TY - JOUR
TI - Silibinin Effect on Fas/FasL, HMGB1, and CD45 Expressions in a Rat Model Subjected to Liver Ischemia-Reperfusion Injury
AU - Tsaroucha, A.K.
AU - Valsami, G.
AU - Kostomitsopoulos, N.
AU - Lambropoulou, M.
AU - Anagnostopoulos, C.
AU - Christodoulou, E.
AU - Falidas, E.
AU - Betsou, A.
AU - Pitiakoudis, M.
AU - Simopoulos, C.E.
JO - Journal of Investigative Surgery
PY - 2018
VL - 31
TODO - 6
SP - 491-502
PB - Taylor and Francis Ltd.
SN - 0894-1939, 1521-0553
TODO - 10.1080/08941939.2017.1360416
TODO - alanine aminotransferase;  aspartate aminotransferase;  Fas ligand;  high mobility group B1 protein;  receptor type tyrosine protein phosphatase C;  silibinin;  tumor necrosis factor receptor superfamily member 6;  biological marker;  Fas ligand;  Hbp1 protein, rat;  high mobility group B1 protein;  protective agent;  Ptprc protein, rat;  receptor type tyrosine protein phosphatase C;  silibinin;  Tnfrsf6 protein, rat;  Tnfsf6 protein, rat;  tumor necrosis factor receptor superfamily member 6, alanine aminotransferase blood level;  animal experiment;  animal model;  animal tissue;  antiinflammatory activity;  Article;  aspartate aminotransferase blood level;  blood vessel occlusion;  controlled study;  drug accumulation;  drug blood level;  drug elimination;  elimination half-life;  hepatic ischemia reperfusion injury;  immunohistochemistry;  laparotomy;  liver function;  liver protection;  male;  maximum concentration;  nonhuman;  priority journal;  protein expression;  rat;  animal;  disease model;  drug effect;  human;  intravenous drug administration;  liver;  metabolism;  pathology;  preclinical study;  randomization;  reperfusion injury;  surgery;  tissue distribution;  Wistar rat, Administration, Intravenous;  Animals;  Biomarkers;  Disease Models, Animal;  Drug Evaluation, Preclinical;  Fas Ligand Protein;  fas Receptor;  HMGB1 Protein;  Humans;  Leukocyte Common Antigens;  Liver;  Male;  Protective Agents;  Random Allocation;  Rats;  Rats, Wistar;  Reperfusion Injury;  Silybin;  Tissue Distribution
TODO - 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. © 2017, Copyright © 2017 Taylor & Francis Group, LLC.
ER -