Vitamin D downregulates key genes of diabetes complications in cardiomyocyte.

OBJECTIVE: Vitamin D deficiency has been reported to be associated with the incidence of type 1 and type 2 diabetes and worsening of diabetes complications. This study was designed to investigate the effect of vitamin D treatment on the expression of five key genes involved in the development of diabetic cardiomyopathy. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups. The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin (STZ) to develop diabetes. Then groups were treated for 4 weeks either with placebo or vitamin D (two injections of 20,000 IU/kg). Serum levels of glucose, insulin, HbA1c, and advanced glycation end products (AGEs), as well as the gene expression of AGE cellular receptor (RAGE), glyoxalase, aldose reductase, O-GlcNAc transferase (OGT), and glutamine-fructose-6-phosphate aminotransferase (GFAT) and nuclear factor-kB (NF-kB) activity of nuclear extracts were assessed at the end of experiment. RESULTS: Increment in serum cholecalciferol could improve hyperglycaemia and hypoinsulinemia in diabetic rats. In addition, a significant reduction was observed in RAGE, OGT, and GFAT gene expression and NF-kB activity in cardiac myocytes. CONCLUSIONS: Vitamin D might contribute in reducing diabetic cardiomyopathy not only by improving blood glucose and insulin levels but also via downregulating AGE and hexosamine pathways and decreasing NF-kB activity in heart tissue.

Quercetin improves bone strength in experimental biliary cirrhosis.

AIM: Metabolic bone disorders and reduced bone mass are common complications in patients with biliary cirrhosis. As a result of there being no clear etiology, no specific therapy has been established yet. Previous studies have reported that quercetin, a plant-derived flavonoid, might improve bone quality. The present study was designed to investigate the effect of quercetin on bone strength of biliary cirrhotic rats. METHODS: Twenty-four male Sprague-Dawley rats aged 6-7 months were randomized into three groups of eight. One group served as control (sham operated), while the other two groups underwent a complete bile duct ligation (BDL). Four weeks after the operation, serum bilirubin, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase were measured in animal blood samples to confirm the occurrence of cirrhosis in the BDL rats. Then, one of the BDL groups received placebo and the other one was injected once a day with 150 µmol/kg of quercetin for 4 weeks. At the end of the study, femora were removed and tested for bone strength and histomorphometric parameters. The serum levels of osteocalcin, C-terminal cross-linked telopeptide of type I collagen, calcium and phosphorus were determined as bone turnover markers. RESULTS: Femur breaking strength was dramatically lower in the BDL group compared with control. However, receiving quercetin could reverse the deteriorating effect of cirrhosis on bone strength of BDL rats. Quercetin could noticeably elevate osteocalcin as a bone formation marker. CONCLUSION: These data suggest that quercetin can significantly improve bone strength particularly due to increasing bone formation in biliary cirrhosis.

Quercetin prevents experimental glucocorticoid-induced osteoporosis: a comparative study with alendronate.

Glucocorticoid-induced osteoporosis (GIO) is the most common type of secondary osteoporosis. The aim of this study was to compare the efficacy of quercetin, a plant-derived flavonoid, with alendronate in the prevention of GIO. Fifty-six Sprague-Dawley rats were randomly distributed among 7 groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg methylprednisolone sodium succinate (MP)/kg body mass; (iii) MP + 40 µg alendronate/kg; (iv) MP + 50 mg quercetin/kg; (v) MP + 40 µg alendronate/kg + 50 mg quercetin/kg; (vi) MP + 150 mg quercetin/kg; and (vii) MP + 40 µg alendronate/kg + 150 mg quercetin/kg. MP and alendronate were injected subcutaneously and quercetin was administered by oral gavage 3 days a week. At the end of the study, femur breaking strength was significantly decreased as a consequence of MP injection. This decrease was completely compensated for in groups receiving 50 mg quercetin/kg plus alendronate, and 150 mg quercetin/kg with or without alendronate. Quercetin noticeably elevated osteocalcin as a bone formation marker, while alendronate did not show such an effect. In addition, administration of 150 mg quercetin/kg increased femoral trabecular and cortical thickness by 36% and 22%, respectively, compared with the MP-treated group. These data suggest that 150 mg quercetin/kg, alone or in combination with alendronate, can completely prevent GIO through its bone formation stimulatory effect.

