RESUMEN
Treatment of rats with ethylbenzene (EB) modulates the hepatic expression of many P450s, with those induced after a single intraperitoneal hydrocarbon injection differing from those induced after more prolonged (3 day) administration. The goals of the current studies are (1) to characterize the induction response after prolonged hydrocarbon exposure, (2) to explain why the elevation of these P450s is attenuated after continued treatment, and (3) to determine how P450 2B protein remains elevated without an elevation of P450 2B1/2 RNA. P450 2C11 protein was decreased after a single EB injection and remained depressed throughout the treatment period. P450 2C11 RNA was only decreased with prolonged, but not acute treatment. P450 2E1 was induced after a single EB injection; however, the initial induction was attenuated with more prolonged treatment. P450 2B1 and P450 2B2 RNAs exhibited a similar response, being elevated after acute administration, but returned to control levels with prolonged EB administration. Interestingly, P450 2B protein levels remained elevated despite the decrease in P450 2B1 and P450 2B2 RNA to control levels. We then tested the possibility that the multiphasic induction pattern of P450 2E1 and P450 2B1/2 RNA was due to differences in the pharmacokinetics of EB. The disappearance of EB with time was measured in rats that were either (1) untreated, (2) pretreated with EB for 1 day, or (3) pretreated with EB for 3 days. These results demonstrated that prior hydrocarbon exposure caused an increase in EB clearance, which decreased the overall levels of EB in the body. Consequently, EB levels were sufficiently diminished to decrease EB's effectiveness as an inducer leading to the decrease in P450 2E1 protein and P450 2B1 and P450 2B2 RNA after continued EB administration. A further consequence of the decreased overall EB concentration is that the hydrocarbon was capable of producing only a transient elevation of P450 2B1 RNA levels. This transient elevation appears to be sufficient to maintain elevated P450 2B protein.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Derivados del Benceno/toxicidad , Citocromo P-450 CYP2B1/biosíntesis , Citocromo P-450 CYP2E1/biosíntesis , Sistema Enzimático del Citocromo P-450/biosíntesis , Esteroide 16-alfa-Hidroxilasa , Esteroide Hidroxilasas/biosíntesis , Animales , Derivados del Benceno/farmacocinética , Citocromo P-450 CYP2B1/genética , Citocromo P-450 CYP2E1/genética , Sistema Enzimático del Citocromo P-450/genética , Inducción Enzimática/efectos de los fármacos , Masculino , ARN Mensajero/análisis , Ratas , Esteroide Hidroxilasas/genéticaRESUMEN
Ethylbenzene (EB) treatment to male Holtzman rats was shown to alter the expression of cytochrome P-450s 1A1, 2B, 2C11, 2E1, and 3A, with several isozymes exhibiting complex multiphasic induction patterns when treated for 1 and 3 days with the alkylbenzene. Male rats were treated with daily i.p. injections of EB for either one or three days, and the effects on P-450 dependent activities, P-450 immunoreactive protein levels and their corresponding mRNA levels were measured. Although levels of P-450 2B, 2C11, 2E1, and 3A were all modulated by EB treatment, each exhibited different temporal characteristics. P-450 2B1/2B2 were induced after a single EB exposure and continued to be elevated after EB treatment for 3 days. However, P-450 2B1 and 2B2 mRNA levels were elevated about 50-fold after a single injection, and returned to control values after continued EB administration. P-450 2C11 expression was decreased to about 45% of controls after either single or repeated EB exposure with corresponding changes being observed in the levels of 2C11 mRNA. P-450 2E1 was induced by EB according to a complex multistep induction pattern. Both P-450 2E1 protein and RNA levels were increased 2-4-fold after a single EB treatment but returned to control values after continued administration. P-450 3A-dependent testosterone 2beta-hydroxylation and P-450 3A immunoreactive protein levels were both increased about 3-fold after a single EB treatment, whereas levels were only elevated 2-fold after EB treatment for 3 days. In contrast, P-450 3A2 mRNA was unaffected by a single EB injection but was increased 3.5-fold with repeated administration. Changes in P-450 3A1/2 were similar to those observed with P-450 3A2, whereas changes in P-450 3A1/23 and 3A23 mRNAs were not detectable. These data indicate that while EB can influence the expression of several P-450 isozymes, the hydrocarbon appears to alter P-450 expression by acting at different regulatory steps.
