caa a22 4500 445852933 CHVBK 20180317145419.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00204-011-0649-6 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0649-6 Oxidized low-density lipoprotein and tissue factor are involved in monocrotaline/lipopolysaccharide-induced hepatotoxicity [Elektronische Daten] [Mohamed Hammad, Mohamed Abdel-Bakky, Larry Walker, M. Ashfaq] These studies were aimed at characterizing an animal model of inflammation-induced hepatotoxicity that would mimic features of idiosyncratic liver toxicity observed in humans. An attempt was made to identify oxidative damage and the involvement of coagulation system in liver after monocrotaline (MCT) administration under the modest inflammatory condition induced by lipopolysaccharide (LPS) exposure. Mice were given MCT (200mg/kg) or an equivalent volume of sterile saline (Veh.) po followed 4h later by ip injection of LPS (6mg/kg) or vehicle. Mice co-treated with MCT and LPS showed increased plasma alanine aminotransferase (ALT), decrease in platelet number, and a reduction in hematocrit. Accumulation of oxidized low-density lipoprotein (ox-LDL) was remarkably higher in the liver sections of mice co-treated with MCT and LPS compared to those given MCT or LPS alone. A similar trend was observed in the expression of CXCL16 receptor in the same liver sections. Elevated expression of tissue factor (TF) and fibrinogen was also observed in the liver sections of MCT/LPS co-treated mice. The in vitro results showed that incubation of HepG2 cells with CXCL16 antibody strongly diminished uptake of ox-LDL. Expression of ox-LDL, CXCL16, and TF represents an early event in the onset of hepatotoxicity induced by MCT/LPS; thus, it may contribute to our understanding of idiosyncratic liver injury and points to potential targets for protection or intervention. Springer-Verlag, 2011 Hepatotoxicity nationallicence Lipopolysaccharide nationallicence Monocrotaline nationallicence Pyrrolizidine alkaloids nationallicence Tissue factor nationallicence Oxidized low-density lipoprotein nationallicence Hammad Mohamed Department of Pharmacology, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut Abdel-Bakky Mohamed Faculty of Pharmacy, Al-Azhar University, 11884, Cairo, Egypt aut Walker Larry Department of Pharmacology, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut Ashfaq M. National Center for Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut Archives of Toxicology Springer-Verlag 85/9(2011-09-01), 1079-1089 0340-5761 85:9<1079 2011 85 204 https://doi.org/10.1007/s00204-011-0649-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0649-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hammad Mohamed Department of Pharmacology, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut NATIONALLICENCE 700 1- Abdel-Bakky Mohamed Faculty of Pharmacy, Al-Azhar University, 11884, Cairo, Egypt aut NATIONALLICENCE 700 1- Walker Larry Department of Pharmacology, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut NATIONALLICENCE 700 1- Ashfaq M. National Center for Natural Products Research, School of Pharmacy, University of Mississippi, 38677, University, MS, USA aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/9(2011-09-01), 1079-1089 0340-5761 85:9<1079 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer