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1.
China Journal of Chinese Materia Medica ; (24): 412-417, 2020.
Article Dans Chinois | WPRIM | ID: wpr-1008352

Résumé

The bilirubin metabolism mediated by the phase Ⅱ metabolizing enzyme UGT1A1 in the liver was evaluated to study the potential hepatotoxicity risk based on investigation on the inhibitory effect of rhein and its metabolites on the UGT1A1 enzyme in Rhei Radix et Rhizoma. Firstly, in vitro liver microsomes incubation was used to initiate the phase Ⅱ metabolic reaction to investigate the inhibitory effect of rheinon UGT1A1 enzyme. Secondly, the phase Ⅰ and phase Ⅱ metabolic reactions were initiated to investigate the hepatotoxicity risk of rhein metabolites. It was found that the rhein and its phase Ⅱ metabolites had no significant inhibitory effect on UGT1A1 enzyme, but its phase Ⅰ metabolites significantly reduced UGT1A1 enzyme activity. Based on the metabolites analysis, it is speculated that the rhein phase Ⅰ metabolite rheinhydroxylate and its tautomers have certain hepatotoxicity risks, while the toxicity risk induced by the prototype and phase Ⅱ metabolites of rheinglucoside, rheinglucuronic acid and rhein sulfate is small.


Sujets)
Humains , Anthraquinones/toxicité , Lésions hépatiques dues aux substances , Médicaments issus de plantes chinoises/toxicité , Glucuronosyltransferase/métabolisme , Foie/enzymologie , Microsomes du foie/effets des médicaments et des substances chimiques , Rhizome
2.
China Journal of Chinese Materia Medica ; (24): 4043-4047, 2019.
Article Dans Chinois | WPRIM | ID: wpr-1008324

Résumé

The purpose of this study was to investigate the effect of apigenin on UGT1 A1 enzyme activity and to predict the potential drug-drug interaction of apigenin in clinical use. First,on the basis of previous experiments,the binding targets and binding strength of apigenin to UGT1 A1 enzyme were predicted by computer molecular docking method. Then the inhibitory effect of apigenin on UGT1 A1 enzyme was evaluated by in vitro human liver microsomal incubation system. Molecular docking results showed that apigenin was docked into the active region of UGT1 A1 enzyme protein F,consistent with the active region of bilirubin docking,with moderate affinity. Apigenin flavone mother nucleus mainly interacted with amino acid residues ILE343 and VAL345 to form hydrophobic binding Pi-Alkyl. At the same time,the hydroxyl group on the mother nucleus and the amino acid residue LYS346 formed an additional hydrogen bond,which increased the binding of the molecule to the protein. These results suggested that the flavonoid mother nucleus structure had a special structure binding to the enzyme protein UGT1 A1,and the introduction of hydroxyl groups into the mother nucleus can increase the binding ability. In vitro inhibition experiments showed that apigenin had a moderate inhibitory effect on UGT1 A1 enzyme in a way of competitive inhibition,which was consistent with the results of molecular docking. The results of two experiments showed that apigenin was the substrate of UGT1 A1 enzyme,which could inhibit the activity of UGT1 A1 enzyme competitively,and there was a risk of drug interaction between apigenin and UGT1 A1 enzyme substrate in clinical use.


Sujets)
Humains , Apigénine/composition chimique , Bilirubine/composition chimique , Interactions médicamenteuses , Glucuronosyltransferase/métabolisme , Liaison hydrogène , Microsomes du foie/effets des médicaments et des substances chimiques , Simulation de docking moléculaire
3.
Bol. latinoam. Caribe plantas med. aromát ; 16(2): 88-98, mar. 2017. tab, graf
Article Dans Anglais | LILACS | ID: biblio-881315

Résumé

Inflammation is a cellular defensive mechanism associated to oxidative stress. The administration of nitrofurantoin, nifurtimox and acetaminophen generates oxidative stress by their biotransformation through CYP450 system. The main adverse effect described for the first two drugs is gastrointestinal inflammation and that of the last, hepatitis. Therefore, standardised dry extracts from Rosmarinus officinalis, Buddleja globosa Hope, Cynara scolymus L., Echinacea purpurea and Hedera helix were tested to evaluate their capacity to decrease drug-induced oxidative stress. For that, rat liver microsomes were incubated with drugs in the presence of NADPH (specific CYP450 system cofactor) to test oxidative damage on microsomal lipids, thiols, and GST activity. All drugs tested induced oxidation of microsomal lipids and thiols, and inhibition of GST activity. Herbal extracts prevented these phenomena in different extension. These results show that antioxidant phytodrugs previously evaluated could alleviate drugs adverse effects associated to oxidative stress.


