[Post-operative peridural analgesia: its performance in a general hospital center].
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Adult↗
Biomedical subjects
J Brodeur
Publications and source records attributed to J Brodeur.
Species differences in the urinary disposition of some metabolites of ethylene oxide.
Some aspects of the qualitative and quantitative urinary disposition of some metabolites of ethylene oxide in three rodent species, mouse, rat, and rabbit, were examined by determining urinary N-acetyl-S-(2-hydroxyethyl)-L-cysteine, S-(2-hydroxyethyl)-L-cysteine, S-carboxymethyl-L-cysteine, and ethylene glycol after ethylene oxide exposure by iv and inhalation routes. The animals were given ethylene oxide at 20 and 60 mg/kg, and urine samples were collected at 6 and 24 hr. Important differences were observed between the three species in the urinary metabolic disposition of ethylene oxide. Mice excreted significant quantities of N-acetyl-S-(2-hydroxyethyl)-L-cysteine, S-(2-hydroxyethyl)-L-cysteine, S-carboxymethyl-L-cysteine, and ethylene glycol (8.3, 5.8, 1.9, and 3.3% of the lower dose, respectively, in 24 hr), whereas in rats only N-acetyl-S-(2-hydroxyethyl)-L-cysteine (31%) and ethylene glycol (6%) were apparent. In contrast, the rabbits were found to excrete only ethylene glycol (2%). This study further reveals species-related differences in the urinary excretion of N-acetyl-S-(2-hydroxyethyl)-L-cysteine and ethylene glycol during the two collection periods. The observed differences between the three species in the metabolic disposition of ethylene oxide were found to be qualitatively independent of the route of exposure, i.e., inhalation at 200 ppm or iv. These results suggest that care should be exercised when using an animal species as a model for human disposition of ethylene oxide.
Administration, Inhalation↗
Urinary excretion of mercapturic acids and thiocyanate in rats exposed to acrylonitrile: influence of dose and route of administration.
Adult male Sprague-Dawley rats were exposed acutely to acrylonitrile (ACN) according to 1 of 3 different routes of administration: inhalation (6 h), i.v., or i.p. Urinary metabolites measured 24 h after administration were 2-cyanoethylmercapturic acid (CMA), 2-hydroxyethylmercapturic acid (HMA) and thiocyanate (TCN). In all 3 series of experiments, the relationship between excretion of total urinary metabolites and the degree of exposure was reasonably linear. However, there was a marked influence of the route of administration on the pattern of metabolic excretion. For example, after i.p. and i.v. injection CMA was the most important metabolite while after inhalation it was TCN. Our results also indicate an important effect of the dose on the pattern of excretion for all types of administration.
Acetylcysteine↗
Effect of a cysteine prodrug (L-2-oxothiazolidine-4-carboxylic acid) on the metabolism and toxicity of bromobenzene: a repeated exposure study.
The relationship between dose, toxicity, and metabolism of bromobenzene and the use of urinary metabolite excretion as an index of internal exposure to the reactive electrophilic intermediate bromobenzene 3,4-epoxide after repeated treatments with bromobenzene in presence or absence of L-2-oxothiazolidine-4-carboxylic acid (OTCA) were evaluated in mice. Repeated treatments with bromobenzene doses of 0.5, 0.75, and 1.0 mmol/kg ip twice a day for 18 d produced a marked reduction in 24-h urinary excretion of bromophenylmercapturic acid and p-bromophenol; this was accompanied by increases in plasma transaminases. Treatment with OTCA (1.0-3.0 mmol/kg) prevented toxicity and enhanced the 24-h urinary excretion of various bromobenzene metabolites by approximately 30-75, 104-145, and 164-269% for bromobenzene doses of 0.5, 0.75, and 1.0 mmol/kg, respectively. The effect of OTCA was further characterized by investigating the metabolism of bromobenzene given as a challenge dose of 4.0 mmol/kg to mice pretreated with bromobenzene and OTCA for 18 d. Pretreatment with bromobenzene reduced the 0- to 6-h urinary excretion of all metabolites after the challenge dose; this effect was virtually reversed by OTCA. It is concluded that repeated bromobenzene administration reduces its own detoxification to mercapturic acid and phenolic metabolites and elicits toxicity. This phenomenon is reversed after OTCA administration. This study further provides evidence that internal exposure to the reactive electrophilic intermediate bromobenzene 3,4-epoxide could be assessed more accurately by summing the urinary excretion of bromophenylmercapturic acid and p-bromophenol after OTCA treatment.
