Development of a rat model of D-galactosamine/lipopolysaccharide induced hepatorenal syndrome

Wang, Jingbo; Wang, Haitao; Li, Luping; Ying-chun, Yan; Wang, Wei; Liu, Jingyang; Zhao, Yitong; Gao, Wei-Shu; Zhang, Mingxiang

doi:10.3748/wjg.v21.i34.9927

Cited by 14 publications

(11 citation statements)

References 33 publications

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“…The liver and kidney typically indicate organ failure (Nguyen, Cruz, & Carcillo, ; Straub, ; J. B. Wang et al, ). Different indicators, such as FIB, PT, and aPTT can be used to diagnose DIC.…”

Section: Discussionmentioning

confidence: 99%

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Paeoniflorin alleviates lipopolysaccharide‐induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation

Fang

et al. 2020

Drug Development Research

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Lipopolysaccharide (LPS) is a toxic component of the outer membrane of gram-negative bacteria that can activate the blood coagulation system, leading to disseminated intravascular coagulation (DIC). DIC is a syndrome characterized by thromboembolism and multiple organ failure. Herein, the beneficial effect of paeoniflorin (PF) on the alleviation of LPS-induced DIC was investigated with an experimental DIC mouse model. Briefly, mice were randomly divided into the following six groups: (1) control; (2) LPS; (3) heparin;(4) low-PF treatment; (5) medium-PF treatment; and (6) high-PF treatment. The histological morphology of the liver and kidney was observed, and the coagulation indicators (such as prothrombin time), function indicators (such as alanine transferase), and inflammatory factors (such as TNF-α) were detected. Additionally, an in vitro cell inflammation model using RAW 264.7 murine macrophages was established. Activation of the nuclear factor kappa B (NF-κB) signaling pathway and tumor necrosis factor-α (TNF-α) were determined by western blotting. Based on our findings, PF could significantly improve the histological morphology of the liver and kidney, indicating that PF protects the liver and kidney against damage induced by LPS. Additionally, PF improved the function and coagulation indicators and reduced the production of inflammatory factors. In vitro, PF inhibited the expression of TNF-α by suppressing NF-κB signaling pathway activation.Collectively, our findings support the hypothesis that PF has anti-inflammatory and anticoagulation effects for the alleviation of LPS-induced DIC. PF is thus a potential cotreatment option for DIC. K E Y W O R D S disseminated intravascular coagulation (DIC), heparin, lipopolysaccharide (LPS), paeoniflorin (PF), tumor necrosis factor-α (TNF-α)

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Section: Discussionmentioning

confidence: 99%

“…As a toxic component of gram‐negative bacteria, LPS can damage organs, and promote the release of inflammatory cytokines, thereby leading to DIC (Chang et al, ; Shibazaki et al, ; Stief, ; J. B. Wang et al, ).…”

Section: Discussionmentioning

confidence: 99%

Paeoniflorin alleviates lipopolysaccharide‐induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation

Fang

et al. 2020

Drug Development Research

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“…On 15 th day the groups II, III, IV and V, received D-GalN/LPS (400 mg/kg and 30 μg/kg, i.p.) [29]. After 24 h of D-GalN induced hepatotoxicity, the blood was withdrawn from retro orbital plexus under anesthesia in tubes containing di-sodium EDTA.…”

Section: Methodsmentioning

confidence: 99%

Hepatoprotective activity of Lepidium sativum seeds against D-galactosamine/lipopolysaccharide induced hepatotoxicity in animal model

Raish

Ahmad

Alkharfy

et al. 2016

BMC Complement Altern Med

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BackgroundFulminant hepatic failure (FHF) is clinical syndrome with very poor prognosis and high mortality there is urgent need for the development of safe and non-toxic hepatoprotective agents for the adequate management of hepatitis. Hepatoprotective effect of the Lepidium sativum ethanolic extract (LSEE) was assessed by D-galactosamine-induced/lipopolysaccharide (400 mg/kg and 30 μg/kg) liver damage model in rats.MethodsHepatoprotective activity of LSEE (150 and 300 mg/kg) and silymarin on D-GalN/LPS induced FHF in rat was assessed using several liver function enzyme parameters. Antioxidant properties as antioxidant stress enzymes were assessed in hepatic Liver as well as mRNA expression of cytokines genes such as TNF-α, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. Protein expression of apoptotic genes were evaluated through western blot. MPO and NF-κB DNA-binding activity was analyzed by ELISA. The magnitude of hepatic impairment was investigated through histopathological evaluation.ResultsMarked amelioration of hepatic injuries by attenuation of serum and lipid peroxidation has been observed as comparable with silymarin (25 mg/kg p.o). D-GalN/LPS induced significant decrease in oxidative stress markers protein level, and albumin. LSEE significantly down-regulated the D-GalN/LPS induced pro-inflammatory cytokines TNFα and IL-6 mRNA expression in dose dependent fashion about 0.47 and 0.26 fold and up-regulates the IL-10 by 1.9 and 2.8 fold, respectively. While encourages hepatoprotective activity by down-regulating mRNA expression of iNOS and HO-1. MPO activity and NF-κB DNA-binding effect significantly increased and was mitigated by LSEE in a dose-dependent style as paralleled with silymarin.ConclusionOur data suggests that pretreatment of LSEE down regulates the caspase 3 and up-regulates the BCl2 protein expression. The above findings revealed that Lepidium sativum has significant hepatoprotective activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1483-4) contains supplementary material, which is available to authorized users.

