Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats

BACKGROUND: Carbon tetrachloride (CCl4) induces hepatotoxicity in animal models, including the increased blood flow and cytokine accumulation that are characteristic of tissue inflammation. The present study investigates the hepato-protective effect of rutin on CCl4-induced hepatotoxicity in rats. R...

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Autores principales:	Hafez,Mohamed M, Al-Harbi,Naif O, Al-Hoshani,Ali Rashed, Al-hosaini,Khaled A, Al Shrari,Shakir D, Al Rejaie,Salim S, Sayed-Ahmed,Mohamed M, Al-Shabanah,Othman A
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2015
Materias:	Hepatotoxicity Rutin Inflammatory cytokine MEK5 FADD STAT3 JAK genes expression
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100030
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spelling	oai:scielo:S0716-976020150001000302016-02-16Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in ratsHafez,Mohamed MAl-Harbi,Naif OAl-Hoshani,Ali RashedAl-hosaini,Khaled AAl Shrari,Shakir DAl Rejaie,Salim SSayed-Ahmed,Mohamed MAl-Shabanah,Othman A Hepatotoxicity Rutin Inflammatory cytokine MEK5 FADD STAT3 JAK genes expression BACKGROUND: Carbon tetrachloride (CCl4) induces hepatotoxicity in animal models, including the increased blood flow and cytokine accumulation that are characteristic of tissue inflammation. The present study investigates the hepato-protective effect of rutin on CCl4-induced hepatotoxicity in rats. RESULTS: Forty male Wistar rats were divided into four groups. Group I (control group) received 1 mL/kg of dimethyl sulfoxide intragastrically and 3 mL/kg olive oil intraperitoneally twice a week for 4 weeks. Group II received 70 mg/ kg rutin intragastrically. Groups III and IV received CCl4 (3 mL/kg, 30 % in olive oil) intraperitoneally twice a week for 4 weeks. Group IV received 70 mg/kg rutin intragastrically after 48 h of CCl4 treatment. Liver enzyme levels were determined in all studied groups. Expression of the following genes were monitored with real-time PCR: interleukin-6 (IL-6), dual-specificity protein kinase 5 (MEK5), Fas-associated death domain protein (FADD), epidermal growth factor (EGF), signal transducer and activator of transcription 3 (STAT3), Janus kinase (JAK), B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra-large (Bcl-XL). The CCl4 groups showed significant increases in biochemical markers of hepatotoxicity and up-regulation of expression levels of IL-6, Bcl-XL, MEK5, FADD, EGF, STAT3 and JAK compared with the control group. However, CCl4 administration resulted in significant down-regulation of Bcl2 expression compared with the control group. Interestingly, rutin supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. CONCLUSION: CCl4 administration causes alteration in expression of IL-6/STAT3 pathway genes, resulting in hepatotoxicity. Rutin protects against CCl4-induced hepatotoxicity by reversing these expression changes.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.48 20152015-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100030en10.1186/S40659-015-0022-Y
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Hepatotoxicity Rutin Inflammatory cytokine MEK5 FADD STAT3 JAK genes expression
spellingShingle	Hepatotoxicity Rutin Inflammatory cytokine MEK5 FADD STAT3 JAK genes expression Hafez,Mohamed M Al-Harbi,Naif O Al-Hoshani,Ali Rashed Al-hosaini,Khaled A Al Shrari,Shakir D Al Rejaie,Salim S Sayed-Ahmed,Mohamed M Al-Shabanah,Othman A Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats
description	BACKGROUND: Carbon tetrachloride (CCl4) induces hepatotoxicity in animal models, including the increased blood flow and cytokine accumulation that are characteristic of tissue inflammation. The present study investigates the hepato-protective effect of rutin on CCl4-induced hepatotoxicity in rats. RESULTS: Forty male Wistar rats were divided into four groups. Group I (control group) received 1 mL/kg of dimethyl sulfoxide intragastrically and 3 mL/kg olive oil intraperitoneally twice a week for 4 weeks. Group II received 70 mg/ kg rutin intragastrically. Groups III and IV received CCl4 (3 mL/kg, 30 % in olive oil) intraperitoneally twice a week for 4 weeks. Group IV received 70 mg/kg rutin intragastrically after 48 h of CCl4 treatment. Liver enzyme levels were determined in all studied groups. Expression of the following genes were monitored with real-time PCR: interleukin-6 (IL-6), dual-specificity protein kinase 5 (MEK5), Fas-associated death domain protein (FADD), epidermal growth factor (EGF), signal transducer and activator of transcription 3 (STAT3), Janus kinase (JAK), B-cell lymphoma 2 (Bcl2) and B-cell lymphoma-extra-large (Bcl-XL). The CCl4 groups showed significant increases in biochemical markers of hepatotoxicity and up-regulation of expression levels of IL-6, Bcl-XL, MEK5, FADD, EGF, STAT3 and JAK compared with the control group. However, CCl4 administration resulted in significant down-regulation of Bcl2 expression compared with the control group. Interestingly, rutin supplementation completely reversed the biochemical markers of hepatotoxicity and the gene expression alterations induced by CCl4. CONCLUSION: CCl4 administration causes alteration in expression of IL-6/STAT3 pathway genes, resulting in hepatotoxicity. Rutin protects against CCl4-induced hepatotoxicity by reversing these expression changes.
author	Hafez,Mohamed M Al-Harbi,Naif O Al-Hoshani,Ali Rashed Al-hosaini,Khaled A Al Shrari,Shakir D Al Rejaie,Salim S Sayed-Ahmed,Mohamed M Al-Shabanah,Othman A
author_facet	Hafez,Mohamed M Al-Harbi,Naif O Al-Hoshani,Ali Rashed Al-hosaini,Khaled A Al Shrari,Shakir D Al Rejaie,Salim S Sayed-Ahmed,Mohamed M Al-Shabanah,Othman A
author_sort	Hafez,Mohamed M
title	Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats
title_short	Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats
title_full	Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats
title_fullStr	Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats
title_full_unstemmed	Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats
title_sort	hepato-protective effect of rutin via il-6/stat3 pathway in ccl4-induced hepatotoxicity in rats
publisher	Sociedad de Biología de Chile
publishDate	2015
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602015000100030
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Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats

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