Acetylcysteine↗
Effect of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid, on the metabolism and toxicity of bromobenzene: an acute study.
The effect of a cysteine prodrug, L-2-oxothiazolidine-4-carboxylic acid (OTCA), on certain aspects of the metabolism and toxicity of bromobenzene administered acutely to mice was investigated by (i) characterizing the influence of OTCA on the metabolic profile of low and high bromobenzene dose at 0-6, 6-12, and 12-24 h, (ii) determining the effective doses range and administration time for OTCA, as well as the optimum period for urine sampling; and (iii) measuring the efficacy of OTCA for protection against bromobenzene induced toxicity. Coadministration of OTCA and bromobenzene enhanced the urinary excretion of mercapturic acid and phenolic metabolites, during 6-12 h, by approximately 152 and 193%, respectively. Maximum efficacy was observed when OTCA (16.0 mmol/kg) was administered concomitantly with bromobenzene (4.0 mmol/kg). Finally, OTCA administration was found to afford substantial protection against elevation of plasma transaminases used as indices of bromobenzene-induced hepatotoxicity. N-acetylcysteine, another cysteine prodrug, had essentially similar effects on the metabolism and toxicity of bromobenzene. Thus, administration of cysteine prodrugs enhances the urinary excretion of several metabolites of bromobenzene and affords protection against bromobenzene-induced hepatotoxicity.
Acetylcysteine↗
Correlation between acetone-potentiated CCl4-induced liver injury and blood concentrations after inhalation or oral administration.
In studies of acetone-potentiated liver injury induced by haloalkanes, acetone is usually given by gavage, whereas industrial exposure to acetone normally occurs by inhalation. It was of interest to verify if the route of administration influences the potentiation. Male Sprague-Dawley rats were exposed for 4 hr to acetone vapors or treated orally with acetone; the minimal effective dose (MED) levels for potentiating CCl4-induced liver injury were estimated to be 2500 ppm and 0.25 ml/kg, respectively. Groups were treated with acetone using 0.4, 1, 2, 4, or 6 times the MED. Half of each group was killed at various time intervals after treatment for blood acetone measurements by gas chromatography; the other half was challenged with CCl4 (0.1 ml/kg, ip) 18 hr after acetone, and killed 24 hr later. Plasma alanine aminotransferase (ALT) activity and bilirubin concentrations were measured. Inhalation and oral administration of acetone both potentiated CCl4 toxicity. Rats exposed repetitively to acetone vapors (10 daily exposures) and subsequently challenged with CCl4 exhibited liver toxicity that was not significantly different from that of rats subjected to a single exposure. Correlations between ALT activities and maximal blood acetone concentrations were found to be linear (positive) and significant for both routes. For a given blood acetone concentration, however, toxicity was least severe following acetone exposure by inhalation. When the concept of threshold concentrations was applied to the data, the severity of the toxic response was dependent on the blood acetone concentration above the threshold, irrespective of the route of administration.
Acetone↗
Metabolites and ketone body production following methyl n-butyl ketone exposure as possible indices of MnBK potentiation of carbon tetrachloride hepatotoxicity.
While the biotransformation of methyl n-butyl ketone (MnBK) in animals is well characterized, little is known about the quantitative relationship between hepatic and plasma MnBK concentrations. This study provides such information and emphasizes the usefulness of MnBK metabolite quantification, as well as MnBK-induced metabolic ketosis for the biological monitoring of MnBK exposure in rats. Elimination of MnBK was followed 24 hr after oral administration (0.95, 1.90, and 5.70 mmol/kg in corn oil) to male Sprague-Dawley rats. Two metabolites [2-hexanol (2HOL), and 2,5-hexanedione (2,5HD)] were also monitored and their kinetics determined. These data were compared to ketone body (KB) concentrations found in plasma and liver during the same period. Plasma concentrations of MnBK and 2,5HD correlated well with those in the liver. This was not the case for 2HOL. MnBK, 2HOL, and 2,5HD were no longer detected in plasma and liver 18 hr after dosing. Meanwhile, a marked ketosis was observed from 12 to 24 hr. This ketotic state was due to an increase in beta-hydroxybutyrate (BOHB), while acetoacetate remained at its basal levels. These data indicate that MnBK can induce ketosis in rats and suggest that the resulting BOHB might be used as an alternative biological monitor of MnBK exposures at high concentrations.
