RESUMEN
We have studied the association of polymorphic variants of CYP2C9 genes with the risk of drug-induced liver injury (DILI) during antiretroviral therapy of HIV-infected patients. The analysis of polymorphic variants of CYP2C9*2.(Argl44Cys) and CYP2C9*3 (Ile359Leu) genes showed that the dominant genotype of CYP2C9*2 was the honiozygous CC carriership and for CYP2C9*3 it was the prevalence of AA genotype, the incidence of which was close and amounted to 80%. There was no association of these genotypes CYP2C9 with the risk of DILI. Thus, the carriership of individual C and T alleles in the case of CYP2C9*2 gene, as well as A and C for CYP2C9*3 is not a predictor of antiretroviral DILI.
Asunto(s)
Antirretrovirales/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Citocromo P-450 CYP2C9/genética , Genotipo , Infecciones por VIH , Polimorfismo Genético , Alelos , Antirretrovirales/administración & dosificación , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1 , Humanos , MasculinoRESUMEN
The aim of the present study was to investigate the role of nitric oxide (NO) in the regulation of hemoglobin oxygen affinity (HOA) in the presence of different oxygen partial pressure. In this research the effect of NO donors on gas-transport, acid-base balance, HOA indexes, metHb, iron-nitrosylhemoglobin amounts, and total nitrite/nitrate concentration was estimated in vitro. Experimentally, positive correlation was found between NO-dependent shift of HOA and hemoglobin oxygen saturation level. In conclusion, NO is a component of autonomous intraerythrocytic system of HOA regulation, which action is determined by oxygen in the blood. We assume that the physiological significance of such NO action is to maintain aerobic metabolism through optimal blood oxygenation in the pulmonary circulation, on the one hand, and, on the other hand, its compensation under low oxygen tension in the working tissues.
Asunto(s)
Hemoglobinas/química , Óxido Nítrico/química , Oxígeno/química , Equilibrio Ácido-Base , Animales , Cisteína/análogos & derivados , Cisteína/química , Espectroscopía de Resonancia por Spin del Electrón , Hidrazinas/química , Concentración de Iones de Hidrógeno , Masculino , Metahemoglobina/química , Nitratos/sangre , Donantes de Óxido Nítrico/química , Nitritos/sangre , Oxihemoglobinas/química , Conejos , S-Nitroso-N-Acetilpenicilamina/química , S-Nitrosotioles/químicaRESUMEN
Peroxynitrite (ONOO-) besides its toxic possesses regulatory action that includes the modulation of oxygen binding properties of blood. The aim of this work was to estimate ONOO- effect on the haemoglobin oxygen affinity (HOA) in vitro in presence of different partial pressure of carbon dioxide (CO2). The ONOO- presence in venous blood in conditions of hypercapnia induced oxyhaemoglobin dissociation curve shift leftward while in hypocapnic conditions the result of a different character was obtained. The revealed effect of ONOO- is realized, possibly, through various modifications ofhaemoglobin whose formation is dependent on the CO2 pressure. The ONOO- influences the HOA in different manner that can be important in regulation of blood oxygenation in lungs and maintenance of oxygen consumption in tissues.
Asunto(s)
Dióxido de Carbono/sangre , Hemoglobinas/metabolismo , Hipercapnia/sangre , Hipocapnia/sangre , Oxígeno/sangre , Ácido Peroxinitroso , Animales , Hemoglobinas/química , Masculino , Oxidación-Reducción/efectos de los fármacos , Presión Parcial , Ácido Peroxinitroso/farmacología , Unión Proteica/efectos de los fármacos , ConejosRESUMEN
The biological roles of nitric oxide (NO)-hemoglobin (Hb) derivatives are obscure. It is proposed that NO can function as an allosteric regulator of hemoglobin oxygen-binding properties. We aimed to estimate the effects of NO donors and NO-synthase substrate (L-arginine) on hemoglobin-oxygen affinity (HOA) in experiments in vitro with the various ratios between NO formed and Hb and various oxygen pressures. HOA index (p50), blood pH, plasma and red blood cell (RBC) concentrations of nitrite/nitrate and methemoglobin amounts were measured after the experiments. In our experiments, blood incubation with NO donors (glyceryltrinitrate, molsidomine, sodium nitroprusside, S-nitrosocysteine) or NO-synthase substrate (L-arginine) did not change HOA even at NO:Hb ratio of 1:1. At the same time our results showed that oxygenated blood incubation with S-nitrosocysteine induced an oxyhemoglobin dissociation curve shift leftwards. This indicates a leading role of met-Hb in a modification of Hb oxygen-binding properties. However other NO-modified forms of hemoglobin (S-nitroso- and nitrosylhemoglobin) also may be involved in the regulation of HOA. The results obtained indicate that nitric oxide can be the allosteric effector of hemoglobin, increasing or decreasing its oxygen affinity - possibly, through the generation of different NO-Hb derivatives.