RESUMEN
BACKGROUND: Metabolic syndrome (MetS) defines a well-known cluster of metabolic disturbances associated with an increased risk of cardiovascular disease and diabetes. The aim of this study was to examine the distribution of soluble lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (sLOX-1) levels in patients with MetS, possible association of sLOX-1 with oxidized LDL (oxLDL), endothelial nitric oxide synthase (eNOS), nitric oxide (NOx), endothelin-1 (ET-1), paraoxonase 1 (PON1), and arylesterase (ARE) activities, and these parameters compared with healthy controls. METHODS: A total of 55 patients (37 women, 18 men) with MetS and 29 healthy controls (19 women, 10 men) with a body mass index (BMI) less than 25 kg/m(2) were enrolled in the study. RESULTS: sLOX-1, oxLDL, and ET-1 levels were significantly higher in patients with MetS than in control subjects (P = 0.023 P < 0.001, and P < 0.001, respectively). MetS patients have significantly lower eNOS and NOx levels, and PON1 and ARE activities than control subjects (P = 0.017, P < 0.004, P < 0.001, and P = 0.010, respectively). A positive correlation was observed between the sLOX-1 levels and the oxLDL, ET-1, BMI, glucose levels. ET-1 levels also exhibited significant negative correlation with ARE activity. CONCLUSION: sLOX-1 levels are associated with cardiovascular risk factors, such as increased oxLDL, obesity, and diabetes, in patients with MetS. An increased concentration of sLOX-1 could be an early predictor of endothelial damage in MetS. In addition, it appears that oxLDL, ET-1, eNOS, NOx, PON1, and ARE activities may accurately reflect the levels of endothelial dysfunction in MetS patients.
Asunto(s)
Endotelina-1/sangre , Enfermedades Metabólicas/sangre , Receptores Depuradores de Clase E/sangre , Adulto , Arildialquilfosfatasa/sangre , Índice de Masa Corporal , Femenino , Humanos , Lipoproteínas LDL/sangre , Modelos Logísticos , Masculino , Enfermedades Metabólicas/metabolismo , Persona de Mediana Edad , Óxido Nítrico/sangre , Óxido Nítrico Sintasa de Tipo III/sangre , Curva ROCRESUMEN
AIM: The aim of the study was to evaluate circulatory AGE-peptide levels in diabetic nephropathy and to observe the effects of thiamine (vitamin B1) and pyridoxine (vitamin B6) therapy. METHODS: Type 2 diabetic patients (N.=57) were divided into two groups as "with nephropathy" (N.=27) and "without nephropathy" (N.=30). Diabetic nephropathy patients were treated with either B6 (N.=12) (250 mg/day) or B1+B6 (N.=15) (250 mg/day, each) for five months. At the beginning and the end of the experimentation period, glucose, HbA1c, triglyceride, cholesterol, insulin, C-peptide, thiamine pyrophosphate, pyridoxal phosphate and AGE- peptides were measured. RESULTS: AGE-peptides were higher in the diabetic group with nephropathy than without nephropathy (P=0.005). Within five months AGE-peptides increased in the diabetic group without nephropathy (P=0.042) but not in the group with nephropathy treated either with B1+B6 or B6. In B6 treated group a substantial decrease was observed in HbA1c (P=0.033). B1+B6 or B6 treatment both caused an increase in C-peptide (P=0.006, P=0.004). CONCLUSION: Among the parameters measured, plasma AGE-peptides was the only parameter found to be higher in type 2 diabetes mellitus patients "with nephropathy" than "without nephropathy". However, patients with nephropathy treated with B1+B6 or B6 did not display any further increase in AGE-peptides within five months. Both of the treatments caused an increase in C-peptide.
Asunto(s)
Péptido C/sangre , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Productos Finales de Glicación Avanzada/sangre , Piridoxina/uso terapéutico , Tiamina/uso terapéutico , Complejo Vitamínico B/uso terapéutico , Anciano , Anciano de 80 o más Años , Glucemia/análisis , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Fosfato de Piridoxal/sangre , Tiamina Pirofosfato/sangre , Triglicéridos/sangreRESUMEN
The effects of Cu(II) supplementation on glycemic parameters, advanced glycation end products (AGEs), antioxidant status (glutathione; GSH and total antioxidant capacity; TAOC) and lipid peroxidative damage (thiobarbituric acid-reactive substances, TBARS) were investigated in streptozotocin (STZ) induced diabetic rats. The study was carried out on Wistar albino rats grouped as control (n = 10), CuCl(2) treated (n = 9), STZ (n = 10) and STZ,CuCl(2) treated (n = 9). STZ was administered intraperitoneally at a single dose of 65 mg/kg and CuCl(2), 4 mg copper/kg, subcutaneously, every 2 days for 60 days. At the end of this period, glucose(mg/dl), Cu(microg/dl), TBARS(micromol/l), TAOC(mmol/l) were measured in plasma, GSH(mg/gHb) in erythrocytes and glycated hemoglobin (GHb)(%) in blood. Plasma AGE-peptides(%) were measured by HPLC flow system with spectrofluorimetric and spectrophotometric detectors connected on-line. Data were analyzed by the non-parametric Kruskal-Wallis and Mann-Whitney U test. In the STZ group glucose, GHb and AGE-peptide levels were all significantly higher than the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). CuCl(2) treated group had significantly lower glucose but significantly higher GHb, TAOC and TBARS levels than the control group (P < 0.05, P < 0.001, P < 0.05 and P < 0.001, respectively). STZ,CuCl(2) treated group had significantly higher GHb, TAOC and TBARS levels compared with the control group (P < 0.001, P < 0.05 and P < 0.05, respectively); but only TAOC level was significantly higher than the STZ group (P < 0.01). This experimental study provides evidence that copper intake increases total antioxidant capacity in both nondiabetic and diabetic states. However despite the potentiated antioxidant defence, lipid peroxidation and glycation enhancing effects of CuCl(2) are evident under nondiabetic conditions.
Asunto(s)
Antioxidantes/metabolismo , Cobre/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Suplementos Dietéticos , Productos Finales de Glicación Avanzada/metabolismo , Animales , Diabetes Mellitus Experimental/inducido químicamente , Modelos Animales de Enfermedad , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Estreptozocina , Tiobarbitúricos/metabolismoRESUMEN
OBJECTIVES: In this study, plasma lipid peroxidation as assessed by thiobarbituric acid reactive substances and erythrocyte antioxidant status markers namely CuZn superoxide dismutase, glutathione peroxidase, glutathione and plasma levels of vitamin C and E were investigated in 20 patients with larygneal carcinoma and 15 healthy controls. DESIGN AND METHODS: Lipid peroxidation was observed to be significantly higher (0.01 > p > 0.001) in the larynx carcinoma group in comparison to the healthy controls. Both stage I + 11 and stage III carcinoma patients were observed to have significantly higher thiobarbituric acid reactive substances than the control group. A significant difference was found in plasma vitamin E level between the control group and stage I + 11 and stage III carcinoma patients (p < 0.01, 0.05 > p > 0.02, respectively). RESULTS: Our findings reveal the presence of increased lipooxidative damage in laryngeal carcinoma patients, but no change with respect to the endogenous antioxidant components-GSH, GSH Px, and CuZn SOD.
