New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats using different natural antioxidants

Nouf Mohamed Al-Rasheed, Laila Mohamed Fadda, Hanaa Mahmoud Ali, Nayira A. Abdel Baky, Naglaa F. El-Orabi, Nawal Mohamed Al-Rasheed, Hazar Ibrahim Yacoub

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Transforming growth factor-β (TGF-β1) enhances the expression of apoptosis induced by certain cytokines and oncogenes. Activation of small mother against decapentaplegic (Smads) by TGF-β results in fibrotic, apoptotic processes. PI-3/AKT focal adhesion kinase-phosphatidylinositol3- kinase (AKT), the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) pathways are influence in COX-2 and VEGF-stimulating pathways. NFE2- related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. The objective of this study is to examine whether silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against MAPK, STAT3, AKT, Smad-2 and TGF-β protein expressions that produced apoptotic damage in rat's liver by the administration of carbon tetrachloride (CCl4). The results of the present work revealed that CCl4-induced an elevation of serum alanine aminotransferase (ALT) with concomitant increase in MAPK, STAT3, AKT, Smad-2 and TGF-β hepatic protein expression, administration of silymarin alone down regulates these expressions. Treatment with vitamin E and/or curcumin along with silymarin produced best results in this concern. On the other hand, Nrf2 protein expression was down regulated by CCl4 whereas concurrent treatment with vitamin E and/or curcumin along with silymarin increased this expression. It was concluded that CCl4-induced protein expression of apoptotic and fibenorgenic factors. Whereas administration of silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against the previous aforementioned apoptotic factors expressions. The use of vitamin E and/or curcumin potentiates the anti-apoptotic action of silymarin. So this combination can be used as hepatoprotective agent against other hepatotoxic substances.

Original languageEnglish
Pages (from-to)243-250
Number of pages8
JournalToxicology Mechanisms and Methods
Volume26
Issue number4
DOIs
Publication statusPublished - 23 Mar 2016

Fingerprint

Silymarin
Carbon Tetrachloride
Curcumin
Rats
Vitamin E
Antioxidants
Modulation
STAT3 Transcription Factor
Mitogen-Activated Protein Kinases
Liver
Proteins
Focal Adhesion Protein-Tyrosine Kinases
Transforming Growth Factors
Alanine Transaminase
Oncogenes
Gene expression
Vascular Endothelial Growth Factor A
Transcription Factors
Phosphotransferases
Down-Regulation

Keywords

  • AKT
  • Carbon tetrachloride
  • MAPK
  • Smad-2
  • STAT3
  • TGF-β

Cite this

Al-Rasheed, Nouf Mohamed ; Fadda, Laila Mohamed ; Ali, Hanaa Mahmoud ; Abdel Baky, Nayira A. ; El-Orabi, Naglaa F. ; Al-Rasheed, Nawal Mohamed ; Yacoub, Hazar Ibrahim. / New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats using different natural antioxidants. In: Toxicology Mechanisms and Methods. 2016 ; Vol. 26, No. 4. pp. 243-250.
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abstract = "Transforming growth factor-β (TGF-β1) enhances the expression of apoptosis induced by certain cytokines and oncogenes. Activation of small mother against decapentaplegic (Smads) by TGF-β results in fibrotic, apoptotic processes. PI-3/AKT focal adhesion kinase-phosphatidylinositol3- kinase (AKT), the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) pathways are influence in COX-2 and VEGF-stimulating pathways. NFE2- related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. The objective of this study is to examine whether silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against MAPK, STAT3, AKT, Smad-2 and TGF-β protein expressions that produced apoptotic damage in rat's liver by the administration of carbon tetrachloride (CCl4). The results of the present work revealed that CCl4-induced an elevation of serum alanine aminotransferase (ALT) with concomitant increase in MAPK, STAT3, AKT, Smad-2 and TGF-β hepatic protein expression, administration of silymarin alone down regulates these expressions. Treatment with vitamin E and/or curcumin along with silymarin produced best results in this concern. On the other hand, Nrf2 protein expression was down regulated by CCl4 whereas concurrent treatment with vitamin E and/or curcumin along with silymarin increased this expression. It was concluded that CCl4-induced protein expression of apoptotic and fibenorgenic factors. Whereas administration of silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against the previous aforementioned apoptotic factors expressions. The use of vitamin E and/or curcumin potentiates the anti-apoptotic action of silymarin. So this combination can be used as hepatoprotective agent against other hepatotoxic substances.",
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New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats using different natural antioxidants. / Al-Rasheed, Nouf Mohamed; Fadda, Laila Mohamed; Ali, Hanaa Mahmoud; Abdel Baky, Nayira A.; El-Orabi, Naglaa F.; Al-Rasheed, Nawal Mohamed; Yacoub, Hazar Ibrahim.

In: Toxicology Mechanisms and Methods, Vol. 26, No. 4, 23.03.2016, p. 243-250.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats using different natural antioxidants

AU - Al-Rasheed, Nouf Mohamed

AU - Fadda, Laila Mohamed

AU - Ali, Hanaa Mahmoud

AU - Abdel Baky, Nayira A.

AU - El-Orabi, Naglaa F.

AU - Al-Rasheed, Nawal Mohamed

AU - Yacoub, Hazar Ibrahim

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AB - Transforming growth factor-β (TGF-β1) enhances the expression of apoptosis induced by certain cytokines and oncogenes. Activation of small mother against decapentaplegic (Smads) by TGF-β results in fibrotic, apoptotic processes. PI-3/AKT focal adhesion kinase-phosphatidylinositol3- kinase (AKT), the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3) pathways are influence in COX-2 and VEGF-stimulating pathways. NFE2- related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. The objective of this study is to examine whether silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against MAPK, STAT3, AKT, Smad-2 and TGF-β protein expressions that produced apoptotic damage in rat's liver by the administration of carbon tetrachloride (CCl4). The results of the present work revealed that CCl4-induced an elevation of serum alanine aminotransferase (ALT) with concomitant increase in MAPK, STAT3, AKT, Smad-2 and TGF-β hepatic protein expression, administration of silymarin alone down regulates these expressions. Treatment with vitamin E and/or curcumin along with silymarin produced best results in this concern. On the other hand, Nrf2 protein expression was down regulated by CCl4 whereas concurrent treatment with vitamin E and/or curcumin along with silymarin increased this expression. It was concluded that CCl4-induced protein expression of apoptotic and fibenorgenic factors. Whereas administration of silymarin alone or in combination with vitamin E and/or curcumin plays a modulatory role against the previous aforementioned apoptotic factors expressions. The use of vitamin E and/or curcumin potentiates the anti-apoptotic action of silymarin. So this combination can be used as hepatoprotective agent against other hepatotoxic substances.

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KW - Carbon tetrachloride

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