Mehmet Berköz1, Seda Ünal2, Fahri Karayakar3, Oruç Yunusoğlu4, Ferbal Özkan-Yılmaz3, Arzu Özlüer-Hunt5, Ali Aslan6,7. 1. Department of Biochemistry, Faculty of Pharmacy, Van Yuzuncu Yil University, Zeve Campus, 65080, Van, Turkey. mehmetberkoz@yyu.edu.tr. 2. Department of Biochemistry, Faculty of Pharmacy, Van Yuzuncu Yil University, Zeve Campus, 65080, Van, Turkey. 3. Department of Basic Sciences, Faculty of Fisheries, Mersin University, Mersin, Turkey. 4. Department of Medical Pharmacology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey. 5. Department of Aquaculture, Faculty of Fisheries, Mersin University, Mersin, Turkey. 6. Department of Biology, Faculty of Science, Kyrgyz-Turkish Manas University, Bishkek, Kyrgyzstan. 7. Department of Pharmacology, Faculty of Pharmacy, Van Yuzuncu Yil University, Van, Turkey.
Abstract
BACKGROUND: Liver has an important role in the initiation and progression of multiple organ failure that occurs in sepsis. Many natural active substances can be used to reduce the liver injury caused by sepsis. For this aim, the effects of myricetin and apigenin on mice model of acute liver injury was evaluated in this study. METHODS AND RESULTS: Thirty-six mice were randomly divided into six groups as; control, lipopolysaccharide (LPS) (5 mg/kg), LPS + myricetin (100 mg/kg), LPS + myricetin (200 mg/kg), LPS + apigenin (100 mg/kg), and LPS + apigenin (200 mg/kg) groups. Myricetin and apigenin were administered orally for 7 days, and LPS was administered intraperitoneally only on the 7th day of the study. 24 h after LPS application, all animals were sacrificed and serum biochemical parameters, histopathology and oxidative stress and inflammation markers of liver tissue were examined. Myricetin and apigenin pre-treatments increased serum albumin and total protein levels, liver GSH level and catalase and SOD activities and decreased serum ALT, AST, ALP, γ-GT, CRP, total and direct bilirubin levels, liver MPO activity, MDA, NOx, PGE2, TNF-α, IL-1β, and IL-6 levels, iNOS and COX-2 mRNA levels, phosphorylation of NF-κB p65, IκB, and IKK proteins but not p38, ERK, and JNK proteins in LPS-treated mice. Myricetin and apigenin administration also regained the hepatic architecture disrupted during LPS application. CONCLUSION: Myricetin and apigenin pre-treatments led to reduction of liver injury indices and oxidative stress and inflammatory events and these flavonoids has probably hepatoprotective effects in acute liver injury.
BACKGROUND: Liver has an important role in the initiation and progression of multiple organ failure that occurs in sepsis. Many natural active substances can be used to reduce the liver injury caused by sepsis. For this aim, the effects of myricetin and apigenin on mice model of acute liver injury was evaluated in this study. METHODS AND RESULTS: Thirty-six mice were randomly divided into six groups as; control, lipopolysaccharide (LPS) (5 mg/kg), LPS + myricetin (100 mg/kg), LPS + myricetin (200 mg/kg), LPS + apigenin (100 mg/kg), and LPS + apigenin (200 mg/kg) groups. Myricetin and apigenin were administered orally for 7 days, and LPS was administered intraperitoneally only on the 7th day of the study. 24 h after LPS application, all animals were sacrificed and serum biochemical parameters, histopathology and oxidative stress and inflammation markers of liver tissue were examined. Myricetin and apigenin pre-treatments increased serum albumin and total protein levels, liver GSH level and catalase and SOD activities and decreased serum ALT, AST, ALP, γ-GT, CRP, total and direct bilirubin levels, liver MPO activity, MDA, NOx, PGE2, TNF-α, IL-1β, and IL-6 levels, iNOS and COX-2 mRNA levels, phosphorylation of NF-κB p65, IκB, and IKK proteins but not p38, ERK, and JNK proteins in LPS-treated mice. Myricetin and apigenin administration also regained the hepatic architecture disrupted during LPS application. CONCLUSION: Myricetin and apigenin pre-treatments led to reduction of liver injury indices and oxidative stress and inflammatory events and these flavonoids has probably hepatoprotective effects in acute liver injury.