title: Encapsulated platelets modulate kupffer cell activation and reduce oxidative stress in a model of acute liver failure.
abstract: Acute liver failure (ALF) is characterized by massive hepatocyte cell death. Kupffer cells (KC) are the first cells to be activated after liver injury. They secrete cytokines and produce reactive oxygen species, leading to apoptosis of hepatocytes. In a previous study, we showed that encapsulated platelets (PLTs) increase survival in a model of ALF. Here, we investigate how PLTs exert their beneficial effect. Wistar rats submitted to 90% hepatectomy were treated with PLTs encapsulated in sodium alginate or empty capsules. Animals were euthanized at 6, 12, 24, 48, and 72 hours after hepatectomy, and livers were collected to assess oxidative stress, caspase activity, and gene expression related to oxidative stress or liver function. The number of KCs in the remnant liver was evaluated. Interaction of encapsulated PLTs and KCs was investigated using a coculture system. PLTs increase superoxide dismutase and catalase activity and reduce lipid peroxidation. In addition, caspase 3 activity was reduced in animals receiving encapsulated PLTs at 48 and 72 hours. Gene expression of endothelial nitric oxide synthase and nuclear factor kappa B were elevated in the PLT group at each time point analyzed. Gene expression of albumin and factor V also increased in the PLT group. The number of KCs in the PLT group returned to normal levels at 12 hours but remained elevated in the control group until 72 hours. Finally, PLTs modulate interleukin (IL) 6 and IL10 expression in KCs after 24 hours of coculture. In conclusion, these results indicate that PLTs interact with KCs in this model and exert their beneficial effect through reduction of oxidative stress that results in healthier hepatocytes and decreased apoptosis. Liver Transplantation 22 1562-1572 2016 AASLD.
authors: Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.|Post-Graduation Program on Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors: Mónica Luján
authors: ML
authors: López
authors: Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.|Post-Graduation Program on Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors: Carolina
authors: C
authors: Uribe-Cruz
authors: Post-Graduation Program in Surgery, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors: Alessandro
authors: A
authors: Osvaldt
authors: Experimental Hepatology Laboratory, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors: Carlos Oscar
authors: CO
authors: Kieling
authors: Post-Graduation Program on Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors: Laura
authors: L
authors: Simon
authors: Cardiovascular Laboratory, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors: Santiago
authors: S
authors: Tobar
authors: Molecular and Protein Analysis Unit, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil.
authors: Michael
authors: M
authors: Andrades
authors: Gene Therapy Center, Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil. umatte@hcpa.edu.br.|Post-Graduation Program on Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil. umatte@hcpa.edu.br.
authors: Ursula
authors: U
authors: Matte
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001691:Biological Therapy / Q000379:methods*; D001792:Blood Platelets; D053148:Caspase 3 / Q000378:metabolism; D018920:Coculture Techniques; D004195:Disease Models, Animal; D006498:Hepatectomy; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000166:cytology; D017114:Liver Failure, Acute / Q000188:drug therapy*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000009:adverse effects
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D016753:Interleukin-10; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C505410:Casp3 protein, rat; D053148:Caspase 3