The Protective Effect of Aspirin Eugenol Ester on Paraquat-Induced Acute Liver Injury Rats

Aspirin eugenol ester (AEE) possesses anti-inflammatory and anti-oxidative effects. The study was conducted to evaluate the protective effect of AEE on paraquat-induced acute liver injury (ALI) in rats. AEE was against ALI by decreasing alanine transaminase and aspartate transaminase levels in blood, increasing superoxide dismutase, catalase, and glutathione peroxidase levels, and decreasing malondialdehyde levels in blood and liver. A total of 32 metabolites were identified as biomarkers by using metabolite analysis of liver homogenate based on ultra-performance liquid chromatography-tandem mass spectrometry, which belonged to purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glycerophospholipid metabolism, primary bile acid biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, histidine metabolism, pantothenate, and CoA biosynthesis, ether lipid metabolism, beta-Alanine metabolism, lysine degradation, cysteine, and methionine metabolism. Western blotting analyses showed that Bax, cytochrome C, caspase-3, caspase-9, and apoptosis-inducing factor expression levels were obviously decreased, whereas Bcl-2 expression levels obviously increased after AEE treatment. AEE exhibited protective effects on PQ-induced ALI, and the underlying mechanism is correlated with antioxidants that regulate amino acid, phospholipid and energy metabolism metabolic pathway disorders and alleviate liver mitochondria apoptosis.

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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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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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Fucosterol Protects against Concanavalin A-Induced Acute Liver Injury: Focus on P38 MAPK/NF-κB Pathway Activity

Gastroenterology Research and Practice ◽

10.1155/2018/2824139 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

Wenhui Mo ◽

Chengfen Wang ◽

Jingjing Li ◽

Kan Chen ◽

Yujing Xia ◽

...

Keyword(s):

Liver Injury ◽

P38 Mapk ◽

Concanavalin A ◽

Molecular Mechanisms ◽

Therapeutic Agent ◽

Acute Liver Injury ◽

Biological Activities ◽

Hepatic Necrosis ◽

Protective Effects ◽

Eisenia Bicyclis

Objective. Fucosterol is derived from the brown alga Eisenia bicyclis and has various biological activities, including antioxidant, anticancer, and antidiabetic properties. The aim of this study was to investigate the protective effects of fucosterol pretreatment on Concanavalin A- (ConA-) induced acute liver injury in mice, and to understand its molecular mechanisms. Materials and Methods. Acute liver injury was induced in BALB/c mice by ConA (25 mg/kg), and fucosterol (dissolved in 2% DMSO) was orally administered daily at doses of 25, 50, and 100 mg/kg. The levels of hepatic necrosis, apoptosis, and autophagy associated with inflammatory cytokines were measured at 2, 8, and 24 h. Results. Fucosterol attenuated serum liver enzyme levels and hepatic necrosis and apoptosis induced by TNF-α, IL-6, and IL-1β. Fucosterol also inhibited apoptosis and autophagy by upregulating Bcl-2, which decreased levels of functional Bax and Beclin-1. Furthermore, reduced P38 MAPK and NF-κB signaling were accompanied by PPARγ activation. Conclusion. This study showed that fucosterol could alleviate acute liver injury induced by ConA by inhibiting P38 MAPK/PPARγ/NF-κB signaling. These findings highlight that fucosterol is a promising potential therapeutic agent for acute liver injury.

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The Protective Effect of Total Flavones from Rhododendron simsii Planch. on Myocardial Ischemia/Reperfusion Injury and Its Underlying Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/6139372 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Sheng-Yong Luo ◽

Qing-Hua Xu ◽

Gong Peng ◽

Zhi-Wu Chen

Keyword(s):

Myocardial Infarction ◽

Protective Effect ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Underlying Mechanism ◽

