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  1. Article: Adrenergic blocker terazosin potentially suppresses acetaminophen induced-acute liver injury in animal models via CYP2E1 gene.

    Hashmat, Zoya / Channa, Iffat Saeed / Safdar, Muhammad / Ozaslan, Mehmet / Saeed, Muhammad / Siddique, Faisal / Junejo, Yasmeen

    Toxicological research

    2022  Volume 38, Issue 3, Page(s) 323–330

    Abstract: Drug induced liver injury (DILI) is a global issue and acetaminophen (APAP) is considered as the main cause of this. Due to increasing incidents of DILI, current study attempted to investigate an alternative but better role of terazosin (alpha-adrenergic ...

    Abstract Drug induced liver injury (DILI) is a global issue and acetaminophen (APAP) is considered as the main cause of this. Due to increasing incidents of DILI, current study attempted to investigate an alternative but better role of terazosin (alpha-adrenergic blocker) in APAP-induced acute liver injury in an animal model using New Zealand rabbits. APAP (1 g/kg of body weight) was given to New Zealand rabbits either with or without terazosin (0.5 mg/kg) and serum was collected after 4 h. Serum alanine transaminase (ALT), alkaline phosphatase (ALP) and ferritin level were determined to analyze the liver functioning of treated rabbits. Furthermore, total cholesterol (TC), total lipids (TL), high-density lipoproteins (HDL), low-density lipoprotein (LDL) and triglycerides (TG) levels were estimated to find any change in lipid profile of the treated animals. Moreover, the urea and creatinine levels assayed the actual renal functionality. To identify any modification in gene expression, qPCR of cytochrome P2E1 (CYP2E1) was performed. Terazosin in combination with APAP enhanced liver functioning by reducing the levels of liver injury markers viz. ALP and ALT, while lipid profile was also lowered by down regulation of TC, TL, LDL and TG with enhanced HDL levels. It caused significant down regulation of expression level of CYP2E1. It is concluded that terazosin has better effects induced on the recovery of normal liver functioning, by improving the liver profile, lipid profile and renal functioning both at tissue and molecular levels.
    Language English
    Publishing date 2022-01-11
    Publishing country Singapore
    Document type Journal Article
    ZDB-ID 2727978-9
    ISSN 2234-2753 ; 1976-8257
    ISSN (online) 2234-2753
    ISSN 1976-8257
    DOI 10.1007/s43188-021-00116-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Alendronate and FTI-277 combination as a possible therapeutic approach for hepatocellular carcinoma: An in vitro study.

    Ilyas, Amber / Hashim, Zehra / Channa, Iffat Saeed / Zarina, Shamshad

    Hepatobiliary & pancreatic diseases international : HBPD INT

    2018  Volume 17, Issue 3, Page(s) 241–250

    Abstract: Background: An important product of mevalonate pathway is downstream synthesis of isoprenoid units that has long been implicated in development and progression of tumor. It has been speculated that inhibition of protein prenylation might be ... ...

    Abstract Background: An important product of mevalonate pathway is downstream synthesis of isoprenoid units that has long been implicated in development and progression of tumor. It has been speculated that inhibition of protein prenylation might be therapeutically beneficial. The objective of current study was to evaluate antitumor potential of a novel therapeutic combination of mevalonate pathway inhibitors, FTI-277 and alendronate. We also examined differentially expressed proteins in response to treatment using proteomics approach.
    Methods: Huh-7 cells were incubated with different concentrations of FTI-277 alone and in combination with alendronate. Differential protein and gene expression was examined through two dimensional gel electrophoresis and real-time quantitative polymerase chain reaction (qPCR), respectively. Proteins were identified using tandem mass spectrometry analysis.
    Results: Treatment of hepatocellular carcinoma (HCC) cell line with FTI-277 alone showed cell death in a time and dose dependent manner while in combination with alendronate, a synergistic apoptotic effect at 24 h was observed. Proteomic studies on the 20 µmol/L FTI-277 and 5 µmol/L alendronate +20 µmol/L FTI-277 treated cells revealed altered expression of different proteins including peroxiredoxin 2 (Prx2), glutathione S transferase 1 (GSTP1), Rho GTPase activating protein (RhoGAP), triosephosphate isomerase (TPI), and heat shock protein 60 (HSP60). Down-regulated expression of Prx2 and GSTP1 in treated cells was also confirmed by real-time qPCR analysis.
    Conclusions: Combined treatment of FTI-277 and alendronate on Huh-7 HCC cells showed cell death suggesting their anticancer potential. Such treatment approaches are likely to offer new therapeutic strategies.
    MeSH term(s) Alendronate/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Apoptosis/drug effects ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Electrophoresis, Gel, Two-Dimensional ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inhibitory Concentration 50 ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Methionine/analogs & derivatives ; Methionine/pharmacology ; Proteomics/methods ; Signal Transduction/drug effects ; Tandem Mass Spectrometry ; Time Factors
    Chemical Substances Biomarkers, Tumor ; FTI 277 ; Methionine (AE28F7PNPL) ; Alendronate (X1J18R4W8P)
    Language English
    Publishing date 2018-03-24
    Publishing country Singapore
    Document type Journal Article
    ZDB-ID 2241386-8
    ISSN 1499-3872
    ISSN 1499-3872
    DOI 10.1016/j.hbpd.2018.03.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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