Flávio Reis

Effects of Sitagliptin Treatment on Dysmetabolism, Inflammation, and Oxidative Stress in an Animal Model of Type 2 Diabetes (ZDF Rat)

The purpose of this paper is to evaluate the chronic effect of sitagliptin on metabolic profile, inflammation, and redox status in the Zucker Diabetic Fatty (ZDF) rat, an animal model of obese type 2 diabetes. Diabetic and obese ZDF (fa/fa) rats and their controls (ZDF +/+) were treated during 6 weeks with vehicle (control) and sitagliptin (10 mg/kg/bw). Glucose, HbA1c, insulin, Total-c, TGs, IL-1β, TNF-α, CRPhs, and adiponectin were assessed in serum and MDA and TAS in serum, pancreas, and heart. Pancreatic histology was also evaluated. Sitagliptin in diabetic rats promoted a decrease in glucose, HbA1c, Total-c, and TGs accompanied by a partial prevention of insulinopenia, together, with a decrease in CRPhs and IL-1β. Sitagliptin also showed a positive impact on lipid peroxidation and hypertension prevention. In conclusion, chronic sitagliptin treatment corrected the glycaemic dysmetabolism, hypertriglyceridaemia, inflammation, and hypertension, reduced the severity of the histopathological lesions of pancreatic endocrine and exocrine tissues, together with a favourable redox status, which might be a further advantage in the management of diabetes and its proatherogenic comorbidities.

Diabetic Nephropathy Amelioration by a Low-Dose Sitagliptin in an Animal Model of Type 2 Diabetes (Zucker Diabetic Fatty Rat)

This study was performed to assess the effect of chronic low-dose sitagliptin, a dipeptidyl peptidase 4 inhibitor, on metabolic profile and on renal lesions aggravation in a rat model of type-2 diabetic nephropathy, the Zucker diabetic fatty (ZDF) rat. Diabetic and obese ZDF (fa/fa) rats and their controls ZDF (+/+) were treated for 6 weeks with vehicle (control) or sitagliptin (10 mg/kg/bw). Blood/serum glucose, HbA1c, insulin, Total-c, TGs, urea, and creatinine were assessed, as well as kidney glomerular and tubulointerstitial lesions (interstitial fibrosis/tubular atrophy), using a semiquantitative rating from 0 (absent/normal) to 3 (severe and extensive damage). Vascular lesions were scored from 0–2. Sitagliptin in the diabetic rats promoted an amelioration of glycemia, HbA1c, Total-c, and TGs, accompanied by a partial prevention of insulinopenia. Furthermore, together with urea increment prevention, renal lesions were ameliorated in the diabetic rats, including glomerular, tubulointerstitial, and vascular lesions, accompanied by reduced lipid peroxidation. In conclusion, chronic low-dose sitagliptin treatment was able to ameliorate diabetic nephropathy, which might represent a key step forward in the management of T2DM and this serious complication.

Interleukin (IL)-22, IL-17, IL-23, IL-8, vascular endothelial growth factor and tumour necrosis factor-α levels in patients with psoriasis before, during and after psoralen-ultraviolet A and narrowband ultraviolet B therapy.

Background  Several cross‐sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis.

C-reactive protein and leucocyte activation in psoriasis vulgaris according to severity and therapy

Background  Psoriasis vulgaris is a chronic recurrent inflammatory skin disease and psoriatic lesions have shown leucocyte infiltration.

Circulating adipokine levels in Portuguese patients with psoriasis vulgaris according to body mass index, severity and therapy

Background  Psoriasis vulgaris is associated with overweight/obesity and with increased C‐reactive protein (CRP), tumour necrosis factor (TNF)‐α, interleukin (IL)‐6, leptin and resistin levels and decreased adiponectin levels.

Exercise training decreases proinflammatory profile in Zucker diabetic (type 2) fatty rats

OBJECTIVE In the present study we evaluated the effect of exercise on the plasma levels of proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory molecule uric acid in the Zucker diabetic fatty (ZDF) rats that are more prone to develop type 2 diabetes mellitus. METHODS Sixteen obese ZDF (Gmi fa/fa) rats (8 wk old, 228.40 +/- 4.05 g) were randomly assigned to one of two groups (n = 8 each): an exercise-trained group and a sedentary one. In addition, 16 lean ZDF (Gmi +/+) rats (8 wk old, 199.00 +/- 3.50 g) were subjected to identical sedentary and exercise conditioning (n = 8 each). Initially, rats swam 15 min/d (5 d/wk) in a 36 degrees C bath. The exercise protocol was gradually increased by 15 min/d until a swimming period of 1 h/d (1 wk) was attained. Thereafter, rats swam 1 h/d, 3 d/wk, for an additional period of 11 wk. Rats were sacrificed 48 h after the last training period and the blood and pancreas were collected. Circulating levels of glucose, glycosylated hemoglobin, total cholesterol, triglycerides, insulin, uric acid, IL-6, and TNF-alpha were assessed. The concentrations of proinflammatory cytokines in the pancreas were also evaluated. RESULTS In the diabetic ZDF (fa/fa) rats, exercise decreased hyperuricemia (-37.3%) and IL-6 and TNF-alpha levels (-16.9% and -12.7% respectively) and maintained the weight of the pancreas at near normal. Immunohistochemistry revealed a marked decrease in the expression of TNF-alpha and IL-6 in the pancreatic islet cells of ZDF (fa/fa) rats. CONCLUSION These results indicate that aerobic exercise is anti-inflammatory in nature.

