Potential Anti-carcinogenic Effect of Acetazolamide, a Carbonic Anhydrase Enzyme Inhibitor, in Diethylnitrosamine - Induced Hepatocarcinogenesis in Rats

Abstract Background Despite the progress achieved in early detection and treatment of HCC, it still accounts for a significant number of cancer-related deaths worldwide. Tumoral microenvironment acidity plays a pivotal role in tumoral cell survival, tumoral progression and metastasis. CA-IX and XII are two of several mechanisms by which tumor maintain optimal intracellular pH at the expense of the extracellular environment that turns into acidic pH. ACT is a CA inhibitor that is used in many medical indications. It is effective, safe and inexpensive. It has some side effects and it may be even contraindicated in some cases. Aim of the work To evaluate the possible anticarcinogenic role of ACT in DEN-induced HCC animal model. Materials and Methods This study showed that using DEN for 10 weeks caused significant increase in the levels of AST, ALT, total bilirubin, direct bilirubin and AFP and significant decrease in albumin level in DEN-induced HCC rat groups when compared to normal control rats. Administration of ACT for 3 weeks in ACT-treated DEN-induced HCC group caused marked improvement in the mentioned biochemical measurements (AST, ALT, total bilirubin, direct bilirubin and AFP) when compared to DEN-induced HCC rat group without ACT treatment, yet still higher than the lab values of normal control group. Results The present study demonstrated that using DEN in rat groups had induced polyhedral to round hepatocytes with dense, centrally located vesicular nuclei. The neoplastic areas showed poorly differentiated large cells with hyperchromatic nuclei and prominent nucleoli. The neoplastic cells showed anisokaryosis, anisocytosis, and deeply basophilic scanty cytoplasm and frequent mitotic figures mostly Grade III. The hepatic lobule displayed disorganization of hepatic cords with hyperplasia of Kupffer cells, multinucleated tumor giant cells with prominent basophilic nuclei and basophilic spindle cells. Conclusion Acetazolamide showed significant antitumor effect in DEN-induced HCC in rats, making it a promising agent to use against HCC either individually or in combination with any other therapeutic modalities. Further researches should be conducted in this anti HCC aspect.

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Preliminary phytochemical screening and hepatoprotective activity of methanol extract of Artocarpus hirsutus leaves.

International Journal of Phytomedicine ◽

10.5138/09750185.1900 ◽

2016 ◽

Vol 8 (3) ◽

pp. 379

Author(s):

Jitendra Patel ◽

Venkateshwar Reddy ◽

GS Kumar

Keyword(s):

Total Bilirubin ◽

Methanol Extract ◽

Hepatoprotective Activity ◽

Direct Bilirubin ◽

Control Group ◽

Phytochemical Screening ◽

Methanolic Extracts ◽

Group I ◽

Hepatic Protection

The objective of the present work was investigating the preliminary phytochemical screening and hepatoprotective activity of methanol extract of the leaves of Artocarpus hirsutus.Group I served as vehicle control, Group II served CCL4 (2ml/kg, s.c.), Group III served as standard Silymarin (50 mg/kg, p.o.) Group IV and V served as methanolic extracts of Artocarpus hirsutus (MEAH) at the dose level (250 and 500 mg/kg, p.o.). The degree of protection was determined by measuring level biochemical marker like alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), direct bilirubin, total bilirubin and Cholesterol. The histopathology study also showed the hepatic protection of extracts. The preliminary phytochemical screening was performed to find out the phytoconstituents responsible for the activity.The marker biochemical level such as ALT, AST, ALP, Direct bilirubin, Total bilirubin and Cholesterol were significantly raised in CCL4 treated rats when compared with the normal group (p<0.05), but the MEAH (500 mg/kg, bw) treated rats exhibited maximum depletion. The histopathology study also showed the hepatic protection of extracts. Preliminary phytochemical screening showed the presence of glycosides, flavonoids, Tannins, triterpenoids, carbohydrates and steroids.The results of in vivo hepatoprotective activity showed that the methanol extract of Artocarpus hirsutus exhibit significant hepatoprotective activity. This might be due to flavonoids and tannins; which was confirmed their presence in phytochemical tests.

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Effects of combined ethanol extract of Funtumia africana and Abutilon mauritianum leaves (FAAM) on liver function indices of benign prostatic hyperplasia (BPH) induced rats

Herba Polonica ◽

10.2478/hepo-2020-0013 ◽

2020 ◽

Vol 66 (3) ◽

pp. 24-35

Author(s):

Robert Ikechukwu Uroko ◽

Fatima Amin Adamude ◽

Simeon Ikechukwu Egba ◽

Charles Nnanna Chukwu ◽

Chidimma Lilian Asadu ◽

...