Asunto(s)
Derivados del Benceno/farmacología , Sistema Enzimático del Citocromo P-450/biosíntesis , Isoenzimas/biosíntesis , Microsomas Hepáticos/efectos de los fármacos , ARN Mensajero/biosíntesis , Animales , Citocromo P-450 CYP1A1/biosíntesis , Citocromo P-450 CYP2E1/biosíntesis , Masculino , Microsomas Hepáticos/enzimología , Ratas , Factores de TiempoRESUMEN
The goal of the present study was to examine the time course for changes in P450 expression and hydrocarbon metabolism after acute treatment with the simple aromatic hydrocarbon ethylbenzene (EB) and to correlate these alterations with the changes observed in alkylbenzene metabolism. Male Holtzman rats were treated with a single intraperitoneal injection of EB, and the effects on specific P450-dependent activities, immunoreactive P450 isozyme levels, and RNA levels were measured at various times after injection. Toluene was used as the test alkylbenzene for examination of the EB-mediated changes on in vitro hydrocarbon metabolism. In untreated rats, toluene was metabolized almost entirely by aliphatic hydroxylation (to benzyl alcohol); however, in EB-treated rats, significant quantities of benzyl alcohol, o-cresol, and p-cresol were produced. Interestingly, 5-10 h after EB treatment, there was a 40% decrease in benzyl alcohol production. By 24 h, rates of benzyl alcohol formation returned to control levels, whereas there was a 7-fold increase in o-cresol and a greater that 50-fold increase in p-cresol production. The changes in the disposition of toluene were then correlated with changes in particular P450 isozymes. Several P450 isozymes were induced after EB administration. P450 2B1/2-dependent testosterone 16 beta-hydroxylation and P450 2B1/2-immunoreactive protein were elevated 30-fold after EB administration, reaching maxima by 24 h and remaining elevated 48 h after exposure. Changes in P450 2B1 and 2B2 RNA preceded those of the proteins. Similar results were observed with P450 1A1. P450 2E1 RNA levels were elevated after a single EB injection. However, the elevation in P450 2E1-dependent activities and immunoreactive protein levels preceded the changes in RNA, suggesting that multiple steps are affected by EB exposure. In contrast to the increases in some isozymes, P450 2C11 protein was rapidly suppressed (within the first 2-10 h) after hydrocarbon exposure, suggestive of a destabilization of the protein. When comparing the changes in P450 isozymes to alterations in toluene metabolism, the immediate suppression in aliphatic hydroxylation of toluene (in the first 5-10 h) was consistent with the decrease in P450 2C11. Subsequent to this effect, P450 2B1/2 and 2E1 were induced, which elevated production of this metabolite to control levels. The increase in the aromatic hydroxylation of toluene to both o, and p-cresol was consistent with the induction of P450s 2B1/2, 2E1, and 1A1.
Asunto(s)
Derivados del Benceno/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Microsomas Hepáticos/metabolismo , Tolueno/metabolismo , Animales , Secuencia de Bases , Biotransformación , Inducción Enzimática/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Isoenzimas/metabolismo , Masculino , Datos de Secuencia Molecular , ARN Mensajero/genética , Ratas , Factores de TiempoRESUMEN
The goal of this study was to examine the effect of duration of ethylbenzene exposure on cytochrome P-450-dependent activities. Male rats were treated with ethylbenzene by intraperitoneal injection for either 1 or 3 days, and microsomal preparations were examined for changes in the microsomal proteins and activities as well as the expression of specific P-450 isozymes. Two general patterns of induction were evident when different P-450-dependent activities were examined. (i) Cytochrome P-450 2B-dependent activities (e.g., p-nitroanisole demethylation, benzphetamine demethylation, and aromatic toluene hydroxylations) were induced both after 1 and 3 days of ethylbenzene exposure. (ii) Cytochrome P-450 2E1-dependent activities (e.g., N,N-dimethylnitrosamine demethylation and aniline hydroxylation) were induced after treatment with ethylbenzene for one day; however, after 3 days of ethylbenzene treatment these activities returned to control levels. Changes in these activities were consistent with changes in the levels of specific P-450 isozymes as determined by immunoblotting. Cytochrome P-450 2B levels were increased and P-450 2C11 levels were suppressed at both 1 and 3 days of ethylbenzene exposure. A temporal response in P-450 2E1 expression was observed, with P-450 2E1 levels increasing after a single ethylbenzene injection and returning to controls after administration of the hydrocarbon for 3 days. Rats were also subjected to a pair-feeding regimen to determine whether these effects were related to altered dietary status in ethylbenzene-treated rats. Neither P-450-dependent activities nor immunoreactive protein levels were altered in pair-fed rats. These results demonstrate that prolonging the duration of hydrocarbon exposure can produce differential effects on the expression of P-450 2E1, with levels being elevated after acute hydrocarbon administration, but not after more prolonged hydrocarbon exposure.
