Protective Effects of Smilax glabra Roxb on Carbon Tetrachloride Induced Rat Acute Liver Injury by Inhibiting the Activation of the NLRP3 Inflammasome

NLRP3 inflammasome activation results in severe liver inflammation and injury. Saikosaponin-d (SSd) possesses anti-inflammatory and hepatoprotective effects. This study aimed to determine the protective effects of SSd on carbon tetrachloride (CCl4)-induced acute liver injury in mice, and whether oxidative stress and NLRP3 inflammasome activation participate in the process. The CCl4 mice model and controls were induced. The mice were treated with SSd at 1, 1.5, or 2.0 mg/kg in a total volume of 100 µl/25 g of body weight. Liver injury was assessed by histopathology. Oxidative stress was determined using mitochondrial superoxide production (MSP), malondialdehyde (MDA) content, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. NLRP3, ASC, and Caspase 1 were determined by real-time PCR and western blot. IL-1β and IL-18 levels were determined by ELISA. Significantly elevated oxidative stress was induced in the liver by CCl4, as demonstrated by histopathology and increases of MDA and MSP levels and decreases of SOD, GPx, and CAT activities (all P < 0.01). SSd significantly decreased the MDA and MSP levels and increased the activities of SOD, GPx, and CAT (all P < 0.05). The mRNA expression of NLRP3, ASC, and Caspase 1, and the protein expression of Caspase 1-p10, NLRP3, ASC, IL-1β, and IL-18 were significantly increased after CCl4 induction (all P < 0.01). These changes were reversed by SSd (all P < 0.05). Suppression of the oxidative stress and NLRP3 inflammasome activation were involved in SSd-alleviated acute liver injury in CCl4-induced hepatitis.

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Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Applied Sciences ◽

10.3390/app11010390 ◽

2021 ◽

Vol 11 (1) ◽

pp. 390

Author(s):

Beom-Rak Choi ◽

Il-Je Cho ◽

Su-Jin Jung ◽

Jae-Kwang Kim ◽

Dae-Geon Lee ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Acute Liver Injury ◽

Antioxidant Activities ◽

Body Weight Gain ◽

Histopathological Analysis ◽

Related Factor ◽

Mrna Levels ◽

Protective Effects ◽

Lemon Balm

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

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Protective effects of salecan against carbon tetrachloride-induced acute liver injury in mice

Journal of Applied Toxicology ◽

10.1002/jat.1694 ◽

2011 ◽

Vol 32 (10) ◽

pp. 796-803 ◽

Cited By ~ 17

Author(s):

Peng Chen ◽

Zhongqiu Wang ◽

Liyan Zeng ◽

Shiming Wang ◽

Wei Dong ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Acute Liver Injury ◽

Protective Effects

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Determining the protective effects of Yin-Chen-Hao Tang against acute liver injury induced by carbon tetrachloride using 16S rRNA gene sequencing and LC/MS-based metabolomics

Journal of Pharmaceutical and Biomedical Analysis ◽

10.1016/j.jpba.2019.06.028 ◽

2019 ◽

Vol 174 ◽

pp. 567-577 ◽

Cited By ~ 6

Author(s):

Fang Liu ◽

Zhaolin Sun ◽

Pei Hu ◽

Qiang Tian ◽

Zhou Xu ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

16S Rrna ◽

16S Rrna Gene ◽

Acute Liver Injury ◽

Gene Sequencing ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Protective Effects ◽

Rrna Gene Sequencing

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Protective effects of magnesium isoglycyrrhizinate against carbon tetrachloride-induced acute liver injury in mice

World Chinese Journal of Digestology ◽

10.11569/wcjd.v16.i9.1004 ◽

2008 ◽

Vol 16 (9) ◽

pp. 1004 ◽

Cited By ~ 4

Author(s):

Qi-De Bao ◽

Lan-Lan Yang ◽

Li Wang ◽

Dong-Lai Cui

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Acute Liver Injury ◽

Protective Effects ◽

Magnesium Isoglycyrrhizinate

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Oleoylethanolamide Protects Against Acute Liver Injury by Regulating Nrf-2/HO-1 and NLRP3 Pathways in Mice