Asunto(s)
Carcinoma de Células Escamosas/sangre , Neoplasias Laríngeas/sangre , Estrés Oxidativo/fisiología , Adulto , Antioxidantes/análisis , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Neoplasias Laríngeas/patología , Peroxidación de Lípido/fisiología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Vitamina E/sangreRESUMEN
Oxidative stress was compared in plasma of 15 recently diagnosed (<2 mo) or 15 longstanding (>5 yr) type 1 diabetic patients with 15 healthy volunteers. Lipid peroxidation indices measured in plasma included thiobarbituric acid-reactive substances (TBARS), conjugated dienes, and lipid hydroperoxide (ROOH). The values obtained were corrected for phospholipid to minimize this as a confounding factor. In recently diagnosed diabetics, plasma conjugated lipid dienes were significantly elevated. However, in longstanding diabetics there was a marked increase in TBARS, conjugated dienes, and lipid hydroperoxide levels. Our findings showed increased oxidative stress in type 1 diabetics regardless of metabolic control and that conjugated diene measurement appeared to be the most sensitive bioindicator of oxidant stress in our population.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Estrés Oxidativo/fisiología , Adulto , Envejecimiento/metabolismo , Albuminuria/orina , Diabetes Mellitus Tipo 1/complicaciones , Nefropatías Diabéticas/sangre , Neuropatías Diabéticas/sangre , Retinopatía Diabética/sangre , Femenino , Humanos , Peróxidos Lipídicos/metabolismo , Lípidos/sangre , Masculino , Fosfolípidos/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factores de TiempoRESUMEN
In this study it was of interest to evaluate the impact of nitric oxide (NO) modulation by administration of arginine/NAME, on oxidative stress in experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid. Arginine was used to increase NO levels while NAME lowered oxidant levels. Histopathological findings of colon revealed mucosal inflammation in all groups but significantly higher with arginine alone. The levels of NO and of thiobarbituric acid-reactive substances (TBARS, a marker of lipid peroxidation) were observed to be significantly higher in the arginine-administered group compared to glycine, and these levels were found to decrease on administration of NAME to both glycine- and L-arginine-administered groups. Glutathione peroxidase (GSH-Px) activity and glutathione (GSH) levels were significantly higher in arginine administered group compared to glycine. Significantly higher CuZn superoxide dismutase (CuZn-SOD) activity was observed in the L-arginine + L-NAME group compared to arginine. Data show that NO plays a role in oxidant damage found in experimental colitis and that the use of NAME may potentially inhibit injury.
Asunto(s)
Arginina/farmacología , Colitis/metabolismo , Inhibidores Enzimáticos/farmacología , Peroxidación de Lípido/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Análisis de Varianza , Animales , Colitis/inducido químicamente , Colon/efectos de los fármacos , Colon/patología , Modelos Animales de Enfermedad , Glutatión/sangre , Glutatión Peroxidasa/sangre , Masculino , Óxido Nítrico Sintasa/antagonistas & inhibidores , Ratas , Ratas Wistar , Superóxido Dismutasa/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Ácido Trinitrobencenosulfónico/efectos adversosRESUMEN
Oxidative stress parameters and nitric oxide (NO) values were determined in 27 newly diagnosed Basedow patients before and after 1 mo of propylthiouracil (PTU) therapy and in 15 healthy controls. Basedow patients exhibited increased triiodothyronine (T3) and thyroxine (T4) and decreased thyroid-stimulating hormone (TSH) values compared to controls. Significantly higher thiobarbituric acid-reactive substances (TBARS), NO and glutathione (GSH) levels, and CuZn superoxide dismutase (CuZn SOD) activity were found in Basedow patients in comparison to controls, regardless of sex. Treatment with PTU (3 x 100 mg/d for 30 d) was effective in decreasing T1 and T4 and increasing TSH levels. Significantly decreased NO and TBARS and increased GSH and CuZn SOD levels were observed in PTU-treated Basedow patients compared to pre-PTU administration. PTU-treated patients compared to controls still exhibited significantly higher T3 and lower TSH values and higher NO, TBARS, GSH, and CuZn SOD levels. The induced antioxidant defense and decrease in NO) values in response to PTU therapy emphasizes the role of PTU as an antithyroid drug, where the ability to diminish hyperthyroidism results in decreased catabolism and lower oxidant generation.
Asunto(s)
Antitiroideos/uso terapéutico , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/fisiopatología , Óxido Nítrico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Propiltiouracilo/uso terapéutico , Adulto , Eritrocitos/metabolismo , Femenino , Glutatión/sangre , Enfermedad de Graves/metabolismo , Humanos , Masculino , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
This study was designed to investigate the effect of hyperthyroidism and/or iron supplementation or cardiac oxidative stress parameters--the lipid peroxidation end product glutathione (GSH), glutathione peroxidase (CSH-Px), and superoxide dismutase (CuZnSOD)--in rats. In plasma, ferritin as an indicator of iron status and glutamate oxaloacetate transaminase (GOT) as an indicator of damage to the heart tissue were analyzed. Our findings show that hyperthyroidism increased lipooxidative damage as reflected by higher lipid peroxidation end product levels and elevated antioxidant defense parameters-GSH and GSH-Px. Iron supplementation per se does not affect oxidative stress parameters studied in the euthyroid state. Although iron increased lipid peroxidation in the hyperthyroid state, this effect was less than that seen in euthyroidism. Iron supplementation to hyperthyroid rats significantly lowered plasma ferritin levels, suggesting increased iron elimination with consequently reduced oxidative stress.
