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102 records – page 1 of 11.

7-Alkoxyquinoline O-dealkylation by microsomes from human liver and placenta.

https://arctichealth.org/en/permalink/ahliterature64902
Source
Br J Clin Pharmacol. 1992 Nov;34(5):415-20
Publication Type
Article
Date
Nov-1992
Author
J. Hakkola
J. Mäenpää
R T Mayer
S S Park
H V Gelboin
O. Pelkonen
Author Affiliation
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Source
Br J Clin Pharmacol. 1992 Nov;34(5):415-20
Date
Nov-1992
Language
English
Publication Type
Article
Keywords
Animals
Antibodies, Monoclonal - diagnostic use
Benzyl Compounds - metabolism
Cytochrome P-450 Enzyme System - antagonists & inhibitors - metabolism
Dealkylation
Female
Humans
In Vitro
Male
Mice
Mice, Inbred Strains
Microsomes - enzymology - metabolism
Microsomes, Liver - enzymology - metabolism
Placenta - enzymology - metabolism
Pregnancy
Quinolines - metabolism
Rats
Rats, Wistar
Research Support, Non-U.S. Gov't
Smoking - metabolism
Abstract
1. The O-dealkylation of seven 7-alkoxyquinoline derivatives by human hepatic and placental microsomes and the effect of maternal cigarette smoking on placental 7-alkoxyquinoline metabolism was studied. 2. None of several monoclonal antibodies to isoenzymes of cytochrome P450 had a clear effect on metabolism of the compounds by liver microsomes. 3. Maternal cigarette smoking induced the O-dealkylation of all of the 7-alkoxyquinoline derivatives, being greatest for 7-butoxy- and 7-benzyloxyquinoline. 4. Placental 7-alkoxyquinoline metabolism induced by smoking was partially inhibited by the monoclonal antibody 1-7-1 raised against 3-methylcholanthrene-induced rat liver P450. 5. None of the 7-alkoxyquinoline O-dealkylations could be assigned specifically to any known P450 isoenzyme in human liver or placenta.
PubMed ID
1467136 View in PubMed
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Aberrant iNOS signaling is under genetic control in rodent liver cancer and potentially prognostic for the human disease.

https://arctichealth.org/en/permalink/ahliterature92898
Source
Carcinogenesis. 2008 Aug;29(8):1639-47
Publication Type
Article
Date
Aug-2008
Author
Calvisi Diego F
Pinna Federico
Ladu Sara
Pellegrino Rossella
Muroni Maria R
Simile Maria M
Frau Maddalena
Tomasi Maria L
De Miglio Maria R
Seddaiu Maria A
Daino Lucia
Sanna Valeria
Feo Francesco
Pascale Rosa M
Author Affiliation
Department of Biomedical Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy.
Source
Carcinogenesis. 2008 Aug;29(8):1639-47
Date
Aug-2008
Language
English
Publication Type
Article
Keywords
Animals
Carcinoma, Hepatocellular - enzymology - epidemiology - genetics - pathology
Cell Line, Tumor
Genetic Predisposition to Disease
Humans
Incidence
Liver Neoplasms - enzymology - epidemiology - genetics - pathology
Male
Mice
Mice, Transgenic
Nitric Oxide Synthase Type II - genetics
Prognosis
Rats
Rats, Inbred BN
Rats, Inbred F344
Signal Transduction - physiology
Abstract
Mounting evidence underlines the role of inducible nitric oxide synthase (iNOS) in hepatocellular carcinoma (HCC) development, but its functional interactions with pathways involved in HCC progression remain uninvestigated. Here, we analyzed in preneoplastic and neoplastic livers from Fisher 344 and Brown Norway rats, possessing different genetic predisposition to HCC, in transforming growth factor-alpha (TGF-alpha) and c-Myc-TGF-alpha transgenic mice, characterized by different susceptibility to HCC, and in human HCC: (i) iNOS function and interactions with nuclear factor-kB (NF-kB) and Ha-RAS/extracellular signal-regulated kinase (ERK) during hepatocarcinogenesis; (ii) influence of genetic predisposition to liver cancer on these pathways and role of these cascades in determining a susceptible or resistant phenotype and (iii) iNOS prognostic value in human HCC. We found progressive iNos induction in rat and mouse liver lesions, always at higher levels in the most aggressive models represented by HCC of rats genetically susceptible to hepatocarcinogenesis and c-Myc-TGF-alpha transgenic mice. iNOS, inhibitor of kB kinase/NF-kB and RAS/ERK upregulation was significantly higher in HCC with poorer prognosis (as defined by patients' survival length) and positively correlated with tumor proliferation, genomic instability and microvascularization and negatively with apoptosis. Suppression of iNOS signaling by aminoguanidine led to decreased HCC growth and NF-kB and RAS/ERK expression and increased apoptosis both in vivo and in vitro. Conversely, block of NF-kB signaling by sulfasalazine or short interfering RNA (siRNA) or ERK signaling by UO126 caused iNOS downregulation in HCC cell lines. These findings indicate that iNOS cross talk with NF-kB and Ha-RAS/ERK cascades influences HCC growth and prognosis, suggesting that key component of iNOS signaling could represent important therapeutic targets for human HCC.
PubMed ID
18579559 View in PubMed
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Activation of constitutive androstane receptor under the effect of hepatocarcinogenic aminoazo dyes in mouse and rat liver.