Asunto(s)
Derivados del Benceno/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Microsomas Hepáticos/enzimología , Oxidorreductasas N-Desmetilantes/metabolismo , Compuestos de Anilina/metabolismo , Animales , Anisoles/metabolismo , Derivados del Benceno/administración & dosificación , Citocromo P-450 CYP2E1 , Dimetilnitrosamina/metabolismo , Ingestión de Alimentos/efectos de los fármacos , Hidroxilación , Isoenzimas/metabolismo , Cinética , Masculino , Metilación , Microsomas Hepáticos/efectos de los fármacos , RatasRESUMEN
Rats were treated with a single intraperitoneal injection of ethylbenzene in corn oil and the effects on cytochrome P450 3A-dependent activities, immunoreactive protein levels and RNA levels were examined. Ethylbenzene increased both P450 3A-dependent 2 beta-hydroxylation of testosterone and immunoreactive protein levels. These levels were maximally induced by 24 hr and diminished thereafter. Despite the increase in P450 3A protein, neither P450 3A1 nor P450 3A2 mRNA levels were altered by treatment with the hydrocarbon. These results clearly demonstrate that this P450 isozyme can be induced by either translational activation or stabilization of P450 3A protein and are suggestive of an elevation of P450 3A2 levels.
Asunto(s)
Derivados del Benceno/farmacología , Sistema Enzimático del Citocromo P-450/biosíntesis , Oxigenasas de Función Mixta/biosíntesis , ARN Mensajero/metabolismo , Animales , Secuencia de Bases , Citocromo P-450 CYP2E1 , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Inducción Enzimática , Masculino , Microsomas Hepáticos/enzimología , Oxigenasas de Función Mixta/genética , Oxigenasas de Función Mixta/metabolismo , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , ARN Mensajero/genética , RatasRESUMEN
1. Treatment of male rat with the small aromatic hydrocarbons, benzene, toluene, ethylbenzene, n-propylbenzene, m-xylene, and p-xylene increased several P450-dependent activities, with ethylbenzene, m-xylene, and n-propylbenzene producing the greatest response. Hydrocarbon treatment differentially affected toluene metabolism, producing a response dependent on the metabolite monitored. In untreated rats, benzyl alcohol was the major hydroxylation product of toluene metabolism, comprising > 99% of the total metabolites formed. Hydrocarbon treatment increased the overall rate of toluene metabolism by dramatically increasing the amount of aromatic hydroxylation. Ethylbenzene, n-propylbenzene and m-xylene were the most effective inducers of aromatic hydroxylation of toluene. In contrast, production of the major toluene metabolite benzyl alcohol was increased only after treatment with m-xylene. 2. P450 2B1/2B2 levels were induced by each of the hydrocarbons examined, with the magnitude of induction increasing with increasing hydrocarbon size. P450 1A1 was also induced after hydrocarbon exposure; however, the degree of induction was smaller than that observed for P450 2B1/2B2. P450 2C11 levels were suppressed after treatment with benzene, ethylbenzene and n-propylbenzene. 3. Taken together these results display two induction patterns. The first generally corresponds to changes in the P450 2B subfamily, where activities (e.g. the aromatic hydroxylations of toluene) were most effectively induced by ethylbenzene, n-propylbenzene and m-xylene. In the second, induction was observed only after m-xylene treatment, a pattern that was found when the metabolism of the substrate was catalysed by both the P450 2B subfamily and P450 2C11. Hydrocarbons that both induced P450 2B1/2B2 and suppressed P450 2C11 (such as ethylbenzene and n-propylbenzene) showed little change in activities catalysed by both isozymes (e.g. aliphatic hydroxylation of toluene, and aniline hydroxylation); however, m-xylene treatment led to elevated P450 2B1/2B2 levels without significantly suppressing P450 2C11. m-Xylene produced significant increases in activities efficiently catalysed by both isozymes. Therefore, the unique induction pattern observed after m-xylene treatment can be accounted for by induction of P450 2B1/2B2 without concomitant suppression of P450 2C11.
