scholarly journals Recovery from Liver Failure and Fibrosis in a Rat Portacaval Anastomosis Model after Neurointermediate Pituitary Lobectomy

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Martín Muñoz-Ortega ◽  
Noé Macías-Segura ◽  
Javier Ventura-Juárez ◽  
Manuel Enrique Ávila-Blanco ◽  
Leonardo D. Ponce-Damian ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Liver Damage ◽  
Liver Diseases ◽  
Liver Glycogen ◽  
Serum Levels ◽  
Liver Function Tests ◽  
Portacaval Anastomosis ◽  
Molecular Signaling ◽  
Fibrotic Liver ◽  
Male Wistar Rats

Liver diseases, including cirrhosis, viral hepatitis, and hepatocellular carcinoma, account for approximately two million annual deaths worldwide. They place a huge burden on the global healthcare systems, compelling researchers to find effective treatment for liver fibrosis-cirrhosis. Portacaval anastomosis (PCA) is a model of liver damage and fibrosis. Arginine vasopressin (AVP) has been implicated as a proinflammatory-profibrotic hormone. In rats, neurointermediate pituitary lobectomy (NIL) induces a permanent drop (80%) in AVP serum levels. We hypothesized that AVP deficiency (NIL-induced) may decrease liver damage and fibrosis in a rat PCA model. Male Wistar rats were divided into intact control (IC), NIL, PCA, and PCA+NIL groups. Liver function tests, liver gene relative expressions (IL-1, IL-10, TGF-β, COLL-I, MMP-9, and MMP-13), and histopathological assessments were performed. In comparison with those in the IC and PCA groups, bilirubin, protein serum, and liver glycogen levels were restored in the PCA+NIL group. NIL in the PCA animals also decreased the gene expression levels of IL-1 and COLL-I, while increasing those of IL-10, TGF-β, and MMP-13. Histopathology of this group also showed significantly decreased signs of liver damage with lower extent of collagen deposition and fibrosis. Low AVP serum levels were not enough to fully activate the AVP receptors resulting in the decreased activation of cell signaling pathways associated with proinflammatory-profibrotic responses, while activating cell molecular signaling pathways associated with an anti-inflammatory-fibrotic state. Thus, partial reversion of liver damage and fibrosis was observed. The study supports the crucial role of AVP in the inflammatory-fibrotic processes and maintenance of immune competence. The success of the AVP deficiency strategy suggests that blocking AVP receptors may be therapeutically useful to treat inflammatory-fibrotic liver diseases.

scholarly journals High Risk of Hepatocellular Carcinoma Development in Fibrotic Liver: Role of the Hippo-YAP/TAZ Signaling Pathway

2019 ◽  
Vol 20 (3) ◽  
pp. 581 ◽  
Author(s):  
Hyuk Moon ◽  
Kyungjoo Cho ◽  
Sunyeong Shin ◽  
Do Kim ◽  
Kwang-Hyub Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Fibrosis ◽  
Liver Cancer ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Genetic Alterations ◽  
Molecular Signaling ◽  
Fibrotic Liver ◽  
Molecular Signaling Pathways ◽  
End Stage

Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, making up about 80% of cases. Liver fibrosis and its end-stage disease, cirrhosis, are major risk factors for HCC. A fibrotic liver typically shows persistent hepatocyte death and compensatory regeneration, chronic inflammation, and an increase in reactive oxygen species, which collaboratively create a tumor-promoting microenvironment via inducing genetic alterations and chromosomal instability, and activating various oncogenic molecular signaling pathways. In this article, we review recent advances in fields of liver fibrosis and carcinogenesis, and consider several molecular signaling pathways that promote hepato-carcinogenesis under the microenvironment of liver fibrosis. In particular, we pay attention to emerging roles of the Hippo-YAP/TAZ signaling pathway in stromal activation, hepatic fibrosis, and liver cancer.

scholarly journals SIX1/EYA1 are novel liver damage biomarkers in chronic hepatitis B and other liver diseases

2020 ◽  
Author(s):  
Baoyan Xu ◽  
Zhiqiao Zhang ◽  
Chong Zheng ◽  
Yingzi Tang ◽  
Zhaoxia Tan ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Disease ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Liver Damage ◽  
Liver Diseases ◽  
Serum Levels ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls

Abstract Background: The aim of this study was to investigate the clinicopathological significance of SIX1/ EYA1 in chronic hepatitis B (CHB) and other liver diseases. Materials and methods: Both SIX1 and EYA1 levels were detected in human serum and liver tissues by enzyme linked immunosorbent assay (ELISA) and immunofluorescent staining, respectively. Results: Serum SIX1 and EYA1 levels were 7.24±0.11 ng/ml and 25.21±0.51 ng/ml, respectively, in 313 CHB patients, and these values were significantly higher than those in 33 healthy controls (2.84±0.15ng/ml and 13.11±1.01ng/ml, respectively; P < 0.05). Serum SIX1 and EYA1 were also significantly increased in patients with many other liver diseases including liver fibrosis, hepatocellular carcinoma, fatty liver disease, alcoholic liver disease, fulminant hepatic failure, autoimmune liver disease, and hepatitis C relative to healthy controls ( P < 0.05). Dynamic observation of these proteins over time in 35 selected CHB patients revealed that SIX1 and EYA1 serum levels increased over an interval. Immunofluorescent staining revealed that both SIX1 and EYA1 were only expressed in hepatic stellate cells (HSCs), and their increased expression was evident in CHB liver tissue. Conclusion: Both SIX1 and EYA1 are novel biomarkers of liver damage in CHB and other liver diseases, with potential clinical utility.

Hepatotoxic effects of Diclofenac and Febuxostat combination on mice liver function tests after oral administration

2021 ◽  
Vol 15 (1) ◽  
pp. 45-49
Author(s):  
Saima Naureen ◽  
Rizwan Waseem ◽  
Javaria Fatima ◽  
Azher Abbas Shah ◽  
Huma Manzor ◽  
...  
Keyword(s):  
Liver Damage ◽  
Liver Enzymes ◽  
Serum Levels ◽  
Liver Function Tests ◽  
Oxidase Inhibitor ◽  
P Value ◽  
Xanthine Oxidase Inhibitor ◽  
Natural Substances ◽  
Mice Liver ◽  
Post Hoc

Background: The liver is a major organ and involved in metabolizing various toxins, including chemicals, drugs, and natural substances.1 Diclofenac is a commonly used non-steroidal anti-inflammatory drug. Febuxostat is a novel non-purine xanthine oxidase inhibitor prescribed in various hyperuricemic states. Rise in liver enzymes with diclofenac use is a well-established fact. When both drugs are used in combination, these may lead to profound hepatotoxicity. To find out these facts this study was planned. Subjects and methods: An experimental study on mice was planned to explore these facts in University of Health sciences, Lahore. Animals were divided into 6 groups having 10 animals in each group. The animals were given drugs for 7 days. One served as control. 2nd group was given Diclofenac alone (100mg/kg), 3rd group was given Febuxostat (50mg/kg) alone while rest of three groups were administered drugs combination (Diclofenac + Febuxostat). Dose of Diclofenac (100mg/kg) kept constant while dose of Febuxostat increased in each group (5mg/kg, 10mg/kg and 50mg/kg). All drugs administered orally by gavage. After 7 days, the serum levels of liver enzymes assessed. Statistical analysis was performed using SPSS 20. One way ANOVA and Post hoc Tukey tests were applied. A p-value of ≤0.05 was considered statistically significant. Results: The results showed that Diclofenac and Febuxostat caused liver damage when used separately but hepatotoxicity was much significant (p-value <0.001) when drugs were used in combination. Conclusion: Both drugs Diclofenac and Febuxostat when administered in combination, causes more liver profound liver damage. That is why their use in combination should be avoided in clinical settings.

scholarly journals Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance

2019 ◽  
Vol 30 (5) ◽  
pp. 751-766 ◽  
Author(s):  
Britt Opdebeeck ◽  
Stuart Maudsley ◽  
Abdelkrim Azmi ◽  
Annelies De Maré ◽  
Wout De Leger ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Vascular Calcification ◽  
Serum Levels ◽  
Indoxyl Sulfate ◽  
Arterial Calcification ◽  
Molecular Signaling ◽  
Short Term ◽  
Short Term Exposure ◽  
Cardiovascular Morbidity And Mortality