Inflamación es un mecanismo de defensa el cual está asociado a estrés oxidativo. La administración de nitrofurantoína, nifurtimox y paracetamol genera estrés oxidativo al metabolizarse a través del sistema CYP450. El principal efecto adverso de los dos primeros fármacos es inflamación gastrointestinal y del tercero, hepatitis. Por lo tanto, utilizamos diversos extractos herbales para disminuir el estrés oxidativo inducido por estos fármacos. Para esto se incubaron microsomas hepáticos de rata con dichos fármacos en presencia de NADPH (cofactor específico del sistema CYP450) y se evaluó el daño oxidativo generado sobre los lípidos, los tioles y la actividad GST microsómica. Todos los fármacos indujeron oxidación de los lípidos y los tioles microsómicos e inhibieron la actividad GST. Los extractos herbales previnieron estos fenómenos oxidativos en diferente extensión. Estos resultados indican que fitofármacos antioxidantes previamente evaluados, podrían aliviar los efectos adversos asociados a estrés oxidativo de los fármacos.


Sujets)
Animaux , Mâle , Antioxydants/pharmacologie , Microsomes du foie/effets des médicaments et des substances chimiques , Stress oxydatif/effets des médicaments et des substances chimiques , Extraits de plantes/pharmacologie , Acétaminophène/effets indésirables , Glutathione transferase/métabolisme , Peroxydation lipidique , Microsomes du foie/enzymologie , NADP/analyse , Nifurtimox/effets indésirables , Nitrofurantoïne/effets indésirables , Extraits de plantes/composition chimique , Polyphénols/analyse , Rat Sprague-Dawley , Thiols
5.
Rev. bras. enferm ; 67(6): 972-978, Nov-Dec/2014. tab, graf
Article Dans Portugais | LILACS, BDENF | ID: lil-732826

Résumé

Estudo descritivo cujos objetivos foram elaborar títulos diagnósticos de enfermagem segundo a CIPE®, realizar mapeamento cruzado entre as formulações diagnósticas e os títulos diagnósticos da NANDA-I, identificar dentre os títulos diagnósticos formulados os constantes e não constantes na NANDA-I e realizar mapeamento dos títulos formulados com as Necessidades Humanas Básicas. Utilizou-se técnica de oficina, com 32 enfermeiros de unidades de terapia intensiva, de mapeamento cruzado e de validação por concordância com peritos. Na oficina foram elaborados 1.665 títulos diagnósticos submetidos a processo de refinamento que resultou em 120 títulos, submetidos a mapeamento cruzado com títulos diagnósticos da NANDA-I e com as necessidades humanas básicas. Os produtos do mapeamento foram submetidos à validação de conteúdo por dois enfermeiros peritos, obtendo-se índices de concordância de 92% e 100%. Constatou-se que 63 títulos constavam na NANDA-I e 47 não.


This descriptive study aimed at elaborating nursing diagnostic labels according to ICNP®; conducting a cross-mapping between the diagnostic formulations and the diagnostic labels of NANDA-I; identifying the diagnostic labels thus obtained that were also listed in the NANDA-I; and mapping them according to Basic Human Needs. The workshop technique was applied to 32 intensive care nurses, the cross-mapping and validation based on agreement with experts. The workshop produced 1665 diagnostic labels which were further refined into 120 labels. They were then submitted to a cross-mapping process with both NANDA-I diagnostic labels and the Basic Human Needs. The mapping results underwent content validation by two expert nurses leading to concordance rates of 92% and 100%. It was found that 63 labels were listed in NANDA-I and 47 were not.


