The Protective Effect of Nitroglycerin, N-Acetyl Cysteine and Metoprolol in CCL4 Induced Animal Model of Acute Liver Injury

OBJECTIVE: The current study was designed to determine the hepatoprotective effect of well-known drugs. Nitroglycerin, N-acetyl cysteine and Metoprolol in acute liver injury induced by CCL4. The antioxidant effects of b-blockers, especially carvedilol, have been described by several investigators. However, for metoprolol, the effect is a bit query as there is only one in-vitro study showing a little hepatoprotective effect. Thus, it is worthy to re-study the hepatoprotective effect of metoprolol. AIM: To explore the possible hepatoprotective effect of Nitroglycerin, N-acetyl cysteine and Metoprolol TartrateMATERIAL AND METHODS: The normal serum values of ALP, AST, ALT, TSB and TSP were determined in 35 healthy rabbits allocated to 5 groups before CCL4 induction and at three occasions 24, 72, 120 hrs after induction by CCL4 and treatment with the tested drugs: Nitroglycerin, N-acetyl cysteine and Metoprolol for five successive days.RESULTS: Showed significant decrease in serum levels of ALP, AST, ALT and TSB with a significant increase in TSP level of all the tested drugs measured at 120 hrs compared with the control and their levels measured at 24, 72 hrs.CONCLUSION: All the tested drugs proved in having a hepatoprotective effect when they are given orally to animals. The histopathological sections of the liver tissue supported the real effect of these drugs in the management of ALI.

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5-O-Demethylnobiletin Alleviates CCl4-Induced Acute Liver Injury by Equilibrating ROS-Mediated Apoptosis and Autophagy Induction

International Journal of Molecular Sciences ◽

10.3390/ijms22031083 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1083

Author(s):

Sukkum Ngullie Chang ◽

Se Ho Kim ◽

Debasish Kumar Dey ◽

Seon Min Park ◽

Omaima Nasif ◽

...

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Elevated Serum ◽

In Vitro Study ◽

Biological Properties ◽

Autophagic Flux ◽

Serum Aminotransferase ◽

Ccl4 Treatment

Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.

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In vitro and in vivo protective effect of Lotus seedpod extract against acetaminophen-induced liver injury

10.21203/rs.3.rs-35355/v1 ◽

2020 ◽

Author(s):

Hsien-Chun Tseng ◽

Jen ying Hsu ◽

Xiao-Yin Huang ◽

Hui-Hsuan Lin ◽

Jing-Hsien Chen

Keyword(s):

Liver Injury ◽

In Vitro Study ◽

Serum Levels ◽

Molecular Data ◽

In Vivo Study ◽

Main Compound ◽

Enzyme Markers ◽

Lotus Seedpod

Abstract Background Acetaminophen (APAP) is one of the most widely used analgesic agents while overdose APAP will lead to severe hepatotoxicity. Lotus seedpod, a traditional herbal, is rich in polyphenol and has been shown to possess antioxidant, radioprotective and anti-cancer activities. This study examined the hepatoprotective role of lotus seedpod extracts (LSE) in vitro and in vivo. Methods Firstly, LSE or its main compound epigallocatechin (EGC) dose-dependently improved the survival of human hepatocyte HepG2 cells from APAP-induced loss of viability. In vivo study, the BALB/c mice were supplemented with or without LSE (1% and 2%) during the 9-week treatment period in the presence or absence of APAP (i.p.; 400 mg/kg) twice per week. Results In vitro study revealed that LSE or EGC showed potential in reducing APAP-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the distribution of hypodiploid phase, apoptotic bodies formation, and caspases activation. Molecular data showed that antiapoptotic effects of LSE or EGC mediated via intrinsic, extrinsic and ASK 1/JNK apoptotic signaling pathways. Further data showed that LSE inhibited the APAP-induced the protein expression of iNOS to decrease inflammation. In vivo study showed that LSE treatments significantly decreased the serum levels of the hepatic enzyme markers GOT and GPT induced by APAP. LSE also inhibited the serum levels of inflammatory cytokines (IL-6 and IL-1β) during APAP treatment. LSE at 1% significantly restored the decrease in glutathione (GSH) content and elevated the levels of antioxidant enzymes, including catalase and glutathione reductase (GRd), in the liver. Western blotting data demonstrated that LSE inhibited the expression of caspase − 3, -8, -9 in APAP-induced liver injury. Conclusions LSE protected APAP-induced hepatotoxicity which could be a novo strategy for treatment.

