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.

Quercetin inhibits sodium nitrite‐induced inflammation and apoptosis in different rats organs by suppressing Bax, HIF1‐α, TGF‐β, Smad‐2, and AKT pathways

“…TGF‐β enhances the expression of apoptosis induced by certain cytokines and oncogenes that lead to cell death. Activation of Smads by TGF‐β results in fibrotic, apoptotic processes . PI‐3/AKT focal adhesion kinase‐phosphatidylinositol3‐kinase (AKT), the mitogen‐activated protein kinase and signal transducer and activator of transcription‐3 pathways are influenced in VEGF‐stimulating pathway.…”

Antioxidant and Hepatoprotective Effect of Swertiamarin on Carbon Tetrachloride-Induced Hepatotoxicity via the Nrf2/HO-1 Pathway

“…Several natural antioxidants exert hepatoprotective effects not only by scavenging the free radical, but also by augmenting the expression of cytoprotective and/or antioxidant genes via Nrf2 signaling pathway [43]. Normally, Nrf2 is tethered in the cytoplasm by the Kelth-like ECH-associated protein 1 (Keap1) for subsequent proteasomal degradation.…”

Delivery of curcumin by a pH-responsive chitosan mesoporous silica nanoparticles for cancer treatment

“…Curcumin (1,7-bis (4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione; diferuloylmethane) is a natural polyphenol derived from the rhizome of the Curcuma longa plant (Liu et al 2016, Mirakabad et al 2016 which has anti-inflammatory (Paulino et al 2016), antibacterial (Yun and Lee 2016), antioxidant (Al-Rasheed et al 2016), anti-Alzheimer's (Fang et al 2014) and anticancer properties (Jin et al, 2016, Kilicay et al 2016. Until now, the role of curcumin is known as an inhibition of multiple cell-signaling pathways such as blocking cell transformation, proliferation, invasion and induction of apoptosis and thereby reduces or prevents many types of cancers (Taverna et al 2016, Wu et al 2016.…”