RESUMEN
Oxidative stress may be contributory to the pathophysiology of the abnormalities that underlie the clinical course of sickle cell anemia. We looked for a possible genetic association between the functional polymorphism Ala-9Val in the human Mn-SOD gene and sickle cell anemia. One hundred and twenty-seven patients with sickle cell anemia and 127 healthy controls were recruited into the study. Alanine versus valine polymorphism in the signal peptide of the Mn-SOD gene was evaluated using a primer pair to amplify a 107-bp fragment followed by digestion with the restriction enzyme NgoMIV. In the sickle cell anemia patients, the frequency of Val/Val genotype was approximately 1.4-fold lower and that of Ala/Val was 1.3-fold higher compared to the controls. No significant difference in genotype frequencies was found between patients and controls (χ(2) = 4.561, d.f. = 2, P = 0.101). The Val-9 was the most common allele in patient and healthy subjects. No significant difference in allele frequencies was found between patients and controls (χ(2) = 1.496, d.f. = 1, P = 0.221). We conclude that the Mn-SOD gene polymorphism is not associated with sickle cell anemia.
Asunto(s)
Sustitución de Aminoácidos/genética , Anemia de Células Falciformes/genética , Polimorfismo Genético , Superóxido Dismutasa/genética , Adolescente , Adulto , Alanina/genética , Alelos , Anemia de Células Falciformes/enzimología , Niño , Preescolar , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Humanos , Masculino , Estrés Oxidativo , Superóxido Dismutasa/sangre , Superóxido Dismutasa/metabolismo , Valina/genéticaRESUMEN
The aim of this experimental study was to investigate the possible role of nitric oxide (NO) and the activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the pathogenesis of isoniazid (INH)-induced oxidative damage in red blood cells (RBCs), and also to show the effect of caffeic acid phenethyl ester (CAPE) and erdosteine, antioxidants, in decreasing this toxicity. A total of 25 adult male rats were divided into four experimental groups as follows: control group (n = 7), INH-treated group (n = 6), INH + CAPE-treated group (n = 6), and INH + erdosteine-treated group (n = 6). INH, INH-CAPE, and INH-erdosteine-treated groups were treated orally with INH 50 mg/kg daily and with the tap water for 15 days. Control group was given only tap water. CAPE was intraperitoneally injected for 15 days at a dose of 10 micromol/kg. Erdosteine was treated orally for 15 days at a dose of 10 mg/kg/day. The injection of INH led to a significant increase in the activities of ADA, XO, and NO levels in RBCs of rats. Co-treatment with CAPE caused a significant decrease in the activities of ADA and XO and the levels of NO in RBCs. In addition, co-treatment with erdosteine caused a significant decrease in the activities of ADA and XO and the levels of NO in RBCs. The results of this study showed that ADA, XO, and NO may play an important role in the pathogenesis of INH-induced oxidative stress in RBCs. CAPE and erdosteine may have protective potential in this process and they may become a promising drug in the prevention of this undesired side effect of INH.
Asunto(s)
Antioxidantes/farmacología , Antituberculosos/toxicidad , Ácidos Cafeicos/farmacología , Eritrocitos/efectos de los fármacos , Isoniazida/toxicidad , Óxido Nítrico/metabolismo , Purinas/metabolismo , Tioglicolatos/farmacología , Tiofenos/farmacología , Adenosina Desaminasa/metabolismo , Administración Oral , Animales , Modelos Animales de Enfermedad , Ingestión de Líquidos , Quimioterapia Combinada , Eritrocitos/metabolismo , Inyecciones Intraperitoneales , Masculino , Estrés Oxidativo/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Ratas , Ratas Wistar , Xantina Oxidasa/metabolismoRESUMEN
The aim of this study was to investigate the possible protective role of caffeic acid phenethyl ester on testicular toxicity of methotrexate in rats. Nineteen male rats were divided into three groups as follows: group I, control; group II, methotrexate-treated; group III, methotrexate + caffeic acid phenethyl ester-treated. In the second day of experiment, a single dose of methotrexate was intraperitoneally administered to groups II and III, although a daily single dose of caffeic acid phenethyl ester was intraperitoneally administered to group III for 7 days. At the end of the experiment, the testes of the animals were removed and weighed. In the tissue, the level of lipid peroxidation as malondialdehyde and activities of superoxide dismutase were higher in the methotrexate group than in the control group. Lipid peroxidation levels and superoxide dismutase activities were decreased in caffeic acid phenethyl ester + methotrexate group compared with methotrexate group. The activities of catalase in the methotrexate group decreased insignificantly although its activities were significantly increased by caffeic acid phenethyl ester administration. The activity of glutathione peroxidase did not change in the groups. There was significant difference in body weight between control and methotrexate-induced groups. In conclusion, the administration of methotrexate causes elevation of oxidative stress although treatment with caffeic acid phenethyl ester has protective effects on the oxidative stress in testes.
Asunto(s)
Antimetabolitos Antineoplásicos/toxicidad , Ácidos Cafeicos/farmacología , Citotoxinas/farmacología , Estrés Oxidativo/efectos de los fármacos , Alcohol Feniletílico/análogos & derivados , Testículo/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Antagonismo de Drogas , Inyecciones Intraperitoneales , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído , Metotrexato/toxicidad , Tamaño de los Órganos/efectos de los fármacos , Alcohol Feniletílico/farmacología , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Testículo/metabolismo , Testículo/patologíaRESUMEN
Leishmania sp. are obligate intracellular protozoa that infect and replicate within mammalian macrophages. Macrophages, neutrophils and other phagocytic cells are key components of the antimicrobial and tumoricidal immune responses. These cells are capable of generating large amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS). To examine antioxidant status and lipid peroxidation in cutaneous leishmaniasis (CL) patients, activities of two ROS scavenging enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and the levels of malondialdehyde (MDA) and nitric oxide (NO(.)) have been studied in serum. Blood samples were taken from CL patients before treatment (n = 27) and after the treatment (n = 18). NO(.) and MDA levels, SOD and GSH-Px activities were compared between untreated and treated CL patients and control subjects (n = 23). There was a significant decrease in SOD and GSH-Px activities in the CL patients (P < 0.0001). Significantly higher levels of serum MDA and NO(.) levels were found in CL patients, compared to controls and treated patients. It may be suggested that the overproduction of ROS and RNS results in oxidative stress and the acceleration of lipid peroxidation in CL patients, resulting from altered enzymatic antioxidant activities.