Estudio descriptivo cuyos objetivos fueron la elaboración de etiquetas de diagnósticos de enfermería según la CIPE®, para llevar a cabo lo mapeo cruzado entre el diagnóstico formulado y las etiquetas de los diagnósticos NANDA-I, para identificar entre los títulos de diagnósticos formulados los que eran constantes y no constantes en NANDA-I y asignarlos a las necesidades humanas básicas. Fueron conducidas técnica de oficina con 32 enfermeros de las unidades de cuidados intensivos, mapeo cruzado y validación de acuerdo con los expertos. Se elaboró 1665 títulos diagnósticos en la oficina sometidos a un proceso de refinamiento. El resultado fue de 120 títulos que se presentaron a un proceso de mapeo con los títulos de diagnósticos de la NANDA-I y con las necesidades humanas básicas. Validación de contenido se realizó con los productos de lo mapeo por dos enfermeras expertas y las tasas de concordancia del 92% y 100% fueron obtenidas. Se encontró que 63 títulos estaban contenidos en la NANDA-I y 47 no lo hicieron.


Sujets)
Animaux , Mâle , Rats , Malonates/métabolisme , Microsomes du foie/métabolisme , Toluène/analogues et dérivés , Phénomènes chimiques , Chimie , Relation dose-effet des médicaments , Chromatographie gazeuse-spectrométrie de masse , Glucuronates/métabolisme , Injections veineuses , Microsomes du foie/effets des médicaments et des substances chimiques , Lignées consanguines de rats , Toluène/administration et posologie , Toluène/métabolisme , Xénobiotique
6.
Indian J Exp Biol ; 2007 Nov; 45(11): 959-67
Article Dans Anglais | IMSEAR | ID: sea-59263

Résumé

Aqueous extract of Andrographis paniculata was examined for antioxidant activity using rat liver subcellular organelles as model systems. The study deals with two important biological oxidative agents, ascorbate-Fe(+2) and AAPH generating hydroxyl and peroxyl radical, respectively. Oxidative damage was examined against the inhibition of membrane peroxidation, protein oxidation and restoration in decreased SOD and catalase activity. The antimutagenic activity of Ap was examined following inhibition in AAPH induced strand breaks in plasmid pBR322 DNA. Extract was a potent scavenger of DPPH, ABTS radicals, exemplified by ESR signals, O2-*, *OH and H2O2, displayed excellent reducing power, FRAP potentials to reduce Fe (III) --> Fe (II) and had considerable amount of phenolics/ flavonoids contents, an effective antioxidant index. The observed antioxidant effect might be primarily due to its high scavenging ability for ROS. Effect was confirmed ex vivo following inhibition in peroxidation, restoration in SOD enzyme, SOD band intensity and protein degradation in Ap fed liver homogenate. Based on these results, it was concluded that the aqueous extract of Andrographis paniculata might emerge as a potent antiradical agent against various pathophysiological oxidants.


Sujets)
Amidines/pharmacologie , Andrographis/composition chimique , Animaux , Acide ascorbique/pharmacologie , Altération de l'ADN , Femelle , Piégeurs de radicaux libres/pharmacologie , Radicaux libres/métabolisme , Foie/cytologie , Souris , Microsomes du foie/effets des médicaments et des substances chimiques , Oxydants/pharmacologie , Stress oxydatif/effets des médicaments et des substances chimiques , Extraits de plantes/pharmacologie , Rats , Rat Wistar , Fractions subcellulaires/effets des médicaments et des substances chimiques
7.
Indian J Exp Biol ; 2007 Aug; 45(8): 702-11
Article Dans Anglais | IMSEAR | ID: sea-59507

Résumé

The ethyl ether extract of A. vulgaris inhibited in vitro microsomal lipid peroxidation (IC50 58.8 microg/ml) and showed moderate ability to scavenge superoxide radicals and to chelate iron ions. The extract (100 mg/kg body weight, po) decreased uninduced and enzymatic microsomal lipid peroxidation in the liver of male rats pretreated with CCl4 (1 ml/kg body weight) by 27 and 40%, respectively. Activity of antioxidant and related enzymes (catalase and glucose-6-phosphate dehydrogenase) inhibited by CCl4 was significantly restored after administration of the extract. The extract itself significantly enhanced superoxide dismutase activity. There was no effect of the extract on hepatic glutathione level and cytochrome P450 content, both were decreased by CCl4. Neither CCl4 nor the tested extract affected activities of NADPH-cytochrome P450 reductase and two monooxygenases, aniline hydroxylase and aminopyrine n-demethylase. It can be concluded that the protective effect of the A. vulgaris extract in CCl4-induced liver injury is mediated by inhibition of microsomal lipid peroxidation and restoring activity of some antioxidant and related enzymes.