Regular Physical Exercise as a Strategy to Improve Antioxidant and Anti-Inflammatory Status: Benefits in Type 2 Diabetes Mellitus

Over the last 30 years the combination of both a sedentary lifestyle and excessive food availability has led to a significant increase in the prevalence of obesity and aggravation of rates of metabolic syndrome and type 2 diabetes mellitus (T2DM). Several lines of scientific evidence have been demonstrating that a low level of physical activity and decreased daily energy expenditure leads to the accumulation of visceral fat and, consequently, the activation of the oxidative stress/inflammation cascade, which underlies the development of insulin resistant T2DM and evolution of micro, and macrovascular complications. This paper focuses on the pathophysiological pathways associated with the involvement of oxidative stress and inflammation in the development of T2DM and the impact of regular physical exercise (training) as a natural antioxidant and anti-inflammatory strategy to prevent evolution of T2DM and its serious complications.

Protective effects of the dipeptidyl peptidase IV inhibitor sitagliptin in the blood–retinal barrier in a type 2 diabetes animal model

Aim: The aim of this study was to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV inhibitor (DPP‐IV), in preventing the deleterious effects of diabetes on the blood–retinal barrier in male Zucker Diabetic Fatty (ZDF) rats.

Sitagliptin Prevents Inflammation and Apoptotic Cell Death in the Kidney of Type 2 Diabetic Animals

This study aimed to evaluate the efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor, in preventing the deleterious effects of diabetes on the kidney in an animal model of type 2 diabetes mellitus; the Zucker diabetic fatty (ZDF) rat: 20-week-old rats were treated with sitagliptin (10 mg/kg bw/day) during 6 weeks. Glycaemia and blood HbA1c levels were monitored, as well as kidney function and lesions. Kidney mRNA and/or protein content/distribution of DPP-IV, GLP-1, GLP-1R, TNF-α, IL-1β, BAX, Bcl-2, and Bid were evaluated by RT-PCR and/or western blotting/immunohistochemistry. Sitagliptin treatment improved glycaemic control, as reflected by the significantly reduced levels of glycaemia and HbA1c (by about 22.5% and 1.2%, resp.) and ameliorated tubulointerstitial and glomerular lesions. Sitagliptin prevented the diabetes-induced increase in DPP-IV levels and the decrease in GLP-1 levels in kidney. Sitagliptin increased colocalization of GLP-1 and GLP-1R in the diabetic kidney. Sitagliptin also decreased IL-1β and TNF-α levels, as well as, prevented the increase of BAX/Bcl-2 ratio, Bid protein levels, and TUNEL-positive cells which indicates protective effects against inflammation and proapoptotic state in the kidney of diabetic rats, respectively. In conclusion, sitagliptin might have a major role in preventing diabetic nephropathy evolution due to anti-inflammatory and antiapoptotic properties.

Role of prohepcidin, inflammatory markers and iron status in resistance to rhEPO therapy in hemodialysis patients.

The aim of our study was to assess possible relations between prohepcidin, iron status and inflammatory markers in hemodialysis (HD) patients, as well as its association with resistance to recombinant human erythropoietin (rhEPO) therapy. Fifty HD patients and 25 healthy controls were enrolled in the study. Among HD patients, 25 were non-responders and 25 were responders to rhEPO therapy. Complete blood cell count, reticulocyte count, and circulating levels of ferritin, iron, transferrin saturation, C-reactive protein (CRP), soluble interleukin (IL)-2 receptor (s-IL2R), soluble transferrin receptor (s-TfR), IL-6 and prohepcidin were measured in all patients and controls. HD patients showed higher circulating levels of ferritin, s-TfR, CRP, IL-6, s-IL2R and prohepcidin, and lower levels of transferrin compared to healthy controls. Higher levels of s-TfR, CRP and lower levels prohepcidin were observed among non-responders compared to responders. Prohepcidin levels correlated negatively with s-TfR and reticulocyte count. The weekly rhEPO/kg dose was found to be positively correlated with CRP, hemoglobin and s-TfR. In conclusion, our data show that a close interaction exists between inflammation, iron status and prohepcidin serum levels that ultimately regulate intracellular iron availability. Prohepcidin and s-TfR, together with CRP, may prove to be good markers of resistance to rhEPO therapy in HD patients.