Frontiers in Pharmacology ◽

10.3389/fphar.2020.605065 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jiaji Hu ◽

Zhoujie Zhu ◽

Hanglu Ying ◽

Jie Yao ◽

Huabin Ma ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Nlrp3 Inflammasome ◽

Acute Liver Injury ◽

Inflammatory Factors ◽

High Morbidity ◽

Therapeutic Effects ◽

Protective Effects ◽

Mechanism Study ◽

Oxidation Activity

Acute liver injury is a rapidly deteriorating clinical condition with markedly high morbidity and mortality. Oleoylethanolamide (OEA) is an endogenous lipid messenger with multiple bioactivities, and has therapeutic effects on various liver diseases. However, effects of OEA on acute liver injury remains unknown. In this study, effects and mechanisms of OEA in lipopolysaccharide (LPS)/d-galactosamine (D-Gal)-induced acute liver injury in mice were investigated. We found that OEA treatment significantly attenuated LPS/D-Gal-induced hepatocytes damage, reduced liver index (liver weight/body weight), decreased plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels. Moreover, mechanism study suggested that OEA pretreatment significantly reduced hepatic MDA levels, increased Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-PX) activities via up-regulate Nrf-2 and HO-1 expression to exert anti-oxidation activity. Additionally, OEA markedly reduced the expression levels of Bax, Bcl-2 and cleaved caspase-3 to suppress hepatocyte apoptosis. Meanwhile, OEA remarkedly reduced the number of activated intrahepatic macrophages, and alleviated the mRNA expression of pro-inflammatory factors, including TNF-α, IL-6, MCP1 and RANTES. Furthermore, OEA obviously reduced the expression of IL-1β in liver and plasma through inhibit protein levels of NLRP3 and caspase-1, which indicated that OEA could suppress NLRP3 inflammasome pathway. We further determined the protein expression of PPAR-α in liver and found that OEA significantly increase hepatic PPAR-α expression. In addition, HO-1 inhibitor ZnPP blocked the therapeutic effects of OEA on LPS/D-Gal-induced liver damage and oxidative stress, suggesting crucial role of Nrf-2/HO-1 pathway in the protective effects of OEA in acute liver injury. Together, these findings demonstrated that OEA protect against the LPS/D-Gal-induced acute liver injury in mice through the inhibition of apoptosis, oxidative stress and inflammation, and its mechanisms might be associated with the Nrf-2/HO-1 and NLRP3 inflammasome signaling pathways.

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Mechanism of the Protective Effects of Sumac Gall Extract and Gallic Acid on the Progression of CCl4-induced Acute Liver Injury in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x98000373 ◽

1998 ◽

Vol 26 (03n04) ◽

pp. 333-341 ◽

Cited By ~ 30

Author(s):

Shigeyuki Kanai ◽

Hideyuki Okano

Keyword(s):

Superoxide Dismutase ◽

Carbon Tetrachloride ◽

Liver Injury ◽

Protective Effect ◽

Gallic Acid ◽

Cell Membranes ◽

Acute Liver Injury ◽

Radical Scavenging ◽

Protective Effects ◽

Preventive Effect

To examine the mechanism of the preventive effect of tannins on the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rats, sumac gall (SG) extract and gallic acid (GA) were used as substitutes for crude tannins, because SG is a kind of Chinese traditional medicinal herb containing large amounts of various tannins, and GA is one of the major constituents of SG. The protective effect of oral (p.o.) and intraperitoneal (i.p.) administration of each substance on progression of CCl4-induced hepatitis was investigated in rats. Speculating that the superoxide dismutase (SOD)-like activities (O2 radical-scavenging activities) and/or protective effects of these substances on cell membranes might play a key role in the mechanism opposing the progression of CCl4-induced hepatitis, the O2 radical-scavenging activities in liver cells and serum in rats were monitored. Both substances significantly prevented the progression of acute liver injury with both p.o. and i.p. administration. These findings suggest that the mechanism for this prevention might be due mainly to the protective effect of these substances on cell membranes rather than O2 radical-scavenging activities.

