RESUMEN
INTRODUCTION: Increasing the human lifespan contributes to a higher number of patients with end-stage organ failure, which in turn stimulates the search for alternative sources. Xenotransplantation seems to be a promising approach in this respect. OBJECTIVE: Analysis of changes in interleukin (IL)-6 concentration during 24-hour preservation of transgenic swine livers, depending on the kind of transgenesis and preservation solution used. MATERIALS AND METHODS: The experiment was carried out in swine livers with transferred human genes that were divided into 5 groups. The following human genes were transferred: α1,2-fucosyltransferase (group I and II), α-galactosidase (III), combined α1,2-fucosyltransferase/α-galactosidase transgene (IV), and livers without modification (V). The livers were perfused and subsequently stored for 24 hours in Ringer's (group I) or Biolasol solutions (II-V). Reflush was then performed. IL-6 concentration was analyzed in the solution samples collected at the beginning and end of perfusion, and after 24 hours of preservation. ELISA was used to evaluate IL-6 concentration. RESULTS: In liver homogenates from group I, IL-6 concentration after 24 hours of preservation increased by 8.24% compared to the levels observed after perfusion, whereas in the other groups IL-6 concentration decreased. The most significant decrease, 49.51%, was observed in group II; the least significant in group IV, 10.72%. In case of supernatants, a statistically significant increase of AUC0-30min level in relation to perfusion was observed in every group after 24-hour preservation and reperfusion. The highest values of AUC0-30min were observed in group I (α1,2-fucosyltransferase, Ringer's solution). CONCLUSION: The study indicates the hepatoprotective action of Biolasol solution.
Asunto(s)
Fucosiltransferasas/genética , Interleucina-6/metabolismo , Hígado/metabolismo , alfa-Galactosidasa/genética , Animales , Animales Modificados Genéticamente , Humanos , Soluciones Isotónicas , Preservación de Órganos/métodos , Soluciones Preservantes de Órganos , Perfusión , Reperfusión , Solución de Ringer , PorcinosRESUMEN
Four-month-old female Wistar rats were exposed for 20 days to tobacco smoke obtained from non-filter cigarettes. During the exposure, concentration of tobacco smoke was monitored indirectly by measuring the CO level (1500 mg/m3 air). The efficacy of exposure was assessed by measuring urine nicotine and cotinine levels. Cigarette smoke did not change total cytochrome P450 and b5 protein levels in any of the organs studied, and most of these organs did not show any changes in the activity of reductases associated with these cytochromes. Following exposure to tobacco smoke, fetal rat liver expressed CYP2B1/2 protein; in newborns (day 1) both liver and lung showed CYP2B1/2 protein expression and very low pentoxyresorufin O-dealkylase activity. Western blot analysis of adult liver, lung, heart, but not of brain microsomes, showed that tobacco smoke induced CYP2B1/2 in both nonpregnant and pregnant rats, though its expression was lower in the livers and hearts of pregnant females. In the rat and human placenta, neither rat CYP2B1/2 nor human CYP2B6 showed basal or tobacco smoke-induced expression at the protein level. This study shows clearly that the expression of CYP2B1/2, which metabolizes nicotine and some drugs and activates carcinogens, is controlled in rats by age-, pregnancy-, and tissue-specific regulatory mechanisms.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Citocromo P-450 CYP2B1/biosíntesis , Sistema Enzimático del Citocromo P-450/biosíntesis , Exposición Materna , Fumar , Esteroide Hidroxilasas/biosíntesis , Animales , Cotinina/metabolismo , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Hígado/efectos de los fármacos , Hígado/embriología , Hígado/metabolismo , Pulmón/efectos de los fármacos , Pulmón/embriología , Pulmón/metabolismo , Nicotina/metabolismo , Placenta/efectos de los fármacos , Placenta/metabolismo , Embarazo , Preñez , ARN Mensajero/metabolismo , Ratas , Ratas WistarRESUMEN
The aim of the study was to evaluate the effect of acetaminophen (APAP) and/or trichloroethylene (TRI) on the liver cytochrome P450-dependent monooxygenase system, CYP2E1 and CYP1A2 (two important P450 isoforms), and liver glutathione (GSH) content in rats. Rats were given three different doses of APAP (250, 500 and 1000 mg/kg b...) and then the above-mentioned parameters were measured for 48 h. The lowest APAP dose produced small changes in the cytochrome P450 content of liver. At 500 mg/kg APAP increased the cytochrome P450 content to 230% of the control. The inductive effect was seen at 1000 mg/kg dose but at 24 h and later. NADPH-cytochrome P450 reductase activity was the highest after the lowest dose of APAP, while after the highest dose it was equal to the control value. TRI increased both the cytochrome P450 content and the NADPH-cytochrome P450 reductase activity. When TRI was combined with APAP, both these parameters increased in the first hours of observation, but they returned to the control values at 24 h. When APAP was given at 250 mg/kg, GSH levels decreased to 55% of the control at 8 h and returned to the control values at 24 h. The higher doses of APAP decreased GSH levels more than the lowest dose, but after 24 h GSH levels did not differ from those of the control. When TRI was given at 250 mg/kg, the GSH levels decreased to 68% of the control at 2 h and then they increased gradually and tended to exceed the control values at 48 h. The effect of TRI combined with APAP on the level of GSH was virtually the same as that of APAP alone given at 500 mg/kg.