Keyword(s):

Benign Prostatic Hyperplasia ◽

Liver Function ◽

Normal Control ◽

Total Protein ◽

Total Bilirubin ◽

Ethanol Extract ◽

Prostatic Hyperplasia ◽

Direct Bilirubin ◽

Control Treatment ◽

Liver Functions

Abstract Objective This study evaluated the effects of combined ethanol extract of Funtumia africana and Abutilon mauritianum leaves (FAAM) on the liver function indices of benign prostatic hyperplasia (BPH) induced rats. Materials and Methods The study used 30 rats divided into 5 groups, comprising normal control, BPH control, standard control, and BPH induced rats treated with 200 and 600 mg/kg/day of FAAM respectively. Results The BPH induction caused significant (p<0.05) increases in aspartate transaminase (AST) and alkaline phosphatase (ALP) activities of the BPH control when compared with the normal control. The BPH control also had significantly (p<0.05) reductions in the total protein, albumin and globulin concentrations and significant (p<0.05) elevated total bilirubin and direct bilirubin concentrations relative to the normal control. The FAAM treated BPH-induced rats had non-significantly (p>0.05) reduced AST, and alanine transaminase (ALT) activities relative to the BPH control. The BPH-induced rats treated with 600 mg/kg/day of FAAM had significantly (p<0.05) reduced ALP activities relative to the BPH control. Treatment with FAAM caused significant (p<0.05) increases in the total protein, albumin, globulin concentrations and significant (p<0.05) reductions in the total bilirubin and direct bilirubin concentrations relative to the BPH control. BPH had no observable adverse effects on the liver histomorphology of the rats. Conclusion The findings of this study indicated that BPH impairs liver functions and treatment of BPH with combined ethanol extract of F. africana and A. mauritianum leaves restore normal liver functions in rats with BPH.

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Ursodeoxycholic acid in neonatal sepsis-associated cholestasis

Paediatrica Indonesiana ◽

10.14238/pi54.4.2014.206-12 ◽

2014 ◽

Vol 54 (4) ◽

pp. 206

Author(s):

Rita Mey Rina ◽

Hanifah Oswari ◽

Pustika Amalia

Keyword(s):

Liver Function ◽

Ursodeoxycholic Acid ◽

Total Bilirubin ◽

Controlled Trial ◽

Intervention Group ◽

Direct Bilirubin ◽

Function Parameter ◽

Control Group ◽

Gamma Glutamyl Transpeptidase ◽

Double Blind

Background Sepsis-associated cholestasis (SAC) is an intrahepatic cholestasis caused by inflammatory cytokines. Patients with this condition have poor prognoses. Antibiotics are the mainstay of therapy, however, other adjuvant therapies, such as ursodeoxycholic acid (UDCA), have not been well established.Objective To assess the effect ofUDCA for treatment ofneonatal sepsis-associated cholestasis.Methods We performed a randomized, double-blind, controlled trial in 3 7 neonates who were diagnosed with sepsis-associated cholestasis in the Neonatal Care Unit of Cipto Mangunkusumo Hospital. Subjects were divided into two groups, with 19 neonates randomly allocated to the intervention group (received UDCA at 30 tngikg/day divided into 3 doses for 7 days) and 18 neonates to the control group (received placebo) . After 7 days of treatment, we evaluated the subjects' liver function parameters and performed asurvival analysis.Results Liver function parameter improvements at day 7 were not significantly different between the UDCA group and the control group, including for mean decrease of total bilirubin (TB) levels [2.2 (SD 2.9) mg/dL vs 1.7 (SD 4.6) mg/dL; P=0.080), mean decrease of direct bilirubin (DB) levels [1.1 (SD 2.3) mg/dL vs 0.6 (SD 3.6) mg/dL; P=0.080), median indirect bilirubin (lB) levels [0.4 (range 0.1- 5.6) mg/dL vs 0.9 (range 0.1-4.1) mg/dL; P=0.358) , mean decrease of alanine aminotransferase (ALT) levels [0.5 (-80.0 -21.0) U/L vs -2.0 (ranged -167 .0 - 85.0) U/L; P= 0.730), median aspartate aminotransferase (AST) levels [ 43 .0 (range 14.0-297 .0) U/L vs 150.0 (range 24.0-840.0) U/L; P=0.081), and median gamma-glutamyl transpeptidase (GGf) levels [125.0 (48.0-481.0) U/L vs 235.0 (56.0-456.0) U/L; P=0.108)). Five neonates in control group died compared to two in the UDCA group (P=0.232). In addition, UDCA did not significantly lengthen the survival time (hazard ratio/HR 3.62; 95%CI 0.69 to 18.77) .Conclusion Ursodeoxycholic acid tends to improve total bilirubin, direct bilirubin, and AST levels in sepsis associated cholestasis .

