Evaluation of the hepatoprotective effects of curcumin and nanocurcumin against paraquat‐induced liver injury in rats: Modulation of oxidative stress and Nrf2 pathway

Abstract The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication. An oral administration of different concentrations (100, 200, and 400 mg/kg) of BERM prior to high-dose ethanol via intraperitoneal injection was performed in mice. On the 7th day, liver and kidney sections were dissected out for histopathological examination. The ethanol intoxication caused large areas of liver necrosis while the kidneys were not affected. Pre-BERM administration decreased ethanol-induced liver injury, as compared to the mice treated with ethanol alone. In addition, the pre-BERM administration resulted in a decrement in the level of ethanol-induced oxidative stress, revealed by a concomitant increase of GSH and a decrease of MDA hepatic levels. The BERM extract also reversed the ethanol-induced liver injury and hepatotoxicity, characterized by the low detection of TNF-α gene expression level and fragmented DNA, respectively. Altogether, BERM extract exerts antioxidative activities and present promising hepatoprotective effects against ethanol intoxication. The identification of the related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

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A Discovery of Relevant Hepatoprotective Effects and Underlying Mechanisms of Dietary Clostridium butyricum Against Corticosterone-Induced Liver Injury in Pekin Ducks

Microorganisms ◽

10.3390/microorganisms7090358 ◽

2019 ◽

Vol 7 (9) ◽

pp. 358 ◽

Cited By ~ 2

Author(s):

Yanhan Liu ◽

Cun Liu ◽

Liqing Huang ◽

Zhaofei Xia

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Liver Injury ◽

Signaling Pathway ◽

Basal Diet ◽

Clostridium Butyricum ◽

Pekin Ducks ◽

Injury Model ◽

Hepatoprotective Effects ◽

Underlying Mechanisms

Clostridium butyricum (C. butyricum) can attenuate oxidative stress, inflammation, and hepatic fatty deposition in poultry, however, the underlying mechanisms for this in Pekin ducks remain unclear. This study evaluated these hepatoprotective effects and the underlying mechanisms in a corticosterone (CORT)-induced liver injury model in Pekin ducks fed a C. butyricum intervention diet. A total of 500 Pekin ducks were randomly divided into five groups: one group (CON group) was only provided with a basal diet, three groups were provided a basal diet with 200 mg/kg (LCB group), 400 mg/kg (MCB group), or 600 mg/kg (HCB group) C. butyricum, respectively, and one group was provided a basal diet with 150 mg/kg aureomycin (ANT group) for 42 d. At 37 days-old, all ducks received daily intraperitoneal injections of CORT for five days to establish a liver injury model. C. butyricum intervention alleviated liver injury by decreasing the liver organ indices, hepatic steatosis and hepatocyte necrosis, and improving liver function, antioxidant capacity, and inflammatory factors. Hepatic RNA-seq revealed 365 differentially expressed genes (DEGs) between the MCB and CON groups, with 229 up- and 136 down-regulated DEGs in the MCB group. Between the MCB and ANT groups, 407 DEGs were identified, including 299 up- and 108 down-regulated genes in MCB group. Some DEGs in the MCB group related to oxidative stress and inflammatory responses such as Sod3, Tlr2a/b, and Il10, which were up-regulated, while Apoa1, Cyp7a1, Acsl1/5, Fasn, Ppar-γ, and Scd, which are involved in lipid metabolism, were down-regulated, indicating that these genes were responsive to dietary C. butyricum for the alleviation of corticosterone-induced hepatic injury. Toll-like receptor signaling, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor (PPAR) signaling pathway, adipocytokine and glycerophospholipid metabolism signaling pathway were significantly enriched in the MCB group. These findings indicate that C. butyricum intervention can protect Pekin ducks from corticosterone-induced liver injury by the modulation of immunoregulatory- and lipid metabolism-related genes and pathways.