The association between vitamin D status and sleep duration in school-aged children; the CASPIAN-V study.

Background: Considering the high prevalence of both vitamin D deficiency (VDD) and sleep impairment in children and adolescents, this study was conducted to determine the association between VDD and sleep duration in the Iranian pediatric population. Methods: This multicentric national study was conducted in 2019 on 2564 frozen sera obtained from 7 to 18- year students who were studied in the fifth survey of a national school-based surveillance program conducted in 30 provinces of Iran. Sleep duration was assessed using a questionnaire based on the World Health Organization-Global School-based Student Health Survey protocol. Short sleep duration was defined as sleep duration less than 8 h/day VDD Vitamin D < 20 ng/dL, and vitamin D insufficiency as 20-30 ng/dL.An adjusted logistic regression model was applied to evaluate the associations of vitamin D status with sleep duration. Results: The Mean (SD) of students' age was 12.1(3.0) years; overall 10.6%of participants had VDD and 23% of participants had short sleep duration. in the adjusted logistic model, students with a low level of vitamin D (insufficient and deficient) had a higher odds of short sleep duration in comparison to those with normal vitamin D level (OR: 1.29, 95%CI: 1.02-1.62). Conclusion: The current study showed that low Vitamin D levels (insufficient and deficient)were significantly associated with short sleep duration in school-aged children. Further studies are recommended to determine the efficacy of vitamin D replacement in improving sleep duration and quality.

Gut Microbiota Might Act as a Potential Therapeutic Pathway in COVID-19.

It has been very recently suggested that individuals with chronic gut inflammation are highly susceptible to COVID-19. They constitute the serious cases of COVID-19, in which inflammatory cytokine storm is observed. On the contrary, the healthy gut microbiota is linked with low chronic gut and systemic inflammation. This raises the idea that maintenance of the healthy gut microbiota and prevention of gut microbial dysbiosis in COVID-19 patients might avoid the increased cytokine storm, which in turn might reduce the mortality rate. It has been shown that the modulation of the gut microbiota is an effective strategy to strengthen immunity and might be a possible treatment for individuals with viral infections. Currently, there is no clinical data considering the impact of the modulation of the gut microbiota on the treatment of COVID-19. We hypothesize that targeting the gut microbiota might be a novel therapeutic approach or at least a supportive therapy. In the present review article, we described the interaction between SARS-CoV-2 and gut microbiota dysbiosis through two possible mechanisms, including aberrant immune activation and aberrant mammalian target of rapamycin (mTOR) activation. Further, the disruption of the gastrointestinal reninangiotensin system (GI RAS), dysregulation of the coagulation and fibrinolytic systems, and the activity of human serine proteases in COVID-19 pathogenesis were addressed. We also provided possible strategies to restore all the discussed aspects via gut microbiota modulation.

The predictive power of serum vitamin D for poor outcomes in COVID-19 patients.

Considering the high prevalence of vitamin D deficiency worldwide and its relationship with immune response to viral infections, this study attempted to identify the predictive power of serum vitamin D for poor outcomes among the COVID-19 patients. This retrospective cohort study included all patients with confirmed COVID-19 hospitalized between February 20, 2020, and April 20, 2020, at a designated COVID-19 hospital, located in Tehran province, Iran. General characteristics, medical history and clinical symptoms were recorded by trained physicians. Blood parameters including complete blood count, creatinine, lactate dehydrogenase, creatine phosphokinase, erythrocyte sedimentation rate, C-reactive protein and vitamin D were tested. This study included 290 hospitalized patients with COVID-19 (the mean age [SD]: 61.6 [16.9], 56.6% males), of whom 142 had vitamin D concentrations less than 20 ng/ml, defined as vitamin D deficiency. COVID-19 patients with vitamin D deficiency were more likely to die (Crude OR [95% CI]: 2.30 [1.25-4.26]), require ICU (2.06 [1.22-3.46]) and invasive mechanical ventilation (2.03 [1.04-3.93]) based on univariate logistic regression results. Although, after adjusting for potentials confounders such as gender and age, the association between vitamin D and need to invasive mechanical ventilation lost its significance, adjusted values for the risk of death and ICU requirement were still statistically significant. Vitamin D deficiency can be considered as a predictor of poor outcomes and mortality in COVID-19 patients. Therefore, checking serum 25 (OH) D on admission and taking vitamin D supplements according to the prophylactic or treatment protocols is recommended for all COVID-19 patients.

