Metabolomics approach: Interpretation of changes in rat plasma metabolites after solifenacin treatment

Abstract Changes in metabolite levels of patients using the long-term drug can be comprehensively demonstrated by pharmacometabolomic studies. In this study, biological alterations induced by the administration of solifenacin succinate were investigated with a pharmacometabolomics approach on rat metabolism. Plasma samples obtained from rats were analyzed by LC-Q- TOF/MS/MS. METLIN and HMDB databases were used to identify metabolites. Data were processed and classified with MATLAB 2017b. 53 m/z values were found to be significantly different between the drug and control groups (p ≤ 0.01 and fold analysis > 1.5) and identified by comparing METLIN and HMDB databases. According to multivariate data analysis, changes in arachidonic acid, thromboxane A2, palmitic acid, choline, calcitriol, histamine phosphate, retinyl ester, l-cysteine, l-leucine, beta-alanine, l-histidine levels were found to be statistically significant compare to the control group. Differences in the biosynthesis of phenylalanine, aminoacyl-tRNA, tyrosine, tryptophan, metabolism of glycerophospholipid, cysteine, methionine, histidine, arachidonic metabolism have been successfully demonstrated by the metabolomics approach. Our study provides important information to explain the efficacy and toxicity of chronic administration of solifenacin succinate

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m2], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Valores elevados de leptina e LDL-colesterol em pacientes com hiperplasia adrenal congênita bem controlados / Elevated levels of leptin and LDL-cholesterol in patients with well controlled congenital adrenal hyperplasia

OBJETIVO: O objetivo deste estudo foi avaliar pacientes com HAC clássica antes e após tratamento com glicocorticoides e/ou mineralocorticoides e comparar o perfil metabólico entre o grupo bem controlado (BC) e mal controlado (MC). SUJEITOS E MÉTODOS: Foram selecionados pacientes recém-diagnosticados e pacientes em acompanhamento por HAC, forma clássica, em uso regular ou não de glicocorticoides/mineralocorticoides do Serviço de Genética do Hupes-UFBA, atendidos de março/2004 a maio/2006. Todos os pacientes foram submetidos a avaliação clínica detalhada e exames laboratoriais (glicemia, sódio e potássio, colesterol total, HDL, LDL, triglicerídeos, ácido úrico, leptina, 17-hidroxiprogesterona, testosterona total, peptídeo C e insulina). Os pacientes com valores normais de andrógenos foram classificados como bem controlados (BC) e os com valores elevados de andrógenos em uso ou não de glicocorticoides/mineralocorticoides foram classificados como mal controlados (MC). RESULTADOS: Foram estudados 41 pacientes com HAC: 11 no grupo BC e 30 no grupo MC. Leptina e LDL colesterol estavam mais elevados no grupo BC que no MC (p < 0,05). Valores de ácido úrico eram menores no grupo BC quando comparados com MC (p < 0,05). CONCLUSÃO: O controle adequado da HAC com glicocorticoides parece seguro, pois está associado a alterações discretas no perfil lipídico e da leptina. Não observamos outras alterações metabólicas associadas ao uso de glicocorticoides. O motivo para o menor valor de ácido úrico encontrado nos pacientes com HAC bem controlada não é conhecido e deve ser mais bem estudado.

OBJECTIVE: The objective of this study was to evaluate patients with classic CAH before and after treatment with glucocorticoids/mineralocorticoid and compare the metabolic profile of the well controlled (WC) and poorly controlled (PC) group. SUBJECTS AND METHODS: We selected newly diagnosed patients and patients monitored for CAH, classical form, regularly using or not glucocorticoids/mineralocorticoid in the Genetics Service Hupes-UFBA, seen from March/2004 to May/2006. All patients underwent detailed clinical evaluation and laboratory tests (glucose, sodium and potassium; total cholesterol, HDL, LDL, triglycerides and uric acid; leptin, 17-hydroxyprogesterone, total testosterone, C peptide, and insulin). Patients with normal androgens were classified as well controlled (WC), and those with high levels of androgens either using or not glucocorticoids/mineralocorticoids were classified as poorly controlled (PC). RESULTS: We studied 41 patients with CAH: 11 in the WC group and 30 in PC group. Leptin and LDL cholesterol levels were higher in WC than in the PC group (p < 0.05). Uric acid values ​​were lower in WC compared with the PC group (p < 0.05). CONCLUSION: Adequate control of CAH with steroids seems safe, as it is associated with only mild changes in lipid profile and leptin values. No other metabolic abnormality was associated with glucocorticoid use. The reason for lower uric acid levels found in WC CAH patients is unknown and should be further studied.