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Endogenous n-3 Fatty Acids Alleviate Carbon-Tetrachloride-Induced Acute Liver Injury inFat-1Transgenic Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/7962948 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 10

Author(s):

Ruibing Feng ◽

Meng Wang ◽

Chunyan Yan ◽

Peng Li ◽

Meiwan Chen ◽

...

Keyword(s):

Fatty Acids ◽

Carbon Tetrachloride ◽

Liver Injury ◽

Corn Oil ◽

Acute Liver Injury ◽

Mapk Pathway ◽

Protective Effects ◽

Histopathological Changes ◽

Hepatocyte Apoptosis ◽

Severe Liver

n-3 polyunsaturated fatty acids (PUFAs) are beneficial for numerous models of liver diseases. The probable protective effects of n-3 PUFA against carbon-tetrachloride- (CCl4-) induced acute liver injury were evaluated in afat-1transgenic mouse that synthesizes endogenous n-3 from n-6 PUFA.Fat-1mice and their WT littermates were fed a modified AIN93 diet containing 10% corn oil and were injected intraperitoneally with a single dose of CCl4or vehicle. CCl4challenge caused severe liver injury in WT mice, as indicated by serum parameters and histopathological changes, which were remarkably ameliorated infat-1mice. Endogenous n-3 PUFA decreased the elevation of oxidative stress induced by CCl4challenge, which might be attributed to the activation of Nrf2/keap1 pathway. Additionally, endogenous n-3 PUFA reduces hepatocyte apoptosis via suppressing MAPK pathway. These findings indicate that n-3 PUFA has potent protective effects against acute liver injury induced by CCl4in mice, suggesting that n-3 PUFA can be used for the prevention and treatment of liver injury.

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Indole-3-Carbinol Derivative DIM Mitigates Carbon Tetrachloride-Induced Acute Liver Injury in Mice by Inhibiting Inflammatory Response, Apoptosis and Regulating Oxidative Stress

International Journal of Molecular Sciences ◽

10.3390/ijms21062048 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2048 ◽

Cited By ~ 3

Author(s):

Suvesh Munakarmi ◽

Lokendra Chand ◽

Hyun Beak Shin ◽

Kyu Yun Jang ◽

Yeon Jun Jeong

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Molecular Mechanisms ◽

Acute Liver Injury ◽

Intraperitoneal Administration ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Protective Effects ◽

Serum Transaminases

3,3′-Diindolylmethane (DIM), a metabolic product of indole-3-carbinol extracted from cruciferous vegetables exhibits anti-inflammatory and anti-cancer properties. Earlier, the product has been demonstrated to possess anti-fibrotic properties; however, its protective effects on liver injury have not been clearly elucidated. In this study, we postulated the effects and molecular mechanisms of action of DIM on carbon tetrachloride (CCl4)-induced liver injury in mice. Acute liver injury was induced by a single intraperitoneal administration of CCl4 (1 ml/kg) into mice. DIM was injected via subcutaneous route for three days at various doses (2.5, 5 and 10 mg/kg) before CCl4 injection. Mice were sacrificed and serum was collected for quantification of serum transaminases. The liver was collected and weighed. Treatment with DIM significantly reduced serum transaminases levels (AST and ALT), tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS). CCl4- induced apoptosis was inhibited by DIM treatment by the reduction in the levels of cleaved caspase-3 and Bcl2 associated X protein (Bax). DIM treated mice significantly restored Cytochrome P450 2E1, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in CCl4 treated mice. In addition, DIM downregulated overexpression of hepatic nuclear factor kappa B (NF-κB) and inhibited CCl4 mediated apoptosis. Our results suggest that the protective effects of DIM against CCl4- induced liver injury are due to the inhibition of ROS, reduction of pro-inflammatory mediators and apoptosis.

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