Sujets)
Animaux , Ancolie commune/composition chimique , Tétrachloro-méthane/antagonistes et inhibiteurs , Oxyde de diéthyle/composition chimique , Piégeurs de radicaux libres/pharmacologie , Concentration inhibitrice 50 , Peroxydation lipidique/effets des médicaments et des substances chimiques , Maladies du foie/induit chimiquement , Mâle , Microsomes du foie/effets des médicaments et des substances chimiques , Stress oxydatif/effets des médicaments et des substances chimiques , Oxidoreductases/métabolisme , Extraits de plantes/pharmacologie , Rats
8.
Hindustan Antibiot Bull ; 2005-2006; 47-48(): 13-9
Article Dans Anglais | IMSEAR | ID: sea-2280

Résumé

The effect of Picroliv on hepatic microsomal mixed-function oxidases (MFO) and glutathione conjugating enzyme system in cholestatic rats was studied. Bile duct ligation in male rats for one weeks caused significant increase in both serum sorbitol dehydrogenase activity and serum bile acide concentration indicating cholestatic liver injury. Furthermore, a rise in the hepatic hydroxyproline level indicating collagen accumulation was observed. As a result of these alterations, the hepatic microsomal MFO system was imparied as evidenced by a decrease in cytochrome P-450 system content and in the activities of NADPH-cytochrome C reductase and aminopyrine demethylase. While the hepatic glutathione content remained unaffected, the cytosolic glutathione S-transferase activity was clearly suppressed due to subchronic cholestasis. Oral administration of Picroliv (25 mg/kg/day for 21 days)--a standardized irioid glycoside fraction of Picrorhiza kurroa in bile ligation induced cholestatic rats, singnificantly prevented the biochemical changes induced in liver and serum of cholestatic rats. These results suggested that picroliv has anti-cholestatic activity which may be attributed to antioxidant property or it's specific role in protein synthesis.


Sujets)
Animaux , Antioxydants/métabolisme , Cholestase/enzymologie , Cinnamates/administration et posologie , Glutathion/analyse , Hétérosides/administration et posologie , Mâle , Microsomes du foie/effets des médicaments et des substances chimiques , Mixed function oxygenases/effets des médicaments et des substances chimiques , Rats , Acide vanillique/administration et posologie
9.
Indian J Exp Biol ; 2004 Apr; 42(4): 373-7
Article Dans Anglais | IMSEAR | ID: sea-61773

Résumé

Cashew nut shell oil has been reported to possess tumour promoting property. Therefore an attempt has been made to study the modulatory effect of cashew nut (Anlacardium occidentale) kernel oil on antioxidant potential in liver of Swiss albino mice and also to see whether it has tumour promoting ability like the shell oil. The animals were treated orally with two doses (50 and 100 microl/animal/day) of kernel oil of cashew nut for 10 days. The kernel oil was found to enhance the specific activities of SOD, catalase, GST, methylglyoxalase I and levels of GSH. These results suggested that cashew nut kernel oil had an ability to increase the antioxidant status of animals. The decreased level of lipid peroxidation supported this possibility. The tumour promoting property of the kernel oil was also examined and found that cashew nut kernel oil did not exhibit any solitary carcinogenic activity.


Sujets)
7,12-Diméthyl-benzo[a]anthracène/toxicité , Anacardium/composition chimique , Animaux , Antioxydants/métabolisme , Cancérogènes/toxicité , Catalase/métabolisme , Femelle , Glutathion/métabolisme , Glutathione transferase/métabolisme , Lactoyl glutathione lyase/métabolisme , Foie/effets des médicaments et des substances chimiques , Souris , Microsomes du foie/effets des médicaments et des substances chimiques , Noix/composition chimique , Papillome/induit chimiquement , Huiles végétales/pharmacologie , Tumeurs cutanées/induit chimiquement , Superoxide dismutase/métabolisme
10.
Braz. j. med. biol. res ; 33(1): 85-90, Jan. 2000. tab
Article Dans Anglais | LILACS | ID: lil-252261