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Changes in serum adenosine deaminase and isoenzyme levels in addition to routine liver biochemical parameters in sheep with chronic fascioliasis

Ciência Rural ◽

10.1590/0103-8478cr20210152 ◽

2022 ◽

Vol 52 (4) ◽

Author(s):

Nuri Altuğ ◽

Yıldıray Başbuğan ◽

Nazmi Yuksek

Keyword(s):

Bile Duct ◽

Adenosine Deaminase ◽

Total Protein ◽

Biochemical Parameters ◽

Total Bilirubin ◽

Clinical Signs ◽

Infected Group ◽

Direct Bilirubin ◽

Control Group ◽

And Control

ABSTRACT: This study assessed changes in the levels of adenosine deaminase (ADA) and its isoenzymes in addition to routine liver biochemical parameters in sheep with fascioliasis. The study was conducted on 35 Akkaraman sheep. Of these, 25 sheep were diagnosed with fascioliasis based on anamnesis and clinical signs, and had endoparasites based on parasitological examinations (Fasciola-infected group). The remaining 10 sheep that were sampled from a single healthy herd (same flock) different from the infected group did not have any clinical signs or endoparasites (control group). Total protein (TP), albumin (ALB), and globulin (GLB) levels gradually increased on days after treatment compared to the values measured before treatment; the increases were statistically significant on all days for TP levels but only on day 14 after treatment for GLB levels (P < 0.05). Although, the ALB levels did not increase significantly on days after treatment, the ALB level and ALB/GLB ratio on days 7 and 14 after treatment were still lower than the values of day 21 after treatment and control group (P < 0.05). Total bilirubin (T-Bil) and direct bilirubin (D-Bil) levels on days 14 and 21 were significantly lower than that of day 0 (before treatment) and day 7 after treatment (P < 0.05). These results indicated that the increase in adenosine deaminase (ADA) and ADA1 levels may be due to possible concomitant infection of Fasciola larvae (in the parenchyma) and adults (in the bile duct).

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Higher Level of Serum Heme Oxygenase-1 in Patients With Intracerebral Hemorrhage

International Surgery ◽

10.9738/intsurg-d-14-00086.1 ◽

2015 ◽

Vol 100 (7-8) ◽

pp. 1220-1224 ◽

Cited By ~ 5

Author(s):

Xin Li ◽

Changqing Li ◽

Lichun Hou ◽

Mei He ◽

Guangfu Song ◽

...

Keyword(s):

Blood Pressure ◽

Serum Level ◽

Intracerebral Hemorrhage ◽

Heme Oxygenase ◽

Total Bilirubin ◽

Direct Bilirubin ◽

Control Group ◽

Heme Oxygenase 1 ◽

Serum Total Bilirubin ◽

Significant Difference

The objective of this paper was to investigate the association of the serum level of heme oxygenase-1 in patients with intracerebral hemorrhage (ICH) with the risk of ICH. Heme oxygenase-1(HO-1) metabolizes heme into biliverdin, bilirubin, carbon monoxide, and iron, our recent study showed that serum level of HO-1 was increased in stroke patients, yet the association of HO-1 level with risk of intracerebral hemorrhage (ICH) is poorly known. Forty patients with ICH and another 40 patients without ICH were recruited. The serum level of HO-1, total, and direct bilirubin were measured. The level of HO-1, serum total bilirubin, and direct bilirubin, as well as blood pressure were increased in ICH group than in control group (P < 0.001). The level of HO-1, both systolic and diastolic blood pressure had a significant difference between subgroups (P < 0.05). Multivariate regression analysis showed that poor compliance to medicine for hypertension, the serum level of HO-1, and systolic blood pressure were associated with the prevalence of ICH. Blood pressure, serum HO-1, serum total bilirubin, and direct bilirubin were raised in patients with ICH who did not take medicine for hypertension compared with those who did, and increased in ICH patients in comparison with control group. Further investigation in multiple medical centers with large number of cohorts is warranted to verify these results.

