Protective effects of ginsenoside Rk3 against chronic alcohol-induced liver injury in mice through inhibition of inflammation, oxidative stress, and apoptosis

2019 ◽  
Vol 126 ◽  
pp. 277-284 ◽  
Author(s):  
Linlin Qu ◽  
Yanyan Zhu ◽  
Yannan Liu ◽  
Haixia Yang ◽  
Chenhui Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Protective Effects ◽  
Chronic Alcohol

scholarly journals Protective Role of Dietary Curcumin in the Prevention of the Oxidative Stress Induced by Chronic Alcohol with respect to Hepatic Injury and Antiatherogenic Markers

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ravi Varatharajalu ◽  
Mamatha Garige ◽  
Leslie C. Leckey ◽  
Karina Reyes-Gordillo ◽  
Ruchi Shah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Therapeutic Potential ◽  
Protective Role ◽  
Chronic Ethanol ◽  
Paraoxonase 1 ◽  
Protective Effects ◽  
Chronic Alcohol ◽  
Ethanol Group ◽  
Homocysteine Thiolactonase

Curcumin, an antioxidant compound found in Asian spices, was evaluated for its protective effects against ethanol-induced hepatosteatosis, liver injury, antiatherogenic markers, and antioxidant status in rats fed with Lieber-deCarli low menhaden (2.7% of total calories fromω-3 polyunsaturated fatty acids (PUFA)) and Lieber-deCarli high menhaden (13.8% of total calories fromω-3 PUFA) alcohol-liquid (5%) diets supplemented with or without curcumin (150 mg/kg/day) for 8 weeks. Treatment with curcumin protected against highω-3 PUFA and ethanol-induced hepatosteatosis and increase in liver injury markers, alanine aminotransferase, and aspartate aminotransferase. Curcumin upregulated paraoxonase 1 (PON1) mRNA and caused significant increase in serum PON1 and homocysteine thiolactonase activities as compared to highω-3 PUFA and ethanol group. Moreover, treatment with curcumin protected against ethanol-induced oxidative stress by increasing the antioxidant glutathione and decreasing the lipid peroxidation adduct 4-hydroxynonenal. These results strongly suggest that chronic ethanol in combination with highω-3 PUFA exacerbated hepatosteatosis and liver injury and adversely decreases antiatherogenic markers due to increased oxidative stress and depletion of glutathione. Curcumin supplementation significantly prevented these deleterious actions of chronic ethanol and highω-3 PUFA. Therefore, we conclude that curcumin may have therapeutic potential to protect against chronic alcohol-induced liver injury and atherosclerosis.

scholarly journals Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2509 ◽  
Author(s):  
Jing Zhang ◽  
Xin Guo ◽  
Taiji Hamada ◽  
Seiya Yokoyama ◽  
Yuka Nakamura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Critical Role ◽  
Therapeutic Modality ◽  
Protective Effects ◽  
Fibrotic Liver ◽  
Intrahepatic Bile Ducts ◽  
Duct Ligation ◽  
Cholestatic Liver Injury

Accumulating evidence indicates that oxidative stress plays a critical role in initiating the progression of inflammatory and fibrotic liver diseases, including cholestatic hepatitis. Peroxiredoxin 4 (PRDX4) is a secretory antioxidase that protects against oxidative damage by scavenging reactive oxygen species (ROS) in both the intracellular compartments and extracellular space. In this study, we examined the in vivo net effects of PRDX4 overexpression in a murine model of cholestasis. To induce cholestatic liver injury, we subjected C57BL/6J wild-type (WT) or human PRDX4 (hPRDX4) transgenic (Tg) mice to sham or bile duct ligation (BDL) surgery for seven days. Our results showed that the liver necrosis area was significantly suppressed in Tg BDL mice with a reduction in the severity of liver injuries. Furthermore, PRDX4 overexpression markedly reduced local and systemic oxidative stress generated by BDL. In addition, suppression of inflammatory cell infiltration, reduced proliferation of hepatocytes and intrahepatic bile ducts, and less fibrosis were also found in the liver of Tg BDL mice, along with a reduced mortality rate after BDL surgery. Interestingly, the composition of the hepatic bile acids (BAs) was more beneficial for Tg BDL mice than for WT BDL mice, suggesting that PRDX4 overexpression may affect BA metabolism during cholestasis. These features indicate that PRDX4 plays an important role in protecting against liver injury following BDL and might be a promising therapeutic modality for cholestatic diseases.