Résumé

The effect of D002, a defined mixture of higher primary alcohols purified from bee wax, on in vivo and in vitro lipid peroxidation was studied. The extent of lipid peroxidation was measured on the basis of the levels of thiobarbituric acid reactive substances (TBARS). When D002 (5-100 mg/kg body weight) was administered orally to rats for two weeks, a partial inhibition of the in vitro enzymatic and non-enzymatic lipid peroxidation was observed in liver and brain microsomes. Maximal protection (46 percent) occurred at a dose of 25 mg/kg. D002 behaved differently depending on both the presence of NADPH and the integrity of liver microsomes, which suggests that under conditions where microsomal metabolism was favored the protective effect of D002 was increased. D002 (25 mg/kg) also completely inhibited carbon tetrachloride- and toluene-induced in vivo lipid peroxidation in liver and brain. Also, D002 significantly lowered in a dose-dependent manner the basal level of TBARS in liver (19-40 percent) and brain (28-44 percent) microsomes. We conclude that the oral administration of D002 (5, 25 and 100 mg/kg) for two weeks protected rat liver and brain microsomes against microsomal lipid peroxidation in vitro and in vivo. Thus, D002 could be useful as a dietary natural antioxidant supplement. More studies are required before these data can be extrapolated to the recommendation for the use of D002 as a dietary antioxidant supplement for humans


Sujets)
Animaux , Mâle , Rats , Alcools gras/pharmacologie , Peroxydation lipidique/effets des médicaments et des substances chimiques , Microsomes/effets des médicaments et des substances chimiques , Encéphale/métabolisme , Encéphale/ultrastructure , Alcools gras/administration et posologie , Microsomes du foie/effets des médicaments et des substances chimiques , Microsomes du foie/métabolisme , Microsomes/métabolisme , Rat Wistar , Substances réactives à l'acide thiobarbiturique/analyse
11.
Biol. Res ; 33(2): 159-165, 2000. graf
Article Dans Anglais | LILACS | ID: lil-443666

Résumé

The antioxidant ability of nitric oxide (NO) generated by a chemical donor and of commercially available antioxidant preparations was assayed. SNAP (S-Nitroso-N-acetylpenicilamine) was used as the NO donor, and Ginkgo biloba, wheat and alfalfa preparations were tested. Lipid peroxidation was assayed by EPR employing a reaction system consisting of rat liver microsomes, ADP, FeCl3, NADPH and POBN in phosphate buffer, pH=7.4. In vitro NO exposure decreased microsomal lipid peroxidation in a dose-dependent manner. The dose responsible for inhibiting the microsomal content of lipid radical adducts by 50% (LD50) for SNAP was 550 microM (NO generation rate 0.1 microM/min). The addition of 50 microM hemoglobin to the incubation media prevented NO effect on lipid peroxidation. The addition of an amount of the antioxidant preparations equivalent to the LD50 doses inhibited lipid peroxidation by 21, 15, and 33% for wheat, alfalfa, ginkgo biloba preparations respectively in the presence of 550 microM SNAP. We detected a decrease in the content of lipid radical adducts after simultaneous supplementation, although it was less than 50%, even when LD50 doses of the products were added. This suggests that NO and the natural antioxidants inhibit lipid peroxidation by a mechanism that has both common and non-shared features.


Sujets)
Animaux , Mâle , Rats , Antioxydants/pharmacologie , Donneur d'oxyde nitrique/pharmacologie , Microsomes du foie/effets des médicaments et des substances chimiques , Peroxydation lipidique/effets des médicaments et des substances chimiques , N-Acétyl-S-nitroso-pénicillamine/pharmacologie , Extraits de plantes/pharmacologie , Ginkgo biloba , Dose létale 50 , Medicago sativa , Microsomes du foie/métabolisme , Rat Wistar , Piégeage de spin , Triticum
12.
Indian J Exp Biol ; 1999 Oct; 37(10): 1025-6
Article Dans Anglais | IMSEAR | ID: sea-62096

Résumé

Administration of CCl4 to normal rats and consequent oral feeding with ellagic acid (50 mg/kg) provided a significant protection against the biochemical alterations in serum and liver produced by CCl4. In vitro experiments showed that liver microsomes from animals treated with ellagic acid and CCl4, decreased lipid peroxidation compared to microsome prepared from rats exposed to CCl4 alone.