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Increased serum total bilirubin-albumin ratio was associated with bilirubin encephalopathy in neonates

Bioscience Reports ◽

10.1042/bsr20192152 ◽

2020 ◽

Vol 40 (1) ◽

Cited By ~ 1

Author(s):

Yan Wang ◽

Guangyao Sheng ◽

Lina Shi ◽

Xiuyong Cheng

Keyword(s):

Total Bilirubin ◽

Direct Bilirubin ◽

Control Group ◽

Case Group ◽

Serum Total Bilirubin ◽

Natural Childbirth ◽

Albumin Ratio ◽

Indirect Bilirubin ◽

Bilirubin Encephalopathy ◽

Epidemiological Characteristics

Abstract We performed the present study to summarize the recent epidemiological characteristics of bilirubin encephalopathy and assess the role of total bilirubin-albumin ratio in the bilirubin encephalopathy. We retrospectively collected clinical data of 669 neonates with hyperbilirubinemia from the First Affiliated Hospital of Zhengzhou University between January 2015 and July 2018, including 153 neonates belonged to bilirubin encephalopathy and 516 ones were treated as control group. Compared with the control group, those with bilirubin encephalopathy have higher bilirubin-albumin ratio (13.8 ± 3.6 vs. 10.6 ± 2.5, P=0.000). The direct bilirubin and indirect bilirubin level were higher in the case group than that in the control group (P=0.000). On the contrary, the hemoglobin level was lower in the case group than that in the control group (P=0.004). There were no significant differences in gestational age (P=0.510), gender rate (P=0.313), maternal gestational diabetes ratio (P=0.071), natural childbirth ratio (P=0.686), and meconium delay (P=0.091). The results from univariate regression indicated the total bilirubin/albumin ratio was positively associated with bilirubin encephalopathy (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.59–3.14). The total bilirubin, direct bilirubin, and indirect bilirubin were also related to encephalopathy. After adjusting some potential cofounding factors, the total bilirubin-albumin was still associated with bilirubin encephalopathy. The higher total bilirubin-albumin ratio increased the risk of bilirubin encephalopathy by 23% (OR = 1.23, 95% CI: 1.16–2.48). Our results indicated that the bilirubin-albumin ratio is associated with bilirubin encephalopathy in neonates, and could be a potential predictor.

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Study on potential differentially expressed genes in stroke by bioinformatics analysis

Neurological Sciences ◽

10.1007/s10072-021-05470-1 ◽

2021 ◽

Author(s):

Xitong Yang ◽

Pengyu Wang ◽

Shanquan Yan ◽

Guangming Wang

Keyword(s):

Gene Expression ◽

Differentially Expressed Genes ◽

Normal Control ◽

Enrichment Analysis ◽

Normal Control Group ◽

Control Group ◽

Ppi Network ◽

Hub Genes ◽

Pathway Enrichment ◽

Key Genes

AbstractStroke is a sudden cerebrovascular circulatory disorder with high morbidity, disability, mortality, and recurrence rate, but its pathogenesis and key genes are still unclear. In this study, bioinformatics was used to deeply analyze the pathogenesis of stroke and related key genes, so as to study the potential pathogenesis of stroke and provide guidance for clinical treatment. Gene Expression profiles of GSE58294 and GSE16561 were obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IS and normal control group. The different expression genes (DEGs) between IS and normal control group were screened with the GEO2R online tool. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were performed. Using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and gene set enrichment analysis (GSEA), the function and pathway enrichment analysis of DEGS were performed. Then, a protein–protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes (STRING) database. Cytoscape with CytoHubba were used to identify the hub genes. Finally, NetworkAnalyst was used to construct the targeted microRNAs (miRNAs) of the hub genes. A total of 85 DEGs were screened out in this study, including 65 upward genes and 20 downward genes. In addition, 3 KEGG pathways, cytokine − cytokine receptor interaction, hematopoietic cell lineage, B cell receptor signaling pathway, were significantly enriched using a database for labeling, visualization, and synthetic discovery. In combination with the results of the PPI network and CytoHubba, 10 hub genes including CEACAM8, CD19, MMP9, ARG1, CKAP4, CCR7, MGAM, CD79A, CD79B, and CLEC4D were selected. Combined with DEG-miRNAs visualization, 5 miRNAs, including hsa-mir-146a-5p, hsa-mir-7-5p, hsa-mir-335-5p, and hsa-mir-27a- 3p, were predicted as possibly the key miRNAs. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of ischemic stroke, and provide a new strategy for clinical therapy.

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Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol

Scientific Reports ◽

10.1038/s41598-021-81109-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shukun Jiang ◽

Guojie Liu ◽

Huiya Yuan ◽

Enyu Xu ◽

Wei Xia ◽

...