Rhizophora Mucronata Lam. (Mangrove) Bark Extract Prevents Ethanol-induced Liver Injury, Oxidative Stress and Apoptosis in Swiss Albino Mice

2021 ◽  
Author(s):  
Chitra Jairaman ◽  
Sabine Matou-Nasri ◽  
Zeyad I Alehaideb ◽  
Syed Ali Mohamed Yacoob ◽  
Anuradha Venkataraman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Histopathological Examination ◽  
Bark Extract ◽  
High Dose ◽  
Protective Effects ◽  
Rhizophora Mucronata ◽  
Ethanol Intoxication ◽  
Hepatoprotective Effects

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.

scholarly journals Vitamin D Deficiency Aggravates Hepatic Oxidative Stress and Inflammation during Chronic Alcohol-Induced Liver Injury in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Chun-Qiu Hu ◽  
Qing-Li Bo ◽  
Lan-Lan Chu ◽  
Yong-Di Hu ◽  
Lin Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Liver Injury ◽  
Vitamin D Deficiency ◽  
Chronic Alcohol ◽  
Cytokines And Chemokines ◽  
Hepatic Oxidative Stress ◽  
Oxide Synthase ◽  
Etoh Group ◽  
Inducible Nitric Oxide

Vitamin D deficiency has been reported in alcoholics. This study is aimed at evaluating the effects of vitamin D deficiency on chronic alcohol-induced liver injury in mice. Mice were fed with modified Lieber-DeCarli liquid diets for 6 weeks to establish an animal model of chronic alcohol-induced liver injury. In the VDD+EtOH group, mice were fed with modified diets, in which vitamin D was depleted. Vitamin D deficiency aggravated alcohol-induced liver injury. Furthermore, vitamin D deficiency aggravated hepatocyte apoptosis during alcohol-induced liver injury. Although it has a little effect on hepatic TG content, vitamin D deficiency promoted alcohol-induced hepatic GSH depletion and lipid peroxidation. Further analysis showed that vitamin D deficiency further increased alcohol-induced upregulation of hepatic inducible nitric oxide synthase (inos), two NADPH oxidase subunits p47phox and gp91phox, and heme oxygenase- (HO-) 1. By contrast, vitamin D deficiency attenuated alcohol-induced upregulation of hepatic antioxidant enzyme genes, such as superoxide dismutase (sod) 1 and gshpx. In addition, vitamin D deficiency significantly elevated alcohol-induced upregulation of hepatic proinflammatory cytokines and chemokines. Taken together, these results suggest that vitamin D deficiency aggravates hepatic oxidative stress and inflammation during chronic alcohol-induced liver injury.

scholarly journals Methane Alleviates Acetaminophen-Induced Liver Injury by Inhibiting Inflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis through the Nrf2/HO-1/NQO1 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yang Feng ◽  
Ruixia Cui ◽  
Zeyu Li ◽  
Xia Zhang ◽  
Yifan Jia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Hepatic Injury ◽  
Protective Effects ◽  
Serum Aminotransferase ◽  
Anti Inflammatory

Acetaminophen- (APAP-) induced hepatic injury is an important clinical challenge. Oxidative stress, inflammation, apoptosis, and endoplasmic reticulum stress (ERS) contribute to the pathogenesis. Methane has potential anti-inflammatory, antioxidant, and antiapoptotic properties. This project was aimed at studying the protective effects and relative mechanisms of methane in APAP-induced liver injury. In the in vivo experiment, C57BL/6 mice were treated with APAP (400 mg/kg) to induce hepatic injury followed by methane-rich saline (MRS) 10 ml/kg i.p. after 12 and 24 h. We observed that MRS alleviated the histopathological lesions in the liver, decreased serum aminotransferase levels, reduced the levels of inflammatory cytokines, suppressed the nuclear factor-κB expression. Further, we found that MRS relieved oxidative stress by regulating the Nrf2/HO-1/NQO1 signaling pathway and their downstream products after APAP challenge. MRS also regulated proteins associated with ERS-induced apoptosis. In the in vitro experiment, the L-02 cell line was treated with APAP (10 mM) to induce hepatic injury. We found that a methane-rich medium decreased the levels of reactive oxygen species (DHE fluorescent staining), inhibited apoptosis (cell flow test), and regulated the Nrf2/HO-1/NQO1 signaling pathway. Our data indicated that MRS prevented APAP-induced hepatic injury via anti-inflammatory, antioxidant, anti-ERS, and antiapoptotic properties involving the Nrf2/HO-1/NQO1 signaling pathway.