Asunto(s)
Hipertiroidismo/metabolismo , Hierro/farmacocinética , Miocardio/metabolismo , Estrés Oxidativo , Animales , Aspartato Aminotransferasas/sangre , Suplementos Dietéticos , Modelos Animales de Enfermedad , Ferritinas/sangre , Glutatión/análisis , Glutatión Peroxidasa/análisis , Hierro/administración & dosificación , Peroxidación de Lípido , Masculino , Miocardio/enzimología , Ratas , Ratas Wistar , Superóxido Dismutasa/análisis , Hormonas Tiroideas/sangreRESUMEN
Increased production of oxygen free radicals and infiltration of neutrophils into tissue subjected to ischemia-reperfusion have emphasized that neutrophils play a direct role in the development of injury. The present study was designed to elucidate the effect of FK506, a new immunosuppressive drug, on 11 hours of complete ischemia and reperfusion of the inguinal island skin flaps in rats. Group 1 (n = 10) control animals underwent ischemia and reperfusion and no treatment. Group 2 (n = 10) animals received FK 506 0.3 mg/kg/day, and group 3 (n = 9) animals received 0.5 mg/kg/day intramuscularly for 3 days before the ischemia. The effect of the drug was evaluated by measuring flap survival and tissue malondialdehyde content and myeloperoxidase activity and also by histopathologic examination of the skin specimens taken at the 1st and 24th hour after reperfusion. The survival of flaps controlled for 7 days was found to be significantly improved in group 2 (65.0 +/- 10.93 percent) and group 3 (93 +/- 6.25 percent) when compared with the control group (14 +/- 10.12 percent) (p < 0.04 and p < 0.0001). The tissue contents of malondialdehyde and activities of myeloperoxidase were significantly lower in groups 2 and 3 than in the control group. Three days of pretreatment with FK506 significantly reduced neutrophil infiltration in groups treated with either of the doses. These results showed that neutrophils play an important role in island flap survival associated with ischemia-reperfusion injury. Increased neutrophil infiltration was found related with increased levels of malondialdehyde and myeloperoxidase. Flap necrosis and the increase in malondialdehyde, myeloperoxidase, and neutrophil infiltration were improved by FK506 pretreatment, a neutrophil modulating agent.
Asunto(s)
Neutrófilos/fisiología , Daño por Reperfusión/patología , Trasplante de Piel/patología , Colgajos Quirúrgicos/patología , Animales , Radicales Libres/metabolismo , Supervivencia de Injerto/efectos de los fármacos , Ingle , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Inyecciones Intramusculares , Isquemia/metabolismo , Isquemia/patología , Isquemia/fisiopatología , Recuento de Leucocitos/efectos de los fármacos , Masculino , Malondialdehído/análisis , Activación Neutrófila/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Peroxidasa/análisis , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Piel/química , Piel/enzimología , Piel/patología , Trasplante de Piel/fisiología , Colgajos Quirúrgicos/irrigación sanguínea , Colgajos Quirúrgicos/fisiología , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéuticoRESUMEN
This study was performed on 17 hyperthyroid patients and 15 healthy controls. The patients were under propylthiouracil (PTU) therapy at a dosage of 3 x 100 mg/day for one month. Blood samples, taken at the beginning and on the 30th day of therapy, were analyzed for hormonal parameters (T3, T4, TSH), lipid peroxidation endproduct [thiobarbituric acid reactive substances (TBARS)] and antioxidant status parameters: glutathione (GSH), glutathione peroxidase (GSH-Px) and CuZn superoxide dismutase (CuZn SOD). Hyperthyroid patients were observed to have significantly higher TBARS, GSH and CuZn SOD levels than controls (P < 0.05, P < 0.001, P < 0.001, respectively). PTU therapy caused a relief in oxidative stress as reflected by significantly decreased TBARS levels (P < 0.001) and a selective modification in the antioxidant status parameters: significant decreases in GSH and CuZn SOD levels (P < 0.001) and a significant increase in GSH Px (P < 0.01) activity. Our findings suggest a selective modification of the antioxidative profile in hyperthyroidism. PTU should also be considered as an in vivo antioxidant, in addition to its antithyroid action.