Keyword(s):

Chronic Exposure ◽

Molecular Mechanisms ◽

Fatty Acid Biosynthesis ◽

Serum Proteins ◽

Enzyme Inhibitor ◽

Bile Secretion ◽

Control Group ◽

Protein Digestion ◽

Metabolomic Profile ◽

Apolipoprotein C

AbstractTramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic exposure to tramadol. In this study, we analyzed the proteomic and metabolomic profile by TMT-labeled quantitative proteomics and untargeted metabolomics between the tramadol and the control group. Proteomic analysis revealed 31 differential expressed serum proteins (9 increased and 22 decreased) in tramadol-treated mice (oral, 50 mg/kg, 5 weeks) as compared with the control ones. Bioinformatics analysis showed that the dysregulated proteins mainly included: enzyme inhibitor-associated proteins (i.e. apolipoprotein C-III (Apoc-III), alpha-1-antitrypsin 1–2 (Serpina 1b), apolipoprotein C-II (Apoc-II), plasma protease C1 inhibitor, inter-alpha-trypsin inhibitor heavy chain H3 (itih3)); mitochondria-related proteins (i.e. 14-3-3 protein zeta/delta (YWHAZ)); cytoskeleton proteins (i.e. tubulin alpha-4A chain (TUBA4A), vinculin (Vcl)). And we found that the differential expressed proteins mainly involved in the pathway of the protein digestion and absorption. Metabolomics analysis revealed that differential expressed metabolites mainly involved in protein ingestion and absorption, fatty acid biosynthesis, steroid hormone biosynthesis and bile secretion. Our overall findings revealed that chronic exposure to tramadol changed the proteomic and metabolomic profile of mice. Moreover, integrated proteomic and metabolomic revealed that the protein digestion and absorption is the common enrichment KEGG pathway. Thus, the combination of proteomics and metabolomics opens new avenues for the research of the molecular mechanisms of tramadol toxicity.

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Risk factors for the failure to achieve normal albumin serum levels after albumin transfusion in neonates

Paediatrica Indonesiana ◽

10.14238/pi56.3.2016.129-33 ◽

2016 ◽

Vol 56 (3) ◽

pp. 129

Author(s):

Nadya Arafuri ◽

Pudjo Hagung Widjajanto ◽

Ekawaty L. Haksari

Keyword(s):

Risk Factors ◽

Critical Illness ◽

Very Low Birth Weight ◽

Significant Risk ◽

Albumin Level ◽

Control Group ◽

Case Group ◽

Severe Bleeding ◽

Normal Albumin ◽

Neonatal Ward

Background Albumin transfusion for the treatment of neonatal hypoalbuminemia may reduce morbidity. In conditions with disrupted endothelial integrity (e.g., sepsis and critical illness), the administered albumin may leak into the interstitial space, hence, serum albumin levels may fall below expected levels after transfusion. To date, few studies have been done to evaluate the risk factors for failure to achieve normal neonatal albumin levels after transfusion.Objectives To determine the risk factors for failure to achieve normal neonatal albumin levels after transfusion.Methods We performed a case-control study in the Neonatal Ward of Dr. Sardjito Hospital from 2007 to 2012. Normal albumin level was defined as above 3 g/dL. The case group included neonates with post-transfusion albumin levels <3 g/dL and the control group included those with post-transfusion albumin ≥3 g/dL. Subjects received intravenous transfusions of 25% or 20% albumin according to the clinical standard of the Neonatal Ward of Dr. Sardjito Hospital. Neonates with very low birth weight, severe birth trauma, burn injuries, severe bleeding, or incomplete medical records were excluded. The data were analyzed with logistic regression test.Results From January 2007 to December 2012, 124 neonates were enrolled in the study. Multivariate analysis showed that low albumin levels before transfusion (OR 12.27; 95%CI 2.17 to 69.30), presence of critical illness (OR 4.01; 95%CI 1.49 to 10.79), diagnosis of sepsis (OR 3.56; 95%CI 1.36 to 9.32), and the >24-hour interval between albumin examination and transfusion (OR 0.06; 95%CI 0.01 to 0.37) were significant risk factors affecting the failure to achieve normal albumin levels.Conclusions Failure to achieve normal albumin levels after transfusion in neonates was significantly associated with low albumin level prior to transfusion, critical illness, sepsis, and >24-hour interval between transfusion and post-transfusion albumin examination.[Paediatr Indones. 2016;56:129-33.].

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