title: Hepato-protective effect of rutin via IL-6/STAT3 pathway in CCl4-induced hepatotoxicity in rats.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. Mohhafez_2000@yahoo.com.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Hafez
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. nharbi1@ksu.edu.sa.
authors.forename: Naif O
authors.initials: NO
authors.lastname: Al-Harbi
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. ahoshani@ksu.edu.sa.
authors.forename: Ali Rashed
authors.initials: AR
authors.lastname: Al-Hoshani
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. kalhosaini@ksu.edu.sa.
authors.forename: Khaled A
authors.initials: KA
authors.lastname: Al-Hosaini
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. shakir9556@gmail.com.
authors.forename: Shakir D
authors.initials: SD
authors.lastname: Al Shrari
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. rejaie@hotmail.com.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Al Rejaie
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. sayedahmedmm@hotmail.com.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Kingdom of Saudi Arabia. shabanah@ksu.edu.sa.
authors.forename: Othman A
authors.initials: OA
authors.lastname: Al-Shabanah
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004815:Epidermal Growth Factor / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D048671:MAP Kinase Kinase 5 / Q000378:metabolism; D008297:Male; D020011:Protective Agents / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012431:Rutin / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053200:Fas-Associated Death Domain Protein; D015850:Interleukin-6; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D051020:bcl-X Protein; D012431:Rutin; D004815:Epidermal Growth Factor; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053612:Janus Kinases; D048671:MAP Kinase Kinase 5; C482565:Map2k5 protein, rat