Paracetamol injury to rat liver slices, and its subsequent prevention by some anti-oxidants
| Autor: | Andre E. M. McLean, L. Nuttall |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
Time Factors
Metabolite In Vitro Techniques Biochemistry Promethazine Antioxidants Catechin chemistry.chemical_compound Hydrolysis biology.animal medicine Animals Acetaminophen Chromatography biology Phthalate Metabolism Small intestine Isocitrate Dehydrogenase Rats Methylene Blue Phthalic acid medicine.anatomical_structure chemistry Liver Potassium Dimethyl phthalate Baboon |
| Zdroj: | Biochemical Society transactions. 4(4) |
| ISSN: | 0300-5127 |
| Popis: | phthalate diesters were studied by the method of Albro & Thomas (1973) for cholatedispersed substrates. Portions of the incubated extracts were analysed by t.1.c. to permit the determination of the relative amounts of monoester and phthalic acid formed. Both rat hepatic post-mitochondria1 supernatant and intestinal-mucosal preparations hydrolysed di-n-butyl phthalate at a faster rate than di-(2-ethylhexyl) phthalate (Fig. 1). Generally, with both tissue preparations from all three species examined, the rates of hydrolysis of dimethyl, diethyl and di-n-butyl phthalates were much faster than those of di-n-octyl, di-(2ethylhexyl) and dicyclohexyl phthalates. In the hepatic studies a considerable species variation in the rate of hydrolysis of the phthalate esters was observed. The rate of hydrolysis of dimethyl phthalate by baboon and rat liver preparations was 14 and 2.7 times respectively the rate of metabolism by ferret hepatic preparations. With all the six phthalate diesters, liver preparations from the baboon were always the most active, whereas ferret liver preparations were the least active. In the intestinal-mucosal studies the preparations from the baboon and rat were again more active than the preparations from the ferret. For example, the rates of hydrolysis of dimethyl phthalate by baboon, rat and ferret intestinal-mucosal preparations were 6.7, 1 . 1 and 0.05 (pmol of product formed/h per mg. of intestinal-mucosal-cell protein) respectively. The examination of both hepatic and intestinal-mucosal-tissue incubated extracts from the three animal species revealed that with all six phthalate diester substrates examined the formation of the corresponding monoester accounted for more than 90% of the total metabolite formed. These results show that both hepatic and intestinal-mucosal preparations from all the three species examined were qualitatively similar with respect to the metabolism in vitro of phthalate diesters to the corresponding monoester derivatives. Thus orally administered phthalate diesters would probably be absorbed from the small intestine of the rat, ferret and baboon as the monoester derivatives. Further, these results show a similarity in metabolism between a rodent, a non-rodent and a primate species. It would clearly be desirable to study the metabolism of phthalate diesters by human intestinal-mucosal preparations to assess the present data in terms of the exposure of man to phthalates. |
| Databáze: | OpenAIRE |
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