Failure of Kupffer cell blockade to prevent disseminated intravascular coagulation in endotoxemic rats despite improved survival

Rüttinger, Dominik; Vollmar, Brigitte; Kempter, B.; Meßmer, K.

doi:10.1007/s004230050095

Cited by 12 publications

(4 citation statements)

References 31 publications

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“…It has previously been reported that gadolinium administration is not able to prevent the haemodynamic alterations of acute endotoxaemia (Fujii et al 1998). Similarly, despite improved survival, gadolinium chloride failed to prevent laboratory and clinical signs of disseminated intravascular coagulation in endotoxaemic rats (Ruttinger et al 1998).…”

Section: Discussionmentioning

confidence: 96%

Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression

Granado¹,

Martín²,

Priego³

et al. 2006

Journal of Endocrinology

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Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the IGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P<0·01), as well as in their gene expression in the liver. LPS-injected rats had increased serum concentrations of ACTH, corticosterone (P<0·05), tumour necrosis factor-(TNF-) and nitrites (P<0·01). Pretreatment of the animals with gadolinium chloride blocked the inhibitory effect of LPS on body weight, and on serum concentrations of IGF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serum concentrations of ACTH, corticosterone and TNF-. These results suggest that Kupffer cells are important mediators in the inhibitory effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serum concentrations of IGF-I and IGFBP-3.

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Section: Discussionmentioning

confidence: 96%

Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression

Granado¹,

Martín²,

Priego³

et al. 2006

Journal of Endocrinology

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“…Although activation of Kupffer cells has been significantly inhibited by GdCl 3 in models of both in vivo hepatic I/R and isolated perfused rat liver [21][22][23][24], there is evidence that administration of GdCl 3 results in a pronounced rise in serum cytokine activity, es-pecially TNF, and a slight rise in liver enzyme activity [22]. In contrast, there is strong evidence that administration of high-dose IVIG can suppress Kupffer cell activation and down-regulate proinflammatory cytokine expression.…”

Section: Discussionmentioning

confidence: 99%

“…Although activation of Kupffer cells has been significantly inhibited by gadolinium chloride (GdCl 3 ) (Aldrich Chemical, Milwaukee, WI, USA) in models of in vivo hepatic I/R and isolated‐perfused rat liver [15, 18, 19, 20,21, 22, 23], the mechanisms mediating this inhibition have not been totally elucidated. It has been demonstrated that application of GdCl 3 during hepatic I/R decreases the mortality rate [24], attenuates purine nucleoside phosphorylase [25], improves functional parameters of the liver [18, 26], reduces platelet accumulation in cold perfused rat liver, prevents apoptosis of sinusoidal endothelial cells [27], attenuates neutrophil infiltration, and decreases myeloperoxidase activity [28].…”

mentioning

confidence: 99%

High Dose Intravenous Immunoglobulin G Pretreatment: Effect on Lipid Peroxidation and Reperfusion Injury to the Liver

et al. 2003

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The aim of this study was to examine the effect of intravenous immunoglobulin G (IVIG) compared with that of gadolinium chloride (GdCl3) in the inhibition of Kupffer cell activation on lipid peroxidation after severe total hepatic ischemia/reperfusion (I/R). Male Wistar rats ( n = 40) were randomly divided into four equal groups: a sham-operation group, a control I/R group, and two I/R groups pretreated with either IVIG or GdCl3 intravenously. Following 60 minutes of total hepatic ischemia and 120 minutes of reperfusion, the rats were sacrificed and liver and blood samples collected. Additional animals ( n = 80) were followed up for survival rate determination. Results showed that I/R decreased the survival rate to 10%, increased the levels of aspartate (AST) and alanine (ALT) transaminase and lactate dehydrogenase (LDH) in serum to 2487, 2189, and 4236 IU/L, respectively, and increased malondialdehyde (MDA) levels in liver to 1.552 nmol/g compared with 1.114 nmol/g in the sham operation group. Pretreatment with GdCl3 increased the survival rate to 50% and decreased the levels of AST, ALT, and LDH in serum to 1496, 1298, and 3245 IU/l, respectively. Pretreatment with IVIG increased the survival rate to 60% and decreased the levels of AST, ALT, and LDH in serum to 449, 367, and 1456 IU/l, respectively, and the levels of MDA in liver to 1.153 and 1.148 nmol/g for GdCl3 and IVIG respectively. Histologic examination showed protection of liver parenchyma in the animals treated with GdCl3 or IVIG.

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“…A number of studies suggest that the inhibitory effect of gadolinium chloride (GdCl 3 ) against Kupffer cell (KCs) activation shows potential as a protective intervention in rat models of in vivo hepatic reperfusion injury and isolated perfused livers (1–3). It has also been shown that treatment of liver ischemia-reperfusion injury with GdCl 3 reduces the mortality rate, attenuates neutrophil infiltration and decreases myeloperoxidase activity, improves hepatic function, reduces platelet accumulation in cold perfused livers, and prevents apoptosis of sinusoidal endothelial cells (4).…”

Section: Introductionmentioning

confidence: 99%

Gadolinium chloride suppresses acute rejection and induces tolerance following rat liver transplantation by inhibiting Kupffer-cell activation

Wang

et al. 2014

Experimental and Therapeutic Medicine

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The aim of the present study was to investigate the mechanism by which gadolinium chloride (GdCl3) inhibits Kupffer cell (KC) activation and its ability to suppress acute rejection and induce tolerance following liver transplantation in rats. Rats were randomly divided into control, liver transplantation with GdCl3 pretreatment and liver transplantation with normal saline pretreatment groups. The survival rate, liver function, hepatic pathological histology, cytokine levels in the liver and bile, activity of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in KCs, and expression levels of membranous molecules on the KCs were observed. It was identified that the one-month survival rate in the GdCl3 group was significantly higher compared with that in the saline group (P<0.05). The liver function in the GdCl3 group gradually recovered following transplantation surgery; however, it progressively deteriorated in the saline group. There were minor changes of hepatic pathological histology in the GdCl3 group, whereas changes typical of acute rejection occurred in the saline group. In the GdCl3 group, the levels of interferon γ and interleukin (IL)-2 were significantly lower whereas the levels of IL-10 were significantly higher compared with those in the control and saline groups (all P<0.01). The IL-4 levels in the GdCl3 and control groups were similar. The activity of NF-κB in the saline group was significantly higher compared with those in the control and GdCl3 groups (P<0.01). The expression levels of major histocompatibility complex-II, cluster of differentiation (CD)80 and CD86 on the KC membranes in the GdCl3 group was significantly lower compared with those in the control group (P<0.05); however, these membranous proteins were highly expressed in the saline group. These data indicate that GdCl3 efficiently inhibits the immunological activity of KCs, suppresses acute rejection and induces tolerance following liver allograft transplantation in rats.

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Failure of Kupffer cell blockade to prevent disseminated intravascular coagulation in endotoxemic rats despite improved survival

Cited by 12 publications

References 31 publications

Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression

Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression

High Dose Intravenous Immunoglobulin G Pretreatment: Effect on Lipid Peroxidation and Reperfusion Injury to the Liver

Gadolinium chloride suppresses acute rejection and induces tolerance following rat liver transplantation by inhibiting Kupffer-cell activation

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