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 E and Lactobacillus Provide Protective Effects Against Liver Injury Induced by HgCl2: Role of CHOP, GPR87, and mTOR Proteins

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110113
Author(s):  
Ahlam Alhusaini ◽  
Shahad Alghilani ◽  
Waad Alhuqbani ◽  
Iman H. Hasan
Keyword(s):  
Oxidative Stress ◽  
Vitamin E ◽  
Liver Injury ◽  
Histopathological Examination ◽  
Male Rats ◽  
High Dose ◽  
Protective Effects ◽  
Sod Activity ◽  
Tnf Α

Background and Objective: Mercury is one of the most harmful heavy metals and its toxicity causes severe multi-organ dysfunction. This study was designed to explore novel molecular pathways involved in the hepatoprotective effect of vitamin E (Vit-E) and Lactobacillius plantarum (Lac-B) against mercury toxicity.[Formula: see text] Method: Acute hepatotoxicity was induced by administration of high dose of mercuric chloride (HgCl2) in male rats, Vit-E or/and Lac-B were given along with HgCl2 for 2 weeks. The effects of those antioxidants were studied focusing on their anti-apoptotic, anti-oxidative stress and anti-inflammatory eficacies. Histopathological examinations were also conducted. Results: The administration of HgCl2 induced liver injury which manifested by elevation in serum ALT and AST. Liver MDA, caspase-3 and TNF-α levels were markedly increased; whereas, GSH level and SOD activity were declined. HgCl2 significantly elevated the expressions of hepatic CHOP, GPR87, NF-κB and mTOR. Histopathological examination revealed massive hepatocyte degeneration following HgCl2 administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved hepatic architecture. Conclusion: Vit-E and Lac-B provided protective effect against HgCl2-induced hepatotoxicity via reduction of oxidative stress and inflammation, and downregulation of CHOP, GPR87, NF-κB and mTOR proteins’ expressions.

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

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.

Evaluation of the Potential Cardioprotective Activity of Some Saudi Plants against Doxorubicin Toxicity

2012 ◽  
Vol 67 (5-6) ◽  
pp. 297-307 ◽  
Author(s):  
Osama M. Ashour ◽  
Ashraf B. Abdel-Naim ◽  
Hossam M. Abdallah ◽  
Ayman A. Nagy ◽  
Ahmed M. Mohamadin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activities ◽  
Histopathological Examination ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Serum Markers ◽  
Protective Effects ◽  
Medicinal Uses ◽  
Cordia Myxa

Doxorubicin (DOX) is an anthracycline antibiotic widely used as a chemotherapeutic agent in the treatment of several tumours. However, its cardiac toxicity limits its use at maximum therapeutic doses. Most studies implicated increased oxidative stress as the major determinant of DOX cardiotoxicity. The local Saudi flora is very rich in a variety of plants of quite known folkloric or traditional medicinal uses. Tribulus macropterus Boiss., Olea europaea L. subsp. africana (Mill.) P. S. Green, Tamarix aphylla (L.) H. Karst., Cynomorium coccineum L., Cordia myxa L., Calligonum comosum L’ Hér, and Withania somnifera (L.) Dunal are Saudi plants known to have antioxidant activities. The aim of the current study was to explore the potential protective effects of methanolic extracts of these seven Saudi plants against DOX-induced cardiotoxicity in rats. Two plants showed promising cardioprotective potential in the order Calligonum comosum > Cordia myxa. The two plant extracts showed potent in vitro radical scavenging and antioxidant properties. They significantly protected against DOX-induced alterations in cardiac oxidative stress markers (GSH and MDA) and cardiac serum markers (CK-MB and LDH activities). Additionally, histopathological examination indicated a protection against DOX-induced cardiotoxicity. In conclusion, C. comosum and C. myxa exerted protective activity against DOX-induced cardiotoxicity, which is, at least partly, due to their antioxidant effect

scholarly journals In vitrofolate supplementation alleviates oxidative stress, mitochondria-associated death signalling and apoptosis induced by 7-ketocholesterol