Sujets)
Animaux , Antioxydants/pharmacologie , Tétrachloro-méthane/toxicité , Acide ellagique/pharmacologie , Peroxydation lipidique/effets des médicaments et des substances chimiques , Foie/effets des médicaments et des substances chimiques , Mâle , Microsomes du foie/effets des médicaments et des substances chimiques , Rats
13.
Indian J Biochem Biophys ; 1998 Jun; 35(3): 179-83
Article Dans Anglais | IMSEAR | ID: sea-28358

Résumé

A quantitative structure-activity relationship (QSAR) analysis of 4,5-diphenyl-2-(substituted thio)-1H-imidazoles as the potential inhibitors of acyl CoA: cholesterol acyltransferase is presented with a view to reflect upon the parametric requirement of various substitutions. For this purpose the van der Waals volume, Vw which is the measure of molecular bulk/size of substituents present at R1- and R2-positions has emerged as the befitting correlative parameter. A number of correlations obtained amongst different subclasses of the title compounds have helped in ascertaining the relative importance of X-substituents and the role of Vw(R1) and Vw(R2). Finally, a significant correlation between the sum of van der Waals volume of R1- and R2-substituents, sigma Vw and biological activities of the entire series was also derived. From the resulting parabolic QSAR equation, an optimum molecular bulk of 1.846 x 10(2) A3 leading to the highest potent compound of the series, specially among those congeners which have X = -NH-, was predicted. This finding has, therefore, hinted at the existence of a cavity, capable of accommodating the maximum steric bulk, on to the receptor.


Sujets)
Animaux , Conception de médicament , Antienzymes/composition chimique , Imidazoles/composition chimique , Microsomes du foie/effets des médicaments et des substances chimiques , Rats , Sterol O-acyltransferase/métabolisme , Relation structure-activité , Urée/analogues et dérivés
14.
Indian J Exp Biol ; 1997 Oct; 35(10): 1125-7
Article Dans Anglais | IMSEAR | ID: sea-61777

Résumé

Two vitamin A2 compounds (3-dehydroretinol and 3-dehydroretinyl palmitate) which are predominantly present in fresh water fish have been found to be very effective in inhibiting the microsome catalysed formation of DNA adduct by the carcinogen aflatoxin B1. The inhibition appears to be due to modulation of microsomal enzymes which activate the carcinogen. Such inhibition may suggest a potential chemopreventive role of these compounds against carcinogenesis induced by aflatoxin B1.


Sujets)
Aflatoxine B1/antagonistes et inhibiteurs , Animaux , Cancérogènes/antagonistes et inhibiteurs , Microsomes du foie/effets des médicaments et des substances chimiques , Rats , Rétinol/analogues et dérivés
15.
Indian J Exp Biol ; 1997 Jan; 35(1): 46-9
Article Dans Anglais | IMSEAR | ID: sea-59845

Résumé

Phenobarbital (PB; 80 mg/kg, ip) or 3-methylcholantrene (3-MC; 20 mg/kg, ip) was administered to Wistar male rats at the end of the feeding period of 30 days and the effects of food restriction (FR) and FR followed by inducer treatment on hepatic drug metabolizing enzymes, microsomal electron transport components, NADPH dependent lipid peroxidation and glutathione-s-transferase activities were studied. In both, PB and 3-MC treatment, the magnitude of increase in microsomal protein content, cytochrome b5 and aminopyrine N-demethylase (APND) activity was less in FR animals than in ad libitum fed; while cytochrome P-450 levels and activities of cytochrome c reductase and acetanilide hydroxylase (ACOH) were higher in FR animals. NADPH dependent lipid peroxidation and cytosolic glutathione-s-transferase activity were also enhanced due to PB and 3-MC treatment but the magnitude of increase was less in FR animals. The ACOH activity increased to a greater extent than APND activity in FR animals following PB and 3-MC treatment. It is suggested that the response to inducers in the FR animals differ from that in the ad libitum fed rats.


