Acute liver injury attenuation of a novel recombinant sTNFR through blocking hepatic apoptosis

Luo, Mansheng; Zhao, Ai; Li, Jinlong; Chen, Yueping; Tian, Dandan; Wang, Caihong; Hu, Zhiming; Gao, Jimin

doi:10.3109/08923973.2015.1035390

Cited by 5 publications

(3 citation statements)

References 28 publications

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“…LPS/GalN/DMSO substantially increased caspase 3 expression, but CFZ post-treatment decreased caspase 3 expression. In agreement with our data, caspase 3 inhibitors protect mice from LPS/GalN-induced ALF [34,[40][41][42][43]. The mechanism of CFZ's anti-apoptotic effect may be related to its ability to decrease TNF-α secretion.…”

Section: Discussionsupporting

confidence: 89%

Carfilzomib Mitigates Lipopolysaccharide/D-Galactosamine/Dimethylsulfoxide-Induced Acute Liver Failure in Mice

Alhareth,

Alanazi,

Alanazi

et al. 2023

Biomedicines

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Acute liver failure (ALF) is a disease accompanied by severe liver inflammation. No effective therapy is available yet apart from liver transplantation; therefore, developing novel treatments for ALF is urgently required. Inflammatory mediators released by NF-кB activation play an essential role in ALF. Proteasome inhibitors have many medical uses, such as reducing inflammation and NF-кB inhibition, which are believed to account for most of their repurposing effects. This study was undertaken to explore the possible protective effects and the underlying mechanisms of carfilzomib, a proteasome inhibitor, in a mouse model of ALF induced by lipopolysaccharide/D-galactosamine/dimethylsulfoxide (LPS/GalN/DMSO). Carfilzomib dose-dependently protected mice from LPS/GalN/DMSO-induced liver injury, as indicated by the decrease in serum alanine aminotransferase and aspartate aminotransferase levels. LPS/GalN/DMSO increased TNF-α, NF-кB, lipid peroxidation, NO, iNOS, cyclooxygenase-II, myeloperoxidase, and caspase-3 levels. Carfilzomib administration mitigated LPS/GalN/DMSO-induced liver damage by decreasing the elevated levels of TNF-α, NF-кB, lipid peroxidation, nitric oxide, iNOS, cyclooxygenase-II, myeloperoxidase, caspase-3, and histopathological changes. A restored glutathione level was also observed in the carfilzomib-treated LPS/GalN/DMSO mice. Our results demonstrate that carfilzomib protects against LPS/GalN/DMSO-induced ALF by inhibiting NF-кB, decreasing inflammatory mediators, oxidative/nitrosative stress, neutrophil recruitment, and apoptosis, suggesting that carfilzomib may be a potential therapeutic agent for ALF.

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Section: Discussionsupporting

confidence: 89%

Carfilzomib Mitigates Lipopolysaccharide/D-Galactosamine/Dimethylsulfoxide-Induced Acute Liver Failure in Mice

Alhareth,

Alanazi,

Alanazi

et al. 2023

Biomedicines

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“…In addition to the uncontrolled inflammatory response, accumulating evidence indicates that excessive hepatocyte apoptosis is a hallmark of LPS/D-Gal-induced hepatic damage. 4,21,33,36 In the current study, glutamine treatment prevented LPS/D-Gal-induced activation of the caspase cascade, which initiated hepatocyte apoptosis. In addition, glutamine reduced the number of TUNEL-positive cells in the LPS/D-Gal-challenged liver.…”

Section: Discussionsupporting

confidence: 52%

Protective effects of glutamine on lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice

Yang

Zhang

Zhao

et al. 2022

Exp Biol Med (Maywood)