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Curcumin Attenuates Oxaliplatin-Induced Liver Injury and Oxidative Stress by Activating the Nrf2 Pathway

Drug Design Development and Therapy ◽

10.2147/dddt.s224318 ◽

2020 ◽

Vol Volume 14 ◽

pp. 73-85 ◽

Cited By ~ 9

Author(s):

Yulei Lu ◽

Shengming Wu ◽

Bangde Xiang ◽

Lequn Li ◽

Youzhi Lin

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Nrf2 Pathway ◽

And Oxidative Stress

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Gamma-Glutamylcysteine Ethyl Ester Protects against Cyclophosphamide-Induced Liver Injury and Hematologic Alterations via Upregulation of PPARγand Attenuation of Oxidative Stress, Inflammation, and Apoptosis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/4016209 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 27

Author(s):

Sultan Alqahtani ◽

Ayman M. Mahmoud

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Ethyl Ester ◽

Peroxisome Proliferator ◽

Enzymatic Antioxidants ◽

Peroxisome Proliferator Activated Receptor ◽

Hepatoprotective Effects ◽

Serum Aminotransferases ◽

Hematological Alterations

Gamma-glutamylcysteine ethyl ester (GCEE) is a precursor of glutathione (GSH) with promising hepatoprotective effects. This investigation aimed to evaluate the hepatoprotective effects of GCEE against cyclophosphamide- (CP-) induced toxicity, pointing to the possible role of peroxisome proliferator activated receptor gamma (PPARγ). Wistar rats were given GCEE two weeks prior to CP. Five days after CP administration, animals were sacrificed and samples were collected. Pretreatment with GCEE significantly alleviated CP-induced liver injury by reducing serum aminotransferases, increasing albumin, and preventing histopathological and hematological alterations. GCEE suppressed lipid peroxidation and nitric oxide production and restored GSH and enzymatic antioxidants in the liver, which were associated with downregulation of COX-2, iNOS, and NF-κB. In addition, CP administration significantly increased serum proinflammatory cytokines and the expression of liver caspase-3 and BAX, an effect that was reversed by GCEE. CP-induced rats showed significant downregulation of PPARγwhich was markedly upregulated by GCEE treatment. These data demonstrated that pretreatment with GCEE protected against CP-induced hepatotoxicity, possibly by activating PPARγ, preventing GSH depletion, and attenuating oxidative stress, inflammation, and apoptosis. Our findings point to the role of PPARγand suggest that GCEE might be a promising agent for the prevention of CP-induced liver injury.

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Hepatoprotective Effects of Antrodia cinnamomea: The Modulation of Oxidative Stress Signaling in a Mouse Model of Alcohol-Induced Acute Liver Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7841823 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 15

Author(s):

Yange Liu ◽

Juan Wang ◽

Lanzhou Li ◽

Wenji Hu ◽

Yidi Qu ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Mouse Model ◽

Caspase 3 ◽

Acute Liver Injury ◽

Nuclear Factor ◽

Related Factors ◽

Inflammatory Infiltration ◽

Hepatoprotective Effects ◽

Underlying Mechanisms

In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.

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Hepatoprotective effects of chamazulene against alcohol-induced liver damage by alleviation of oxidative stress in rat models

Open Life Sciences ◽

10.1515/biol-2020-0026 ◽

2020 ◽

Vol 15 (1) ◽

pp. 251-258

Author(s):

Xu Wang ◽

Ke Dong ◽

Yujing Ma ◽

Qizhi Jin ◽

Shujun Yin ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Serum Alkaline Phosphatase ◽