Vitamin D suppresses proangiogenic factors in patients with ulcerative colitis: A randomized double blind placebo controlled clinical trial.

BACKGROUND: Angiogenesis and inflammation are involved in the pathogenesis of ulcerative colitis (UC). This study aimed to assess the effect of vitamin D on serum levels of proangiogenic factors, visfatin and vascular endothelial growth factor (VEGF), in patients with UC. MATERIALS AND METHODS: Ninety patients were randomized to receive either a single intramuscular injection of 300,000 IU vitamin D or normal saline. Visfatin, VEGF, and 25-hydroxyvitamin D [25(OH)D] concentrations were assessed before and 90 days after the intervention. RESULTS: There were no significant differences in visfatin and VEGF levels between the two groups following supplementation. In patients with vitamin D insufficiency, visfatin increase was significantly lower in the intervention versus placebo group. There was an inverse correlation between serum 25(OH)D and visfatin in the subgroup with vitamin D insufficiency. CONCLUSION: Vitamin D might be beneficial in decreasing proangiogenic factors such as visfatin in UC patients with low 25(OH)D levels.

Effects of probiotic, cinnamon, and synbiotic supplementation on glycemic control and antioxidant status in people with type 2 diabetes; a randomized, double-blind, placebo-controlled study.

PURPOSE: The aim of this study was to investigate the effect of probiotic bacteria of Lactobacillus acidophilus, cinnamon powder and their combinations on the glycemic and antioxidant indices in patients with type 2 diabetes. METHODS: A total of 136 patients randomized with type 2 diabetes entered the study and were randomly divided into four groups who were matched for age and gender. Thereafter, alongside their routine pharmacotherapy, each group followed one of the following diets: Group A: Lactobacillus acidophilus 108 cfu and 0.5 g of powdered cinnamon (synbiotic). Group B: Lactobacillus acidophilus (probiotic), Group C: powdered cinnamon. Group D: rice flour powder as placebo. At the beginning and end of the intervention, fasting blood sugar (FBS), HbA1c, advance glycation end products (AGE), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and antioxidant enzymes of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured. RESULTS: Following 3 months of treatment, the mean FBS level was decreased significantly in probiotic, cinnamon, and synbiotic supplementation groups compared with control (P < 0.01). FBS levels in probiotic, cinnamon, and synbiotic groups were significantly decreased compared with the control group (P = 0.001, P = 0.063 and P = 0.001, respectively). The mean HbA1C in probiotic, cinnamon, and synbiotic groups were also decreased (P = 0.001, P = 0.001 and P = 0.04, respectively). The mean AGE in synbiotic group was significantly decreased (P = 0.037). Probiotic, cinnamon and synbiotic all could improve antioxidant enzyme activity modestly. However, the most significant effect was seen in probiotic group. CONCLUSIONS: According to the current results, the use of probiotic supplements (individually or in combination with cinnamon) leads to a reduction in blood glucose and an increase in antioxidant enzymes in people with type 2 diabetes.

Quercetin Ameliorates Lipid and Apolipoprotein Profile in High-Dose Glucocorticoid Treated Rats. / Quercetina Melhora o Perfil Lipídico e Apolipoproteico em Ratos Tratados com Glicocorticóides em Altas Doses.

Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.).

Effect of vitamin D supplementation on CREB-TrkB-BDNF pathway in the hippocampus of diabetic rats.