Assay Method ◽

Protective Effects ◽

Rhododendron Simsii ◽

Rhoa Activity ◽

Protein Expressions

Objectives. Total flavones from Rhododendron simsii Planch. (TFR) are the effective part extracted from the flowers of Rhododendron simsii Planch. and have obvious protective effects against cerebral ischemic or myocardial injuries in rabbits and rats. However, their mechanism of cardioprotection is still unrevealed. Therefore, the present study was designed to investigate the effect of TFR on myocardial I/R injury and the underlying mechanism. Methods. TFR groups were treated by gavage once a day for 3 days at a dose of 20, 40, and 80 mg/kg, respectively, and then the model of myocardial I/R injury was established. Myocardial infarction, ST-segment elevation, and the expression of UTR, ROCK1, ROCK2, and p-MLC protein in rat myocardium were determined at 90 min after reperfusion. UTR siRNA in vivo transfection and competition binding assay method were used to study the relationship between the protective effect of TFR and UTR. Results. The expression of UTR protein markedly decreased in myocardium of UTR siRNA transfection group rats. TFR could significantly reduce the infarct size and inhibit the increase of RhoA activity and ROCK1, ROCK2, and p-MLC protein expressions both in WT and UTR knockdown rats. The reducing rate of TFR in myocardial infarction area, RhoA activity, and ROCK1, ROCK2, and p-MLC protein expressions in UTR knockdown rats decreased markedly compared with that in WT rats. In addition, TFR had no obvious effect on the increase of ΣST in UTR knockdown rats in comparison with that in model group. In particular, TFR could significantly inhibit the combination of [I125]-hu-II and UTR, and IC50 was 0.854 mg/l. Conclusions. The results indicate that the protective effect of TFR on I/R injury may be correlated with its blocking UTR and the subsequent inhibition of RhoA/ROCK signaling pathway.

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Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21217894 ◽

2020 ◽

Vol 21 (21) ◽

pp. 7894 ◽

Cited By ~ 2

Author(s):

Il-Gyu Ko ◽

Jun-Jang Jin ◽

Lakkyong Hwang ◽

Sang-Hoon Kim ◽

Chang-Ju Kim ◽

...

Keyword(s):

Liver Injury ◽

Protective Effect ◽

Inflammatory Cytokines ◽

Intraperitoneal Injection ◽

Acute Liver Injury ◽

Adenosine A2a Receptor ◽

Liver Index ◽

A2a Receptor ◽

Adenosine A2a ◽

Pro Inflammatory Cytokines

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 μL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

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The Late-Stage Protective Effect of Mito-TEMPO against Acetaminophen-Induced Hepatotoxicity in Mouse and Three-Dimensional Cell Culture Models

Antioxidants ◽

10.3390/antiox9100965 ◽

2020 ◽

Vol 9 (10) ◽

pp. 965

Author(s):

Mohammad Abdullah-Al-Shoeb ◽

Kenta Sasaki ◽

Saori Kikutani ◽

Nanami Namba ◽

Keiichi Ueno ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Culture ◽

Liver Injury ◽

Protective Effect ◽

Acute Liver Injury ◽

Three Dimensional ◽

3D Cell Culture ◽

Cell Culture Model ◽

Culture Model ◽

Apap Hepatotoxicity

An overdose of acetaminophen (APAP), the most common cause of acute liver injury, induces oxidative stress that subsequently causes mitochondrial impairment and hepatic necroptosis. N-acetyl-L-cysteine (NAC), the only recognized drug against APAP hepatotoxicity, is less effective the later it is administered. This study evaluated the protective effect of mitochondria-specific Mito-TEMPO (Mito-T) on APAP-induced acute liver injury in C57BL/6J male mice, and a three dimensional (3D)-cell culture model containing the human hepatoblastoma cell line HepG2. The administration of Mito-T (20 mg/kg, i.p.) 1 h after APAP (400 mg/kg, i.p.) injection markedly attenuated the APAP-induced elevated serum transaminase activity and hepatic necrosis. However, Mito-T treatment did not affect key factors in the development of APAP liver injury including the activation of c-jun N-terminal kinases (JNK), and expression of the transcription factor C/EBP homologous protein (CHOP) in the liver. However, Mito-T significantly reduced the APAP-induced increase in the hepatic oxidative stress marker, nitrotyrosine, and DNA fragmentation. Mito-T markedly attenuated cytotoxicity induced by APAP in the HepG2 3D-cell culture model. Moreover, liver regeneration after APAP hepatotoxicity was not affected by Mito-T, demonstrated by no changes in proliferating cell nuclear antigen formation. Therefore, Mito-T was hepatoprotective at the late-stage of APAP overdose in mice.

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