Effect ofLactobacillus supplementation with and without arginine on liver damage and bacterial translocation in an acute liver injury model in the rat

The objective of this study is to establish poultry liver injury model induced by (CCl4) and seek effective hepatoprotective herbals for clinical application. Different doses of CCl4dissolved in vegetable oil (1 : 1,V/V) were injected via pectoral muscle to induce acute liver injury model in chickens. An herbal formula, Longyin decoction, was prepared for hepatoprotection test on chicken acute liver injury models. The pathologic changes of the liver were observed, and the activities of ALT and AST were, respectively, detected to evaluate the hepatoprotective effects of Longyin decoction on chickens. The chicken acute liver injury model was successfully established by injecting CCl4via pectoral muscle. The best dose of CCl4inducing chicken liver injury was 4.0 mL/kg·BW (body weight). The results of qualitative determination by HPTLC showed that the components of Longyin decoction containedGentian, Capillaries, Gardenia,andBupleurum root. In the high-dose Longyin group and the middle-dose Longyin group, the pathological changes of the damaged liver were mitigated and the activities of ALT and AST in serum were reduced significantly. Longyin decoction has obvious hepatoprotective effect on acute liver injury induced by CCl4.

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Indoline derivatives mitigate liver damage in a mouse model of acute liver injury

Pharmacological Reports ◽

10.1016/j.pharep.2017.03.025 ◽

2017 ◽

Vol 69 (5) ◽

pp. 894-902 ◽

Cited By ~ 3

Author(s):

Efrat Finkin-Groner ◽

Shlomi Finkin ◽

Shani Zeeli ◽

Marta Weinstock

Keyword(s):

Liver Injury ◽

Mouse Model ◽

Liver Damage ◽

Acute Liver Injury

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Salvianolic acid B exerts a protective effect in acute liver injury by regulating the Nrf2/HO-1 signaling pathway

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2019-0349 ◽

2020 ◽

Vol 98 (3) ◽

pp. 162-168 ◽

Cited By ~ 3

Author(s):

Yong-mei Jin ◽

Xiang-ming Tao ◽

Yi-ning Shi ◽

Youjin Lu ◽

Jin-yu Mei

Keyword(s):

Liver Injury ◽

Signaling Pathway ◽

Acute Liver Injury ◽

Damage Model ◽

Underlying Mechanism ◽

Salvianolic Acid B ◽

Salvianolic Acid ◽

Injury Model

Salvianolic acid B (Sal B) exerts strong antioxidant activity and eliminates the free radical effect. However, how it affects the antioxidant pathway is not very clear. The objective of this study was to investigate the underlying mechanism of Sal B in CCl4-induced acute liver injury, especially its effect on the Nrf2/HO-1 signaling pathway. For the in vivo experiment, an acute liver injury model was induced using CCl4 and treated with Sal B. For the in vitro experiment, an oxidative damage model was established followed by Sal B treatment. Serum biochemical indicators and reactive oxygen species activity were detected using corresponding kits. Oxidant/antioxidant status was determined based on the levels of malondialdehyde, glutathione, and superoxide dismutase. Nrf2 and HO-1 levels were analyzed by Western blotting and immunohistochemical staining. Sal B treatment improved liver histology, decreased the aminotransferase levels, and attenuated oxidative stress in the acute liver injury model. Nrf2 and HO-1 levels were increased both in vivo and in vitro. Sal B suppresses acute liver injury and Nrf2/HO-1 signaling plays a key role in this process.

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Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1822173116 ◽

2019 ◽

Vol 116 (18) ◽

pp. 9125-9134 ◽

Cited By ~ 8

Author(s):

Min-Jung Park ◽

Louis G. D’Alecy ◽

Michelle A. Anderson ◽

Venkatesha Basrur ◽

Yongjia Feng ◽

...

