RESUMO
BACKGROUND: Oxidative stress plays an important role in the pathophysiology of diabetes mellitus. The aim of this study was to evaluate the formation of cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with impaired glucose tolerance (IGT) and diabetes. METHODS: Blood plasma levels of cholesterol oxidation products were determined in the following groups: type 1 diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (C1) and adults without diabetes (C2). The serum levels of cholest-5-ene-3alpha,7alpha-diol (7alpha-hydroxycholesterol, 7alpha-OH), cholest-5-ene-3beta,7beta-diol (7beta-hydroxycholesterol, 7beta-OH), 3beta-hydroxycholest-5-7-one (7-ketocholesterol, 7-K), 5alpha-cholestane-3beta,5,6beta-triol (cholestanetriol), 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol (cholesterol-5alpha,6alpha-epoxide,), 5,6beta-epoxy-5beta-cholestan-3beta-ol (cholesterol-5beta,6beta-epoxide) and cholest-5-eno-3beta,25-diol (25-hydroxycholesterol, 25-OH) (trivial name and abbreviations indicated in parentheses) were quantified by gas chromatography using flame ionization detection. RESULTS: The levels of total ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects without diabetes (p < 0.05). The concentrations of 7beta-hydroxycholesterol, cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral hypoglycemic drugs associated with insulin resulted in lower concentrations of nitrotyrosine in the blood plasma without significant changes in the concentrations of glucose and glycated hemoglobin. Moreover, combination with statins in both treatments decreased the concentrations of ChOx. CONCLUSIONS: ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients.
Assuntos
Colesterol/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Biomarcadores , Criança , Colestanóis/sangue , Colesterol/análogos & derivados , Colesterol/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Intolerância à Glucose/sangue , Humanos , Hidroxicolesteróis/sangue , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Cetocolesteróis/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Background Oxidative stress plays an important role in the pathophysiology of diabetes mellitus. The aim of this study was to evaluate the formation of cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with impaired glucose tolerance (IGT) and diabetes. Methods Blood plasma levels of cholesterol oxidation products were determined in the following groups: type 1 diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (C1) and adults without diabetes (C2). The serum levels of cholest-5-ene-3£/,7£/-diol (7£/-hydroxycholesterol, 7£/-OH), cholest- 5-ene-3£],7£]-diol (7£]-hydroxycholesterol, 7£]-OH), 3£]-hydroxycholest-5-7- one (7-ketocholesterol, 7-K), 5£/-cholestane-3£],5,6£]-triol (cholestanetriol), 5,6£/-epoxy-5£/-cholestan-3£/-ol (cholesterol-5£/,6£/-epoxide,), 5,6£]-epoxy- 5£]-cholestan-3£]-ol (cholesterol-5£],6£]-epoxide) and cholest-5-eno-3£],25-diol (25-hydroxycholesterol, 25-OH) (trivial name and abbreviations indicated in parentheses) were quantified by gas chromatography using flame ionization detection. Results The levels of total ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects without diabetes (p < 0.05).The concentrations of 7£]-hydroxycholesterol, cholesterol-£/-epoxide and cholesterol-£]-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral hypoglycemic drugs associated with insulin resulted in lower concentrations of nitrotyrosine in the blood plasma without significant changes in the concentrations of glucose and glycated hemoglobin. Moreover, combination with statins in both treatments decreased the concentrations of ChOx.Conclusions ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients. Copyright ÆÉ 2006 John Wiley & Sons, Ltd.
Assuntos
Colesterol , Hipoglicemia , Inibidores de Hidroximetilglutaril-CoA Redutases , Insulina , Lipídeos , ÓxidosAssuntos
Choque Séptico/fisiopatologia , Úlcera Gástrica/etiologia , Estômago/irrigação sanguínea , Animais , Pressão Sanguínea , Débito Cardíaco , Isótopos de Cério , Isótopos do Cromo , Endotoxinas/administração & dosagem , Escherichia coli , Mucosa Gástrica/irrigação sanguínea , Isquemia/complicações , Isquemia/etiologia , Microesferas , Fluxo Sanguíneo Regional , Choque Séptico/complicações , Estresse Fisiológico/complicações , SuínosAssuntos
Bile/metabolismo , Doenças Biliares/metabolismo , Clindamicina/metabolismo , Bioensaio , Colecistectomia , Colecistite/metabolismo , Colecistite/cirurgia , Clindamicina/análise , Clindamicina/sangue , Ducto Colédoco/análise , Vesícula Biliar/análise , Humanos , Staphylococcus/efeitos dos fármacos , Fatores de TempoRESUMO
Cephalexin was given to 24 patients before and after operation on the bile ducts and gall bladder. Two patients had obstructive jaundice. Samples of the bile were taken either directly from the gall bladder at operation or via the T-tube. Cephalexin was excreted in the bile, peak levels being obtained after two to three hours. These levels could be raised if probenecid was given concurrently. Higher levels were found in patients with functioning gall-bladders. A trial of cephalexin seems justified for the treatment of typhoid carriers.