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“…Liver cells, including Kupffer cells, hepatocytes and sinusoidal endothelial cells, can take up circulating LPS, following both ex vivo exposure to LPS and LPS injection (9). d-galactosamine (d-GalN) can increase the sensitivity of liver cells to LPS, and induce liver injury, as well as elevate serum TNF-α levels abnormally in the presence of low-dose LPS (10). Therefore, the combined use of LPS and d-GalN is used to establish a successful liver dysfunction model (10).…”

Section: Introductionmentioning

confidence: 99%

“…d-galactosamine (d-GalN) can increase the sensitivity of liver cells to LPS, and induce liver injury, as well as elevate serum TNF-α levels abnormally in the presence of low-dose LPS (10). Therefore, the combined use of LPS and d-GalN is used to establish a successful liver dysfunction model (10).…”

Section: Introductionmentioning

confidence: 99%

GDF‑15 prevents LPS and D‑galactosamine‑induced inﬂammation and acute liver injury in mice

Song

Huang

et al. 2018

Int J Mol Med

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Growth differentiation factor‑15 (GDF‑15) is a transforming growth factor (TGF)‑β superfamily member with a poorly characterized biological activity, speculated to be implicated in several diseases. The present study aimed to determine whether GDF‑15 participates in sepsis‑induced acute liver injury in mice. Lipopolysaccharide (LPS) and D‑galactosamine (D‑GalN) were administered to mice to induce acute liver injury. Survival of mice, histological changes in liver tissue, and levels of inflammatory biomarkers in serum and liver tissue were evaluated following treatment with GDF‑15. The underlying mechanism was investigated by western blotting, ELISA, flow cytometry, and reverse transcription‑quantitative polymerase chain reaction using Kupffer cells. The results demonstrated that GDF‑15 prevented LPS/D‑GalN‑induced death, increase in inflammatory cell infiltration and serum alanine aminotransferase and aspartate aminotransferase activities. In addition, GDF‑15 treatment reduced the production of hepatic malondialdehyde and myeloperoxidase, and attenuated the increase of interleukin (IL)‑6, tumor necrosis factor (TNF)‑α, and IL‑1β expression in serum and liver tissue, accompanied by inducible nitric oxide synthase (iNOS) inactivation in the liver. Similar changes in the expression of inflammatory cytokines, IL‑6, TNF‑α and IL‑1β, and iNOS activation were observed in the Kupffer cells. Further mechanistic experiments revealed that GDF‑15 effectively protected against LPS‑induced nuclear factor (NF)‑κB pathway activation by regulating TGFβ‑activated kinase 1 (TAK1) phosphorylation in Kupffer cells. In conclusion, GDF‑15 reduced the activation of pro‑inflammatory factors, and prevented LPS‑induced liver injury, most likely by disrupting TAK1 phosphorylation, and consequently inhibiting the activation of the NF‑κB pathway in the liver.

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Development of a rat model of D-galactosamine/lipopolysaccharide induced hepatorenal syndrome

Abstract: The joint use of D-galactosamine and LPS can induce liver and kidney dysfunction and decline of glomerular filtration rate in rats which is a successful rat model of hepatorenal syndrome.

Cited by 14 publications

References 33 publications

Paeoniflorin alleviates lipopolysaccharide‐induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation

Paeoniflorin alleviates lipopolysaccharide‐induced disseminated intravascular coagulation by inhibiting inflammation and coagulation activation

Hepatoprotective activity of Lepidium sativum seeds against D-galactosamine/lipopolysaccharide induced hepatotoxicity in animal model

GDF‑15 prevents LPS and D‑galactosamine‑induced inﬂammation and acute liver injury in mice

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