OBJECTIVES: Cyclic AMP (adenosine monophosphate) response element-binding protein (CREB) and Brain-derived neurotrophic factor (BDNF) are reported to broadly involve in learning capacity and memory. BDNF exerts its functions via tropomyosin receptor kinase B (TrkB). BDNF transcription is regulated by stimulating CREB phosphorylation. The CREB-TrkB-BDNF pathway is reported to be affected by diabetes, which may contribute to its cognitive deficits. This study was conducted to investigate the effect of vitamin D supplementation on the hippocampal fraction of this pathway in an animal model of type-1 diabetes mellitus (T1DM). MATERIALS AND METHODS: Thirty-six adult male Sprague-Dawley rats were randomly divided into 4 groups as follows: Group 1: normal healthy rats (n=8); group 2: normal healthy rats receiving sesame oil supplementation as placebo (n=8); Group 3: diabetic rats receiving sesame oil (n=10); and Group 4: diabetic rats treated with 4300 IU/kg/week vitamin D dissolved in sesame oil (n=10). Diabetes was induced by intraperitoneal (IP) injection of streptozotocin. Blood and hippocampal samples were acquired at the end of the experiment. RNA was extracted from the hippocampus, and real-time PCR (polymerase chain reaction) was performed for BDNF and TrkB gene expression. RESULTS: Administration of vitamin D (4300 IU/kg/week) in a T1DM animal model increased CREB phosphorylation in the hippocampus, but the serum and hippocampal BDNF levels and TrkB and BDNF gene expression did not change significantly. CONCLUSION: Vitamin D increased hippocampal CREB phosphorylation in a T1DM animal model. Our findings showed that vitamin D might be protective against central nervous system complications in diabetes. However, future studies are warranted.

The Effect of Vitamin D on Cellular Pathways of Diabetic Nephropathy.

BACKGROUND: Diabetic nephropathy is one of the most important microvascular complications and a major cause of morbidity and mortality in diabetic patients. This study was designed to investigate the effect of vitamin D on the expression of three key genes involved in the development of diabetic nephropathy. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups. The first group served as control and the other two groups received intraperitoneal injections of 45 mg/kg STZ to develop diabetes. The groups were treated for four weeks either with placebo or two vitamin D injections of 20,000 IU/kg. Serum glucose, insulin, and HbA1c levels, and AGE cellular receptor (RAGE), aldose reductase (AR) and glutamine: fructose-6-phosphate aminotransferase (GFAT) gene expression were assessed in kidney tissue at the end of the experiment. RESULTS: Vitamin D treatment resulted in a significant increase in insulin concentration, which could improve hyperglycaemia in diabetic rats. Serum HbA1c decreased slightly but insignificantly following the vitamin D injections. In addition, expression of GFAT, a key regulatory enzyme in the hexosamine pathway, was significantly reduced following vitamin D administration. CONCLUSION: Vitamin D may reduce diabetic nephropathy not only by improving blood glucose and insulin levels, but also by modulating hexosamine pathways in kidney.

The Effect of Vitamin D Supplementation on Serum and Muscle Irisin Levels, and FNDC5 Expression in Diabetic Rats.

BACKGROUND: Diabetes mellitus and metabolic disorders are a major burden on the healthcare system. Irisin is a novel myokine reported to have beneficial effects on glucose and lipid metabolism. Vitamin D deficiency has been implicated in the development of diabetes and hold a critical role in diabetes-related complications. In the present study, we examined the efficacy of vitamin D supplementation on serum irisin levels, skeletal muscle irisin levels, and the expression of the irisin precursor, FNDC5 (fibronectin-type III domain-containing 5) in type I diabetes mellitus rats. METHODS: Thirty-six adult male Sprague-Dawley rats (150 - 250 g) were randomly divided into four groups: group I: healthy control rats with no treatment (n=8), group II: healthy control rats receiving sesame oil as a placebo (n=8), group III: diabetic rats receiving sesame oil as placebo (n=10), group IV: diabetic rats treated with 4300 IU/kg/week vitamin D (n=10). Diabetes was induced by intraperitoneal (IP) injection of streptozotocin. At the end of the vitamin D intervention blood and triceps muscle samples were collected. RNA was extracted from muscle and real-time PCR was performed to examine FNDC5 gene expression. RESULTS: Our study showed that the administration of vitamin D (4300 IU/kg/week) in a streptozotocin-diabetic rat model resulted in increased serum vitamin D levels, FNDC5 gene expression and muscle irisin levels. However, the levels of serum irisin were not significantly changed by the administration of vitamin D. CONCLUSION: In conclusion, we show that vitamin D supplementation enhances serum vitamin D levels, FDNC5 gene expression and muscle irisin levels in the streptozotocin-diabetic rat model. Our study highlights the potential therapeutic effect of vitamin D supplementation for diabetes mellitus.