Positive Control ◽

Ethanol Administration ◽

Control Group ◽

Protective Effects ◽

Alcoholic Liver Injury ◽

Rat Models ◽

Hepatoprotective Effects

AbstractLiver injury and disease caused by alcohol is a common complication to human health worldwide. Chamazulene is a natural proazulene with antioxidant and anti-inflammatory properties. This study aims to investigate the hepatoprotective effects of chamazulene against ethanol-induced liver injury in rat models. Adult Wistar rats were orally treated with 50% v/v ethanol (8–12 mL/kg body weight [b.w.]) for 6 weeks to induce alcoholic liver injury. Chamazulene was administered orally to rats 1 h prior to ethanol administration at the doses of 25 and 50 mg/kg b.w. for 6 weeks. Silymarin, a commercial drug for hepatoprotection, was orally administered (50 mg/kg b.w.) for the positive control group. Chamazulene significantly reduced (p < 0.05) the levels of serum alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde, whereas the levels of antioxidant enzymes (glutathione peroxidase, catalase, and superoxide dismutase) and reduced glutathione were significantly restored (p < 0.05) in contrast to the ethanol model group. The levels of pro-inflammatory cytokines (tumour necrosis factor-α and interleukin-6) were suppressed by chamazulene (p < 0.05) with relevance to ethanol-induced liver injury. Histopathological alterations were convincing in the chamazulene-treated groups, which showed protective effects against alcoholic liver injury. Chamazulene has a significant hepatoprotective effect against ethanol-induced liver injury through alleviation of oxidative stress and prevention of inflammation.

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The protective effect of Veronica ciliata Fisch. extracts on relieving oxidative stress-induced liver injury via activating AMPK/p62/Nrf2 pathway

Journal of Ethnopharmacology ◽

10.1016/j.jep.2021.113775 ◽

2021 ◽

pp. 113775

Author(s):

Qiuxia Lu ◽

Yueyue Shu ◽

Li Wang ◽

Guoxiu Li ◽

Shiyan Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Protective Effect ◽

Nrf2 Pathway

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Vitamin E protects against cadmium-induced sub-chronic liver injury associated with the inhibition of oxidative stress and activation of Nrf2 pathway

Ecotoxicology and Environmental Safety ◽

10.1016/j.ecoenv.2020.111610 ◽

2021 ◽

Vol 208 ◽

pp. 111610

Author(s):

Jing Fang ◽

Heng Yin ◽

Zhuangzhi Yang ◽

Maoyun Tan ◽

Fengyuan Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin E ◽

Liver Injury ◽

Chronic Liver ◽

Chronic Liver Injury ◽

Nrf2 Pathway

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Cytoprotective potential of tiron and methyl palmitate against acetaminophen-induced acute liver injury

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0270 ◽

2016 ◽

Vol 94 (2) ◽

pp. 147-154 ◽

Cited By ~ 3

Author(s):

Amal M. Shoeib ◽

Eman Said ◽

Elsayed M. Ammar

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Inflammatory Response ◽

Biochemical Markers ◽

Methyl Palmitate ◽

Inflammatory Cytokine ◽

Acute Liver Injury ◽

Histopathological Examination ◽

Hepatoprotective Effects ◽

And Oxidative Stress

Acute liver injury is a debilitating disorder associated with loss of synthetic and detoxifying functions of the liver. This investigation was designed to assess cytoprotective efficacy of daily oral tiron (300 mg/kg) and daily oral methyl palmitate (300 mg/kg) against acetaminophen-induced acute liver injury. Rats were orally pretreated with either tiron or methyl palmitate at doses (300 mg/kg) for 7 days prior to oral acetaminophen (3 g/kg). Biochemical assay of markers of hepatotoxicity indices and oxidative stress was undertaken. Expression of inflammatory cytokine IL-6 was also evaluated. Histopathological examination of liver specimens was carried out as well. Both methyl palmitate and tiron significantly reversed the acetaminophen-induced elevation of biochemical markers (ALT, AST, and ALP) with restoration of SOD levels. Serum albumin levels and GSH liver contents increased, but in a nonsignificant manner. Moreover, methyl palmitate and tiron significantly decreased the level of serum LDH and serum IL-6 levels. Histopathology revealed that tiron markedly reduced the extent of acetaminophen-induced necrosis and methyl palmitate moderately decreased the necrosis in liver tissue. Methyl palmitate (300 mg/kg) and tiron (300 mg/kg) demonstrated promising hepatoprotective effects against acetaminophen-induced acute liver injury via modulation of inflammatory response and alleviation of the oxidative stress, allowing the preservation of hepatic functions.

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