Insulin Treatment Improves Hepatic Morphology and Function Through Modulation of Hepatic Signals After Severe Trauma

Klein, Dagmar; Schubert, Thomas; Horch, Raymund E.; Jauch, Karl‐Walter; Jeschke, Marc G.

doi:10.1097/01.sla.0000133353.57674.cd

Cited by 77 publications

(57 citation statements)

References 37 publications

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“…In addition, proinflammatory cytokines such as IL-1 and tumor necrosis factor (TNF)-α have been described to be an apoptotic signal (30,(39)(40)(41)(42). After a thermal injury, serum and hepatic concentration of proinflammatory cytokines such as IL-1α/β, IL-6, and TNF-α are increased (14,(43)(44)(45) and we, therefore, suggest that two possible mechanisms are involved in increased hepatocyte apoptosis: decreased splanchnic bloodflow; and elevation of proinflammatory cytokines, initiating intracellular signaling mechanisms. Signals that may be involved encompass many signals that play an important role during the acute phase response.…”

Section: Hepatic Changes In Response To a Burn And The Hepatic Acute mentioning

confidence: 99%

“…Trop et al (55,56) investigated some possible mechanisms by which a burn causes RES dysfunction, and found that hemolysis may play a role in the alterations in RES phagocytic activity. We (15,16,22,43,57), along with others, have shown that the liver also contributes to the inflammatory and acute phase response by expressing proinflammatory cytokines and acute phase proteins, indicating the central role of the liver in the inflammatory, acute phase, and immune response.…”

Section: Reticuloendothelial System (Res)mentioning

confidence: 99%

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The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

Jeschke

2009

Mol Med

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142

102

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Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury. Studies have evaluated the role and function of the liver during the postburn response and showed that liver integrity and function are essential for survival, and that hepatic acute phase proteins are strong predictors for postburn survival. This review discusses these studies and delineates the pivotal role of the liver in patients following severe thermal injury.

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Section: Hepatic Changes In Response To a Burn And The Hepatic Acute mentioning

confidence: 99%

Section: Reticuloendothelial System (Res)mentioning

confidence: 99%

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

Jeschke

2009

Mol Med

Self Cite

142

102

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“…In addition, proinflammatory cytokines such as IL-1 and tumor necrosis factor (TNF)- have been described to be an apoptotic signal (30,(39)(40)(41)(42). After a thermal injury serum and hepatic concentration of proinflammatory cytokines such as IL-1/, IL-6 and TNF- are increased (14,(43)(44)(45) and we, therefore, suggest that two possible mechanisms are involved in increased hepatocyte apoptosis, decreased splanchnic blood-flow, and elevation of pro-inflammatory cytokines, initiating intracellular signaling mechanisms. Signals that may be involved encompass many signals that play an important role during the acute phase response.…”

Section: Wwwintechopencommentioning

confidence: 99%

“…Trop et al (55,56) investigated some possible mechanisms by which a burn causes RES dysfunction and found that hemolysis may play a role in the alterations in RES phagocytic activity. Others and we (15,16,22,43,57) have shown that the liver also contributes to the inflammatory and acute phase response by expressing proinflammatory cytokines and acute phase proteins indicating the central role of the liver in the inflammatory, acute phase, and immune response.…”

Section: Reticuloendothelial System (Res)mentioning

confidence: 99%

The Hepatic Acute Phase Response to Thermal Injury

Jeschke¹

2011

Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins

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“…A severe burn is a devastating injury affecting every organ system and leading to complications with poor outcome. The liver plays an important role in metabolism, inflammation, homeostasis and host defence mechanisms (Klein et al 2004), and is a major organ responsible for initiating multiorgan dysfunction syndrome (MODS) following burn injury. The mechanism of burn-induced injury is not completely understood; however, several mechanisms, including hypoxia, free radicals, inflammation, and apoptosis are thought to be involved (Jeschke et al 2001).…”

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confidence: 99%

Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway

Bekyarova¹,

Tzaneva²,

Hristova³

2015

Vet. Med. - Czech

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Melatonin exerts beneficial effects on early liver injury by modulating hepatic oxidative stress. In order to understand the protective effect of melatonin against burn-induced hepatic injury we investigated the expression of 4-hydroxynonenal (4-HNE), a main product of lipid peroxidation and mediator of oxidative injury, the inducible heme-oxygenase-1 (HO-1), an antioxidant enzyme, and the anti-oxidative stress regulator erythroid 2-related factor 2 (Nrf2) in a burn rat model. Expression and localisation of HO-1, 4-HNE and Nrf2 in liver were investigated using light immunochemistry. Thermal skin injury caused a significant elevation in hepatic 4-HNE and degenerative liver changes. Concurrently, there was increased expression of HO-1, a rate-limiting enzyme for haem degradation and an oxidative stress marker in sinusoidal endothelial cells (SECs) and hepatocytes without changes in Nrf2 expression in the liver. Melatonin (20 mg/kg b.w.) augmented the increase in HO-1 expression, upregulated Nrf2 expression and also led to decreased 4-HNE levels and reduced levels of histopathological changes in rat liver. In conclusion, our results suggest that melatonin ameliorates burn-induced liver injury through the inhibition of oxidative stress, upregulation of the antioxidant enzyme HO-1 and activation of the antioxidant Nrf2 pathway. Stimulation of cellular protective mechanisms by activating the antioxidant stress response through Nrf2 is a new mechanism for protection against liver damage in burns.

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Insulin Treatment Improves Hepatic Morphology and Function Through Modulation of Hepatic Signals After Severe Trauma

Abstract: Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring hepatic homeostasis, which has been shown to be critical for organ function and survival of critically ill patients.

Cited by 77 publications

References 37 publications

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

The Hepatic Acute Phase Response to Thermal Injury

Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway

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