scholarly journals A Comparative Study for the Evaluation of Two Doses of Ellagic Acid on Hepatic Drug Metabolizing and Antioxidant Enzymes in the Rat

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Gurbet Celik ◽  
Aslı Semiz ◽  
Serdar Karakurt ◽  
Sevki Arslan ◽  
Orhan Adali ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Ellagic Acid ◽  
Enzyme Activities ◽  
Mrna Levels ◽  
Glutathione S Transferase ◽  
Qrt Pcr ◽  
Dose Dependent ◽  
Cyp3a Enzyme ◽  
Different Doses

The present study was designed to evaluate different doses of ellagic acid (EA)in vivoin rats for its potential to modulate hepatic phases I, II, and antioxidant enzymes. EA (10 or 30 mg/kg/day, intragastrically) was administered for 14 consecutive days, and activity, protein, and mRNA levels were determined. Although the cytochrome P450 (CYP) 2B and CYP2E enzyme activities were decreased significantly, the activities of all other enzymes were unchanged with the 10 mg/kg/day EA. In addition, western-blot and qRT-PCR results clearly corroborated the above enzyme expressions. On the other hand, while the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activities were increased significantly, CYP1A, 2B, 2C, 2E, and 19 enzyme activities were reduced significantly with 30 mg/kg/day EA. In addition, CYP2B, 2C6, 2E1, and 19 protein and mRNA levels were substantially decreased by the 30 mg/kg/day dose of EA, but the CYP1A protein, and mRNA levels were not changed. CYP3A enzyme activity, protein and mRNA levels were not altered by neither 10 nor 30 mg/kg/day ellagic acid. These results indicate that EA exerts a dose-dependent impact on the metabolism of chemical carcinogens and drugs by affecting the enzymes involved in xenobiotics activation/detoxification and antioxidant pathways.

scholarly journals In vivo examination of the effects of hydroxycinnamic acid on xenobiotic metabolizing and antioxidant enzymes

2017 ◽  
Vol 69 (1) ◽  
pp. 103-110 ◽  
Author(s):  
Asli Semiz ◽  
Gurbet Celik-Turgut ◽  
Serdar Karakurt ◽  
Hakan Akca ◽  
Sevki Arslan ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Enzyme Activities ◽  
Anticancer Agent ◽  
Wistar Rat ◽  
Mrna Levels ◽  
Protein Levels ◽  
Glutathione S Transferases ◽  
The Impact ◽  
Potential Use

In the last decade, hydroxycinnamic acids (HCA) have gained increasing attention from researchers due to their antioxidant potential. The aim of this study was to examine in detail the impact of dietary HCA on particular types of P450 and also selected phase II and antioxidant enzymes in Wistar rat. HCA (10 mM/kg/day, i.p.) was administered for ten continuous days. Examination of the activities and mRNA and protein levels revealed that CYP2B, 2C6 and 3A enzyme activities were not altered significantly, with Western blot and qRT-PCR results corroborating this result. While treatment with HCA led to a significant reduction in CYP1A1/CYP1A2-associated enzyme activities, CYP1A1 protein, and mRNA levels were found to be unchanged. Aromatase (CYP19) activity, as well as protein and mRNA levels, were significantly reduced with HCA treatment. On the other hand, the NAD(P)H:quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferases (GSTs) activities were increased significantly. Also, HCA treatment significantly increased the GST-mu and GST-theta mRNA levels. These observations may be of importance given the potential use of HCA as a chemopreventive and as an anticancer agent.

scholarly journals Knockdown of Long Non-Coding RNA XIST Inhibited Doxorubicin Resistance in Colorectal Cancer by Upregulation of miR-124 and Downregulation of SGK1

2018 ◽  
Vol 51 (1) ◽  
pp. 113-128 ◽  
Author(s):  
Jia Zhu ◽  
Rui Zhang ◽  
Dongxiang Yang ◽  
Jibin Li ◽  
Xiaofei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Western Blot ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Glutathione S Transferase ◽  
Protein Levels ◽  
Qrt Pcr ◽  
Ic50 Value

