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. 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.
Subject(s)
Animals , Male , Rats , Rutin/pharmacology , Signal Transduction/drug effects , Interleukin-6/metabolism , STAT3 Transcription Factor/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Aspartate Aminotransferases/blood , Carbon Tetrachloride , Biomarkers , Gene Expression/drug effects , Rats, Wistar , Proto-Oncogene Proteins c-bcl-2/metabolism , Protective Agents/pharmacology , MAP Kinase Kinase 5/metabolism , Alanine Transaminase/blood , Epidermal Growth Factor/metabolism , bcl-X Protein/metabolism , Janus Kinases/metabolism , Fas-Associated Death Domain Protein/metabolism , Real-Time Polymerase Chain Reaction , Liver/drug effectsABSTRACT
The present study has designed to investigate the effect of thymoquinone (THQ) on the status of hepatic oxidative stress and antioxidant defense system following ovariectomy (OVX) in Wistar rats. Animals were randomly assigned into five groups; sham, OVX and OVX+THQ treated groups in three doses (2.5, 5 and 10 mg/kg/day) orally by gavage for eight weeks. In serum, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels were estimated. In liver tissue, thiobarbituric acid reactive substances (TBARS), total glutathione (T-GSH), non-protein sulfhydryl groups (NP-SH) levels as well assuperoxide dismutase (SOD) and catalase (CAT) activities were also determined. Serum pre-oxidative markers (AST, ALT and ALP) were significantly increased in OVX rats compared to sham group. THQ inhibited these levels in a dose dependent manner. The lipid peroxidation product, TBARS, was significantly increased in OVX animals, which was inhibited by the THQ. In contrast, T-GSH and NP-SH levels were decreased in OVX rats, THQ treatments ameliorated these levels. Activities of SOD and CAT were significantly reduced in OVX group. THQ treatments significantly enhanced their activities in a dose dependent manner.The present results revealed the preventive effect of THQ on hepatic oxidative damage-induced by ovariectomy in rats.