The relationship between anthropometric status and rheumatoid arthritis. Exploring the role of nesfatin and asymmetric dimethylarginine.

OBJECTIVE: The aim of this study was to explore the anthropometric status of rheumatoid arthritis (RA) patients, as well as two controversial adipokines, namely nesfatin-1 and asymmetric dimethylarginine (ADMA), to reveal the possible relationships between them and RA. METHODS: This study included RA patients who fulfilled the American college of rheumatology classification criteria. Anthropometric parameters including height, weight, and waist circumference (WC) were measured and body mass index (BMI) was calculated. Disease activity was assessed by 28 joints disease activity score (DAS28). Fasting plasma samples were collected and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), nesfatin-1 and asymmetric dimethylarginine (ADMA) were determined using commercial kits. Statistical analyses were done using the BMI SPSS Statistics. RESULTS: A total of 77 patients including 63 females, with an average age of 48.45±11.26 and disease duration of 9.99±5.80 years participated the study, 62% of whom were overweight or obese. Disease activity was significantly higher in obese patients. In addition, BMI and WC were correlated with CRP and ESR, indicating higher level of inflammation in obese patients. DAS28 was also found to be correlated with CRP, ESR and ADMA (r=0.38, 0.61, 0.21 respectively). Higher protein intake was accompanied with higher CRP and ESR and higher carbohydrate intake was related to higher CRP and lower nesfatin-1. CONCLUSIONS: Weight, BMI, and WC were correlated with the activity of RA and the concentrations of CRP and ESR went up in tandem with BMI. In addition, ADMA, but not nesfatin-1, was associated with BMI and disease activity in RA patients.

Vitamin D suppresses cellular pathways of diabetes complication in liver.

OBJECTIVES: The aim of this study was to investigate the effect of vitamin D on glucose metabolism, as well as the expression of five key genes involved in the development of diabetes complications in liver tissue of diabetic rats. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups (8 rats in each group). The first group served as control and the other two groups received an intraperitoneal injection of 45 mg/kg streptozotocin to develop diabetes. Groups were treated for four weeks either with placebo or vitamin D (two injections of 20000 IU/kg). Thereafter, serum levels of glucose, insulin and HbA1c were assessed. Liver tissue was examined for the level of advanced glycation end products (AGEs) and the gene expression of AGE cellular receptor (AGER), glyoxalase-1 (GLO-1), aldose reductase (AR), O-linked N-acetylglucosamine transferase (OGT) and glutamine/ fructose-6-phosphate aminotransferase (GFAT). RESULTS: Vitamin D injection resulted in a significant increase in plasma level of 25-hydroxycholecalciferol, which could improve hyperglycemia about 11% compared to placebo-receiving diabetic rats (P=0.005). Insulin level increased as a result of vitamin D treatment compared to control (3.31±0.65 vs. 2.15±0.79; P= 0.01). Serum HbA1c and liver AGE concentrations had a slight but insignificant reduction following vitamin D intake. Moreover, a significant decline was observed in gene expression of AGER and OGT in liver tissue (P=0.04 and P<0.001 respectively). CONCLUSION: Vitamin D might contribute in ameliorating diabetes complications not only by improving blood glucose and insulin levels, but also by suppressing AGER and OGT gene expression in the liver.