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Association between Vitamins and Minerals with Antioxidant Effects and Coronary Artery Calcification in Adults and Older Adults: A Systematic Review

Current Pharmaceutical Design ◽

10.2174/1381612825666190722101954 ◽

2019 ◽

Vol 25 (22) ◽

pp. 2474-2479 ◽

Cited By ~ 1

Author(s):

Alisson Diego Machado ◽

Gustavo Rosa Gentil Andrade ◽

Jéssica Levy ◽

Sara Silva Ferreira ◽

Dirce Maria Marchioni

Keyword(s):

Systematic Review ◽

Older Adults ◽

Coronary Artery ◽

Coronary Artery Calcification ◽

Serum Levels ◽

Antioxidant Compounds ◽

Increased Risk ◽

Coronary Events ◽

Antioxidant Effects

Background: Coronary Artery Calcification (CAC) is considered an important cardiovascular risk factor. There is evidence that CAC is associated with an increased risk of atherosclerosis, coronary events and cardiovascular mortality. Inflammation is one of the factors associated with CAC and despite the interest in antioxidant compounds that can prevent CAC, its association with antioxidants remains unclear. Objective: This study aimed to systematically review the association between vitamins and minerals with antioxidant effects and CAC in adults and older adults. Methods: We conducted a systematic review using PubMed for articles published until October 2018. We included studies conducted in subjects aged 18 years and older with no previous cardiovascular disease. Studies involving animal or in vitro experiments and the ones that did not use reference methods to assess the CAC, dietary intake or serum levels of vitamin or mineral were excluded. Results: The search yielded 390 articles. After removal of duplicates, articles not related to the review, review articles, editorials, hypothesis articles and application of the inclusion and exclusion criteria, 9 articles remained. The results of the studies included in this systematic review suggest that magnesium is inversely associated with CAC and results on the association between CAC and vitamin E have been conflicting. Conclusion: Additional prospective studies are needed to elucidate the role of these micronutrients on CAC.

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

International Journal of Immunopathology and Pharmacology ◽

10.1177/20587384211031417 ◽

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.

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Hepatoprotective effect of anemoside B4 against sepsis-induced acute liver injury through modulating the mTOR/p70S6K-mediated autophagy

Chemico-Biological Interactions ◽

10.1016/j.cbi.2021.109534 ◽

2021 ◽

pp. 109534

Author(s):

Liang Pei ◽

Linxi He

Keyword(s):

Liver Injury ◽

Acute Liver Injury ◽

Hepatoprotective Effect

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Cerium oxide nanoparticles improve liver regeneration after acetaminophen-induced liver injury and partial hepatectomy in rats

Journal of Nanobiotechnology ◽

10.1186/s12951-019-0544-5 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 7

Author(s):

Bernat Córdoba-Jover ◽

Altamira Arce-Cerezo ◽

Jordi Ribera ◽

Montse Pauta ◽

Denise Oró ◽

...

Keyword(s):

Liver Injury ◽

Liver Regeneration ◽

Cerium Oxide ◽

Partial Hepatectomy ◽

Experimental Models ◽

Cerium Oxide Nanoparticles ◽

Hepatic Regeneration ◽

Oxide Nanoparticles ◽

Acetyl Cysteine

Abstract Background and aims Cerium oxide nanoparticles are effective scavengers of reactive oxygen species and have been proposed as a treatment for oxidative stress-related diseases. Consequently, we aimed to investigate the effect of these nanoparticles on hepatic regeneration after liver injury by partial hepatectomy and acetaminophen overdose. Methods All the in vitro experiments were performed in HepG2 cells. For the acetaminophen and partial hepatectomy experimental models, male Wistar rats were divided into three groups: (1) nanoparticles group, which received 0.1 mg/kg cerium nanoparticles i.v. twice a week for 2 weeks before 1 g/kg acetaminophen treatment, (2) N-acetyl-cysteine group, which received 300 mg/kg of N-acetyl-cysteine i.p. 1 h after APAP treatment and (3) partial hepatectomy group, which received the same nanoparticles treatment before partial hepatectomy. Each group was matched with vehicle-controlled rats. Results In the partial hepatectomy model, rats treated with cerium oxide nanoparticles showed a significant increase in liver regeneration, compared with control rats. In the acetaminophen experimental model, nanoparticles and N-acetyl-cysteine treatments decreased early liver damage in hepatic tissue. However, only the effect of cerium oxide nanoparticles was associated with a significant increment in hepatocellular proliferation. This treatment also reduced stress markers and increased cell cycle progression in hepatocytes and the activation of the transcription factor NF-κB in vitro and in vivo. Conclusions Our results demonstrate that the nanomaterial cerium oxide, besides their known antioxidant capacities, can enhance hepatocellular proliferation in experimental models of liver regeneration and drug-induced hepatotoxicity.

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Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v13i2.35514 ◽

2018 ◽

Vol 13 (2) ◽

pp. 149 ◽

Cited By ~ 1

Author(s):

Naureen Shehzadi ◽

Khalid Hussain ◽

Nadeem Irfan Bukhari ◽

Muhammad Islam ◽

Muhammad Tanveer Khan ◽

...