https://arctichealth.org/en/permalink/ahliterature86237
Source
Bull Exp Biol Med. 2007 Sep;144(3):338-41
Publication Type
Article
Date
Sep-2007
Author
Pakharukova M Y
Smetanina M A
Kaledin V I
Kobzev V F
Romanova I V
Merkulova T I
Author Affiliation
Institute of Cytology and Genetics, Siberian Division of Russian Academy of Sciences, Novosibirsk. pmaria@yandex.ru
Source
Bull Exp Biol Med. 2007 Sep;144(3):338-41
Date
Sep-2007
Language
English
Publication Type
Article
Keywords
Animals
Coloring Agents - metabolism
Humans
Ligands
Liver Neoplasms - chemically induced
Male
Methyldimethylaminoazobenzene - metabolism
Mice
Rats
Rats, Wistar
Receptors, Cytoplasmic and Nuclear - genetics - metabolism
Transcription Factors - genetics - metabolism
o-Aminoazotoluene - metabolism
Abstract
Selective increase of DNA-binding activity of constitutive androstane receptor was detected in rat and mouse liver in response to aminoazo dyes exhibiting hepatocarcinogenic activity for these species (ortho-aminoazotoluene for mice and 3'-methyl-4-dimethylaminobenzene for rats). Competition of azo dyes with 3H-5alpha-androst-16-ene-3alpha-ol (a well-known ligand of constitutive androstane receptor) for binding to liver cell cytosol proteins was studied. Ortho-aminoazotoluene and 3'-methyl-4-dimethylaminobenzene were better competitors for cytosol proteins from mouse and rat liver, respectively.
PubMed ID
18457031 View in PubMed
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Activity and concentration of cathepsin B as prognostic criteria for the development of mouse LS lymphosarcoma and Lewis lung adenocarcinoma.

https://arctichealth.org/en/permalink/ahliterature18997
Source
Bull Exp Biol Med. 2002 Apr;133(4):392-5
Publication Type
Article
Date
Apr-2002
Author
T A Korolenko
S Ya Zhyanaeva
O N Poteryaeva
O V Falameeva
O A Levina
V I Kaledin
I. Shandula
Author Affiliation
Institute of Physiology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk. T.A.Korolenko@iph.ma.ru
Source
Bull Exp Biol Med. 2002 Apr;133(4):392-5
Date
Apr-2002
Language
English
Publication Type
Article
Keywords
Animals
Carcinoma, Lewis Lung - enzymology - pathology
Cathepsin B - metabolism
Liver - enzymology
Lymphoma, Diffuse - enzymology - pathology
Male
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
Prognosis
Spleen - enzymology
Tumor Markers, Biological - metabolism
Abstract
We measured activity and content of cathepsin B in tumor tissues, liver, and spleen in mice with Lewis adenocarcinoma and LS-lymphosarcoma. Cathepsin B activity in Lewis adenocarcinoma cells was lower than in LS-lymphosarcoma cells, which was probably related to differences in their metastatic properties. Antitumor therapy increased activity and content of cathepsin B in tumor tissues. Changes in the content and activity of cathepsin B in tumor tissues can serve as a prognostic criterion for tumor regression during therapy. Cathepsin B is probably involved in apoptosis of tumor cells during chemotherapy of lymphosarcoma-LS with cyclophosphamide.
PubMed ID
12124655 View in PubMed
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[Activity and induction of CYP2B, CYP2C, and CYP3A in tissues of cyclophosphane-sensitive and resistant neoplasms and the liver of neoplasm-carrying mice]