Asunto(s)
Antitiroideos/uso terapéutico , Glutatión/sangre , Hipertiroidismo/tratamiento farmacológico , Hipertiroidismo/metabolismo , Peróxidos Lipídicos/metabolismo , Oxidorreductasas/sangre , Propiltiouracilo/uso terapéutico , Adulto , Eritrocitos/metabolismo , Femenino , Glutatión Peroxidasa/sangre , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Superóxido Dismutasa/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
The antioxidant defense system in liver tissue in experimental hyperthyroidism and/or in iron supplementation was investigated. Thyroid hormones (T3, T4, TSH), ferritin (marker of iron status), antioxidant status components (glutathione [GSH], glutathione peroxidase [GSH-Px], superoxide dismutase [SOD]), and serum transaminases (GOT and GPT, both of which are known to be released from damaged hepatocytes), were measured. Hyperthyroidism in rats, induced by L-thyroxine administration, significantly raised SOD activity (p < 0.05), but significantly decreased GSH-Px activity and GSH values (p < 0.001) in the liver. In the L-thyroxine administered and iron supplemented (TI) group, GSH and GSH-Px values of liver tissues were significantly lower than those of control rats (p < 0.05). GSH-Px levels of the TI group were higher (p < 0.001), and SOD levels significantly lower (p < 0.001) than those of the L-thyroxine administered group. We conclude that hyperthyroidism induces SOD activity in liver; ferritin levels increase in hyperthyroidism, contributing to the antioxidant defense system; GSH-Px and GSH levels are decreased significantly in hyperthyroidism either due to inactivation due to increased oxidative stress or to insufficient synthesis; iron supple- and GPT analysis); iron decreases the effect of T4. This must be taken into consideration during iron supplementation.
Asunto(s)
Hipertiroidismo/metabolismo , Hierro/farmacología , Hígado/metabolismo , Animales , Suplementos Dietéticos , Ferritinas/sangre , Glutatión/análisis , Glutatión Transferasa/análisis , Hígado/enzimología , Masculino , Ratas , Ratas Wistar , Superóxido Dismutasa/análisis , Hormonas Tiroideas/sangre , Tiroxina/toxicidadRESUMEN
BACKGROUND: It is well known that advanced glycation plays an important role in the progression of diabetic complications. Although several studies have been done on protein glycation, studies related to DNA glycation is limited. The aim of this study is primarily to investigate DNA glycation in diabetes mellitus and secondarily to observe the effects of vitamins B(1) and B(6). MATERIALS AND METHODS: Patients with diabetes (n=31) were divided into 2 groups as patients with nephropathy (n=17) and without nephro-pathy (n=14). The control group was recruited from age and sex matched healthy individuals (n=30). In the experimental groups, DNA glycation was measured in DNA isolated from leukocytes. HbA(1c), thiamine pyrophosphate (TPP) and pyridoxal 5-phosphate (PLP) levels were determined in whole blood; glucose and insulin levels in plasma. Patients with nephropathy were further divided into 2 groups and were administered either vitamins B(1) + B(6) (n=6) or B(6) (n=11), for 5 months. All the measurements were performed both before and after the vitamin administration period. RESULTS: AGE-DNA levels were found significantly higher in diabetic patients (p<0.05) than the healthy controls. AGE-DNA and PLP levels were negatively correlated in control patients (r= - 0.361, p<0.05). The combined administration of B(1) and B(6) caused a significant decrease in AGE-DNA values (p<0.05). CONCLUSION: This study shows that the combined administration of vitamins B(1) and B(6) to diabetic nephropathy patients causes a decrease in DNA glycation in leukocytes. Importantly the administration of vitamin B(6) alone did not have such an effect. To our knowledge, these are the first reported findings related to glycation of leukocyte nuclear DNA in diabetic nephropathy.