Effect of Omega-3 Supplementation on Lipocalin 2 and Retinol-Binding Protein 4 in Type 2 Diabetic Patients.

BACKGROUND: Serum levels of lipocalin 2 (LCN 2) and retinol-binding protein-4 (RBP 4), increase in type 2 diabetes mellitus (T2DM). We sought to determine whether serum LCN 2 and RBP 4 change after an intervention with omega-3 fatty acids supplementation in diabetic patients. METHODS: Forty-five type 2 diabetic patients from Iranian Diabetic Association in Tehran, Iran in 2013 were randomly recruited into two groups: one group received 4 g/d omega-3 for 10 wk; and the control group received placebo. Blood samples, food intake records, anthropometric measurements were obtained from all participants at the beginning and end of the study. RESULTS: Fasting RBP 4 plasma levels significantly changed after 10 wk supplementation (P = 0.01). The LCN 2 concentrations decreased in omega-3 group, but the changes were not statistically significant. Omega-3 supplementation had no noticeable effect on anthropometric factors. CONCLUSION: These findings provide a rationale for omega-3 supplements aimed at lowering serum RBP 4 levels in T2DM.

Effect of Omega-3 Supplementation on Lipocalin 2 and Retinol-Binding Protein 4 in Type 2 Diabetic Patients.

BACKGROUND: Serum levels of lipocalin 2 (LCN 2) and retinol-binding protein-4 (RBP 4), increase in type 2 diabetes mellitus (T2DM). We sought to determine whether serum LCN 2 and RBP 4 change after an intervention with omega-3 fatty acids supplementation in diabetic patients. METHODS: Forty-five type 2 diabetic patients from Iranian Diabetic Association in Tehran, Iran in 2013 were randomly recruited into two groups: one group received 4 g/d omega-3 for 10 wk; and the control group received placebo. Blood samples, food intake records, anthropometric measurements were obtained from all participants at the beginning and end of the study. RESULTS: Fasting RBP 4 plasma levels significantly changed after 10 wk supplementation (P = 0.01). The LCN 2 concentrations decreased in omega-3 group, but the changes were not statistically significant. Omega-3 supplementation had no noticeable effect on anthropometric factors. CONCLUSIONS: These findings provide a rationale for omega-3 supplements aimed at lowering serum RBP 4 levels in T2DM.

Lipid peroxidation and antioxidant enzymes activity in controlled and uncontrolled Type 2 diabetic patients.

BACKGROUND: This study was designed to compare lipid peroxidation and antioxidant enzymes activity in Type 2 diabetes patients with good or weak glycemic control. METHODS: In this case-control study, 62 Type 2 diabetic patients with glycated hemoglobin (HbA1c) between 6 and 8 were enrolled as the controlled group and 55 patients with HbA1c > 8 were selected as an uncontrolled group. Patients were all referred to Iranian Diabetes Association in Tehran, Iran, from 2010 onward. Groups were chosen by convenience sampling and were matched based on age, sex and duration of disease. Demographic questionnaire, two 24-hour food recall, HbA1c, insulin, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase were measured in blood samples. Data were analyzed by Food Processor II and SPSS software. RESULTS: A mean daily consumption of energy, carbohydrate, protein, and fat was not significantly different between two groups. MDA in the uncontrolled group was significantly higher than controlled group (2.03 ± 0.88 vs. 1.65 ± 1.01 nmol/ml; P = 0.030). A mean SOD was slightly higher in the uncontrolled group comparing to the control group (843.3 ± 101.9 vs. 828.0 ± 127.3 U/g Hb; P = 0.400). CONCLUSION: These data suggest that MDA as a lipid peroxidation indicator is higher in uncontrolled diabetes probably due to chronic high blood sugar followed by higher oxidative stress.

Effects of vitamin A, C and E, or omega-3 fatty acid supplementation on the level of paraoxonase and arylesterase activity in streptozotocin-induced diabetic rats: an investigation of activities in plasma, and heart and liver homogenates.

