Kupffer cell depletion attenuates IL-6/STAT3 mediates hepatocyte apoptosis in immunological liver injury of trichloroethylene sensitized mice

Zhang, Jiaxiang; Li, Na; Xu, Qiongying; Yang, Yi; Xie, Haibo; Shen, Tong; Zhu, Qingsan

doi:10.1016/j.intimp.2020.106897

Cited by 18 publications

(7 citation statements)

References 32 publications

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“…Our results demonstrated that H 2 S not only reduced the apoptosis caused by ER stress, but also decreased the levels of inflammatory factors, and this may play a crucial role in the protective effect of H 2 S in I/R induced liver injury. Ischemia causes an initial injury to the liver, and this is followed by more extensive damage during the period of re-perfusion, which is driven by abundant inflammatory factors, including IL-6, IL-1β, and IL-18 (31)(32)(33). In our study, H 2 S was found to efficiently repress the inflammatory levels in the serum of rats following I/R injury, suggesting that H 2 S may exert an anti-inflammation role in I/R induced liver injury.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide alleviates ischemia induced liver injury by repressing the SPHK1/S1P pathway

Chen¹,

Lin²,

Yang³

et al. 2023

Ann Transl Med

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Background Ischemia/reperfusion (I/R) induced liver injury is a severe pathological process which frequently occurs during clinical hepatic operations. The current study investigated the protective function and underlying mechanisms of hydrogen sulfide (H 2 S) in I/R induced liver injury. Methods The effects of H 2 S were examined using the fibroblast-like rat liver cell line BRL-3A (the name of normal hepatocytes in rats) cultured under hypoxic conditions and an I/R rat model. The viability of BRL-3A cells was assessed using the methylthiazolyldiphenyl-tetrazolium (MTT) assay and Hoechst analysis. The expression of C/EBP homologous protein (CHOP), sphingosine kinase 1 (SPHK1), and sphingosine 1-phosphate (S1P) were determined in hypoxic BRL-3A cells with or without H 2 S treatment. CHOP was overexpressed in hypoxic BRL-3A cells to further evaluate whether H 2 S protected the liver against I/R injury by decreasing endoplasmic reticulum (ER) stress. Finally, the inflammation levels in the serum and the histopathological changes of liver were examined in the I/R rat model to evaluate the therapeutic function of H 2 S on I/R induced liver injury in vivo . Results H 2 S alleviated hypoxic damage in BRL-3A cells. In addition, hypoxia increased the expression of CHOP, SPHK1, and S1P in BRL-3A cells, and this was abolished by H 2 S pretreatment. Notably, overexpression of CHOP significantly inhibited the effect of H 2 S on the viability of BRL-3A cells during hypoxia. Overall, H 2 S effectively protected against I/R induced liver injury, decreased the inflammatory responses, and attenuated apoptosis of hepatocyte via inhibiting the ER stress response. Conclusions These findings demonstrated that pre-treatment of H 2 S protected against I/R induced liver injury by repressing the SPHK1/S1P pathway via inhibition of ER stress, suggesting an effective therapeutic method for the treatment of I/R induced liver injury.

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Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide alleviates ischemia induced liver injury by repressing the SPHK1/S1P pathway

Chen¹,

Lin²,

Yang³

et al. 2023

Ann Transl Med

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“…Current research shows that there are about 2 million new cases of liver disease worldwide each year, and millions of deaths from liver disease related to chemical liver injury, accounting for about 3.5% of all deaths [ 21 ]. If liver damage is not promptly treated, it can lead to many forms of liver disease, such as acute and chronic hepatitis, granulomatous hepatitis, cholestasis due to bile duct damage, cholestasis with or without hepatitis, steatohepatitis, vascular disease, and tumors [ 22 , 23 ]. However, at present, chemical drugs are mostly used in the clinical treatment of liver injury, which have obvious side effects and are relatively expensive [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Comparison of Eight Major Compounds of Lonicerae japonicae flos after Oral Administration in Normal Rats and Rats with Liver Injury

et al. 2022

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Traditional Chinese medicine considers Lonicerae japonicae flos to have antibacterial detoxification, liver protection, and gallbladder protection. At present, studies have proven that Lonicerae japonicae flos has a good therapeutic effect on liver injury. Therefore, to confirm the clinical applicability of Lonicerae japonicae flos in the treatment of liver injury, we were the first to compare the pharmacokinetics of an oral ethanol extract of Lonicerae japonicae flos in normal rats and carbon tetrachloride-induced liver injury model rats. A method was developed for the simultaneous determination of 3-caffeoylquinic acid, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, protocatechuic acid, Sweroside, and Secoxyloganin in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry. The results show that the method is reliable and reproducible and can be used for quantitative determination of biological samples. The pharmacokinetic parameters showed that the area under the concentration–time curve of eight compounds in the model group was significantly increased. The results showed that the total absorption of the active components of Lonicerae japonicae flos in the blood increased, the clearance rate slowed down, and the bioavailability of Lonicerae japonicae flos increased in liver injury diseases.