Sujets)
Animaux , Induction enzymatique , Privation alimentaire , Mâle , 1,2-Dihydro-méthyl-benzo[j]acéanthrylène/pharmacologie , Microsomes du foie/effets des médicaments et des substances chimiques , Mixed function oxygenases/biosynthèse , Phénobarbital/pharmacologie , Rats , Rat Wistar
16.
Indian J Biochem Biophys ; 1996 Oct; 33(5): 377-83
Article Dans Anglais | IMSEAR | ID: sea-28351

Résumé

The effect of Ca2+ on kinetics and thermodynamics of lipid peroxidation in microsomes prepared from liver of male Swiss albino mice (7-8 weeks old) was studied. Ca2+ was found to increase the Vmax in temperature dependent manner. Michaelis-Menten constant (Km) also increased with temperature. However, the linearity and extent of change in Km remained unaffected in presence of Ca2+, and was suggestive of non-competitive and mixed type of activation. The activation constant (Ka) obtained by the replotting of slopes of the Lineweaver-Burk plots against the reciprocal of Ca2+ concentration showed linear variation with temperature. The linear pattern of Arrhenius plots indicated non-involvement of parallel reactions of other intermediate species in the lipid peroxidation. Thermodynamic parameters delta H degree, delta S degree and delta G degree, associated with lipid peroxidation process were studied. The positive value of delta H degree is suggestive of the endothermic nature of the process. It appears that the NADPH induced lipid peroxidation is an entropy driven process.


Sujets)
Animaux , Calcium/pharmacologie , Cinétique , Peroxydation lipidique/effets des médicaments et des substances chimiques , Mâle , Souris , Microsomes du foie/effets des médicaments et des substances chimiques , NADP/métabolisme , NADPH-ferrihemoprotéine reductase/métabolisme , Thermodynamique
17.
Indian J Exp Biol ; 1996 Oct; 34(10): 1010-4
Article Dans Anglais | IMSEAR | ID: sea-59653

Résumé

Effect of 6-MFA (sixth mycelial fraction of acetone), an interferon inducer obtained from fungus A. ochraceus on hepatic mixed function oxidase system (MFO) of rat has been investigated. Treatment with 6-MFA, 100 mg/kg/day, ip for 1-5 days to adult rats inhibited significantly the different indices of MFO system, viz. hepatic cytochrome P-450, cytochrome b5 content, cytochrome c reductase, aminopyrine-N-demethylase and acetanilide hydroxylase activities. Similar treatment for 3 days in young growing rats significantly inhibited MFO system's components except acetanilide hydroxylase activity which showed marked elevation. These effects seem to be specific as in vitro experiments suggested that 6-MFA does not compete with subsdtrates nor it acts as a sponge reacting with the end product to give false inhibitory effect. It is concluded from the present study that 6-MFA like other interferon inducers depresses MFO system in rats. Its possible clinical implications are discussed.


Sujets)
Animaux , Aspergillus ochraceus , Antienzymes/toxicité , Protéines fongiques/isolement et purification , Inducteurs de l'interféron/isolement et purification , Mâle , Microsomes du foie/effets des médicaments et des substances chimiques , Mixed function oxygenases/antagonistes et inhibiteurs , Rats
18.
Indian J Biochem Biophys ; 1995 Oct; 32(5): 272-8
Article Dans Anglais | IMSEAR | ID: sea-26773

Résumé

The dependence of microsomal glucose-6-phosphatase (G-6-Pase) activity on Ca2+ as well as the membrane lipid microviscosity was studied by the effect of Ca(2+)-channel blockers (namely verapamil and nifedipine), Ca(2+)-ionophore, A23187 and pyrene excimer formation. Channel blockers depressed the G-6-Pase and Ca(2+)-ATPase while the ionophore increased these activities. Dimethyl sulfoxide, a known membrane surface active agent showed no change. Ca(2+)-uptake into the membrane has expectedly been lowered by the channel blockers while the ionophores facilitated the ion flux. Excimer formation of the fluorescent probe, pyrene as an indicator of increased membrane fluidity, and microviscosity calculated from there on, showed that Ca(2+)- and lipid microenvironment in the membrane significantly influenced the activity of G-6-Pase. Membrane lipid composition such as phospholipid/cholesterol molar ratio which also indicates an increased membrane fluidity is markedly increased with the ionophore but decreased with the channel blockers, while protein/phospholipid ratio remained unchanged. Microsomal G-6-Pase is a multicomponent multifunctional protein. It is argued that Ca2+ may play the role of an obligatory cofactor not only for the hydrolysis of G-6-P (catalytic part of the enzyme) but also involved in the regulation of substrate and product transport in or out of the endoplasmic reticulum lumen.