2004 ◽  
Vol 92 (6) ◽  
pp. 887-894 ◽  
Author(s):  
R.-F. S. Huang ◽  
H.-C. Yaong ◽  
S.-C. Chen ◽  
Y.-F. Lu
Keyword(s):  
Oxidative Stress ◽  
Nuclear Dna ◽  
High Dose ◽  
Protective Effects ◽  
Folate Supplementation ◽  
Mitochondria Membrane Potential ◽  
Induced Apoptosis ◽  
Apoptotic Damage

Folate has recently been proposed as a new antioxidant. Folate supplementation may have a protective effect in counteracting oxidant-induced apoptotic damage. The present studies were undertaken to examine whether there is a direct link between folate levels, antioxidant capability and reduced apoptotic damage. Using anin vitrocellular model of 7-ketocholesterol (KC)-induced apoptosis, U937 cells were pre-cultured with a folate-deficient medium supplemented with various levels of folate (2–1500μmol/l) before treatment with 7-KC. Apoptotic markers, mitochondria-associated death signals and levels of reactive oxygen species were assayed. After treatment with 7-KC for 30h, low and high levels of folate supplementation significantly (P<0.05) reduced nuclear DNA loss. Only high levels of folate supplementation (>1000μmol/l) were effective in counteracting 7-KC-promoted apoptotic membrane phosphatidylserine exposure and DNA laddering. The attenuation of 7-KC-induced apoptotic damage by high-dose folate supplementation coincided with a partial normalization of mitochondria membrane potential dissipation, a suppression of cytochromecrelease and an inhibition of procaspase 3 activation. The prevention of mitochondrial dysfunctions and apoptotic processes was associated with antioxidant actions of high-dose folate by a marked scavenging of intracellular superoxide. Collectively, our present results demonstrate thatin vitrofolate supplementation exerts differentially protective effects against 7-KC-induced damage. High-dose supplementation alleviates oxidative stress, mitochondria-associated death signalling and apoptosis induced by 7-KC. However, thein vivorelevance is not clear and requires further study.

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

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.

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

2016 ◽  
Vol 94 (2) ◽  
pp. 147-154 ◽  
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.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals Allopurinol ameliorates liver injury in type 1 diabetic rats through activating Nrf2

2021 ◽  
Vol 35 ◽  
pp. 205873842110314
Author(s):  
Fei Zeng ◽  
Jierong Luo ◽  
Hong Han ◽  
Wenjie Xie ◽  
Lingzhi Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Caspase 3 ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Heme Oxygenase 1 ◽  
Liver Protein ◽  
Lipid Peroxidation Product ◽  
Protein Expressions

Hyperglycemia-induced oxidative stress plays important roles in the development of non-alcoholic fatty liver disease (NAFLD), which is a common complication in diabetic patients. The Nrf2-Keap1 pathway is important for cell antioxidant protection, while its role in exogenous antioxidant mediated protection against NAFLD is unclear. We thus, postulated that antioxidant treatment with allopurinol (ALP) may attenuate diabetic liver injury and explored the underlying mechanisms. Control (C) and streptozotocin (STZ)-induced diabetes rats (D) were untreated or treated with ALP for 4 weeks starting at 1 week after diabetes induction. Serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), production of lipid peroxidation product malondialdehyde (MDA), and serum superoxide dismutase (SOD) were detected. Liver protein expressions of cleaved-caspase 3, IL-1β, nuclear factor-erythroid-2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1), P62, Kelch-like ECH-associated protein 1 (Keap1), and LC3 were analyzed. In vitro, cultured rat normal hepatocytes BRL-3A were grouped to normal glucose (5.5 mM, NG) or high glucose (25 mM, HG) and treated with or without allopurinol (100 µM) for 48 h. Rats in the D group demonstrated liver injury evidenced as increased serum levels of ALT and AST. Diabetes increased apoptotic cell death, enhanced liver protein expressions of cleaved-caspase 3 and IL-1β with concomitantly increased production of MDA while serum SOD content was significantly reduced (all P < 0.05 vs C). In the meantime, protein levels of Nrf2, HO-1, and P62 were reduced while Keap1 and LC3 were increased in the untreated D group as compared to control ( P < 0.05 vs C). And all the above alterations were significantly attenuated by ALP. Similar to our findings obtained from in vivo study, we got the same results in in vitro experiments. It is concluded that ALP activates the Nrf2/p62 pathway to ameliorate oxidative stress and liver injury in diabetic rats.

Sign in / Sign up

Export Citation Format

Share Document