BackgroundProtein-bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (PCS) have been associated with cardiovascular morbidity and mortality in patients with CKD. However, direct evidence for a role of these toxins in CKD-related vascular calcification has not been reported.MethodsTo study early and late vascular alterations by toxin exposure, we exposed CKD rats to vehicle, IS (150 mg/kg per day), or PCS (150 mg/kg per day) for either 4 days (short-term exposure) or 7 weeks (long-term exposure). We also performed unbiased proteomic analyses of arterial samples coupled to functional bioinformatic annotation analyses to investigate molecular signaling events associated with toxin-mediated arterial calcification.ResultsLong-term exposure to either toxin at serum levels similar to those experienced by patients with CKD significantly increased calcification in the aorta and peripheral arteries. Our analyses revealed an association between calcification events, acute-phase response signaling, and coagulation and glucometabolic signaling pathways, whereas escape from toxin-induced calcification was linked with liver X receptors and farnesoid X/liver X receptor signaling pathways. Additional metabolic linkage to these pathways revealed that IS and PCS exposure engendered a prodiabetic state evidenced by elevated resting glucose and reduced GLUT1 expression. Short-term exposure to IS and PCS (before calcification had been established) showed activation of inflammation and coagulation signaling pathways in the aorta, demonstrating that these signaling pathways are causally implicated in toxin-induced arterial calcification.ConclusionsIn CKD, both IS and PCS directly promote vascular calcification via activation of inflammation and coagulation pathways and were strongly associated with impaired glucose homeostasis.

scholarly journals Beta vulgaris L. (Beetroot) Methanolic Extract Prevents Hepatic Steatosis and Liver Damage in T2DM Rats by Hypoglycemic, Insulin-Sensitizing, Antioxidant Effects, and Upregulation of PPARα

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1306
Author(s):  
Laila Naif Al-Harbi ◽  
Ghedeir M. Alshammari ◽  
Alhanouf Mohammed Al-Dossari ◽  
Pandurangan Subash-Babu ◽  
Manal Abdulaziz Binobead ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Liver Damage ◽  
Body Weight Gain ◽  
Serum Levels ◽  
Serum Glucose ◽  
Mrna Levels ◽  
Hepatic Lipid Accumulation ◽  
Reduced Body ◽  
Male Wistar Rats ◽  
Factor Α

The present study examined if methanolic beetroot extract (BE) could prevent dyslipidemia and hepatic steatosis and damage in a type-2 diabetes mellitus (T2DM) rat model and studied some mechanisms of action. T2DM was induced in adult male Wistar rats by a low single dose of streptozotocin (STZ) (35 mg/kg, i.p) and a high-fat diet (HFD) feeding for 5 weeks. Control or T2DM rats then continued on standard or HFDs for another 12 weeks and were treated with the vehicle or BE (250 or 500 mg/kg). BE, at both doses, significantly improved liver structure and reduced hepatic lipid accumulation in the livers of T2DM rats. They also reduced body weight gain, serum glucose, insulin levels, serum and hepatic levels of cholesterol, triglycerides, free fatty acids, and serum levels of low-density lipoproteins in T2DM rats. In concomitant, they significantly reduced serum levels of aspartate and alanine aminotransferases, hepatic levels of malondialdehyde, tumor-necrosis factor-α, interleukin-6, and mRNA of Bax, cleaved caspase-3, and SREBP1/2. However, both doses of BE significantly increased hepatic levels of total glutathione, superoxide dismutase, and mRNA levels of Bcl2 and PPARα in the livers of both the control and T2DM rats. All of these effects were dose-dependent and more profound with doses of 500 mg/kg. In conclusion, chronic feeding of BE to STZ/HFD-induced T2DM in rats prevents hepatic steatosis and liver damage by its hypoglycemic and insulin-sensitizing effects and its ability to upregulate antioxidants and PPARα.