Asunto(s)
Sistema Enzimático del Citocromo P-450/biosíntesis , Hidrocarburos/toxicidad , Animales , Benceno/toxicidad , Derivados del Benceno/toxicidad , Sistema Enzimático del Citocromo P-450/clasificación , Inducción Enzimática/efectos de los fármacos , Hidrocarburos/química , Hidrocarburos/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Ratas , Relación Estructura-Actividad , Tolueno/metabolismo , Tolueno/toxicidad , Xilenos/toxicidadRESUMEN
The subject of hydrocarbon inhibition of cytochrome P450-dependent reactions as well as data on other enzyme-catalyzed reactions from the literature was examined to determine the relationship between the "hydrophobicity" of the hydrocarbons and their ability to act as inhibitors. The compounds used in these studies (benzene, toluene, ethylbenzene, n-propylbenzene, and n-butylbenzene) behave as competitive inhibitors, with the affinity increasing as the size of the inhibiting hydrocarbon increases. A similarity was seen in the size dependence for both hydrocarbon inhibition of cytochrome P450-dependent activities (-0.6 to -0.7 kcal/mol/methylene group) and transfer of these compounds between aqueous and organic phases (-0.68 kcal/mol/methylene group), suggesting that the active site of cytochrome P450, in some ways, is comparable to an organic solvent in its ability to accommodate hydrophobic compounds. A more detailed examination of this process was initiated to separate the "hydrophobic effect" into its two component processes: (i) hydration of the hydrocarbon ligand and (ii) transfer of the unhydrated hydrocarbon onto the enzyme active site. In other words, do larger hydrocarbons bind more avidly to the active site because they are drawn more effectively into that site (pull), or is the size-dependent increase in hydrocarbon binding the result of the larger compounds being more efficiently expelled from the aqueous medium (push)? The results indicate that the predominant force involved in binding is the ability of the active site of cytochrome P450 and an impressive number of other enzymes to draw the hydrocarbon from the aqueous medium. The hydration of the hydrocarbon is much less dependent on the size of the hydrocarbon, indicating that dehydration or partial dehydration of the hydrocarbon molecule (upon leaving the solution and combining with the enzyme) contributes to the overall binding process to a much lesser extent; hydrophobic binding in the most widely used sense (entropy driven) is not the primary driving force that is responsible for the observed size dependence effects. It is pointed out that not all types of binding would be expected to follow the law which describes the size dependence for simple hydrocarbons because of heat-entropy relationships. The different temperature dependence of these heat-entropy relationships further complicates the analogy between enzyme-ligand binding and ligand partitioning between aqueous and organic phases. The maximum contribution that can be attributed to entropy driven hydrophobic binding (in the most widely used sense) is -0.1 to -0.2 kcal/mol/methylene group for the aromatic hydrocarbons examined here.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Compuestos Policíclicos/metabolismo , Animales , Técnicas In Vitro , Ligandos , Masculino , Microsomas/enzimología , Unión Proteica , Conejos , Solubilidad , Relación Estructura-Actividad , Termodinámica , Agua/químicaRESUMEN
