Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation

Xiong, Xi; Ren, Yan; Cui, Yun; Li, Rui; Wang, Chunxia; Zhang, Yucai

doi:10.1016/j.biopha.2017.11.083

Cited by 92 publications

(47 citation statements)

References 41 publications

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“…Studies have found that activating transcription factor 4 (ATF4) directly targets the activation of autophagy, and ATF4 expression is inhibited 48 h after LPS-induced acute liver injury. Obeticholic acid (OCA) protected mice from LPS-induced liver injury, possibly in contribution with ATF4-mediated autophagy activity in hepatocytes (Xiong et al, 2017). The lack of autophagy during sepsis may prevent the removal of hepatic mitochondrial damage and dysfunction.…”

Section: Mechanism Of Action Of Autophagy In Different Organsmentioning

confidence: 99%

The Role of Autophagy in Sepsis: Protection and Injury to Organs

et al. 2019

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Sepsis is a systemic inflammatory disease with infection, and autophagy has been shown to play an important role in sepsis. This review summarizes the main regulatory mechanisms of autophagy in sepsis and its latest research. Recent studies have shown that autophagy can regulate innate immune processes and acquired immune processes, and the regulation of autophagy in different immune cells is different. Mitophagy can select damaged mitochondria and remove it to deal with oxidative stress damage. The process of mitophagy is regulated by other factors. Non-coding RNA is also an important factor in the regulation of autophagy. In addition, more and more studies in recent years have shown that autophagy plays different roles in different organs. It tends to be protective in the lungs, heart, kidneys, and brain, and tends to be damaging in skeletal muscle. We also mentioned that some drugs can regulate autophagy. The process of modulating autophagy through drug intervention appears to be a new potential hope for the treatment of sepsis.

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Section: Mechanism Of Action Of Autophagy In Different Organsmentioning

confidence: 99%

The Role of Autophagy in Sepsis: Protection and Injury to Organs

et al. 2019

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“…Sepsis is a major cause of mortality and critical illness in intensive care units and is defined as a life-threatening organ dysfunction caused by a dysregulated host response against infection that triggers systemic inflammatory response syndrome (1,2). Among the organ failures involved in sepsis, hepatic dysfunction is a prominent complication that contributes to an increased risk of development of multiple organ failure and is a strong independent predictor of mortality (3,4).…”

Section: Introductionmentioning

confidence: 99%

Protective role of thymoquinone in sepsis‑induced liver injury in BALB/c mice

et al. 2019

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Sepsis increases the risk of developing liver injury. Previous studies have demonstrated that thymoquinone (TQ) exhibits hepatoprotective properties in vivo as well as in vitro . The present study aimed to investigate the underlying mechanisms of the protective effects of TQ against liver injury in septic BALB/c mice. Male BALB/c mice (age, 8 weeks) were randomly divided into four groups, namely, the control, TQ (50 mg/kg/day) treatment, cecal ligation and puncture (CLP), and TQ + CLP groups. CLP was performed following gavage of TQ for 2 weeks. At 48 h post-CLP, the histopathological alterations in the liver tissue (LT) and plasma levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were assessed. The present study evaluated microtubule-associated protein light chain 3 (LC3), sequestosome-1 (p62) and beclin 1 protein expression by western blotting and immunostaining , as well as interleukin (IL)-6, IL-1β, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) mRNA expression by RT-qPCR. The results of the present study indicated that administration of TQ to mice reduced the histological alterations caused by CLP in LT. TQ inhibited the plasma levels of ALT, AST and ALP in the CLP group. TQ significantly inhibited the elevation of p62, IL-1β, IL-6, MCP-1 and TNF-α levels as well as increased the LC3, beclin 1 and IL-10 levels in LT. PI3K expression in the TQ + CLP group was significantly decreased compared with that in the CLP group. TQ treatment effectively modulated the expression levels of p62, LC3, beclin 1, PI3K and proinflammatory cytokines, and may be an important agent for the treatment of sepsis-induced liver injury.

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“…The persistent release of cytokines, such as TNF-α and IL-6, induces hepatocellular inflammation and apoptosis, ultimately leading to liver injury (Jiang et al, 2018). The inhibition of inflammatory cytokines serves as a potential interventional strategy in the treatment of sepsis-induced liver injury (Jiang et al, 2018;Xiong et al, 2017). The function of ERRγ in inflammatory diseases has not been clearly understood (Ambhore et al, 2018;Son and Chun, 2018;Yuk et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Estrogen-Related Receptor γ Agonist DY131 Ameliorates Lipopolysaccharide-Induced Acute Liver Injury

Liu

et al. 2021

Front. Pharmacol.

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Sepsis-associated liver dysfunction remains a challenge in clinical practice with high mortality and limited specific therapies. DY131 is a pharmacological agonist of the orphan receptor estrogen-related receptor (ERR) γ which plays a crucial role in regulating energy generation, oxidative metabolism, cell apoptosis, inflammatory responses, etc. However, its role in acute liver injury is unknown. In this study, we evaluated the effect of DY131 on lipopolysaccharide (LPS)-induced liver injury. Mice were pretreated with DY131 through intraperitoneal injection at a dose of 5 mg/kg/day for 3 days prior to LPS challenge (10 mg/kg). 24 h later, they were anesthetized and sacrificed. Blood and liver tissues were collected for further studies. In a separate experiment, mice were treated with saline (vehicle) or DY131 for 3 days to evaluate the toxicity of DY131. We found that ERRγ was downregulated in the liver tissues from LPS-treated mice. Pretreatment with DY131 ameliorated LPS-induced liver injury as demonstrated by reduced liver enzyme release (ALT, AST, and LDH), improved liver morphological damage, and attenuated oxidative stress, inflammation and apoptosis. Meanwhile, DY131 had no significant side effects on hepatic and renal functions in mice. Finally, transcriptomics analysis revealed that the dysregulated pathways associated with inflammation and metabolism were significantly reversed by DY131 in LPS-treated mice, providing more evidence in favor of the protective effect of DY131 against LPS-induced liver injury. Altogether, these findings highlighted the protective effect of DY131 on LPS-induced hepatotoxicity possibly via suppressing oxidative stress, inflammation, and apoptosis.

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Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation

Cited by 92 publications

References 41 publications

The Role of Autophagy in Sepsis: Protection and Injury to Organs

The Role of Autophagy in Sepsis: Protection and Injury to Organs

Protective role of thymoquinone in sepsis‑induced liver injury in BALB/c mice

Estrogen-Related Receptor γ Agonist DY131 Ameliorates Lipopolysaccharide-Induced Acute Liver Injury

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