Asunto(s)
ADN/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Piridoxina/farmacología , Tiamina/farmacología , Anciano , Glucemia/análisis , ADN/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/metabolismo , Femenino , Hemoglobina Glucada/análisis , Productos Finales de Glicación Avanzada/sangre , Glicosilación/efectos de los fármacos , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Piridoxina/uso terapéutico , Tiamina/uso terapéutico , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The impact of exercise tolerance test on oxidative stress was assessed by thiobarbituric acid reactive substances and markers of antioxidant status, namely Cu Zn superoxide dismutase, glutathione peroxidase, glutathione and vitamin E in blood samples of patients with exertional angina. The study was aimed to differentiate patients with positive exercise test (coronary heart disease patients) from patients with negative exercise test, at rest and peak exercise with respect to the investigated variables. Significantly lower values for both glutathione peroxidase activity and glutathione level were observed in patients after exercise test (p<0.01 and p<0.05, respectively). Only the patients with positive exercise test had significantly lower values for Cu Zn superoxide dismutase, glutathione peroxidase and glutathione, and a significantly higher ratio of thiobarbituric acid reactive substances/glutathione after exercise, as compared to before (p<0.05, p<0.05, p<0.05, p<0.01, respectively). Our findings indicate that the exercise test applied to patients with exertional angina oxidatively stresses the erythrocytes to a greater extent in exercise test (+) patients than in exercise test (-) patients.
Asunto(s)
Antioxidantes/análisis , Enfermedad Coronaria/fisiopatología , Ejercicio Físico , Estrés Oxidativo , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Adulto , Anciano , Biomarcadores/sangre , Femenino , Glutatión/sangre , Glutatión Peroxidasa/sangre , Humanos , Masculino , Persona de Mediana Edad , Superóxido Dismutasa/sangre , Vitamina E/sangreRESUMEN
The purpose of this study was to investigate the role of neutrophils in ischemic tissue injury and the possible inhibition by pretreatment with FK506, a neutrophilic modulating agent. A dorsal caudally based skin flap (3 x 9 cm) was used as an ischemic injury model in experimental groups. Prior to flap elevation, FK506 at doses of 0.3 mg per kilogram (group 2), 0.5 mg per kilogram (group 3), and 1.0 mg per kilogram (group 4) was given for 3 days intramuscularly. The relationship among neutrophil accumulation (histopathologically), myeloperoxidase (MPO) activity, malondialdehyde (MDA) content (biochemically) of the flap tissue, and flap survival were studied. Skin flaps showed reduced necrosis in the FK506-treated groups (p < 0.08, p < 0.0001, and p < 0.0001 respectively). The increase in accumulation of neutrophils, and MDA and MPO levels (which were induced by ischemia) observed 1 and 24 hours after flap elevation was diminished by FK506 pretreatment. The increased neutrophilic infiltration, and raised tissue MDA content and MPO activity revealed involvement of both free radical production and neutrophils in ischemia. This injury was decreased by FK506, probably by inhibition of neutrophilic chemotaxis, infiltration, and releasing factors.
Asunto(s)
Inmunosupresores/farmacología , Isquemia/etiología , Neutrófilos/fisiología , Colgajos Quirúrgicos/irrigación sanguínea , Tacrolimus/farmacología , Animales , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/fisiología , Isquemia/metabolismo , Isquemia/patología , Masculino , Malondialdehído/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/patología , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Piel/irrigación sanguínea , Piel/metabolismo , Piel/patología , Colgajos Quirúrgicos/patología , Colgajos Quirúrgicos/fisiologíaRESUMEN
OBJECTIVE: To measure the amount of lipid peroxidation and erythrocyte antioxidation in patients undergoing laparoscopic and open cholecystectomy and healthy controls. DESIGN: Non-randomised study. SETTING: University hospital, Istanbul. SUBJECTS: 31 patients, of whom 14 underwent open and 17 laparoscopic cholecystectomy, and 15 healthy controls. INTERVENTIONS: Heparinised blood samples were taken from the patients immediately after operation and from the healthy controls. MAIN OUTCOME MEASURES: Lipid peroxidation index as expressed by thiobarbituric-acid-reactive substances (TBARS) and components of the erythrocyte antioxidant defence system, namely reduced glutathione, reduced glutathione peroxidase (glutathione-Px) and CuZn superoxide dismutase (CuZn SOD) in patients undergoing open or laparoscopic cholecystectomy and healthy controls. RESULTS: All 4 variables were significantly higher in the cholecystectomy groups than in controls (p < 0.001), and laparoscopic cholecystectomy caused significantly less oxidative stress than the open operation (p < 0.001). CONCLUSION: Both types of cholecystectomy cause oxidative stress and lead to an adaptive antioxidant response in the body. However; both oxidative stress and the antioxidant response are more pronounced after traditional open cholecystectomy.