Male and female Holtzman rats were exposed to ethylbenzene, and the effect on liver microsomal activities was studied. Hydrocarbon- and sex-dependent effects on P450-dependent metabolism of drugs and aromatic hydrocarbons were investigated. Hydrocarbon treatment produced two patterns of induction in cytochrome P450-dependent activities: (1) induction common to both sexes; and (2) induction exclusively in females. Benzphetamine N-demethylation, 7-ethoxycoumarin O-deethylation, p-nitroanisole O-demethylation and aromatic hydroxylation of toluene were induced in both sexes after rats were exposed to ethylbenzene. The rate of benzphetamine N-demethylation increased 4-fold in females and nearly doubled in males. The increase in O-deethylation of 7-ethoxycoumarin was 3-fold in females and doubled in males, while p-nitroanisole O-demethylation increased 4-fold in both sexes after exposure to ethylbenzene. Ethylbenzene had its greatest effect upon the formation of aromatic hydroxylated metabolites of toluene. Ethylbenzene exposure increased the rate of o-cresol formation by 4- and 9-fold in female and male rats, respectively. The formation rate of p-cresol was undetectable in either sex prior to hydrocarbon exposure; however, after the rats were given ethylbenzene, rates increased to 0.4 nmol/min/mg protein in females and to 0.9 nmol/min/mg protein in the males. Ethylbenzene exposure selectively induced aminopyrine demethylation, aniline hydroxylation, N,N-dimethylnitrosamine N-demethylation (DMNA) and aliphatic hydroxylation of toluene in females. Rates for aminopyrine, aniline, and DMNA were increased 50% over controls, while formation of benzyl alcohol from toluene was enhanced to 260% of control. Western immunoblotting indicated that ethylbenzene treatment induced cytochrome P450 2B1/2B2 to a greater extent in male rats and cytochrome P450 2E1 only in females. Ethylbenzene exposure did not affect significantly the level of cytochrome P450 1A1.
Asunto(s)
Derivados del Benceno/farmacología , Sistema Enzimático del Citocromo P-450/biosíntesis , Microsomas Hepáticos/efectos de los fármacos , Animales , Alcohol Bencilo , Alcoholes Bencílicos/metabolismo , Western Blotting , Cresoles/metabolismo , Citocromo P-450 CYP2E1 , Citocromos b5/biosíntesis , Inducción Enzimática/efectos de los fármacos , Femenino , Hidroxilación , Masculino , Microsomas Hepáticos/enzimología , NADH Deshidrogenasa/biosíntesis , Oxidorreductasas N-Desmetilantes/biosíntesis , Ratas , Factores Sexuales , Tolueno/metabolismoRESUMEN
Substrate has recently been shown to affect (a) the high spin content of cytochrome P450 (b) the rate of first electron transfer when LM2 (P450 2B4) and reductase were in a preformed complex, and (c) the rate of functional complex formation between NADPH-cytochrome P450 reductase and cytochrome P450 LM2. When comparing the effect of substrate on each of these parameters, the strongest correlation was demonstrated between the rate of first electron transfer through the preformed complex and the rate of functional complex formation (W.L. Backes and C.S. Eyer, 1989, J. Biol. Chem. 264, 6252-6259). The relationship among high spin content, reduction rate, and the rate of functional complex formation was examined using a number of different cytochrome P450 isozymes. The goal of this study was to determine if the previously established relationship between reduction rate and the rate of reductase-P450 complex formation was a feature only of LM2, or a general characteristic of the cytochrome P450 system. Substrate addition caused an increase in first electron transfer for each of the isozymes examined, with high spin content being increased with cytochromes P450 2B1 (PBRLM5) and P450 2B2 (PBRLM6). Substrate addition to cytochrome P450 2C6 (PBRLM4) resulted in a small decrease in high spin content. P450 2B1 and P450 2B2 showed a positive correlation between substrate-mediated stimulation of reduction and high spin content, whereas P450 2C6 showed a negative correlation between these variables. Substrate also increased the rate of reductase-P450 association for each of the isozymes examined. When compared to the degree of stimulation of reduction through a preformed complex, a strong positive correlation was obtained with each isozyme examined. These results demonstrate that the increase in both the rate of functional reductase-P450 complex formation and the rate of first electron transfer is not simply a property of LM2, but appears to be a general characteristic of many cytochrome P450 isozymes.