Keyword(s):

Molecular Docking ◽

Video Clip ◽

Serum Levels ◽

Docking Studies ◽

Normal Serum ◽

Yeast Cells ◽

Drug Candidate ◽

Molecular Docking Studies

The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM) through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%), ɑ-glucosidase (40.3-93.1%) and hemoglobin glycosylation (9.0%-54.9%) inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%). The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each) intoxicated rats with OXCPM (100 mg/kg, p.o.) resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin) and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase) biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta2-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.Video Clip of Methodology:Glucose uptake by yeast cells: 4 min 51 sec <a href="https://www.youtube.com/v/8cJkuMtV0Wc">Full Screen</a> <a href="https://www.youtube.com/watch?v=8cJkuMtV0Wc">Alternate</a>

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Human umbilical cord blood-derived cells differentiate into hepatocyte-like cells in the Fas-mediated liver injury model

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00049.2005 ◽

2005 ◽

Vol 289 (6) ◽

pp. G1091-G1099 ◽

Cited By ~ 33

Author(s):

Kazunobu Nonome ◽

Xiao-Kang Li ◽

Terumi Takahara ◽

Yusuke Kitazawa ◽

Naoko Funeshima ◽

...

Keyword(s):

Liver Injury ◽

Umbilical Cord Blood ◽

Fas Ligand ◽

In Vitro Study ◽

Cell Types ◽

Human Umbilical Cord Blood ◽

Specific Gene ◽

Human Umbilical Cord

Human umbilical cord blood (HUCB) contains stem/progenitor cells, which can differentiate into a variety of cell types. In this study, we investigated whether HUCB cells differentiate into hepatocytes in vitro and in vivo. We also examined whether CD34 could be the selection marker of stem cells for hepatocytes. HUCB cells were obtained from normal full-term deliveries, and CD34+/−cells were further separated. For in vitro study, HUCB cells were cultured for 4 wk, and expressions of liver-specific genes were examined. For the in vivo study, nonobese diabetic/severe combined immunodeficient mice were subjected to liver injury by a Fas ligand-carried adenoviral vector or only radiated. Mice were treated simultaneously with or without cell transplantation of HUCB, CD34+, or CD34−cells. After 4 wk, human-specific gene/protein expression was examined. In the in vitro study, human liver-specific genes were positive after 7 days of culture. The immunofluorescent study showed positive staining of α-fetoprotein, cytokeratin 19, and albumin in round-shaped cells. In the in vivo study, immunohistochemical analysis showed human albumin-positive, hepatocyte-specific antigen-positive cells in mouse livers of the Fas ligand/transplantation group. Fluorescence in situ hybridization analysis using the human Y chromosome also showed positive signals. However, no difference between transplanted cell types was detected. In contrast, immunopositive cells were not detected in the irradiated/transplantation group. The RT-PCR result also showed human hepatocyte-specific gene expressions only in the Fas ligand/transplantation group. HUCB cells differentiated into hepatocyte-like cells in the mouse liver, and liver injury was essential during this process. The differences between CD34+and CD34−cells were not observed in human hepatocyte-specific expression.

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Mechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/6140360 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Weitao Ji ◽

Hongyun Shi ◽

Hailin Shen ◽

Jing Kong ◽

Jiayi Song ◽

...

Keyword(s):

Liver Injury ◽

Signaling Pathway ◽

Acute Liver Injury ◽

Control Group ◽

Necrosis Factor Alpha ◽

Protein Levels ◽

Klf4 Expression ◽

Mrna And Protein Expression

Krüppel-like factor 4 (KLF4) is a key transcription factor that regulates genes involved in the proliferation or differentiation in different tissues. Apelin plays roles in cardiovascular functions, metabolic disease, and homeostatic disorder. However, the biological function of apelin in liver disease is still ongoing. In this study, we investigated the mechanism of KLF4-mediated protection against acute liver injury via the inhibition of the apelin signaling pathway. Mice were intraperitoneally injected with carbon tetrachloride (CCl4; 0.2 mL dissolved in 100 mL olive oil, 10 mL/kg) to establish an acute liver injury model. A KLF4 expression plasmid was injected through the tail vein 48 h before CCl4 treatment. In cultured LX-2 cells, pAd-KLF4 or siRNA KLF4 was overexpressed or knockdown, and the mRNA and protein levels of apelin were determined. The results showed that the apelin serum level in the CCl4-injected group was higher than that of control group, and the expression of apelin in the liver tissues was elevated while KLF4 expression was decreased in the CCl4-injected group compared to the KLF4-plasmid-injected group. HE staining revealed serious hepatocellular steatosis in the CCl4-injected mice, and KLF4 alleviated this steatosis in the mice injected with KLF4 plasmid. In vitro experiments showed that tumor necrosis factor-alpha (TNF-α) could downregulate the transcription and translation levels of apelin in LX-2 cells and also upregulate KLF4 mRNA and protein expression. RT-PCR and Western blotting showed that the overexpression of KLF4 markedly decreased basal apelin expression, but knockdown of KLF4 restored apelin expression in TNF-α-treated LX-2 cells. These in vivo and in vitro experiments suggest that KLF4 plays a key role in inhibiting hepatocellular steatosis in acute liver injury, and that its mechanism might be the inhibition of the apelin signaling pathway.

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