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1.
Lipids Health Dis ; 14: 128, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26463841

RESUMO

BACKGROUND: This study investigated the possible roles of arginine (Arg) in ameliorating oxidative damage of intralipid (IL)-induced steatohepatitis (NASH). METHODS: NASH was induced in Sprague-Dawley rats by intravenous administration of 20 % IL for three weeks and then rats were pre- and post-treated with intraperitoneal injection of Arg for two weeks. Several biochemical parameters (blood and hepatic lipid peroxidation, glutathione, glutathione peroxidase and superoxide dismutase, hepatic cytochrome P450 2El monooxygenase (CYP2E1), nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and tumor necrosis factor-α "TNF-α") and liver histopathology were detected for rat groups. RESULTS: The administration of Arg either before or after IL significantly ameliorated uncontrolled elevation of TBARS content, CYP2E1 activity (0.32 ± 0.01 or 0.3 ± 0.02 IU/mg) and TNF-α level. These effects were associated with a significant increase in the levels of glutathione, activities of antioxidant enzymes, NO level (1.649 ± 0.047 or 1.957 ± 0.073 µmol/g) and activity of hepatic eNOS (0.05 ± 0.002 or 0.056 ± 0.002 IU/mg) compared to the IL-treated rats. Moreover, the injection of Arg in NASH-induced rats showed normal hepatocytes, no steatosis and no bile duct proliferation but mild inflammation in the group which received IL after Arg. CONCLUSIONS: These results proved that pre- and post-treatment with Arg blocked oxidative stress-induced NASH by inhibiting CYP2E1 activity, decreasing TNF- α level and restoration activities of eNOS and antioxidant enzymes as well as glutathione level. This antioxidant effect of Arg leads to reverse signs of liver pathology of NASH with amelioration of liver and kidney functions.


Assuntos
Antioxidantes/farmacologia , Arginina/farmacologia , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Substâncias Protetoras/farmacologia , Animais , Citocromo P-450 CYP2E1/metabolismo , Emulsões , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Injeções Intraperitoneais , Injeções Intravenosas , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Fosfolipídeos , Ratos , Ratos Sprague-Dawley , Óleo de Soja , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
Saudi Med J ; 35(12): 1482-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25491213

RESUMO

OBJECTIVES: To produce an effective recombinant streptokinase (rSK) from pathogenic Streptococcus pyogenes isolate in yeast, and evaluate its potential for thrombolytic therapy. METHODS: This study was conducted from November 2012 to December 2013 at King Khalid University, Abha, Kingdom of Saudi Arabia (KSA). Throat swabs collected from 45 pharyngitis patients in Asser Central Hospital, Abha, KSA were used to isolate Streptococcus pyogenes. The bacterial DNA was used for amplification of the streptokinase gene (1200 bp). The gene was cloned and in vitro transcribed in an eukaryotic expression vector that was transformed into yeast Pichia pastoris SMD1168, and the rSK protein was purified and tested for its thrombolytic activity. RESULTS: The Streptococcus pyogenes strain was isolated and its DNA nucleotide sequence revealed similarity to other Streptococcus pyogenes in the Gene bank. Sequencing of the amplified gene based on DNA nucleotide sequence revealed a SK gene closely related to other SK genes in the Gene bank. However, based on deduced amino acids sequence, the gene formed a separate cluster different from clusters formed by other examined genes, suggesting a new bacterial isolate and accordingly a new gene. The purified protein showed 82% clot lysis compared to a commercial SK (81%) at an enzyme concentration of 2000 U/ml. CONCLUSION: The present yeast rSK showed similar thrombolytic activity in vitro as that of a commercial SK, suggesting its potential for thrombolytic therapy and large scale production. 


Assuntos
Fibrinolíticos/farmacologia , Pichia , Streptococcus pyogenes/genética , Estreptoquinase/biossíntese , Terapia Trombolítica , Tempo de Lise do Coágulo de Fibrina , Vetores Genéticos , Humanos , Faringite/microbiologia , Proteínas Recombinantes/biossíntese , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/isolamento & purificação , Estreptoquinase/genética , Estreptoquinase/farmacologia , Trombina/efeitos dos fármacos
3.
J Biochem Mol Biol ; 36(5): 499-504, 2003 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-14536034

RESUMO

There has been increasing interest in studying the various effects of organophosphate insecticides in humans and experimental animals. Only a few data are available on the effect of the organophosphate insecticide, diazinon, on lipid metabolism. The aim of this study was to evaluate the effect of diazinon on plasma lipid constituents in mammalian animals. The plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and phospholipids (PL) were measured in albino rats that were orally treated with a single dose of diazinon at a level of LD(50) or with repeated daily doses at the levels of 1/2, 1/8, and 1/32 LD(50) for 2, 8, and 32 days, respectively. After a 24 h post-treatment with a single LD(50) dose of diazinon, TC was not significantly changed, the HDL-C and PL levels were significantly decreased, but the LDL-C and TG levels were significantly increased. Separate daily oral administrations of diazinon at 1/2 LD(50), 1/8 LD(50), and 1/32 LD(50) doses resulted in a significant decrease in HDL-C and PL, with no significant change in TG. The LDL-C levels were significantly increased and TC showed no significant change with 1/2 LD(50) and 1/32 LD(50) doses of diazinon, whereas a significant decrease in the levels of TC, HDL-C, as well as LDL-C, was observed with the 1/8 LD(50) dose. These data suggest that diazinon may interfere with lipid metabolism in mammals.


Assuntos
Diazinon/farmacologia , Inseticidas/farmacologia , Lipídeos/sangue , Animais , Ratos
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