Efeito dos aditivos do tabaco na iniciação e manutenção do tabagismo

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Effects of pregnancy and protein-energy malnutrition on monooxygenase O-dealkylation activity in rat liver microsomes

Submitted by Fátima Lopes ([email protected]) on 2019-11-25T17:00:51Z No. of bitstreams: 1 EffectsPregnacy.pdf: 168734 bytes, checksum: 5db99ca4bccae86c857927c72fb142f3 (MD5)Approved for entry into archive by Fátima Lopes ([email protected]) on 2019-11-25T17:20:23Z (GMT) No. of bitstreams: 1 EffectsPregnacy.pdf: 168734 bytes, checksum: 5db99ca4bccae86c857927c72fb142f3 (MD5)Made available in DSpace on 2019-11-25T17:20:23Z (GMT). No. of bitstreams: 1 EffectsPregnacy.pdf: 168734 bytes, checksum: 5db99ca4bccae86c857927c72fb142f3 (MD5) Previous issue date: 2000Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.Xenobiotic metabolism is influenced by a variety of physiological and environmental factors including pregnancy and nutritional status of the individual. Pregnancy has generally been reported to cause a depression of hepatic monooxygenase activities. Low-protein diets and protein-energy malnutrition have also been associated with a reduced activity of monooxygenases in nonpregnant animals. We investigated the combined effects of pregnancy and protein-energy malnutrition on liver monooxygenase O-dealkylation activity. On pregnancy day 0 rats were assigned at random to a group fed ad libitum (well-nourished, WN) or to a malnourished group (MN) which received half of the WN food intake (12 g/day). WN and MN rats were killed on days 0 (nonpregnant), 11 or 20 of pregnancy and ethoxy- (EROD), methoxy- (MROD) and penthoxy- (PROD) resorufin O-dealkylation activities were measured in liver microsomes. Only minor changes in enzyme activities were observed on pregnancy day 11, but a clear-cut reduction of monooxygenase activities (pmol resorufin min-1 mg protein-1) was noted near term (day 0 vs 20, means ± SD, Student t-test, P<0.05) in WN (EROD: 78.9 ± 15.1 vs 54.6 ± 10.2; MROD: 67.8 ± 10.0 vs 40.9 ± 7.2; PROD: 6.6 ± 0.9 vs 4.3 ± 0.8) and in MN (EROD: 89.2 ± 23.9 vs 46.9 ± 15.0; MROD: 66.8 ± 13.8 vs 27.9 ± 4.4; PROD: 6.3 ± 1.0 vs 4.1 ± 0.6) dams. On pregnancy day 20 MROD was lower in MN than in WN dams. Malnutrition did not increase the pregnancy-induced reduction of EROD and PROD activities. Thus, the present results suggest that the activities of liver monooxygenases are reduced in near-term pregnancy and that protein-energy malnutrition does not alter EROD or PROD in pregnant rats

A newly validated high-performance liquid chromatography method with diode array ultraviolet detection for analysis of the antimalarial drug primaquine in the blood plasma

Abstract INTRODUCTION: Primaquine (PQ) diphosphate is an 8-aminoquinoline antimalarial drug with unique therapeutic properties. It is the only drug that prevents relapses of Plasmodium vivax or Plasmodium ovale infections. In this study, a fast, sensitive, cost-effective, and robust method for the extraction and high-performance liquid chromatography with diode array ultraviolet detection (HPLC-DAD-UV ) analysis of PQ in the blood plasma was developed and validated. METHODS: After plasma protein precipitation, PQ was obtained by liquid-liquid extraction and analyzed by HPLC-DAD-UV with a modified-silica cyanopropyl column (250mm × 4.6mm i.d. × 5μm) as the stationary phase and a mixture of acetonitrile and 10mM ammonium acetate buffer (pH = 3.80) (45:55) as the mobile phase. The flow rate was 1.0mL·min-1, the oven temperature was 50OC, and absorbance was measured at 264nm. The method was validated for linearity, intra-day and inter-day precision, accuracy, recovery, and robustness. The detection (LOD) and quantification (LOQ) limits were 1.0 and 3.5ng·mL-1, respectively. The method was used to analyze the plasma of female DBA-2 mice treated with 20mg.kg-1 (oral) PQ diphosphate. RESULTS: By combining a simple, low-cost extraction procedure with a sensitive, precise, accurate, and robust method, it was possible to analyze PQ in small volumes of plasma. The new method presents lower LOD and LOQ limits and requires a shorter analysis time and smaller plasma volumes than those of previously reported HPLC methods with DAD-UV detection. CONCLUSIONS: The new validated method is suitable for kinetic studies of PQ in small rodents, including mouse models for the study of malaria