Species differences in the haemorrhagic response to butylated hydroxytoluene.
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Biomedical subjects
Publications and source records attributed to K Hiraga.
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Induction of testicular atrophy by monoesters of phthalic acid were compared in male Wistar rats. Dietary administration of monobutyl (MBP), mono-iso-butyl (MIBP) and mono-2-ethylhexyl phthalate (MEHP) induced severe atrophy of the testes. Furthermore, high testosterone concentration in the testes was found in MBP- and MIBP-treated rats, whereas low zinc concentration was found in MBP-, MIBP- and MEHP-treated rats. On the other hand, in monooctyl phthalate (MOP)-treated rats, testosterone and zinc concentrations in the testes were not changed. These were similar to the results with their diesters.
Effects of three phthalic acid esters (PAEs) on mouse testes are described and discussed. Zinc concentrations in the testes of mice fed a diet containing 2% dibutyl (DBP), di-iso-butyl (DIBP) or di-2-ethylhexyl phthalate (DEHP) were less than those of control animals. Testosterone concentrations in the testes were decreased in DEHP-treated mice, and the relative testis weight of DBP-, DIBP- and DEHP-treated mice was increased.
Effects of phthalic acid monoesters on mouse testes have been studied. Testosterone concentrations in the testes on mice fed diets containing 2% of mono-n-butyl (MBP), mono-iso-butyl (MIBP), mono-2-ethylhexyl (MEHP) or mono-n-octyl phthalate (MOP) were lower than in control animals and relative testicular weights were increased in all mice except those which received MOP. Zinc concentration in the testes decreased in mice that received MBP, MIBP or MEHP.
The concentration of phenols in the urine or feces of rats receiving a diet containing 1.00% butylated hydroxytoluene (BHT) for 10 days was determined colorimetrically. The cumulative intake of BHT was approx. 5.0 mmol/rat for 10 days. The total amount of phenols excreted in urine and feces was 3.65 mmol/rat for 10 days, i.e. 73% of the administered BHT. About 48% was excreted in the urine, and 25% in the feces; about 30%, or 11%, of the dose appeared to be present as unconjugated phenols in the urine, or feces, respectively. The major metabolite detected was 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT acid).
Male Sprague-Dawley rats were fed with 3,5-di-tert-butylphenol, 2,4-di-tert-butylphenol, 4-tert-butyl-2,6-diisopropylphenol, 2-tert-butyl-4-sec-butylphenol or 2-,6-di-tert-butyl-4-methylphenol (BHT) at a level of 2.27 mmol% in the diet for 1 week. One rat given 4-tert-butyl-2,6diisopropylphenol died: post mortem examination revealed hematocoelia, intratesticular, intraepididymal and intramuscular hematoma. The other rats in this group suffered from severe hemorrhagic anemia; and the prothombin index was significantly decreased.
Toxicity of tri-n-butyl phosphate (TBP) was investigated in male rats with special reference to body and organ weights, serum components and cholinesterase (ChE) activity. Body weights of the treated groups were significantly lower than those of the control group. There was no difference in ChE activity in the serum, but that in the brain was significantly increased in vivo. The blood coagulation time of treated groups was significantly prolonged.
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The effect of polychlorinated biphenyl (PCB), dibenzofuran (CDF) and dibenzo-p-dioxin (CDD) on endotoxin sensitivity was studied in male mice. The oral administration of CDF and CDD, once a week for 4 weeks, increased endotoxin sensitivity, whereas, PCB was not affective. On the other hand, residual levels of PCB were detected in thymus but CDF and CDD were not.
