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

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.

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

2020 ◽  
Vol 21 (6) ◽  
pp. 2048 ◽  
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.

scholarly journals A Polyphenol-Rich Fraction from Eugenia uniflora Exhibits Antioxidant and Hepatoprotective Activities In Vivo

2020 ◽  
Vol 13 (5) ◽  
pp. 84
Author(s):  
Mansour Sobeh ◽  
Marwa S. Hamza ◽  
Mohamed L. Ashour ◽  
Mona Elkhatieb ◽  
Mohamed A El Raey ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Ethyl Acetate ◽  
Acute Liver Injury ◽  
Antioxidant Activities ◽  
Biological Effects ◽  
Ethyl Acetate Fraction ◽  
Eugenia Uniflora ◽  
Quercetin Derivatives

Leaves from Eugenia uniflora, the red Brazilian cherry, have a high content of flavonoids that possess several biological effects such as anti-inflammatory, antioxidant, and antidiabetic activities. However, their influence on carbon tetrachloride (CCl4)-induced acute liver injury in rats has not been investigated. In the current study, a bioguided fractionation assay revealed that the ethyl acetate fraction (EAF) of Eugenia uniflora is the safest and most active fraction. LC-MS analysis of the ethyl acetate fraction revealed 22 secondary metabolites, mainly myricetin and quercetin derivatives. EAF did not show toxicity up to 2000 mg/kg, and exhibited antioxidant activities in vitro in DPPH assay with IC50 of 3.35 µg/mL. Additionally, EAF exhibited substantial antioxidant activities in vivo by counteracting the oxidative damage of the prooxidant juglone [80 µM] in Caenorhabditis elegans model organism and increased its survival rate in a dose-dependent fashion through the DAF-16/Foxo pathway. Furthermore, the hepatoprotective activity of EAF (200 mg/kg against carbon tetrachloride (CCl4) intoxicated male Wistar rats was assessed. EAF significantly inhibited CCl4-induced elevation of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TB), total cholesterol (TC), and triglycerides (TG), in the blood serum and prevented lipid peroxidation and restored superoxide dismutase (SOD) activity and glutathione (GSH) content in liver tissues. The observed hepatoprotective effects of EAF, which were supported by histopathological observations as pretreatment with EAF, effectively attenuated the CCl4-induced histopathological changes. In conclusion, EAF of Eugenia uniflora leaves has substantial hepatoprotective activities against CCl4 induced acute liver injury in rats due to its antioxidant activity.

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

2011 ◽  
Vol 32 (10) ◽  
pp. 796-803 ◽  
Author(s):  
Peng Chen ◽  
Zhongqiu Wang ◽  
Liyan Zeng ◽  
Shiming Wang ◽  
Wei Dong ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Protective Effects

scholarly journals Caveolin-1 Deficiency Protects Mice Against Carbon Tetrachloride-Induced Acute Liver Injury Through Regulating Polarization of Hepatic Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziheng Yang ◽  
Jie Zhang ◽  
Yan Wang ◽  
Jing Lu ◽  
Quan Sun
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Liver Diseases ◽  
Acute Liver Injury ◽  
Mrna Levels ◽  
Alcoholic Fatty Liver ◽  
Caveolin 1 ◽  
Hepatic Macrophages ◽  
M1 Phenotype

Polarization of hepatic macrophages plays a crucial role in the injury and repair processes of acute and chronic liver diseases. However, the underlying molecular mechanisms remain elusive. Caveolin-1 (Cav1) is the structural protein of caveolae, the invaginations of the plasma membrane. It has distinct functions in regulating hepatitis, cirrhosis, and hepatocarcinogenesis. Given the increasing number of cases of liver cancer, nonalcoholic steatohepatitis, and non-alcoholic fatty liver disease worldwide, investigations on the role of Cav1 in liver diseases are warranted. In this study, we aimed to investigate the role of Cav1 in the pathogenesis of acute liver injury. Wild-type (WT) and Cav1 knockout (KO) mice (Cav1tm1Mls) were injected with carbon tetrachloride (CCl4). Cav1 KO mice showed significantly reduced degeneration, necrosis, and apoptosis of hepatocytes and decreased level of alanine transaminase (ALT) compared to WT mice. Moreover, Cav1 was required for the recruitment of hepatic macrophages. The analysis of the mRNA levels of CD86, tumor necrosis factor (TNF), and interleukin (IL)-6, as well as the protein expression of inducible nitric oxide synthase (iNOS), indicated that Cav1 deficiency inhibited the polarization of hepatic macrophages towards the M1 phenotype in the injured liver. Consistent with in vivo results, the expressions of CD86, TNF, IL-6, and iNOS were significantly downregulated in Cav1 KO macrophages. Also, fluorescence-activated cell sorting (FACS) analysis showed that the proportion of M1 macrophages was significantly decreased in the liver tissues obtained from Cav1 KO mice following CCl4 treatment. In summary, our results showed that Cav1 deficiency protected mice against CCl4-induced acute liver injury by regulating polarization of hepatic macrophages. We provided direct genetic evidence that Cav1 expressed in hepatic macrophages contributed to the pathogenesis of acute liver injury by regulating the polarization of hepatic macrophages towards the M1 phenotype. These findings suggest that Cav1 expressed in macrophages may represent a potential therapeutic target for acute liver injury.