Asunto(s)
Sistema Enzimático del Citocromo P-450/química , NADPH-Ferrihemoproteína Reductasa/química , Animales , Transporte de Electrón , Isoenzimas/metabolismo , Cinética , Masculino , Complejos Multienzimáticos/química , Oxidación-Reducción , Ratas , Especificidad por SustratoRESUMEN
The effect of dilauroylphosphatidylcholine (DLPC) concentration on cytochrome P-450 LM2 (LM2)-dependent reduction and monooxygenase activities was examined as a function of preincubation time. Purified NADPH-cytochrome P-450 reductase (reductase) and LM2 were reconstituted at different DLPC to LM2 ratios by preincubation of the proteins in the presence of DLPC for either 5 min or 2 hr at room temperature. After preincubation was complete, the samples were assayed for either monooxygenase activity or first-electron transfer activity. When preincubated for 5 min, overall monooxygenase activity was dependent on the [DLPC]:[LM2] ratio, beginning at a low level in the absence of phospholipid and increasing to a maximum at a 160:1 ratio. At [DLPC]:[LM2] ratios above 160:1, the rate was decreased to 80% of the maximum rate. When the samples were preincubated for 2 hr, again low monooxygenase activities were obtained in the absence of DLPC, which increased to a maximum at 160:1 [DLPC]:[LM2] ratio. Above this [DLPC]:[LM2]ratio, the rate was decreased to less than 50% of the maximum value. These changes in overall activities appear to be related to changes in the amount of functional reductase-LM2 complex formed. Similar results were found when LM2 reduction was examined. When preincubated for 5 min, LM2 reduction was shown to be diminished as the DLPC to LM2 ratio decreased below 160:1. The DLPC-dependent effect on reduction was primarily characterized by alterations in the fraction of LM2 reduced in the first phase, with the first-phase rate constant and the slow phase parameters being largely unaffected. Below a 16:1 ratio [( DLPC]:[LM2]), no phospholipid stimulation of LM2 reduction was observed. When the [DLPC]:[LM2] ratio was increased above a 160:1 ratio, only a small effect on the kinetic constants was observed, which was characterized by a 20% decrease in the fraction of LM2 reduced in the first phase. LM2 reduction was more sensitive to DLPC concentration after longer preincubations (2 hr), with a 50% decrease in the fraction of reduction in the first phase being observed at [DLPC]:[LM2] ratios above 160:1. The results are consistent with a dual role for phospholipid in the stimulation of LM2-dependent activities. First, DLPC facilitates the association of reductase and LM2 and, second, DLPC provides a matrix for the incorporation of LM2 and reductase. Facilitation of the protein association appears to be a relatively rapid process, occurring after a 5-min preincubation, whereas a 2-hr preincubation altered the protein interactions in a manner consistent with incorporation of the LM2 and reductase into the phospholipid.
Asunto(s)
Sistema Enzimático del Citocromo P-450/análisis , Fosfatidilcolinas/farmacología , Animales , Anisoles/metabolismo , Relación Dosis-Respuesta a Droga , Nonoxinol , Oxidación-Reducción , Oxigenasas/análisis , Polietilenglicoles/farmacología , Conejos , Ratas , Factores de TiempoRESUMEN
The effect of substrate on LM2 reduction was examined using a reconstituted system containing dilauroylphosphatidylcholine, NADPH-cytochrome P-450 reductase, and cytochrome P-450 LM2 in a 160:1.5:1 molar ratio. In general, most substrates increased the rate constants of both the first and second phases of reduction as well as the fraction of LM2 reduced in the first phase. The correlation between the high spin content of the cytochrome and each of these kinetic parameters was weaker than expected if spin state controlled LM2 reduction. Further, substrate was shown to exert a rapid effect on both the high spin content and stimulation of reduction indicating that the low spin to high spin shift cannot be responsible for the slow phase of reduction for this particular isoform. Cytochrome P-450 reduction was also examined in both phospholipid-containing and soluble systems where the LM2 and reductase were not present as a preformed complex. In these systems the reactions were substantially slower than with the standard reconstituted system. Addition of substrate enhanced the rate of reduction, indicating that the rate of association between LM2 and the reductase was increased by substrate addition. The strong correlation between the rate of LM2 reduction in a preformed complex and the logarithm of the rate of LM2 and reductase association implicates the rate of functional complex formation as the factor controlling the slow phase of reduction.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , NADPH-Ferrihemoproteína Reductasa/metabolismo , Animales , Benzfetamina/farmacología , Cinética , Microsomas Hepáticos/enzimología , Oxidación-Reducción , Conejos , Relación Estructura-ActividadRESUMEN