Administration, Oral↗
Acetone potentiation of rat liver injury induced by trichloroethylene-carbon tetrachloride mixtures.
Acetone potentiation of haloalkane-induced hepatotoxicity is well recognized. Others reported that trichloroethylene (TCE) can potentiate the hepatotoxicity induced by CCl4. The purpose of the present study was to determine if acetone (A) can potentiate the hepatotoxicity of haloalkane (HA) mixtures. We derived dose-response curves for the potentiation of TCE, CCl4, and TCE-CCl4 induced hepatotoxicity by acetone. Male Sprague-Dawley rats received acetone (0.25-1.5 ml/kg, po); 18 hr later, they received an ip injection of either TCE, 0.25 ml/kg; CCl4, 0.1 or 0.6 ml/kg; or a mixture of TCE and CCl4. Rats were killed 24 hr later, the livers excised, and plasma ALT activities and bilirubin concentrations determined. Histological evaluations were also performed. Neither A, TCE, or both in combination modified the biochemical indices. Acetone potentiation of CCl4-induced liver injury was greater than TCE-potentiation of CCl4. Acetone enhanced the hepatotoxic response of the TCE-CCl4 mixture. Thus, CCl4-induced hepatotoxicity was enhanced by the simultaneous administration of TCE, and this response was potentiated by the previous administration of acetone.
Acetone↗
1,3-Butanediol-induced increases in ketone bodies and potentiation of CCl4 hepatotoxicity.
Evidence previously reported suggest that 1,3-butanediol (BD) enhances the hepatotoxic effect of a single small dose of carbon tetrachloride (CCl4) in a dose-related manner. The present study provides additional information concerning the quantitative relationship between the severity of the ketotic state produced by BD and the magnitude of the potentiation observed and emphasizes the use of ketone bodies (KB) to predict the potential hazard of the BD-CCl4 interaction. Liver damage was modulated in male Sprague-Dawley rats by varying the concentration of the BD solutions ingested prior to a CCl4 challenge (0.1 ml/kg, i.p.). These data were compared to ketone bodies in plasma, hepatic tissue and urine. BD produced a dose-dependent metabolic ketosis observable at dosages between 1.1 and 9.9 g/kg per day given for 7 days. Plasma and liver data correlated well together. Concomitantly, potentiation of the CCl4-induced liver injury was also dose-related for the same dosage range; the minimum effective dosage of BD for potentiation was estimated as 1.1 g/kg per day. The linear correlations between hepatic or plasma KB values and the indices of hepatic dysfunction (ALT, OCT) were highly significant. Using a semiquantitative method, a correlation was also found for the urinary KB data. These results suggest that plasma KB concentrations might be useful for predicting possible potentiation of the hepatonecrotic effect of CCl4 by BD.
Acidosis↗
Influence of mercuric chloride on the metabolism and hepatotoxicity of bromobenzene in rats.
When male Sprague-Dawley rats were treated with 1 mg mercuric chloride (HgCl2)/kg, sc 6 hr prior to or simultaneously with a single 2.5-mmole/kg ip dose of bromobenzene and sacrificed 48 hr after the bromobenzene dose, the activities of serum transaminases (SGOT and SGPT) were found to be significantly reduced when compared with those obtained in bromobenzene-alone-treated rats. Similar phenomena were observed when rats were treated simultaneously with 1 or 2 mg HgCl2/kg and 1 mmole bromobenzene/kg, but not when bromobenzene was given 6 hr prior to HgCl2 injection. When 5 mmole bromobenzene/kg and 1 mg HgCl2/kg were given simultaneously to the animals, such an apparent reduction in bromobenzene toxicity was again observed. In each case, HgCl2 alone had no effect on the transaminase activities. HgCl2 (1 mg/kg, sc) treatment reduced the hepatic microsomal cytochrome P-450 content. Treatment with 1 mg HgCl2/kg 6 hr prior to bromobenzene injection (2.5 mmole/kg) significantly reduced the urinary excretion of para- and metabromophenols, and parabromocatechol during 0 to 24-hr period without affecting the urinary thioethers. These data suggest a possible reduction in the rate of formation of bromobenzene epoxide intermediate due to mercury pretreatment, resulting in a lowering of the steady state level of this epoxide so that an inhibition of hepatotoxicity due to bromobenzene could occur. However, simultaneous treatments of HgCl2 and bromobenzene failed to modify the urinary metabolic excretion pattern of bromobenzene. When rats were given 10, 50, and 100 ppm of HgCl2 in drinking water daily for 4 weeks prior to an ip injection of 2.5 mmole bromobenzene/kg and were sacrificed 48 hr after the dose, no changes in SGOT and SGPT activities were observed. These results indicate that changes in the metabolism and hepatotoxicity of bromobenzene due to mercury depend on (a) the dose and time of mercury administration, and (b) the mode of administration of mercury, acute or chronic.