scholarly journals SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Longcheng Shang ◽  
Haozhen Ren ◽  
Shuai Wang ◽  
Hanyi Liu ◽  
Anyin Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Reperfusion Injury ◽  
Liver Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Macrophage Polarization ◽  
Protective Effects ◽  
Inflammation Response ◽  
Stat3 Signaling

Ischemia-reperfusion injury (IRI) is a common complication in liver surgeries. It is a focus to discover effective treatments to reduce ischemia-reperfusion injury. Previous studies show that oxidative stress and inflammation response contribute to the liver damage during IRI. SS-31 is an innovated mitochondrial-targeted antioxidant peptide shown to scavenge reactive oxygen species and decrease oxidative stress, but the protective effects of SS-31 against hepatic IRI are not well understood. The aim of our study is to investigate whether SS-31 could protect the liver from damages induced by IRI and understand the protective mechanism. The results showed that SS-31 treatment can significantly attenuate liver injury during IRI, proved by HE staining, serum ALT/AST, and TUNEL staining which can assess the degree of liver damage. Meanwhile, we find that oxidative stress and inflammation were significantly suppressed after SS-31 administration. Furthermore, the mechanism revealed that SS-31 can directly decrease ROS production and regulate STAT1/STAT3 signaling in macrophages, thus inhibiting macrophage M1 polarization. The proinflammation cytokines are then significantly reduced, which suppress inflammation response in the liver. Taken together, our study discovered that SS-31 can regulate macrophage polarization through ROS scavenging and STAT1/STAT3 signaling to ameliorate liver injury; the protective effects against hepatic IRI suggest that SS-31 may be an appropriate treatment for liver IRI in the clinic.

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

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.

scholarly journals Luteolin Alleviates AflatoxinB1-Induced Apoptosis and Oxidative Stress in the Liver of Mice through Activation of Nrf2 Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1268
Author(s):  
Shahid Ali Rajput ◽  
Aftab Shaukat ◽  
Kuntan Wu ◽  
Imran Rashid Rajput ◽  
Dost Muhammad Baloch ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Aflatoxin B1 ◽  
Physiological Saline ◽  
Protective Effects ◽  
Biochemical Alterations ◽  
Protein Levels ◽  
Nrf2 Signaling Pathway ◽  
Induced Apoptosis

Aflatoxin B1 (AFB1), a threatening mycotoxin, usually provokes oxidative stress and causes hepatotoxicity in animals and humans. Luteolin (LUTN), well-known as an active phytochemical agent, acts as a strong antioxidant. This research was designed to investigate whether LUTN exerts protective effects against AFB1-induced hepatotoxicity and explore the possible molecular mechanism in mice. A total of forty-eight mice were randomly allocated following four treatment groups (n = 12): Group 1, physiological saline (CON). Group 2, treated with 0.75 mg/kg BW aflatoxin B1 (AFB1). Group 3, treated with 50 mg/kg BW luteolin (LUTN), and Group 4, treated with 0.75 mg/kg BW aflatoxin B1 + 50 mg/kg BW luteolin (AFB1 + LUTN). Our findings revealed that LUTN treatment significantly alleviated growth retardation and rescued liver injury by relieving the pathological and serum biochemical alterations (ALT, AST, ALP, and GGT) under AFB1 exposure. LUTN ameliorated AFB1-induced oxidative stress by scavenging ROS and MDA accumulation and boosting the capacity of the antioxidant enzyme (CAT, T-SOD, GSH-Px and T-AOC). Moreover, LUTN treatment considerably attenuates the AFB1-induced apoptosis in mouse liver, as demonstrated by declined apoptotic cells percentage, decreased Bax, Cyt-c, caspase-3 and caspase-9 transcription and protein with increased Bcl-2 expression. Notably, administration of LUTN up-regulated the Nrf2 and its associated downstream molecules (HO-1, NQO1, GCLC, SOD1) at mRNA and protein levels under AFB1 exposure. Our results indicated that LUTN effectively alleviated AFB1-induced liver injury, and the underlying mechanisms were associated with the activation of the Nrf2 signaling pathway. Taken together, LUTN may serve as a potential mitigator against AFB1-induced liver injury and could be helpful for the development of novel treatment to combat liver diseases in humans and/or animals.

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