Glycine decarboxylase, tentatively called P-protein as a constituent of the glycine cleavage system, was purified to near homogeneity from rat liver mitochondria. The purified P-protein was a homodimer with a molecular weight of about 210,000, consisting of identical subunits with a molecular weight of 105,000. In the exchange reaction of the carboxyl carbon of glycine wih CO2 catalyzed by the purified P-protein in the presence of H-protein, the pH optimum was 6.7, Km for glycine was 6.6 mM, and Km for H-protein was 7.4 microM. A specific rabbit antibody against the purified rat liver P-protein was prepared. Ouchterlony double diffusion analysis and immunoinhibition experiments using this antibody revealed immunological cross-reactivity among the P-proteins from various species of animals such as carp, frog, snake, chicken, bovine, and human, suggesting a quite conservative evolution of the glycine cleavage system.
The effect of pretreatment with BHT on the binding of 14C-BHT to lung microsomes was examined in vitro. The amount of radioactivity bound to microsomal macromolecules significantly decreased by pretreatment of rats with BHT. This decrease was accompanied by a decrement in the content of cytochrome P-450 and in BHT oxidase activity. Furthermore, the behaviour of these components was dependent upon the dose of BHT given. On the other hand, these three components were unchanged in phenobarbital-pretreated rats.
Hepatic 9,000 x g supernatant (S9) fraction from 3-methylcholanthrene (MC)-treated rats showed a significantly low activity in the in vitro conversion of 2-acetylaminofluorene (AAF) to mutagen(s), while S9 fraction from untreated or phenobarbital (PB)-treated rats showed a remarkable activity. The S9 fraction from MC-treated rats actually suppressed the PB-S9 mediated AAF mutagenicity. Since the suppressive effect of MC-S9 was lost by the addition of 10(-4) M alpha-naphthoflavone (alpha-NF), rat specific cytochrome P-448 may be responsible for this suppressive effect.
We have examined the effect of dietary protein deficiency on rat hepatic drug-metabolizing enzyme system for a period of two months. Cytochrome P-450 and b5 contents in liver microsomes, which were plotted on semilogarithmic paper as a function of the time of deficiency, showed biphasical reductions during protein deficiency: rapid decreases in the first 3 weeks were followed by more gradual decreases. However, the three enzymatic activities examined, i.e. aminopyrine demethylase, aniline hydroxylase and p-nitroanisole demethylase, were not reduced at a uniform rate. In the earlier phase, activities of the former two enzymes were reduced more rapidly than that of the last phase. This biphasical and non-uniform reduction of enzymatic activities suggests the existence of two or more cytochrome P-450 subspecies in non-depleted male rats. Intraperitoneal administration of well-known environmental pollutants, polychlorinated dibenzofurans and biphenyls (100 micrograms and 100 mg/kg, respectively) to the depleted rats resulted in a marked induction of drug-metabolizing enzymes. However, as the deficiency became more severe (2 months), the induction declined to a considerable degree, especially in the case of polychlorinated biphenyl administration.
Five week-old, Wistar-JCL male and female rats and C57BL/6N male mice give a 0.5% butylated hydroxytoluene (BHT)-containing diet for 6 days produced a marked increase in hepatic weight and microsomal protein content. However, the augmentations of cytochrome P-450 content and drug oxidation activities were much more significant, i.e. 2.5-fold and more than three-fold increases were observed on a body weight basis, respectively. BHT-induced cytochrome P-450 cannot be distinguished from phenobarbital (PB)-induced cytochrome in many respects we have examined: i.e. 1) a broad substrate specificity; 2) absence of the blue shift in the CO-binding difference spectrum; 3) no rise in the peak height ratio of ethylisocyanide difference spectrum; 4) absence of alpha-naphthoflavone inhibition of p-nitroanisole demethylase activity; 5) marked increases of 50,000 and 54,000 molecular weight polypeptides in SDS-polyacrylamide gel electrophoresis. However, the induction of 46,000 molecular weight polypeptide by BHT in rats was more conspicuous than that by PB, and this induction was not observed in mice. In contrast to this marked induction, the administration of BHT to MC nonresponsive DBA/2N mice produced neither heptic enlargement nor induction of cytochromes, but did not produce an extremely high mortality.
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