Sujets)
Animaux , A-23187/pharmacologie , Inhibiteurs des canaux calciques/pharmacologie , Glucosephosphatase/effets des médicaments et des substances chimiques , Ionophores/pharmacologie , Mâle , Microsomes du foie/effets des médicaments et des substances chimiques , Pyrènes/composition chimique , Lapins
19.
Indian J Physiol Pharmacol ; 1995 Jul; 39(3): 231-6
Article Dans Anglais | IMSEAR | ID: sea-107192

Résumé

Spontaneous motor activity (SMA), conditioned avoidance response (CAR), muscle coordination (MC) and pentobarbital sleep were tested in rats treated orally for 90 days with tolerated doses of the cyclodiene insecticides, aldrin (1 mg/kg) and endosulfan (2 mg/kg). The same tests were repeated in similarly treated animals after injecting chlorpromazine (4 mg/kg, i.p.). Both the insecticides shortened pentobarbital sleeping time indicating their microsomal enzyme inducing property. Aldrin suppressed SMA, CAR and MC, whereas endosulfan stimulated SMA, inhibited CAR and unaltered MC. However, their concurrent action with CPZ did not result in change in the central depressive effects of the latter, but its potency during the course of its action was altered. Its potency 15 min after injection was greater and 60-180 min later was lesser in these animals than that observed in control animals. This finding was interpreted to suggest that aldrin and endosulfan has quickened the biotransformation of CPZ and thereby shortened its duration of action. A temporary promotion of its potency was accounted to its active metabolites, since prior to inactivation, CPZ is known to be metabolized by the microsomal enzymes to active compounds.


Sujets)
Aldrine/pharmacologie , Animaux , Apprentissage par évitement/effets des médicaments et des substances chimiques , Comportement animal/effets des médicaments et des substances chimiques , Dépresseurs du système nerveux central/pharmacologie , Chlorpromazine/pharmacologie , Antagonistes de la dopamine/pharmacologie , Endosulfan/pharmacologie , Hypnotiques et sédatifs/pharmacologie , Insecticides/pharmacologie , Mâle , Microsomes du foie/effets des médicaments et des substances chimiques , Activité motrice/effets des médicaments et des substances chimiques , Pentobarbital/pharmacologie , Équilibre postural/effets des médicaments et des substances chimiques , Rats , Rat Wistar , Sommeil/effets des médicaments et des substances chimiques
20.
Indian J Exp Biol ; 1995 May; 33(5): 342-7
Article Dans Anglais | IMSEAR | ID: sea-55988

Résumé

Lipid peroxidation in microsomes prepared from liver of mice was initiated by NADPH, ascorbic acid and ferrous ions. The presence of Ca2+ modulated the lipid peroxidation in all these three systems. The mode and magnitude depend on the system and concentration of cofactors used for initiation of lipid peroxidation. In ascorbate system, Ca2+ enhanced the lipid peroxidation up to 30 microM concentration of ascorbic acid and beyond 30 microM concentration it inhibited. Ca2+ increased NADPH-dependent lipid peroxidation at all concentrations. Depending on concentration of Fe2+, lipid peroxidation was either decreased or increased in presence of Ca2+. It suggested that the in vitro findings may be cautiously extrapolated to the animal systems. In absence of cofactors, Ca2+ enhanced lipid peroxidation. EGTA inhibited Ca2+-enhanced lipid peroxidation. However in presence of ionophore A23187, Ca2+ potentiated lipid peroxidation. Since Ca2+ has a closed-shell electronic state and lacks electronic transitions, it may not participate directly in lipid peroxidation process. The effect of Ca2+ on lipid peroxidation may be through some biochemical processes or its interactions with membranes leading to various changes in their characteristics.


Sujets)
Animaux , Calcium/pharmacologie , Peroxydation lipidique/effets des médicaments et des substances chimiques , Mâle , Souris , Microsomes du foie/effets des médicaments et des substances chimiques
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