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

1998 ◽  
Vol 26 (03n04) ◽  
pp. 333-341 ◽  
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.

scholarly journals Preventive Effect of Lactobacillus Plantarum HFY15 on Oxidative Damage and Acute Liver Injury Induced by Carbon Tetrachloride (CCl 4 ) in Mice

2021 ◽  
Author(s):  
Xingyao Long ◽  
Pan Wang ◽  
Yujing Zhou ◽  
Qiang Wang ◽  
Lixuan Ren ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Oxidative Damage ◽  
Lactobacillus Plantarum ◽  
Acute Liver Injury ◽  
Animal Experiments ◽  
B Cell Lymphoma ◽  
Related Factor ◽  
Preventive Effect ◽  
Antioxidant Genes

Abstract BackgroundCarbon tetrachloride (CCl4) is a widely used hepatic toxin that causes acute liver injury through pathological mechanisms such as oxidative stress, inflammation, and apoptosis. In this experiment, mice were treated with Lactobacillus plantarum (LP) HFY15, silymarin, and Lactobacillus delbruechii subsp. bulgaricus (LDSB) for two weeks, and intraperitoneal injection of CCl4-induced acute liver injury to study the preventive effect of LP-HFY on CCl4-induced acute liver injury, especially in oxidative damage. ResultsThe survival rate of LP-HFY15 in artificial gastric juice is 92.1%, and the growth efficiency in bile salt is 78.8%. Animal experiments show that LP-HFY15 reduces the liver index of mice, reduces the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the content of triglycerides (TG), malondialdehyde (MDA) and reactive oxygen species (ROS) in the serum of mice. LP-HFY15 also increased the antioxidant genes, such as nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase (HO-1), NAD(P)H:quinone oxidoreductase (NQO1), and increases the activity of superoxide dismutation (SOD), catalase (CAT), and glutathione (GSH) in the serum and gene level. At the same time, LP-HFY15 reduced the levels of cytokines IL-6, TNF-α, and IFN-γ in the serum and liver, increased antiapoptosis gene B-cell lymphoma-2 (Bcl-2) expression in the liver of mice, and inhibit the expression of proapoptotic genes Bcl-2-associated X (Bax) and Caspase-3. ConclusionsCompared with LDSB, LP-HFY15 has a greater alleviating effect on the liver injury caused by CCl4. These findings demonstrate that LP-HFY15 has great potential and research value in the future as a food supplement for preventing acute liver damage.

scholarly journals Inhibition of oxidative stress and NLRP3 inflammasome by Saikosaponin-d alleviates acute liver injury in carbon tetrachloride-induced hepatitis in mice

2020 ◽  
Vol 34 ◽  
pp. 205873842095059
Author(s):  
Yirong Chen ◽  
Renye Que ◽  
Liubing Lin ◽  
Yanting Shen ◽  
Jinkai Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Nlrp3 Inflammasome ◽  
Acute Liver Injury ◽  
Inflammasome Activation ◽  
Protective Effects ◽  
Mice Model ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation

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.

scholarly journals IL-22 ameliorates LPS-induced acute liver injury by autophagy activation through ATF4-ATG7 signaling

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Lujing Shao ◽  
Xi Xiong ◽  
Yucai Zhang ◽  
Huijie Miao ◽  
Yuqian Ren ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Responses ◽  
Acute Liver Injury ◽  
Mrna Levels ◽  
Protective Effects ◽  
Activating Transcription Factor 4 ◽  
Pre Treatment ◽  
Underlying Mechanisms

Abstract Uncontrollable inflammatory response acts as a driver of sepsis-associated liver injury (SALI). IL-22 plays an important role in regulating inflammatory responses, but its role in SALI remains unknown. The aim of the study was to assess the association of serum IL-22 with SALI in pediatric patients and to enclose the underlying mechanisms of IL-22 involved in lipopolysaccharide (LPS) - induced acute liver injury (ALI) in mice. Serum IL-22 levels in patients with SALI were significantly lower than in septic patients without liver injury, and the area under receiver operating characteristic (ROC) curve of IL-22 for discriminating SALI was 0.765 (95% CI: 0.593–0.937). Pre-administration of recombinant murine IL-22 alleviated LPS-induced ALI in mice, and serum IL-6 levels and the mRNA levels of TNF-α, IL-1β, and IL-6 in livers were decreased in response to IL-22 pre-treatment in mice. More importantly, IL-22 pre-treatment activated hepatic autophagy mediated by activating transcription factor 4 (ATF4)-autophagy-related gene 7 (ATG7) signaling in vivo and in vitro in response to LPS administration. Moreover, knockdown of ATF4 in mice aggravated LPS-induced ALI, which was associated with suppressed ATG7-related autophagy. In addition, the protective effects of IL-22 on LPS-induced ALI was partially blocked by ATF4 knockdown, which was associated with lower expression of LC3II/I in the livers of ATF4 knockdown (HT or Atf4+/−) mice compared with wild-type mice (WT or Atf4+/+) mice. In conclusion, low serum IL-22 level is associated with SALI occurrence, and IL-22 pre-administration activates autophagy in hepatocytes and protects mice against LPS-induced ALI partially related to ATF4-ATG7 signaling pathway.

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