Augmenter of liver regeneration attenuates inflammatory response in the postischemic mouse liver in vivo

Khandoga, Andrej; Mende, Konstantin; Iskandarov, Emil; Rosentreter, Dirk; Schelcher, Celine; Reifart, Jörg; Jauch, Karl‐Walter; Thasler, Wolfgang E.

doi:10.1016/j.jss.2014.05.026

Cited by 9 publications

(8 citation statements)

References 40 publications

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“…In this regard, it is possible that hypothyroidism increases the expression of thyroid TRs α and β in the liver as has been observed in pancreatic islets [20], which could promote the hepatic proliferation [37]. This increment in the hepatocytes proliferation could counteract a possible ischemic liver injury [38].…”

Section: Discussionmentioning

confidence: 95%

Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver Regeneration, Mast Cells Infiltration, and Changes in the Expression of the Farnesoid X Receptor

Rodríguez-Castelán

Corona-Pérez

Nicolás-Toledo

et al. 2016

Exp Clin Endocrinol Diabetes

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Hypothyroidism is associated with the development of non-alcoholic steatohepatitis, but cellular mechanisms have been scarcely analyzed. Thyroid hormones regulate the synthesis and secretion of bile acids that are endogenous ligands of the farnesoid receptor (FXRα), which have been involved in the development of non-alcoholic steatohepatitis. However, the relationship between thyroid hormones and FXRα expression in the liver is yet unknown. Control (=6) and methimazole-induced hypothyroid (=6) female rabbits were used to evaluate the amount of lipids and glycogen, vascularization, hepatocytes proliferation, immune cells infiltration, and expression of FXRα. Student- or Mann-Whitney tests were carried out to determine significant differences. Hypothyroidism induced steatosis, glycogen loss, fibrosis, and a minor vascularization in the liver. In contrast, hypothyroidism increased the proliferation of hepatocytes and the infiltration of mast cells, but did not modify the number of immune cells into sinusoids. These changes were associated with a minor anti-FXRα immunoreactivity of periportal hepatocytes and pericentral immune cells. Our results suggest that hypothyroidism induces a moderate non-alcoholic steatohepatitis, alllowing the hepatic regeneration. The FXRα may be involved in the development of non-alcoholic steatohepatitis in hypothyroid subjects.

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Section: Discussionmentioning

confidence: 95%

Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver Regeneration, Mast Cells Infiltration, and Changes in the Expression of the Farnesoid X Receptor

Rodríguez-Castelán

Corona-Pérez

Nicolás-Toledo

et al. 2016

Exp Clin Endocrinol Diabetes

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“…Many studies have demonstrated the anti-apoptosis function of ALR in the liver. A recent study showed that exogenous administration of ALR attenuated the apoptotic, necrotic and inflammatory response to hepatocellular IRI in vivo [18]. In intraperitoneal hepatocyte transplantation rats, ALR can reduce pro-inflammatory cytokines, and apoptotic hepatocytes [19].…”

Section: Discussionmentioning

confidence: 99%

Augmenter of liver regeneration attenuates inflammation of renal ischemia/reperfusion injury through the NF-kappa B pathway in rats

et al. 2015

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“…Consistent with the experimental studies mentioned above, this effect is likely mediated by lowering the inflammatory response and reducing pro-inflammatory cytokine production [14,15]. Furthermore, recombinant human ALR has been shown to reduce IRI in rat kidneys [16] and livers [17], accompanied by lower serum transaminases, diminished apoptosis and less infiltration of inflammatory cells (neutrophils), but details on how rALR exerts this beneficial effect on hepatic IRI are still missing.…”

Section: Introductionmentioning

confidence: 60%

Augmenter of Liver Regeneration Reduces Ischemia Reperfusion Injury by Less Chemokine Expression, Gr-1 Infiltration and Oxidative Stress

Weiss

Lupke

Dayoub

et al. 2019

Cells

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Hepatic ischemia reperfusion injury (IRI) is a major complication in liver resection and transplantation. Here, we analyzed the impact of recombinant human augmenter of liver regeneration (rALR), an anti-oxidative and anti-apoptotic protein, on the deleterious process induced by ischemia reperfusion (IR). Application of rALR reduced tissue damage (necrosis), levels of lipid peroxidation (oxidative stress) and expression of anti-oxidative genes in a mouse IRI model. Damage associated molecule pattern (DAMP) and inflammatory cytokines such as HMGB1 and TNFα, were not affected by rALR. Furthermore, we evaluated infiltration of inflammatory cells into liver tissue after IRI and found no change in CD3 or γδTCR positive cells, or expression of IL17/IFNγ by γδTCR cells. The quantity of Gr-1 positive cells (neutrophils), and therefore, myeloperoxidase activity, was lower in rALR-treated mice. Moreover, we found under hypoxic conditions attenuated ROS levels after ALR treatment in RAW264.7 cells and in primary mouse hepatocytes. Application of rALR also led to reduced expression of chemo-attractants like CXCL1, CXCL2 and CCl2 in hepatocytes. In addition, ALR expression was increased in IR mouse livers after 3 h and in biopsies from human liver transplants with minimal signs of tissue damage. Therefore, ALR attenuates IRI through reduced neutrophil tissue infiltration mediated by lower expression of key hepatic chemokines and reduction of ROS generation.

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Augmenter of liver regeneration attenuates inflammatory response in the postischemic mouse liver in vivo

Cited by 9 publications

References 40 publications

Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver Regeneration, Mast Cells Infiltration, and Changes in the Expression of the Farnesoid X Receptor

Hypothyroidism Induces a Moderate Steatohepatitis Accompanied by Liver Regeneration, Mast Cells Infiltration, and Changes in the Expression of the Farnesoid X Receptor

Augmenter of liver regeneration attenuates inflammation of renal ischemia/reperfusion injury through the NF-kappa B pathway in rats

Augmenter of Liver Regeneration Reduces Ischemia Reperfusion Injury by Less Chemokine Expression, Gr-1 Infiltration and Oxidative Stress

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