Background/Aims: Doxorubicin (DOX) is a widely used chemotherapeutic agent for colorectal cancer (CRC). However, the acquirement of DOX resistance limits its clinical application for cancer therapy. Mounting evidence has suggested that aberrantly expressed lncRNAs contribute to drug resistance of various tumors. Our study aimed to explore the role and molecular mechanisms of lncRNA X-inactive specific transcript (XIST) in chemoresistance of CRC to DOX. Methods: The expressions of XIST, miR-124, serum and glucocorticoid-inducible kinase 1 (SGK1) mRNA in DOX-resistant CRC tissues and cells were detected by qRT-PCR or western blot analysis. DOX sensitivity was assessed by detecting IC50 value of DOX, the protein levels of P-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) and apoptosis. The interactions between XIST, miR-124 and SGK1 were confirmed by luciferase reporter assay, qRT-PCR and western blot. Xenograft tumor assay was used to verify the role of XIST in DOX resistance in CRC in vivo. Results: XIST expression was upregulated and miR-124 expression was downregulated in DOX-resistant CRC tissues and cells. Knockdown of XIST inhibited DOX resistance of CRC cells, as evidenced by the reduced IC50 value of DOX, decreased P-gp and GST-π levels and enhanced apoptosis in XIST-silenced DOX-resistant CRC cells. Additionally, XIST positively regulated SGK1 expression by interacting with miR-124 in DOX-resistant CRC cells. miR-124 suppression strikingly reversed XIST-knockdown-mediated repression on DOX resistance in DOX-resistant CRC cells. Moreover, SGK1-depletion-elicited decrease of DOX resistance was greatly restored by XIST overexpression or miR-124 inhibition in DOX-resistant CRC cells. Furthermore, XIST knockdown enhanced the anti-tumor effect of DOX in CRC in vivo. Conclusion: XIST exerted regulatory function in resistance of DOX possibly through miR-124/SGK1 axis, shedding new light on developing promising therapeutic strategy to overcome chemoresistance in CRC patients.

Evaluation of Hepatoprotective activity of Methanol extract of Persicaria hydropiper: An in vivo screening

2021 ◽  
pp. 5819-5824
Author(s):  
Pooja Kamra ◽  
Mahaveer Singh ◽  
Hardarshan Singh Lamba ◽  
Birendra Srivastava
Keyword(s):  
Carbon Tetrachloride ◽  
Intraperitoneal Administration ◽  
Hepatoprotective Activity ◽  
Dependent Manner ◽  
Standard Drug ◽  
Whole Plant ◽  
Dose Dependent ◽  
Histopathological Investigation ◽  
Different Doses

The present study aimed to evaluate the hepatoprotective potential of methanolic whole plant extract of Persicaria hydropiper in carbon tetrachloride (CCl4) induced hepatotoxicity model. Hepatotoxicity was induced in rats by intraperitoneal administration of carbon tetrachloride (CCl4) for seven days. The extract was thereafter administered at two different doses of 200 mg/kg and 400 mg/kg body weight for next seven days. Silymarin was used as a reference standard. The extract revealed hepatoprotective activity in dose dependent manner. The dose of 400 mg/kg exhibited maximum hepatoprotective ability as apparent from several evaluation parameters including liver function profile, bilirubin, antioxidant enzymes as well as histopathological investigation which was comparable to the standard drug Silymarin respectively. These findings sustenance the use of the extract as an adjuvant with existing therapy for treatment of liver ailments.

scholarly journals Suppression of the GnRH Pulse Generator by Neurokinin B Involves a κ-Opioid Receptor-Dependent Mechanism

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4894-4904 ◽  
Author(s):  
P. Grachev ◽  
X. F. Li ◽  
J. S. Kinsey-Jones ◽  
A. L. di Domenico ◽  
R. P. Millar ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Neurokinin B ◽  
Kndy Neurons ◽  
Lh Secretion ◽  
Dose Dependent

Abstract Neurokinin B (NKB) and its receptor (NK3R) are coexpressed with kisspeptin, Dynorphin A (Dyn), and their receptors [G-protein-coupled receptor-54 (GPR54)] and κ-opioid receptor (KOR), respectively] within kisspeptin/NKB/Dyn (KNDy) neurons in the hypothalamic arcuate nucleus (ARC), the proposed site of the GnRH pulse generator. Much previous research has employed intracerebroventricular (icv) administration of KNDy agonists and antagonists to address the functions of KNDy neurons. We performed a series of in vivo neuropharmacological experiments aiming to determine the role of NKB/NK3R signaling in modulating the GnRH pulse generator and elucidate the interaction between KNDy neuropeptide signaling systems, targeting our interventions to ARC KNDy neurons. First, we investigated the effect of intra-ARC administration of the selective NK3R agonist, senktide, on pulsatile LH secretion using a frequent automated serial sampling method to obtain blood samples from freely moving ovariectomized 17β-estradiol-replaced rats. Our results show that senktide suppresses LH pulses in a dose-dependent manner. Intra-ARC administration of U50488, a selective KOR agonist, also caused a dose-dependent, albeit more modest, decrease in LH pulse frequency. Thus we tested the hypothesis that Dyn/KOR signaling localized to the ARC mediates the senktide-induced suppression of the LH pulse by profiling pulsatile LH secretion in response to senktide in rats pretreated with nor-binaltorphimine, a selective KOR antagonist. We show that nor-binaltorphimine blocks the senktide-induced suppression of pulsatile LH secretion but does not affect LH pulse frequency per se. In order to address the effects of acute activation of ARC NK3R, we quantified (using quantitative RT-PCR) changes in mRNA levels of KNDy-associated genes in hypothalamic micropunches following intra-ARC administration of senktide. Senktide down-regulated expression of genes encoding GnRH and GPR54 (GNRH1 and Kiss1r, respectively), but did not affect the expression of Kiss1 (which encodes kisspeptin). We conclude that NKB suppresses the GnRH pulse generator in a KOR-dependent fashion and regulates gene expression in GnRH neurons.