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Fulminant hepatitis remains a critical health problem owing to its high mortality rate and the lack of effective therapies. An increasing number of studies have shown that glutamine supplementation provides protective benefits in inflammation-related disorders, but the pharmacological significance of glutamine in lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced fulminant hepatitis remains unclear. In the present study, the potential effects of glutamine on LPS/D-Gal-induced fulminant hepatitis were investigated. Pretreatment with glutamine decreased plasma activities of alanine and aspartate aminotransferases, and ameliorated hepatic morphological abnormalities in LPS/D-Gal-exposed mice. Glutamine pretreatment also inhibited LPS/D-Gal-induced tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) production. In addition, glutamine pretreatment decreased the level of cleaved cysteinyl aspartate–specific proteinase 3 (caspase-3), suppressed the activities of caspase-3, caspase-8, and caspase-9, and reduced the number of cells positive for TdT-mediated dUTP nick-end labeling in LPS/D-Gal-challenged mice. Interestingly, post-treatment with glutamine also provided protective benefits against LPS/D-Gal-induced acute liver injury, although these effects were less robust than those of glutamine pre-treatment. Thus, glutamine may have potential value as a pharmacological intervention in fulminant hepatitis.

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“…Otherwise, an increase in apoptotic cells will cause liver inflammation and necrosis, resulting in alcoholic hepatitis. 9 Many studies 10 – 12 show that the inhibition of hepatic apoptosis can reduce liver injury. Antioxidants can ameliorate ethanol-induced apoptosis in liver cells.…”

Section: Introductionmentioning

confidence: 99%

The combination of blueberry juice and probiotics reduces apoptosis of alcoholic fatty liver of mice by affecting SIRT1 pathway

Zhu¹,

Ren²,

Zhou³

et al. 2016

DDDT

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PurposeTo explore the effects of the combination of blueberry juice and probiotics on the apoptosis of alcoholic fatty liver disease (AFLD).MethodsHealthy C57BL/6J mice were used in the control group (CG). AFLD mice models were established with Lieber–DeCarli ethanol diet and evenly assigned to six groups with different treatments: MG (model), SI (SIRT1 [sirtuin type 1] small interfering RNA [siRNA]), BJ (blueberry juice), BJSI (blueberry juice and SIRT1 siRNA), BJP (blueberry juice and probiotics), and BJPSI (blueberry juice, probiotics, and SIRT1 siRNA). Hepatic tissue was observed using hematoxylin and eosin (HE) and Oil Red O (ORO) staining. Biochemical indexes of the blood serum were analyzed. The levels of SIRT1, caspase-3, forkhead box protein O1 (FOXO1), FasL (tumor necrosis factor ligand superfamily member 6), BAX, and Bcl-2 were measured by reverse transcription-polymerase chain reaction and Western blotting.ResultsHE and ORO staining showed that the hepatocytes were heavily destroyed with large lipid droplets in MG and SI groups, while the severity was reduced in the CG, BJ, and BJP groups (P<0.05). The levels of superoxide dismutase (SOD), reduced glutathione (GSH), and high-density lipoprotein-cholesterol (HDL-C) were increased in BJ and BJP groups when compared with the model group (P<0.05). In contrast, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total triglycerides (TGs), total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and malondialdehyde (MDA) were lower in BJ and BJP groups than in the model group (P<0.05). The level of SIRT1 was increased, while the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2 were decreased in CG, BJ, and BJP groups (P<0.05). Meanwhile, SIRT1 silence resulted in increase of the levels of FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2.ConclusionThe combination of blueberry juice and probiotics reduces apoptosis in AFLD by suppressing FOXO1, phosphorylated FOXO1, acetylated FOXO1, FasL, caspase-3, BAX, and Bcl-2 via the upregulation of SIRT1.

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Acute liver injury attenuation of a novel recombinant sTNFR through blocking hepatic apoptosis

Cited by 5 publications

References 28 publications

Carfilzomib Mitigates Lipopolysaccharide/D-Galactosamine/Dimethylsulfoxide-Induced Acute Liver Failure in Mice

Carfilzomib Mitigates Lipopolysaccharide/D-Galactosamine/Dimethylsulfoxide-Induced Acute Liver Failure in Mice

Protective effects of glutamine on lipopolysaccharide/D-galactosamine-induced fulminant hepatitis in mice

The combination of blueberry juice and probiotics reduces apoptosis of alcoholic fatty liver of mice by affecting SIRT1 pathway

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