title: New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats using different natural antioxidants.
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. NF-E2-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.
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .
authors.forename: Nouf Mohamed
authors.initials: NM
authors.lastname: Al-Rasheed
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .
authors.forename: Laila Mohamed
authors.initials: LM
authors.lastname: Fadda
authors.affiliation: b Depatment of Genetics and Cytology , National Research Center , Dokki , Egypt .|c Preparatory Year Deanship, King Saud University , Riyadh , Kingdon of Saudi Arabia .
authors.forename: Hanaa Mahmoud
authors.initials: HM
authors.lastname: Ali
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .|d Department of Pharmacology , Faculty of Pharmacy (Girls), Al-Azhar University , Cairo , Egypt , and.
authors.forename: Nayira A
authors.initials: NA
authors.lastname: Abdel Baky
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .|e Department of Pharmacology and Toxicology Faculty of Pharmacy , Suez Canal University , Ismailia , Egypt.
authors.forename: Naglaa F
authors.initials: NF
authors.lastname: El-Orabi
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .
authors.forename: Nawal Mohamed
authors.initials: NM
authors.lastname: Al-Rasheed
authors.affiliation: a Department of Pharmacology , Faculty of Pharmacy, King Saud University , Riyadh , Kingdom of Saudi Arabia .
authors.forename: Hazar Ibrahim
authors.initials: HI
authors.lastname: Yacoub
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D017207:Rats, Sprague-Dawley; D012838:Silymarin / Q000008:administration & dosage / Q000627:therapeutic use*; D014810:Vitamin E / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D012838:Silymarin; D014810:Vitamin E; D002251:Carbon Tetrachloride; D003474:Curcumin
keywords: AKT; MAPK; STAT3; Smad-2; TGF-β; carbon tetrachloride