scholarly journals Preclinical Appraisal of Hematinic Potential of Mandura Bhasma for Treating Anemia

2021 ◽  
pp. 207-214
Author(s):  
Deepak S. Khobragade ◽  
Mrunali S. Potbhare ◽  
Awdhut Pimpale ◽  
Sagar B. Wankhede ◽  
Chandrashekhar R. Tempe
Keyword(s):  
Body Weight ◽  
Ferrous Sulphate ◽  
Standard Drug ◽  
Dependent Activity ◽  
Daily Dose ◽  
Study Institute ◽  
Dose Dependent ◽  
Pharmaceutical Education ◽  
Different Doses

Aims: To evaluate hematinic potential of mandura bhasma. Study Design: Experimental study. Place and Duration of Study: Institute of Pharmaceutical Education and Research, Wardha, Maharashtra, India. 6 Months. Methodology: The anti-anaemic potential of Mandura bhasma in Wistar rats was investigated. Anaemia was induced in rats with phenyl hydrazine hydrochloride at a dose of 10        mg kg-1 body weight by oral administration. Anaemia was treated with mandura bhasma administered in three different doses based on body weight. Results: In vivo investigation showed that though the dose of 6mg kg-1 body weight of mandura bhasm produced only a minimal antianaemic (hematinic) effect, oral daily dose of 11 mg kg-1 body weight and 22mg kg-1 body weight a produced a significant (P < 0.05) antianaemic effect when compared to standard drug ferrous sulphate indicating dose dependent activity. Conclusions: The results indicate that Mandura Bhasm have very potential dose dependant hematinic activity and can be a safe and effective drug for treating anemia.

LNA Anti-MicroRNA-155: A Novel Therapeutic Strategy in Waldenstrom Macroglobulinemia and Chronic Lymphocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2728-2728
Author(s):  
Yong Zhang ◽  
Christopher P. Rombaoa ◽  
Aldo M Roccaro ◽  
Susanna Obad ◽  
Oliver Broom ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Tumor Cells ◽  
Stromal Cells ◽  
Research Funding ◽  
Mrna Levels ◽  
Advisory Committees ◽  
Qrt Pcr

