Platelet increases survival in a model of 90% hepatectomy in rats

López, Mónica Luján; Kieling, Carlos Oscar; Cruz, Carolina Uribe; Osvaldt, Alessandro Bersch; Muñoz, Gustavo Ochs de; Meurer, Luíse; Silla, Lúcia Mariano da Rocha; Matte, Úrsula

doi:10.1111/liv.12326

Cited by 17 publications

(19 citation statements)

References 51 publications

(70 reference statements)

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“…In a previous work, we showed that encapsulated PLTs improve the survival of rats submitted to 90% PH . We also showed that untreated animals (EC group) had swollen hepatocytes because of hydropic degeneration.…”

Section: Discussionmentioning

confidence: 61%

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Encapsulated platelets modulate kupffer cell activation and reduce oxidative stress in a model of acute liver failure

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 61%

“…In a previous study from our group, animals submitted to 90% partial hepatectomy (PH) and treated with PLTs entrapped in alginate microcapsules showed a significant improvement in survival that was directly related to a decrease in hepatocyte hydropic degeneration. Therefore, we further investigated the mechanism of hepatoprotection played by PLTs.…”

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confidence: 83%

Encapsulated platelets modulate kupffer cell activation and reduce oxidative stress in a model of acute liver failure

et al. 2016

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“…So, although liver regeneration is essential for survival, different works point to other factors that influence recovery, including the pace of regeneration [27]. In addition, other studies from our group also point to a positive impact in survival that is not directly linked to hepatocyte regeneration [12, 28]. Thus, it is suggested that BMMC improve survival through mechanisms other than enhancing hepatocyte proliferation.…”

Section: Discussionmentioning

confidence: 88%

“…Acute liver failure promotes a shock septic response by the immune system [27, 28], leading to a disequilibrium in the levels of pro- and anti-inflammatory cytokines [29]. It is well recognized that IL-6 and IL-10 have an important role in improving recovery after acute liver failure [29, 30].…”

Section: Discussionmentioning

confidence: 99%

Paracrine Effects of Bone Marrow Mononuclear Cells in Survival and Cytokine Expression after 90% Partial Hepatectomy

Kieling

Cruz

López

et al. 2017

Stem Cells International

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Acute liver failure is a complex and fatal disease. Cell-based therapies are a promising alternative therapeutic approach for liver failure due to relatively simple technique and lower cost. The use of semipermeable microcapsules has become an interesting tool for evaluating paracrine effects in vivo. In this study, we aimed to assess the paracrine effects of bone marrow mononuclear cells (BMMC) encapsulated in sodium alginate to treat acute liver failure in an animal model of 90% partial hepatectomy (90% PH). Encapsulated BMMC were able to increase 10-day survival without enhancing liver regeneration markers. Gene expression of Il-6 and Il-10 in the remnant liver was markedly reduced at 6 h after 90% PH in animals receiving encapsulated BMMC compared to controls. This difference, however, was neither reflected by changes in the number of CD68+ cells nor by serum levels of IL6. On the other hand, treated animals presented increased caspase activity and gene expression in the liver. Taken together, these results suggest that BMMC regulate immune response and promote apoptosis in the liver after 90% PH by paracrine factors. These changes ultimately may be related to the higher survival observed in treated animals, suggesting that BMMC may be a promising alternative to treat acute liver failure.

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“…Слід відзначити, що із семи родин серотонінових рецепторів у різних клітинних популяціях печінки найбільш інтенсивно експресуються 5-НТ 2 -рецепто-ри, які опосередковують вплив аутокоїда на метаболічні та регенеративні процеси в тканині цього органа [6][7][8][9]. Нині більшість досліджень гепатотропних ефектів серото-ніну спрямовані на з'ясування його дії на регенерацію і канцерогенез у печінковій тканині [10].…”

Section: вступunclassified

Role of Serotonin in the Regulation of Respiration and Bile Secretory Function of the Liver

Yanchuk¹,

Athamnah²,

Reshetnik³

et al. 2015

Fiziol Zh

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Platelet increases survival in a model of 90% hepatectomy in rats

Abstract: Platelets enhance survival of animals with 90% PH, probably by an early protective effect on hepatocytes and the increase in growth factor receptors.

Cited by 17 publications

References 51 publications

Encapsulated platelets modulate kupffer cell activation and reduce oxidative stress in a model of acute liver failure

Encapsulated platelets modulate kupffer cell activation and reduce oxidative stress in a model of acute liver failure

Paracrine Effects of Bone Marrow Mononuclear Cells in Survival and Cytokine Expression after 90% Partial Hepatectomy

Role of Serotonin in the Regulation of Respiration and Bile Secretory Function of the Liver

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