Keyword(s):

Liver Injury ◽

Liver Damage ◽

Half Life ◽

Fas Ligand ◽

Urea Cycle ◽

Acute Liver Injury ◽

Carbamoyl Phosphate ◽

Human Bile ◽

Cycle Enzyme ◽

Short Half Life

Carbamoyl phosphate synthetase-1 (CPS1) is the major mitochondrial urea cycle enzyme in hepatocytes. It is released into mouse and human blood during acute liver injury, where is has a short half-life. The function of CPS1 in blood and the reason for its short half-life in serum are unknown. We show that CPS1 is released normally into mouse and human bile, and pathologically into blood during acute liver injury. Other cytoplasmic and mitochondrial urea cycle enzymes are also found in normal mouse bile. Serum, bile, and purified CPS1 manifest sedimentation properties that overlap with extracellular vesicles, due to the propensity of CPS1 to aggregate despite being released primarily as a soluble protein. During liver injury, CPS1 in blood is rapidly sequestered by monocytes, leading to monocyte M2-polarization and homing to the liver independent of its enzyme activity. Recombinant CPS1 (rCPS1), but not control r-transferrin, increases hepatic macrophage numbers and phagocytic activity. Notably, rCPS1 does not activate hepatic macrophages directly; rather, it activates bone marrow and circulating monocytes that then home to the liver. rCPS1 administration prevents mouse liver damage induced by Fas ligand or acetaminophen, but this protection is absent in macrophage-deficient mice. Moreover, rCPS1 protects from acetaminophen-induced liver injury even when given therapeutically after injury induction. In summary, CPS1 is normally found in bile but is released by hepatocytes into blood upon liver damage. We demonstrate a nonenzymatic function of CPS1 as an antiinflammatory protective cytokine during acute liver injury.

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FOXA2 overexpressed adipose derived stem cells attenuated acute liver injury model

Journal of Hepatology ◽

10.1016/s0168-8278(17)31779-8 ◽

2017 ◽

Vol 66 (1) ◽

pp. S656-S657

Author(s):

Y.J. Chae ◽

D.W. Jun ◽

S.B. Ahn ◽

W.K. Saeed ◽

J.S. Lee ◽

...

Keyword(s):

Stem Cells ◽

Liver Injury ◽

Acute Liver Injury ◽

Adipose Derived Stem Cells ◽

Injury Model

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Histone methyltransferase G9a protects against acute liver injury through GSTP1

Cell Death and Differentiation ◽

10.1038/s41418-019-0412-8 ◽

2019 ◽

Vol 27 (4) ◽

pp. 1243-1258 ◽

Cited By ~ 8

Author(s):

Yu Zhang ◽

Weili Xue ◽

Wenquan Zhang ◽

Yangmian Yuan ◽

Xiuqin Zhu ◽

...

Keyword(s):

Liver Injury ◽

Liver Damage ◽

Acute Liver Injury ◽

Epigenetic Modification ◽

Histone Methyltransferase ◽

Methyltransferase Activity ◽

Detoxifying Enzymes ◽

Apap Overdose ◽

Deficient Mice

Abstract Acute liver injury is commonly caused by bacterial endotoxin/lipopolysaccharide (LPS), and by drug overdose such as acetaminophen (APAP). The exact role of epigenetic modification in acute liver injury remains elusive. Here, we investigated the role of histone methyltransferase G9a in LPS- or APAP overdose-induced acute liver injury. Under d-galactosamine sensitization, liver-specific G9a-deficient mice (L-G9a−/−) exhibited 100% mortality after LPS injection, while the control and L-G9a+/− littermates showed very mild mortality. Moreover, abrogation of hepatic G9a or inhibiting the methyltransferase activity of G9a aggravated LPS-induced liver damage. Similarly, under sublethal APAP overdose, L-G9a−/− mice displayed more severe liver injury. Mechanistically, ablation of G9a inhibited H3K9me1 levels at the promoters of Gstp1/2, two liver detoxifying enzymes, and consequently suppressed their transcription. Notably, treating L-G9a−/− mice with recombinant mouse GSTP1 reversed the LPS- or APAP overdose-induced liver damage. Taken together, we identify a novel beneficial role of G9a-GSTP1 axis in protecting against acute liver injury.

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