Alanine Transaminase↗
Influence of zinc chloride on the metabolism and hepatotoxicity of bromobenzene in rats.
In studying the possible interactive effects of various heavy metals on bromobenzene hepatotoxicity and metabolism, zinc chloride (ZnCl2) (0.5, 2.0, and 10.0 mg/kg) was given ip 24 hr prior to ip administration of bromobenzene (2.5 mmol/kg body wt). Animals were sacrificed 48 hr after bromobenzene. A significant increase in the activities of serum transaminases (serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) was observed at 0.5 mg/kg ZnCl2 and such an effect was not observed at the two higher doses of ZnCl2. However, no such increase in the transaminases activities was observed when rats were treated with identical doses of ZnCl2 48 hr before the administration of bromobenzene. When rats were treated with 2 mg/kg ZnCl2 6 hr prior to the bromobenzene dose, a potentiation of the hepatotoxicity due to bromobenzene was again observed, whereas simultaneous treatment of bromobenzene and ZnCl2 produced no such effect. Treatment with ZnCl2 (0.5 mg/kg) 24 hr prior to bromobenzene injection failed to modify the pattern of the urinary metabolites of bromobenzene. When rats were given 50, 250, or 500 ppm of ZnCl2 in drinking water daily for 4 weeks prior to an ip injection of 2.5 mmol/kg bromobenzene, a reduction in the activities of serum transaminases was observed in 250 ppm ZnCl2-treated rats only. Such a reduction in the hepatotoxicity of bromobenzene is accompanied by a simultaneous reduction of the in vivo metabolism of bromobenzene by zinc, as substantiated by reduction of its urinary thioethers as well as of its total urinary metabolites. The present study has shown that changes in the metabolism and hepatotoxicity of bromobenzene depend on the dose of zinc administered, as well as on the temporal relationship between the zinc and bromobenzene administrations. The definitive mechanism responsible for such interactions remains to be elucidated.
Animals↗
Influence of selenium on the metabolism of bromobenzene and a possible relationship to its hepatotoxicity.
When male Sprague-Dawley rats were treated with sodium selenite (1 mg/kg, sc) 24 hr prior to or simultaneously with bromobenzene (2.5 mmol/kg, ip) and sacrificed 48 hr after the bromobenzene dose, increased levels of the activities of serum transaminases (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) induced in the bromobenzene-treated rats were significantly reduced in the presence of selenium. However, no such reduction in the transaminases activities were observed when rats were either pretreated with selenite for 48 hr or pretreated with 0.1, 0.2, or 0.5 mg/kg of selenite. Although selenium alone had no effect on the hepatic microsomal drug metabolism, simultaneous treatment of selenite (1 mg/kg) with bromobenzene resulted only an increase in the activity of aniline hydroxylase after 48 hr as compared to that in the bromobenzene-treated group. When rats were given 2.5, 10, and 20 ppm of selenite in drinking water daily for 4 weeks prior to an ip injection of 2.5 mmol/kg of bromobenzene and were sacrificed 48 hr after bromobenzene administration, a reduction in the SGOT activities in all the pretreated groups and a reduction of SGPT activity in 20 ppm selenite-treated group were observed when compared with those in the bromobenzene-treated groups. A dose-dependent increase in hepatic GSH concentrations were observed due to such chronic selenium treatment. Treatment with selenite (1 mg/kg) 24 hr prior to bromobenzene injection (2.5 mmol/kg) increased initially both o and p-bromophenols in the rat urine at 0-7.5 hr without affecting urinary thioethers. On the contrary, the ratio of thioethers to p-bromophenol was significantly higher in both 2.5 and 10 ppm selenite-pretreated (4 weeks) rats as well as a significant increase in the ratio of thioethers to total phenolic metabolites in 10 ppm and an increase close to significant in 2.5 ppm selenite-treated rats were observed initially at 0-7.5 hr urine samples. These results indicate that acute selenium pretreatment under certain conditions, favors increased hydroxylation of the intermediate bromobenzene epoxides, whereas higher detoxification of the epoxides involving hepatic glutathione (GSH)/GSH transferases pathway is more favored due to increased biosynthesis of GSH in certain chronic selenium treated rats.
