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1.
J Biochem Mol Toxicol ; 38(1): e23609, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38037266

RESUMO

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia due to insulin deficiency and/or resistance. Vitamin K (VK) is a group of fat-soluble molecules, including naturally occurring vitamin K1 (phylloquinone). vitamin K2 (menaquinone), and synthetic vitamin K3 (menadione). Beyond coagulation, the health benefits of VK have been described to play different roles in both physiological and pathological processes such as inflammation, energy metabolism, neuroprotection, cellular growth, and survival. It was aimed to observe the antioxidant and/or neuroprotective activity of vitamin K1 in our model of chick embryo diabetic neuropathy (DN) induced by streptozotocin (STZ). Ninety White Leghorn, fertile and 0-day-old SPF (specific pathogen-free) eggs (57 ± 4 gr) were used in the study. Chick embryo blood brain tissues were taken for biochemical evaluation. Plasma insulin and glucose levels were measured. In addition, brain tissue total antioxidant level (TAS), total oxidant level (TOS), malondialdehyde (MDA), and vascular endothelial growth factor (VEGF) levels were measured. Plasma glucose levels were higher in the STZ-treated groups and lower in the treatment groups. Plasma insulin levels were observed to be higher in STZ groups in groups treated with high VK. Low TAS, high MDA, TOS, and VEGF levels were recorded in brain tissue STZ groups. Low VEGF, TOS, and MDA levels were recorded in the group treated with the highest VK, while high TAS levels were observed. In our STZ-induced chick embryo diabetic neuropathy model, we observed that VK1 reduced oxidant damage by showing antioxidant properties or by modulating antioxidant enzymes.


Assuntos
Diabetes Mellitus Experimental , Neuropatias Diabéticas , Embrião de Galinha , Animais , Antioxidantes/efeitos adversos , Vitamina K , Fator A de Crescimento do Endotélio Vascular , Vitamina K 1/efeitos adversos , Estreptozocina/efeitos adversos , Galinhas/metabolismo , Neuropatias Diabéticas/induzido quimicamente , Neuropatias Diabéticas/tratamento farmacológico , Neuroproteção , Diabetes Mellitus Experimental/induzido quimicamente , Vitamina K 3 , Vitamina K 2/efeitos adversos , Vitamina K 2/metabolismo , Insulina , Oxidantes , Glicemia/metabolismo
2.
Eur J Ophthalmol ; 31(5): 2535-2545, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33008266

RESUMO

PURPOSE: To determine the levels of serum oxidative, antioxidative markers and inflammatory cytokines in patients diagnosed with diabetic macular edema (DME) whose hyperreflective spots (HRS) were detected by optical coherence tomography (OCT). METHODS: In this prospective cross-sectional clinical study included a total of 88 patients; 31 patients (group-1) with DME and HRS detected by OCT, 29 patients (group-2) with DME without HRS, and 28 patients (group-3) diagnosed with diabetes mellitus (DM) without any diabetic retinopathy findings. The main outcomes were best-corrected visual acuity (BCVA), CMT (central macular thickness), CMV (central macular volume), TMV (total macular volume), CT (choroidal thickness), serum TAS (total antioxidant status), TOS (total oxidant status), VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor) and IL-1b levels. OCT parameters and biochemical measurements were compared statistically between the three groups. RESULTS: A total of 88 patients (43 females (48.9%) and 45 males (51.1%)) were included in the study. The mean age was 56.29 ± 9.23 years. There was no difference between the three groups in age-and-sex. In group-1 and 2, BCVA(LogMAR) was statistically higher than group 3. CMT, CMV, TMV, TAS, TOS, VEGF and FGF were significantly higher in group-1 than in group-3. CMT, CMV, TMV, VEGF and FGF were significantly higher in group-2 than group 3. TOS and VEGF were significantly higher in group-1 than group-2. CONCLUSIONS: This study demonstrates that in patients with DME and HRS, TOS and VEGF levels were higher than those without HRS. Hence, hyperreflective spots may be an inflammatory biomarker.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Idoso , Estudos Transversais , Citocinas , Retinopatia Diabética/diagnóstico , Feminino , Humanos , Edema Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Prospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
3.
Drug Dev Res ; 77(1): 12-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26748675

RESUMO

Preclinical Research Trans-resveratrol has a wide range of biological effects that reflect its antioxidant, anti-inflammatory, anticarcinogenic and cardioprotective properties. This study was conducted to elucidate the potential role of resveratrol on hepatic inflammation and the apoptotic pathway components Bcl-2, Bax and p53 in a streptozotocin (STZ)-induced rat model of diabetes mellitus. Inflammatory and apoptotic biomarkers indicated a reduction in hepatic erythropoietin (1.26-fold) and increased asymmetric dimethylarginine (3.9-fold), visfatin (1.6-fold), inflammatory interleukins and TNF-α contents (approximately twofold each) in the diabetic animals. Induction of inducible nitric oxide synthase gene (2.04-fold) and protein expression (1.24-fold) was also observed. Immunohistochemical studies showed enhancement of the apoptotic biomarkers Bax and p53 in diabetic animals. STZ-induced diabetic male Wistar rats were treated with resveratrol (20 mg/kg/day i.p.). Resveratrol succeeded to recover most of these inflammatory and apoptotic elements. Therefore, inflammatory and apoptotic pathways were proved to be affected by STZ-induced diabetes in several aspects and resveratrol might contribute hepatoprotective effects as evidenced from this study.