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“…While interleukin‐6 (IL‐6) is a pro‐inflammatory cytokine and sustained high level in the serum of patients with HBV‐ACLF 15 and is independently associated with the risk of mortality in patients with HBV‐ACLF 16 . Both the two inflammatory‐related cytokines are proved to be key regulators of liver injury 17,18 . However, to date, little is known about the kinetic profile and diagnostic value of serum IL‐28A and IL‐6 levels in patients with HBV‐ACLF during ALSS treatment.…”

Section: Introductionmentioning

confidence: 99%

“… 16 Both the two inflammatory‐related cytokines are proved to be key regulators of liver injury. 17 , 18 However, to date, little is known about the kinetic profile and diagnostic value of serum IL‐28A and IL‐6 levels in patients with HBV‐ACLF during ALSS treatment. In the present study, we dynamically measured the levels of serum IL‐28A, IL‐6, and other multiple cytokines, including interleukin‐4 (IL‐4), IL‐8, IL‐18, CD40 ligand (CD40L), CC chemokine ligand‐2 (CCL2), CCL4, CCL20, chemokine C‐X‐C ligand‐10 (CXCL‐10), tumor necrosis factor‐α (TNF‐α), transforming growth factor‐beta 1 (TGFβ1), and TGFβ2 in HBV‐ACLF patients before and after ALSS treatment and analyzed the relationship between the cytokines and clinical variables, moreover, explored the biomarkers that could be used to predict the prognosis of ALSS.…”

Section: Introductionmentioning

confidence: 99%

Lower level of IL‐28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV‐ACLF

Huang

Zhang

et al. 2022

Clinical Laboratory Analysis

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Background HBV‐related acute‐on‐chronic liver failure (HBV‐ACLF) is the most common type of liver failure with high mortality. Artificial liver support system (ALSS) is an important mean to reduce the mortality of HBV‐ACLF but lacking index to assess its effectiveness. The cytokines are closely related to the prognosis of HBV‐ACLF patients with ALSS treatment, however, which is not fully understood. Methods One hundred forty‐two patients with HBV‐ACLF and 25 healthy donors were enrolled. The cytokine profile of peripheral blood was determined in the patients before and after ALSS treatment, and their relationship with effectiveness of ALSS treatment in HBV‐ACLF was analyzed. Results Serum IL‐28A levels were markedly lower in ALSS‐effective patients than those in non‐effective patients pre‐ALSS treatment. Similarly, serum IL‐6 was significantly lower in ALSS‐effective patients. Furthermore, for patients with effective treatment, serum IL‐28A levels were positively related with IL‐6 levels post‐ALSS (r = 0.2413, p = 0.0383). The ROC curve analysis showed that serum levels of IL‐28A (AUC = 0.6959 when alone or 0.8795 when combined with total bilirubin, platelet count and INR, both p < 0.0001) and IL‐6 (AUC = 0.6704, p = 0.0005) were useful indices for separating effective from non‐effective ALSS treatment of HBV‐ACLF patients. Multivariate logistic regression analysis demonstrated that lower level of IL‐28A was independently associated with higher effective rate of ALSS treatments. Conclusions Lower level of IL‐28A is a predictive biomarker for ALSS in effective treatment of HBV‐ACLF patients and IL‐28A may be potential target for the treatment of HBV‐ACLF.

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Kupffer cell depletion attenuates IL-6/STAT3 mediates hepatocyte apoptosis in immunological liver injury of trichloroethylene sensitized mice

Cited by 18 publications

References 32 publications

Hydrogen sulfide alleviates ischemia induced liver injury by repressing the SPHK1/S1P pathway

Hydrogen sulfide alleviates ischemia induced liver injury by repressing the SPHK1/S1P pathway

Pharmacokinetic Comparison of Eight Major Compounds of Lonicerae japonicae flos after Oral Administration in Normal Rats and Rats with Liver Injury

Lower level of IL‐28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV‐ACLF

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