A polysaccharide of PFP-1 from Pleurotus geesteranus attenuates alcoholic liver diseases via Nrf2 and NF-κB signaling pathways

2021 ◽  
Author(s):  
Xinling Song ◽  
Wenxue Sun ◽  
Wenxin Cai ◽  
Le Jia ◽  
Jianjun Zhang
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Liver Injury ◽  
Signaling Pathways ◽  
Alcoholic Liver Disease ◽  
Fruiting Body ◽  
Liver Diseases ◽  
Alcoholic Liver Diseases

A polysaccharide named as PFP-1 was isolated from Pleurotus geesteranus fruiting body, and the potential investigations on ameliorating oxidative stress and liver injury against alcoholic liver disease (ALD) were processed...

scholarly journals Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3427
Author(s):  
Reyhaneh Farghadani ◽  
Rakesh Naidu
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Mapk Pathway ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Drug Candidate ◽  
Molecular Signaling ◽  
Her2 Positive ◽  
Therapeutic Implications ◽  
Epidermal Growth

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Despite the overall successes in breast cancer therapy, hormone-independent HER2 negative breast cancer, also known as triple negative breast cancer (TNBC), lacking estrogens and progesterone receptors and with an excessive expression of human epidermal growth factor receptor 2 (HER2), along with the hormone-independent HER2 positive subtype, still remain major challenges in breast cancer treatment. Due to their poor prognoses, aggressive phenotype, and highly metastasis features, new alternative therapies have become an urgent clinical need. One of the most noteworthy phytochemicals, curcumin, has attracted enormous attention as a promising drug candidate in breast cancer prevention and treatment due to its multi-targeting effect. Curcumin interrupts major stages of tumorigenesis including cell proliferation, survival, angiogenesis, and metastasis in hormone-independent breast cancer through the modulation of multiple signaling pathways. The current review has highlighted the anticancer activity of curcumin in hormone-independent breast cancer via focusing on its impact on key signaling pathways including the PI3K/Akt/mTOR pathway, JAK/STAT pathway, MAPK pathway, NF-ĸB pathway, p53 pathway, and Wnt/β-catenin, as well as apoptotic and cell cycle pathways. Besides, its therapeutic implications in clinical trials are here presented.

Apigenin protects mice against 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestasis

2021 ◽  
Vol 12 (5) ◽  
pp. 2323-2334
Author(s):  
Shihong Zheng ◽  
Peichang Cao ◽  
Zequn Yin ◽  
Xuerui Wang ◽  
Yuanli Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Liver Fibrosis ◽  
Liver Damage ◽  
Liver Diseases ◽  
Potential Drug ◽  
Abnormal Lipid Metabolism ◽  
And Oxidative Stress

Apigenin prevented the DDC-induced abnormal lipid metabolism, liver damage and liver fibrosis by reducing inflammation and oxidative stress. Apigenin might be a potential drug for the treatment of cholestatic liver diseases.

scholarly journals Fibrosis after Myocardial Infarction: An Overview on Cellular Processes, Molecular Pathways, Clinical Evaluation and Prognostic Value

2021 ◽  
Vol 9 (1) ◽  
pp. 16
Author(s):  
Renato Francesco Maria Scalise ◽  
Rosalba De Sarro ◽  
Alessandro Caracciolo ◽  
Rita Lauro ◽  
Francesco Squadrito ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathways ◽  
Ventricular Dysfunction ◽  
Healing Process ◽  
Molecular Signaling ◽  
Cellular Processes ◽  
Molecular Signaling Pathways ◽  
Fibrotic Scar ◽  
Life Threatening

The ischemic injury caused by myocardial infarction activates a complex healing process wherein a powerful inflammatory response and a reparative phase follow and balance each other. An intricate network of mediators finely orchestrate a large variety of cellular subtypes throughout molecular signaling pathways that determine the intensity and duration of each phase. At the end of this process, the necrotic tissue is replaced with a fibrotic scar whose quality strictly depends on the delicate balance resulting from the interaction between multiple actors involved in fibrogenesis. An inflammatory or reparative dysregulation, both in term of excess and deficiency, may cause ventricular dysfunction and life-threatening arrhythmias that heavily affect clinical outcome. This review discusses cellular process and molecular signaling pathways that determine fibrosis and the imaging technique that can characterize the clinical impact of this process in-vivo.

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