Alexandra K Tsaroucha1,2, Georgia Valsami3, Nikolaos Kostomitsopoulos4, Maria Lambropoulou5, Constantinos Anagnostopoulos6, Eirini Christodoulou3, Evangelos Falidas1, Afrodite Betsou1, Michael Pitiakoudis1,2, Constantinos E Simopoulos1,2,4. 1. a Postgraduate Program in Hepatobiliary/Pancreatic Surgery, Faculty of Medicine , Democritus University of Thrace , Alexandroupolis , Greece. 2. b 2nd Department of Surgery and Laboratory of Experimental Surgery, Faculty of Medicine , Democritus University of Thrace , Alexandroupolis , Greece. 3. c School of Health Sciences, Department of Pharmacy , National and Kapodistrian University of Athens , Greece. 4. d Department of Experimental Surgery , Bioresearch Foundation of the Academy of Athens , Athens , Greece. 5. e Laboratory of Histology-Embryology, Faculty of Medicine , Democritus University of Thrace , Alexandroupolis , Greece. 6. f Laboratory of Biochemistry, Faculty of Medicine , Democritus University of Thrace , Alexandroupolis , Greece.
Abstract
PURPOSE: We investigated the hepatoprotective effect of Silibinin (SLB) to ischemia-reperfusion (I/R) rat model, by evaluating the histological expression of the tissue markers Fas/FasL, HMGB-1 and CD45, and SLB pharmacokinetics. METHODS: Seventy-three Wistar-type male rats were randomized in 11 groups: Sham control group (open-close laparotomy); four I/R control groups (laparotomy, 45 min vascular occlusion, reperfusion, euthanasia after 60, 120, 180, and 240 min); four SLB (Si) groups (laparotomy, 45 min vascular occlusion, IV administration of SLB, reperfusion, euthanasia after 60, 120, 180, and 240 min); two SLB pharmacokinetics (PK) groups (IV administration of SLB, euthanasia after 45 and 240 min). RESULTS: Fas/FasL increased with reperfusion time in I/R control groups and decreased in the Si groups, reaching, respectively, the highest and lowest values at 240 min of reperfusion (p <.0001). HMGB1 and CD45 increased with time in the I/R control groups up to 240 min and decreased in the Si groups, approaching zero expression after 180 and 60 min, respectively. Pharmacokinetic data showed higher liver accumulation and slower plasma elimination of SLB in ischemic animals. CONCLUSIONS: The hepatoprotective effect of SLB was demonstrated through the reduction of the expression of Fas/FasL, HMGB-1 and CD45 in liver tissue under I/R conditions, and in the pharmacokinetic study. The results document the efficacy of silibinin in the protection of the liver, and are particularly encouraging for its use in hepatic surgery.
PURPOSE: We investigated the hepatoprotective effect of Silibinin (SLB) to ischemia-reperfusion (I/R) rat model, by evaluating the histological expression of the tissue markers Fas/FasL, HMGB-1 and CD45, and SLB pharmacokinetics. METHODS: Seventy-three Wistar-type male rats were randomized in 11 groups: Sham control group (open-close laparotomy); four I/R control groups (laparotomy, 45 min vascular occlusion, reperfusion, euthanasia after 60, 120, 180, and 240 min); four SLB (Si) groups (laparotomy, 45 min vascular occlusion, IV administration of SLB, reperfusion, euthanasia after 60, 120, 180, and 240 min); two SLB pharmacokinetics (PK) groups (IV administration of SLB, euthanasia after 45 and 240 min). RESULTS: Fas/FasL increased with reperfusion time in I/R control groups and decreased in the Si groups, reaching, respectively, the highest and lowest values at 240 min of reperfusion (p <.0001). HMGB1 and CD45 increased with time in the I/R control groups up to 240 min and decreased in the Si groups, approaching zero expression after 180 and 60 min, respectively. Pharmacokinetic data showed higher liver accumulation and slower plasma elimination of SLB in ischemic animals. CONCLUSIONS: The hepatoprotective effect of SLB was demonstrated through the reduction of the expression of Fas/FasL, HMGB-1 and CD45 in liver tissue under I/R conditions, and in the pharmacokinetic study. The results document the efficacy of silibinin in the protection of the liver, and are particularly encouraging for its use in hepatic surgery.
Authors: Nikolaos P E Kadoglou; Chrystalla Panayiotou; Michail Vardas; Nikolaos Balaskas; Nikolaos G Kostomitsopoulos; Alexandra K Tsaroucha; Georgia Valsami Journal: Pharmaceuticals (Basel) Date: 2022-04-27
Authors: Georgios Kyriakopoulos; Georgia Valsami; Christos Tsalikidis; Michail Pitiakoudis; Alexandra K Tsaroucha Journal: Ann Med Surg (Lond) Date: 2020-11-26
Authors: Adamantios Michalinos; Alexandra K Tsaroucha; Maria Lambropoulou; Dimitrios Schizas; Georgia Valsami; Nikolaos Kostomitsopoulos; Michael S Pitiakoudis; Constantinos E Simopoulos Journal: Transl Gastroenterol Hepatol Date: 2020-01-05