Administration, Oral↗
Influence of simultaneous exposure to acrylonitrile and styrene on the toxicity and metabolism of styrene in rats.
Nine groups of adult male rats were given different combinations of styrene and acrylonitrile and each chemical was administered at three doses (styrene 0, 5.8, and 11.6 mmol/kg, ip; acrylonitrile 0, 0.3, and 0.6 mmol/kg, po). The animals were killed 24 hr later and blood and urine samples were collected. The results of biochemical analyses due to the toxicity of both chemicals and of the determination of urinary metabolites of styrene were then subjected to a factorial (3 X 3) analysis of variance. There was: (1) a significant elevation of blood urea nitrogen (BUN) and serum glutamic-pyruvic transaminase (SGPT), and a diminution of urinary creatinine due to styrene; (2) an increase in serum creatinine and serum glutamicoxaloacetic transaminase (SGOT) due to styrene that was further increased by acrylonitrile; and (3) an increase in the concentrations of urinary metabolites (thioethers, mandelic, phenylglyoxylic, and hippuric acids) due to styrene that was considerably reduced by acrylonitrile. These results suggest that styrene causes renal toxicity which may be potentiated by acrylonitrile; furthermore, the significant diminution of the urinary metabolites of styrene due to acrylonitrile obscures interpretation of the results of the biological monitoring of exposure to styrene.
Acrylonitrile↗
Dose-dependent metabolic excretion of bromobenzene and its possible relationship to hepatotoxicity in rats.
Male Sprague-Dawley rats received an intraperitoneal injection of 0.25-, 0.5-, 1.0-, 2.5-, and 5.0-mmol/kg dose of bromobenzene in corn oil. The metabolic fate of bromobenzene was studied by measuring its various urinary metabolites 24 h following bromobenzene administration. The hepatotoxicity of bromobenzene was estimated by determination of the serum glutamic-oxaloacetic and glutamic-pyruvic transaminase activities (SGOT and SGPT) 24 h after dosing. Treatment of rats with bromobenzene at up to 0.5 mmol/kg did not influence the transaminase activities, but significant increases in such activities began to manifest at a dose of 1 mmol/kg. However, no further increase in hepatotoxic response was induced on exposure to higher doses (2.5 and 5.0 mmol/kg) of bromobenzene. The urinary excretion of toxic doses of bromobenzene was nonlinear, based on the quantitative composition of various urinary metabolites. Furthermore, the fraction of the dose converted to thioethers, p-bromophenol, m-bromophenol, and total phenolic metabolites decreased with increasing toxic dose, suggesting their formation to be capacity-limited. The ratios of thioethers to total phenolic metabolites, of thioethers to p-bromophenol, and of thioethers to o-bromophenol decreased with increasing dose of bromobenzene. The correlation of the dose-dependent fate of metabolic excretion of bromobenzene with the results of the dose-hepatotoxic response curves supports the conclusion that there exists an apparent threshold dose (approximately 1-2.5 mmol/kg) for the toxic effects of bromobenzene that coincides with saturation of the metabolic pathways involving both glutathione/glutathione S-transferase(s) and formation of certain phenolic derivatives for its detoxification. All these results further suggest a role of a saturable, metabolic activation process involving 3,4-epoxide rather than 2,3-epoxide of bromobenzene in the development of its hepatotoxicity.
Animals↗
[Effect of growth retardation on the permeability of the blood-brain barrier in the newborn rat exposed to lead].