https://arctichealth.org/en/permalink/ahliterature18154
Source
Biomed Khim. 2003 Jan-Feb;49(1):27-34
Publication Type
Article
Author
A Iu Grishanov
V I Kaledin
T V Zueva
E K Nekhoroshkova
V P Nikolin
V V Liakhovich
Author Affiliation
Institute of Molecular Biology and Biophysics, Siberian Branch of Russian Academy of Medical Sciences, Timakova str., 2, Novosibirsk, 630117, Russia. agrish@cyber.ma.nsc.ru
Source
Biomed Khim. 2003 Jan-Feb;49(1):27-34
Language
Russian
Publication Type
Article
Keywords
Animals
Antineoplastic Agents - pharmacology - therapeutic use
Aryl Hydrocarbon Hydroxylases - biosynthesis - metabolism
Cyclophosphamide - pharmacology - therapeutic use
Cytochrome P-450 CYP2B1 - biosynthesis - metabolism
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - biosynthesis - metabolism
Drug Resistance, Neoplasm
English Abstract
Enzyme Induction
Liver Neoplasms - drug therapy - enzymology
Lymphoma, Diffuse - drug therapy - enzymology
Male
Mice
Mice, Inbred CBA
Microsomes - enzymology
Neoplasm Transplantation
Oxidoreductases, N-Demethylating - biosynthesis - metabolism
Abstract
The activities of three cytochrome P450 families involved in metabolic transformation of cyclophosphamide (CP) (CYP2B and CYP2C responsible for metabolic activation of CP and CYP3A responsible for inactivation of CP) have been investigated in lymphosarcoma and liver microsomes of tumor-bearing CBA mice. Two strains of mouse lymphosarcoma distinguished by their sensitivity to cytostatic action of CP were used in this study for implantation in mice femur muscle. There was certain relationship between CP resistance of lymphosarcoma and tumor P450s activity. CYP2B, CYP2C and CYP3A activities in the CP sensitive tumor were comparable to those in liver, and CYP2B, CYP2C were induced by phenobarbital and dexamethasone. CYP2B and CYP2C in the CP resistant tumor were inactive and only slightly induced by dexamethasone. CYP3A activity was lower than in LS tumor and unchanged during drug treatment. Implantation of LS and RLS tumor in mice caused different effects on P450 activities. LS insignificantly influenced liver CYP2B, CYP2C and CYP3A activities and their inducibility by phenobarbital and dexamethasone was similar to that obtained in liver of mice without tumor. At the same time, CYP2B and CYP2C activity in liver of RLS-bearing mice were essentially reduced, the activity CYP3A remained unchanged, and inducibility of CYP2B, CYP2C and CYP3A by phenobarbital and dexamethasone was similar to that in liver of mice without tumor. These results prove the role of cytochromes P450 activating CP in formation drug resistant phenotype of mice lymphosarcoma and suggest possibility of overcoming of this resistance using cytochrome P450 inducers.
PubMed ID
14569871 View in PubMed
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[Antioxidant properties of novel preparations--bioflavonoid derivatives and tannins]

