Biology and Technology Instituto de Tecnologia do Paraná (Tecpar) instacron:TECPAR Brazilian Archives of Biology and Technology, Vol 60 (2017) |
| Popis: | Acetaminophen (APAP) is a widely-used analgesic, while toxic doses of which induce liver injury. Inducible cyclooxygenase-2 (COX-2) is derived prostaglandins which play an anti-inflammatory role in acetaminophen-induced hepatotoxicity. Selective activation of vascular endothelial growth factor (VEGFR1, flt -1) on endothelial cells increased mRNA levels of hepatocyte mitogens (IL-6) and hepatocyte growth factor leading to prosurvival effects on hepatocytes. The aim of this study was to compare the hepatoprotective effect of N-acetylcysteine (NAC; the antidote for APAP) with that of α-Lipoic acid (ALA) and/or Thymoquinone (THQ) either alone or in combination on liver injury induced by APAP. APAP administration elevated most of the previously measured parameters and decreased GSH, SOD, and total protein levels compared with the control group. Liver sections of H&E demonstrate liver injury characterized by centrilobular hepatocellular necrosis, COX-2, and flt-1 expressions were also increased. Treatment with all fore mentioned antioxidants ameliorated most of the altered parameters compared to APAP-treated group. Treatment with the combination of ALA and THQ was the most effective therapy in the attenuation of liver injury assessed by a decrease in ALT and ALP activities and down-regulation of COX-2 and flt-1 expression. Section of liver from rat received APAP, ALA and THQ shows a marked improvement of hepatic degeneration which restricted to few hepatocytes with mild vacuolation of their cytoplasm while the nuclei appear normal mimic to control cells. It was concluded that the natural antioxidants such as ALA and THQ, may be considered as a potential antidote in combating liver injury induced by APAP. |
| Databáze: | OpenAIRE |
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