Postnatal administration of lead to young rats via maternal milk increases the permeability of the blood-brain barrier to trypan blue. However, since this regimen delays postnatal maturation, the question arises whether growth retardation per se could explain the altered permeability to the dye. The present investigation was undertaken to examine this possibility. A first group of newborn rats were fed by dams having free access to normal food; a second group was fed by dams receiving 3% lead as the acetate salt in their food; a third group was fed by dams whose normal diet was restricted to the amount taken daily by dams of the second group. Signs of encephalopathy as shown by urinary incompetence and hind-limb paralysis were observed only in your pups exposed to lead; similarly, only the latter showed increased brain permeability to trypan blue. These results suggest that the altered permeability of the blood-brain barrier in young rats is the direct consequence of lead toxicity and not of growth retardation secondary to a nutritional effect of lead.
Animals↗
The nephrotoxic potential of styrene in Sprague-Dawley rats.
Pre-fasted (16 h) Sprague-Dawley male rats were treated i.p. with 0, 0.2, 0.4, 0.8 and 1.2 g/kg of styrene in corn oil. Renal functions were assessed at 0-24, 24-48 and 48-72 h after the exposure. Urinary creatinine was decreased at 0.8 g/kg of styrene during 0-24 h after the treatment compared to control, whereas such a decrease was noticed in 1.2 g/kg styrene-treated rats when compared to control groups during 0-24 and 0-48 h after the dose. Urine pH and urinary contents of sodium, potassium and chloride were all decreased in a dose-dependent manner at 0.8 and 1.2 g/kg of styrene compared to both control animals during 0-24 h, whereas urinary proteins were not affected significantly. In another experiment, groups of pre-fasted (16 h) rats were treated i.p. with 0, 0.8 and 1.2 g/kg of styrene in corn oil and were then fasted for another 24 h to induce more stress prior to collection of blood and urine. Urinary pH and excretions of sodium and potassium were all decreased in styrene-treated rats 24 h after the dose. Urinary proteins were elevated and relative kidney weights were increased in 1.2 g/kg styrene-treated rats only compared to both control and 0.8 g/kg styrene-treated groups. A significant increase in serum creatinine and an increase close to significant in blood urea nitrogen were observed at 1.2 g/kg dose. These results suggest an impairment of renal functional parameters due to acute styrene exposure and further demonstrate a possible dose-dependent nephrotoxic potential of styrene in rats.
Animals↗
Presence of cadmium in the saliva of adult male workers.
Samples of mixed saliva were collected from 16 workers exposed to cadmium dusts and fumes and 19 unexposed co-workers. Samples of total blood and plasma were also obtained. Cadmium (Cd) was measured by flameless atomic absorption spectrometry. Cd was found in higher concentrations in saliva than in blood. The concentration of Cd in saliva was markedly elevated in exposed subjects; the difference was less important in blood. Smokers had more Cd in their blood than non-smokers, but this was not the case for saliva. In vitro studies measuring uptake of Cd by slices of rat submaxillary gland indicated that movement of the metal occurs passively.
Cadmium↗
Effects of microsomal induction and inhibition on styrene-induced acute hepatotoxicity in rats.
Administration of a single high dose of styrene (878 mg/kg ip in corn oil) to young male rats produced significant elevations in the activities of serum transaminases: 230, 209, and 71% increases in the activity of serum glutamic-oxaloacetic transaminase (SGOT) and 163, 437, and 227% in that of serum glutamic-pyruvic transaminase (SGPT) at 2, 6, and 24 h, respectively, after the dose. These results demonstrated that styrene could produce acute hepatic injury in young rats. Urinary nonprotein sulfhydryl contents and mandelic, phenylglyoxylic, and hippuric acids were all increased. Pretreatment of rats with phenobarbital and 3-methylcholanthrene did not further enhance the activities of SGOT and SGPT after styrene, but produced changes in other biochemical parameters, for example, an increase in liver weight, decrease in serum albumin and globulin concentrations, increase in serum alkaline phosphatase activity at 2 and 6 h, and increase in urinary urobilinogen concentrations. In addition, such pretreatments further increased the nonprotein sulfhydryl contents at 2 and 6 h after styrene injection. Pretreatment of rats with the microsomal enzyme inhibitor SKF 525-A failed to prevent the hepatotoxicity induced by styrene and did not modify the overall urinary excretion profiles of styrene metabolites. This study suggests that the mechanism of the activation/deactivation process leading to the metabolism and hepatotoxicity of styrene is complex and that alternative pathways not dependent on cytochrome P-450 might also be involved.
Alanine Transaminase↗