A previous study has shown that the addition of small amounts of tin to gamma 1 leads to the formation of a SnHg intergranular precipitate. The purpose of this study was to determine the effect of this precipitate on the creep of gamma 1. Two groups of samples were investigated. Group I included a series of gamma 1 samples with 0, 1, 2, and 3 wt% Sn fabricated by a sintering technique at 55 degrees C and 125 mN/m2 for 72 h. Group II contained the same samples as in Group I that were further annealed at 60 degrees C for 2000 h. Annealing was carried out to allow gamma 1 grain growth and equilibrium distribution of Sn at grain boundaries. Creep tests were conducted according to the American Dental Association Specification 1. The microstructures of all samples were characterized by scanning electron microscopy. The creep of gamma 1 was found to be controlled by the intergranular precipitate when the Sn concentration was above 1%. For a specific concentration of Sn, i.e. the intergranular precipitate, creep was dependent on the distribution of Sn and not on the gamma 1 grain size. The more nearly continuous precipitates found in annealed samples favoured higher creep.
Asunto(s)
Amalgama Dental , Fenómenos Químicos , Química Física , Microscopía Electrónica de Rastreo , Propiedades de Superficie , EstañoRESUMEN
The aim of this study was to understand the relationship between heat treatment, microstructure and corrosion of a low-gold casting alloy. Potentiostatic and potentiodynamic polarization techniques were used to evaluate the chloride corrosion resistance of the alloy in the following conditions: (A) as cast, (B) bench cooled, (C) homogenized, (D) homogenized and aged for 2 h, and (E) homogenized and aged for 4 h. The microstructure of each sample, before and after corrosion, was examined by optical and/or scanning electron microscopy. In general, heterogeneous structures containing dendritic segregations and precipitates were found to be more prone to corrosion than the single phase solid solution structure produced by homogenization. On the basis of the potentiodynamic polarization data, the samples were ranked as follows: C greater than D greater than B greater than A greater than E, C being the most corrosion resistant structure.
Asunto(s)
Revestimiento para Colado Dental , Aleaciones de Oro , Calor , Corrosión , Microscopía Electrónica de Rastreo , Propiedades de Superficie , Factores de TiempoRESUMEN
The solid solubility of Sn in gamma 1 has been studied by examining a series of gamma 1 samples containing 0.25-2.0 wt% Sn by scanning electron microscopy and energy-dispersive X-ray analysis. It has been observed that the addition of Sn to gamma 1 leads to the formation of mainly an intergranular Sn-Hg compound. On the basis of this observation it has been concluded that the solubility of Sn in gamma 1 is virtually nil.
Asunto(s)
Amalgama Dental , Mercurio , Plata , Estaño , Fenómenos Químicos , Química Física , Microanálisis por Sonda Electrónica , Microscopía Electrónica de Rastreo , Solubilidad , Propiedades de SuperficieRESUMEN
With scanning electron micrographs and semiquantitative x-ray analysis, the role of gallium in alloy-porcelain bonding was studied. The insight gained from this study should be of interest to both dentists and laboratory technicians making ceramometal restorations.
Asunto(s)
Recubrimiento Dental Adhesivo , Porcelana Dental , Galio , Aleaciones de Oro , Fenómenos Químicos , Química Física , Oro , Indio , Microscopía Electrónica de Rastreo , Oxidación-Reducción , Propiedades de SuperficieRESUMEN
The effect of gamma 1 and gamma 2 on the creep deformation of dental amalgams has been investigated. It has been shown that the creep of a conventional amalgam is not dependent on gamma 1 as was previously reported. Rather it is strongly influenced by gamma 2 and its volume fraction. It has been speculated that Sn-rich grain boundaries also enhance creep by facilitating grain boundary sliding. The reported correlation between creep and marginal fracture has been explained in terms of this dependence of creep on corrosion-prone Sn-rich microstructural constituents of amalgams.