Asunto(s)
Colecistectomía Laparoscópica , Colecistectomía , Eritrocitos/metabolismo , Depuradores de Radicales Libres/sangre , Peroxidación de Lípido , Estudios de Casos y Controles , Femenino , Glutatión/sangre , Glutatión Peroxidasa/sangre , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Superóxido Dismutasa/sangre , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
In this study the impact of vitamin C supplementation on oxidative damage as assessed by thiobarbituric acid reactive substances and markers of antioxidant status: namely Cu/Zn superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione were investigated in 24 hyperthyroid patients under propylthiouracil therapy (3x100 mg/day) for five days and in 15 healthy controls. Ascorbic acid (1000 mg/day) was given as a supplement for 1 month to both the patients and controls during the study period. Heparinised blood samples were taken at the beginning and the end of one month ascorbic acid supplementation. Comparison of the hyperthyroid patients with the controls revealed higher lipid peroxidation (p<0.001), higher Cu/Zn superoxide dismutase activity (p<0.001), higher glutathione level (p<0.001) and lower glutathione reductase activity (p<0.001). Vitamin C supplementation to hyperthyroid patients caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase activity (p<0.001), whereas there were significant decreases in glutathione reductase (p<0.001) and Cu/Zn superoxide dismutase activities (p<0.01). Thiobarbituric acid reactive substances and thiobarbituric acid reactive substances/glutathione ratio were significantly decreased (p<0.01). Vitamin C supplementation to euthyroid controls caused significant increases in glutathione concentration (p<0.001) and glutathione peroxidase and Cu/Zn superoxide dismutase activities (p<0.001), whereas there was a significant decrease in glutathione reductase (p<0.001). The thiobarbituric acid reactive substances/glutathione ratio was significantly decreased (p<0.05). Our findings reveal the potentiation of antioxidant status and a relief in oxidative stress in both propylthiouracil treated hyperthyroid patients and controls in response to vitamin C supplementation.
Asunto(s)
Antitiroideos/uso terapéutico , Ácido Ascórbico/administración & dosificación , Hipertiroidismo/tratamiento farmacológico , Estrés Oxidativo , Propiltiouracilo/uso terapéutico , Adulto , Estudios de Casos y Controles , Femenino , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Humanos , Hipertiroidismo/enzimología , Hipertiroidismo/metabolismo , Masculino , Persona de Mediana Edad , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido TiobarbitúricoRESUMEN
Secondary venous ischemia caused by anastomotic failure is one of the major causes of failure after free tissue transfers and replantations. The effects of cyclosporin A (CsA) on secondary ischemic injury associated with neutrophil infiltration and lipid peroxidation were evaluated in a rat inferior epigastric island skin flap model. Primary ischemia was produced by arteriovenous occlusion for 2 hours. Twenty-four hours later, secondary venous ischemia was produced by 5 hours of venous occlusion. Nonischemic (n = 5), primary ischemic (n = 5), and secondary ischemic control groups (n = 10), and four treatment groups (n = 10) were created. Treatment groups received either 15 or 30 mg per kilogram per day oral CsA for 3 days before flap elevation, or 15 or 30 mg per kilogram intravenous CsA at 4 hours of secondary venous ischemia. Flap survival area, malondialdehyde (MDA) content, and myeloperoxidase (MPO) activity were assayed for each group. The mean flap survival area of the high-dose posttreatment group was significantly higher than the secondary ischemic control group (29% +/- 39% vs. 3% +/- 8%; p < 0.05, Student's t-test). The MDA and MPO levels of each treatment group were significantly lower than the secondary ischemic control group at hours 1 and 24 (p < 0.0001, Student's t-test). The lowest MDA and MPO levels were achieved in the high-dose posttreatment group. Results suggest that CsA may improve flap survival after secondary venous ischemia by attenuating neutrophil infiltration and by reducing lipid peroxidation.