Abstract Abstract 2728 Background. We and others have previously demonstrated that primary Waldenstrom's Macroglobulinemia (WM) and Chronic lymphocytic leukemia (CLL) cells show increased expression of microRNA-155 (miR-155), suggesting a role in regulating pathogenesis and tumor progression of these diseases. However, developing therapeutic agents that specifically target miRNAs has been hampered by the lack of appropriate delivery of small RNA inhibitors into tumor cells. We tested the effect of a novel LNA (locked nucleic acid)-modified anti-miR-155 in WM and CLL. Methods. WM and CLL cells, both cell lines (BCWM.1; MEC.1) and primary tumor cells; BCWM.1 Luc+ cells; and primary WM bone marrow (BM) stromal cells were used. WM and CLL cells were treated with antisense LNA anti-miR-155 or LNA scramble oligonucleotide. Efficiency of delivering FAM-labeled LNA into cells was determined by flow cytometry. Survival and cell proliferation were assessed by MTT and thymidine uptake assay, respectively. Synergistic effects of LNA with bortezomib were detected on BCWM.1 or MEC1 cells. Co-culture of BCWM.1 or MEC1 cells with WM bone marrow stromal cells was performed to better define the effect of the LNA-anti-miR155 in the context of the bone marrow microenvironment. miR-155 levels were detected in stromal cells from WM patients by qPCR. Co-culture of BCWM.1 or MEC1 cells with either wild-type or miR155−/− mice BM stromal cells was examined after LNA treatment. Gene expression profiling analysis was performed on BCWM.1 cells treated with either LNA anti-miR-155 or scramble control. miR-155 target gene candidates were predicted by TargetScan software. mRNA levels of miR-155, and its known target genes or gene candidates were detected by qRT-PCR. A microRNA luciferase reporter assay was used to determine whether miR-155 target candidates could be directly regulated by miR-155. mRNA levels of miR-155 targets were detected by qRT-PCR from primary WM or CLL cells treated with LNA. The activity of the LNA-anti-miR-155 was also detected in vivo using bioluminescence imaging and mRNA levels of miR-155 targets were detected by qRT-PCR ex vivo. Efficiency of introducing the FAM-labeled LNA into mice BM cells was determined by flow cytometry 1 week or 2 weeks after intravenous injection. Results. The efficiency of delivering LNA oligos into both WM and CLL-derived cell lines and primary samples was higher than 90%. LNA antimiR-155 reduced proliferation of WM and CLL-derived cell lines by 30–50%, as compared to LNA scramble control. In contrast, LNA antimiR-155 didn't exert significant cytotoxicity in BCWM.1 or MEC.1. LNA synergistically decreased BCWM.1 or MEC1 cell growth co-treated with bortezomib and decreased BCWM.1 or MEC1 cell growth co-cultured with WM BM stromal cells in vitro. A higher level of miR-155 was found in WM BM stromal cells compared to normal ones. LNA decreased BCWM.1 or MEC1 cell growth when co-cultured with BM stromal cells from miR155−/− mice compared with wild-type. We demonstrated increased expression of miR-155-known targeted genes, including CEBPβ, SOCS1, SMAD5, and several novel target candidates including MAFB, SH3PXD2A, and SHANK2, in WM cells upon LNA anti-miR-155 treatment. These target candidates were confirmed to be directly regulated by miR-155 using a luciferase reporter assay. mRNA levels of miR-155 targets were upregulated by 1.5–2 fold at 48 hr after direct incubation of the LNA with primary WM or CLL samples, indicating efficient delivery and biologic effect of the LNA in cells. Moreover, this LNA showed significant in vivo activity by inhibiting WM cell proliferation in a disseminated xenograft mouse model. Upregulation of miR-155 targeted genes were confirmed ex vivo, in WM cells isolated from the BM of treated mice compared to control. Mice BM cells were FAM positive 1 or 2 weeks after injection indicating efficient delivery of FAM-labeled LNA into cells in vivo. Summary. A novel LNA (locked nucleic acid)-modified anti-miR against miR-155 could be highly efficiently delivered into tumor cells in vivo in the bone marrow microenvironment. Anti-WM activity of LNA anti-miR-155 was confirmed both in vitro and in vivo and anti-CLL activity was confirmed in vitro. Novel miR-155 direct target genes including MAFB, SH3PXD2A, and SHANK2 were identified. These findings will help to design individualized clinical trials for WM and CLL patients with elevated levels of miR-155 in their tumor cells. Disclosures: Roccaro: Roche:. Obad:Santaris Pharma: Employment. Broom:Electroporation: Employment. Kauppinen:Santaris Pharma: Employment. Brown:Calistoga: Consultancy, Research Funding; Celgene: Honoraria, Research Funding; Genzyme: Research Funding; GSK: Research Funding. Ghobrial:Celgene: Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Noxxon: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium: Research Funding; Bristol-Myers Squibb: Research Funding; Noxxon: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals EFFICACY OF AN ACTIVE COMPOUND OF THE HERB, ASHWAGANDHA IN PREVENTION OF STRESS INDUCED HYPERGLYCEMIA

2018 ◽  
Vol 10 (10) ◽  
pp. 44 ◽  
Author(s):  
Sarjan H. N. ◽  
Yajurvedi H. N.
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Ethanolic Extract ◽  
Dependent Manner ◽  
Stress Exposure ◽  
In Vitro Experiment ◽  
Isolated Compound ◽  
Dose Dependent ◽  
Different Doses