Assuntos
Anti-Inflamatórios/administração & dosagem , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Fígado/imunologia , Estilbenos/administração & dosagem , Animais , Anti-Inflamatórios/farmacologia , Apoptose , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/patologia , Eritropoetina/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Interleucinas/metabolismo , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Resveratrol , Estilbenos/farmacologia , Estreptozocina , Fator de Necrose Tumoral alfa/metabolismo
4.
Gene ; 570(2): 213-20, 2015 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-26071184

RESUMO

Diabetes mellitus is a heterogeneous metabolic disorder essentially characterized by deficiency of insulin secretion, insulin receptor or post-receptor events. This study aims to investigate the effects of resveratrol administration on the metabolic characteristics, hepatic functions, histopathological features and insulin signaling pathway components in streptozotocin induced diabetes. Male Wistar rats were randomly divided into four groups: (1) control/vehicle; (2) control/20mg/kg resveratrol; (3) diabetic/vehicle; and (4) diabetic/20mg/kg resveratrol. Histopathological examinations were carried out to reveal hepatic tissue damage and inflammation. In addition to hepatic glucose, lipid, insulin, ALT, AST, resistin and XOD contents, gene and protein expressions of insulin signaling pathway components such as insulin Rß, IRS-1, IRS-2, eNOS, PI3K, Akt, and FOXO3a were analyzed by qRT-PCR and Western blot. The rats in the diabetes group had significantly lower terminal body weight and hepatic insulin level, but significantly higher hepatic glucose, total cholesterol, triglyceride and resistin concentrations. Diabetes triggered the inflammatory process in the liver tissues that was evidenced by histopathological deformations and increase in the hepatic ALT and AST levels. Hepatic inflammation was considerably associated with insulin signaling pathway ever since a significant down-regulation of insulin signaling components; IRS-1, IRS-2, PI3K, Akt and mTOR have been identified in the diabetic group. To some extent, resveratrol treatment reversed the diabetes-induced changes in the liver tissues. Taken together, resveratrol partly improved hepatic dysfunction induced by diabetes. This may be due to the healing activity of resveratrol on insulin signaling pathway, resistin levels and hepatic glucose-lipid contents.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Inflamação/prevenção & controle , Insulina/metabolismo , Fígado/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Resveratrol , Estreptozocina
5.
Clin Exp Nephrol ; 14(5): 463-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20589406

RESUMO

INTRODUCTION: As a treatment method for chronic renal failure (CRF), hemodialysis (HD) alters inorganic components containing trace elements. It was shown that decreased renal function is accompanied by insufficient antioxidant systems and/or increased free oxygen radicals. In this study, we aimed to investigate the effects of HD on trace element levels and oxidative stress markers. METHODS: We included 111 CRF patients on HD treatment three times a week and 24 healthy controls. Patients were divided into four groups according to HD duration. Plasma malondialdehyde (MDA), protein carbonyls and total sulfhydryl (-SH) levels, zinc (Zn), copper (Cu), and magnesium (Mg) levels, and erythrocyte superoxide dismutase (SOD) activity were measured from blood taken from patients before HD. RESULTS: SH levels and SOD activity in all groups were significantly lower than those in the control group (p < 0.001). All groups had significantly higher plasma MDA levels than did controls (p < 0.001). Whereas there was no significant difference in -SH levels and SOD activity between groups, increased periods of HD were associated with increases in MDA. MDA levels of the third and fourth groups were significantly higher than in the first and second groups (p < 0.05, p < 0.001, respectively). There was no significant difference of Zn, Cu, Mg, and protein carbonyl levels in and between all groups. However, plasma Cu levels and MDA concentrations were correlated (r = 0.26, p < 0.01). CONCLUSION: Prolonged exposure to HD can cause increased oxidative damage but has no effect on trace element concentration.


Assuntos
Biomarcadores/sangue , Falência Renal Crônica , Estresse Oxidativo , Diálise Renal/efeitos adversos , Oligoelementos/sangue , Adulto , Idoso , Cobre/sangue , Eritrócitos/enzimologia , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Superóxido Dismutase/sangue , Fatores de Tempo
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