https://arctichealth.org/en/permalink/ahliterature56645
Source
Eksp Klin Farmakol. 2001 Mar-Apr;64(2):55-9
Publication Type
Article
Author
L V Iakovleva
O A Gerasimova
I V Karbusheva
A K Ivakhnenko
N D Buniatian
T S Sakharova
Author Affiliation
Central Research Laboratory, Ukrainian Pharmaceutical Academy, ul. Pushkinskaya 53, Kharkov, 310002 Ukraine.
Source
Eksp Klin Farmakol. 2001 Mar-Apr;64(2):55-9
Language
Russian
Publication Type
Article
Keywords
Animals
Antioxidants - pharmacology
Carbon Tetrachloride Poisoning - metabolism
Cell Membrane
Ellagic Acid - pharmacology
English Abstract
Female
Flavonoids - pharmacology
Hepatitis, Toxic - metabolism
Hepatocytes - drug effects - ultrastructure
Lipid Peroxidation - drug effects
Liver - drug effects - metabolism - ultrastructure
Male
Mice
Rats
Tannins - pharmacology
Abstract
New medicinal plant preparations of polyphenol nature, representing the derivatives of bioflavonoids (piflamin) and ellagotannins (altan and ellagic acid) were experimentally studied. The drugs exhibited antioxidant properties, which were manifested by inhibition of a pathological lipid peroxidation, restoration of the functional activity of the antioxidant system components, and stabilization of the hepatocyte membranes.
PubMed ID
11548450 View in PubMed
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Antitumor activity of carcinoma-reactive BR96-doxorubicin conjugate against human carcinomas in athymic mice and rats and syngeneic rat carcinomas in immunocompetent rats.

https://arctichealth.org/en/permalink/ahliterature21930
Source
Cancer Res. 1997 Oct 15;57(20):4530-6
Publication Type
Article
Date
Oct-15-1997
Author
H O Sjögren
M. Isaksson
D. Willner
I. Hellström
K E Hellström
P A Trail
Author Affiliation
Department of Cell and Molecular Biology, University of Lund, Sweden.
Source
Cancer Res. 1997 Oct 15;57(20):4530-6
Date
Oct-15-1997
Language
English
Publication Type
Article
Keywords
Adenocarcinoma - drug therapy - pathology - secondary
Animals
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents - therapeutic use
Colonic Neoplasms - drug therapy - pathology
Doxorubicin - therapeutic use
Female
Humans
Immunotoxins - therapeutic use
Liver Neoplasms - drug therapy - pathology - secondary
Mice
Mice, Nude
Rats
Rats, Inbred BN
Research Support, Non-U.S. Gov't
Transplantation, Heterologous
Transplantation, Isogeneic
Tumor Cells, Cultured
Abstract
The internalizing monoclonal antibody BR96 was conjugated to the anticancer drug doxorubicin (DOX) using an acid-labile hydrazone bond to DOX and a thioether bond to the monoclonal antibody. The resulting conjugate, termed BR96-DOX, binds to a tumor-associated Lewis(y) antigen that is abundantly expressed on the surface of human carcinoma cells. BR96-DOX binds to RCA, a human colon carcinoma cell line, and BN7005, a transplantable colon carcinoma induced in a Brown Norway (BN) rat by 1,2-dimethyl-hydrazine. BR96-DOX produces cures of established s.c. RCA human colon carcinomas in athymic mice and rats. BR96-DOX also cured both s.c. and intrahepatic BN7005 tumors in immunocompetent BN rats. Unconjugated DOX, given at its maximum tolerated dose, and matching doses of nonbinding IgG-DOX conjugate were not active against RCA or BN7005 carcinomas. An anticonjugate antibody response was produced in BN rats treated with BR96-DOX. However, this could be largely prevented by administering the immunosuppressive drug deoxyspergualin. These results confirm the concept of antibody-directed therapy in models in which the targeted antigen is expressed both in normal tissues and tumors. The findings in BN7005 further demonstrate efficacy of BR96-DOX therapy in a model in which the tumor is syngeneic and the host is immunocompetent.
PubMed ID
9377565 View in PubMed
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Arctic berry extracts target the gut-liver axis to alleviate metabolic endotoxaemia, insulin resistance and hepatic steatosis in diet-induced obese mice.