Objective: To find out whether an isolated compound (IC) from the ethanolic extract of roots of ashwagandha prevents stress-induced hyperglycemia by direct interference with the action of increased concentration of corticosterone on hepatocytes or by preventing hyper-secretion of corticosterone or both.Methods: A group of rats served as controls, and those in another group were subjected to restraint (1 h) and forced swimming exercise (15 min), after a gap of 4 h daily for 4 w. The third group of rats received orally IC (5 mg/kg bw/rat) 1 h prior to exposure to stressors. After the last treatment period, a blood sample was collected and serum was separated for the estimation of corticosterone and glucose. In in vitro experiment, hepatocytes were treated with different concentrations of corticosterone (100, 200, 300, 400 and 500 ng/ml). In another set of experiment, hepatocytes were treated with different doses of IC (1, 10, 100, 1000 and 10 000 μg/ml of medium) along with corticosterone (400ng/ml). The concentration of glucose and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were determined after the treatment.Results: Stress exposure caused a significant increase in serum concentration of corticosterone and glucose whereas, administration of IC did not result in similar changes. Further, treatment of corticosterone in in vitro significantly increased the activities of PEPCK and G6Pase and concentration of glucose in a dose-dependent manner in hepatocytes. However, treatment with IC did not interfere with the corticosterone-induced an increase in the activities of PEPCK and G6Pase as well as the concentration of glucose in hepatocytes.Conclusion: The in vivo and in vitro results put together reveal that IC does not directly interfere with the action of corticosterone on hepatocytes. However, it prevents stress-induced hyperglycemia by suppressing hyper-secretion of corticosterone. 

In vivo biochemical evaluations of some β-lactam group antibiotics on glutathione reductase and glutathione S- transferase enzyme activities

Life Sciences ◽  
2019 ◽  
Vol 231 ◽  
pp. 116572
Author(s):  
Fikret Türkan ◽  
Zübeyir Huyut ◽  
Mehmet Tahir Huyut ◽  
Mehmet Harbi Calimli
Keyword(s):  
Glutathione Reductase ◽  
Enzyme Activities ◽  
Glutathione S Transferase

Immunomodulating capacity of kefir

2005 ◽  
Vol 72 (2) ◽  
pp. 195-202 ◽  
Author(s):  
Celso G Vinderola ◽  
Jairo Duarte ◽  
Deepa Thangavel ◽  
Gabriela Perdigón ◽  
Edward Farnworth ◽  
...  
Keyword(s):  
Acetic Acid Bacteria ◽  
Fermented Milk ◽  
Mucosal Immune Response ◽  
Dependent Manner ◽  
Tnf Α ◽  
Translocation Assay ◽  
Feeding Trials ◽  
Dose Dependent ◽  
Different Doses

Kefir is a fermented milk produced by the action of lactic acid bacteria, yeasts and acetic acid bacteria, trapped in a complex matrix of polysaccharides and proteins. Beyond its inherent high nutritional value as a source of proteins and calcium, kefir has a long tradition of being regarded as good for health in countries where it is a staple in the diet. However, published human or animal feeding trials to substantiate this view are not numerous. The aim of this work was to determine the immunomodulating capacity of kefir on the intestinal mucosal immune response in mice and to demonstrate the importance of dose and cell viability on this response. BALB/c mice were fed with commercial kefir ad libitum (diluted 1/10, 1/50, 1/100 or 1/200) or pasteurized kefir (diluted 1/6, 1/10, 1/50, 1/100) for 2, 5 or 7 consecutive days. At the end of each feeding period, the bacterial translocation assay was performed in the liver. Small intestine structure was studied by haematoxilin-eosin staining and light microscopy. The number of IgA+ and IgG+ cells was also determined. For the functional doses chosen, cytokines (IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-γ) were determined. Kefir and pasteurized kefir were able to modulate the mucosal immune system in a dose-dependent manner. Kefir was administred 10-times more diluted than pasteurized kefir, but it induced an immunomodulation of similar magnitude, indicating the importance of cell viabilty. The results suggest that a Th1 response was controlled by Th2 cytokines induced by kefir feeding. Pasteurized kefir would induce both Th2 and Th1 responses. This is the first study in vivo regarding the mechanisms involved in the immunomodulating capacity of the oral administration of kefir containing viable or heat-inactivated bacteria at different doses.

Inhibition of gastric H+ secretion, K+-ATPase and K+-phosphatase by estradiol in vivo and in vitro

1982 ◽  
Vol 60 (5) ◽  
pp. 680-684 ◽  
Author(s):  
L. Limlomwongse ◽  
P. Piyachaturawat
Keyword(s):  
Gastric Mucosa ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Enzyme Activities ◽  
Direct Action ◽  
Inhibitory Effect ◽  
Secretory Rate ◽  
Dose Dependent

The effect of estrogen on the gastric acid secretion and H+-transporting enzymes, K+ -ATPase and K+-phosphatase, were investigated in the rat. The maximum H+ secretory rate in response to 1 mM histamine was significantly reduced (P < 0.05) in both the isolated gastric mucosa obtained from the rats treated with estradiol in vivo for 7 days and the mucosa directly incubated in vitro with estradiol. The inhibitory effect on the gastric enzyme activities in vitro showed a dose-dependent pattern of a noncompetitive type. The result suggested that estradiol may have a direct action on the gastric H+ secretion by inhibiting the H+ transport enzyme activities.

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