https://arctichealth.org/en/permalink/ahliterature297424
Source
Diabetologia. 2018 04; 61(4):919-931
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Date
04-2018
Author
Fernando F Anhê
Thibault V Varin
Mélanie Le Barz
Geneviève Pilon
Stéphanie Dudonné
Jocelyn Trottier
Philippe St-Pierre
Cory S Harris
Michel Lucas
Mélanie Lemire
Éric Dewailly
Olivier Barbier
Yves Desjardins
Denis Roy
André Marette
Author Affiliation
Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, Laval University, Bureau Y4340, Québec City, QC, G1V 4G5, Canada.
Source
Diabetologia. 2018 04; 61(4):919-931
Date
04-2018
Language
English
Publication Type
Journal Article
Research Support, Non-U.S. Gov't
Keywords
Animals
C-Peptide - blood
Diet, High-Fat
Endotoxemia - metabolism
Fatty Liver - drug therapy - metabolism
Fruit - chemistry
Glucose - metabolism
Homeostasis
Insulin - blood - metabolism
Insulin Resistance
Intestines - drug effects
Liver - drug effects - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Obese
Obesity - metabolism
Plant Extracts - pharmacology
RNA, Ribosomal, 16S - genetics
Time Factors
Abstract
There is growing evidence that fruit polyphenols exert beneficial effects on the metabolic syndrome, but the underlying mechanisms remain poorly understood. In the present study, we aimed to analyse the effects of polyphenolic extracts from five types of Arctic berries in a model of diet-induced obesity.
Male C57BL/6 J mice were fed a high-fat/high-sucrose (HFHS) diet and orally treated with extracts of bog blueberry (BBE), cloudberry (CLE), crowberry (CRE), alpine bearberry (ABE), lingonberry (LGE) or vehicle (HFHS) for 8 weeks. An additional group of standard-chow-fed, vehicle-treated mice was included as a reference control for diet-induced obesity. OGTTs and insulin tolerance tests were conducted, and both plasma insulin and C-peptide were assessed throughout the OGTT. Quantitative PCR, western blot analysis and ELISAs were used to assess enterohepatic immunometabolic features. Faecal DNA was extracted and 16S rRNA gene-based analysis was used to profile the gut microbiota.
Treatment with CLE, ABE and LGE, but not with BBE or CRE, prevented both fasting hyperinsulinaemia (mean ± SEM [pmol/l]: chow 67.2?±?12.3, HFHS 153.9?±?19.3, BBE 114.4?±?14.3, CLE 82.5?±?13.0, CRE 152.3?±?24.4, ABE 90.6?±?18.0, LGE 95.4?±?10.5) and postprandial hyperinsulinaemia (mean ± SEM AUC [pmol/l?×?min]: chow 14.3?±?1.4, HFHS 31.4?±?3.1, BBE 27.2?±?4.0, CLE 17.7?±?2.2, CRE 32.6?±?6.3, ABE 22.7?±?18.0, LGE 23.9?±?2.5). None of the berry extracts affected C-peptide levels or body weight gain. Levels of hepatic serine phosphorylated Akt were 1.6-, 1.5- and 1.2-fold higher with CLE, ABE and LGE treatment, respectively, and hepatic carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 tyrosine phosphorylation was 0.6-, 0.7- and 0.9-fold increased in these mice vs vehicle-treated, HFHS-fed mice. These changes were associated with reduced liver triacylglycerol deposition, lower circulating endotoxins, alleviated hepatic and intestinal inflammation, and major gut microbial alterations (e.g. bloom of Akkermansia muciniphila, Turicibacter and Oscillibacter) in CLE-, ABE- and LGE-treated mice.
Our findings reveal novel mechanisms by which polyphenolic extracts from ABE, LGE and especially CLE target the gut-liver axis to protect diet-induced obese mice against metabolic endotoxaemia, insulin resistance and hepatic steatosis, which importantly improves hepatic insulin clearance. These results support the potential benefits of these Arctic berries and their integration into health programmes to help attenuate obesity-related chronic inflammation and metabolic disorders.
All raw sequences have been deposited in the public European Nucleotide Archive server under accession number PRJEB19783 ( https://www.ebi.ac.uk/ena/data/view/PRJEB19783 ).
PubMed ID
29270816 View in PubMed
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102 records – page 1 of 11.