INTRODUCTION: This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fatty acid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS: A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fatty acid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS: Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fatty acid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION: Vitamin A, C and E, or omega-3 fatty acid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications.

Vitamin D and diabetic nephropathy: A systematic review and meta-analysis.

OBJECTIVE: There has been a long history documenting the use of different vitamin D derivatives as therapy for renal diseases. However, to our knowledge, there is no comprehensive assessment of the relation between vitamin D deficiency and risk for diabetic nephropathy (DN). Additionally, the effect of vitamin D supplementation on DN is still unclear. The aim of this meta-analysis was to assess these issues by pooling together the results from cross-sectional studies and clinical trials. METHODS: A systematic literature search of PubMed, Scopus, and Google Scholar was conducted, ending in September 2014. For cross-sectional studies, odds ratio was used as a measure of the association between vitamin D status and risk for DN; for clinical trials, mean and SD of the main outcome (urine albumin-to-creatinine ratio [UACR]) in intervention and placebo groups were considered for analysis. RESULTS: The final selected articles were published between 2009 and 2014. In all, 3700 and 219 patients were enrolled in observational and interventional studies, respectively. The pooled odds ratio from six cross-sectional studies was 1.80 (95% confidence interval [CI], 1.25-2.59; P = 0.002), indicating a significant inverse association between serum vitamin D status and risk for nephropathy in patients with diabetes. However, the pooled data of UACR levels in clinical trials suggested no significant change following vitamin D supplementation (17.98; 95% CI, -35.35 to 71.32; P = 0.51). CONCLUSION: This meta-analysis showed the higher risk for nephropathy in vitamin D-deficient patients with diabetes. Pooling the results of available clinical trials after vitamin D supplementation did not support causality in this association.

Quercetina Melhora o Perfil Lipídico e Apolipoproteico em Ratos Tratados com Glicocorticóides em Altas Doses / Quercetin Ameliorates Lipid and Apolipoprotein Profile in High-Dose Glucocorticoid Treated Rats

Resumo Fundamento Os glicocorticóides (GCs) são amplamente prescritos para o tratamento de numerosos distúrbios clínicos devido às suas propriedades anti-inflamatórias e imunomoduladoras, e um dos efeitos indesejáveis mais comuns desses medicamentos é a dislipidemia. Objetivo Avaliar o efeito da quercetina, um flavonoide derivado de plantas, no perfil lipídico de ratos tratados com glicocorticóides em altas doses. Métodos Um total de 32 ratos Sprague-Dawley foram distribuídos aleatoriamente entre quatro grupos (8 ratos por grupo) e tratados por 6 semanas com uma das seguintes opções : (i) solução salina normal; (ii) 40 mg/kg de succinato sódico de metilprednisolona (MP); (iii) MP + 50 mg/kg de quercetina; (iv) MP + 150 mg/kg de quercetina. O MP foi injetado por via subcutânea e a quercetina foi administrada por gavagem oral 3 dias por semana. No final do estudo, o perfil lipídico dos animais foi medido através de kits enzimáticos. Os dados foram analisados e a significância estatística foi estabelecida em p <0,05. Resultados Os níveis séricos médios de colesterol total (CT), triglicerídeos (TG) e LDL aumentaram drasticamente em animais tratados com GC em comparação com o grupo controle. Ambas as doses de quercetina (50 e 150 mg/kg) melhoraram o CT (43% e 45%), LDL (56% e 56%) e TG (46% e 55%, respectivamente). A razão Apo B/A1 diminuiu mais de 20% após a ingestão de Anti-Inflamatory Agents. Conclusões Esses dados sugerem que a ingestão de quercetina Quercetin; induzida por glicocorticóides. (Arq Bras Cardiol. 2020; 115(1):102-108)

Abstract Background Glucocorticoids (GCs) are widely prescribed for the treatment of numerous clinical disorders due to their anti-inflammatory and immune-modulatory properties and one of the most common untoward effects of these drugs is dyslipidemia. Objective To evaluate the effect of quercetin, a plant-derived flavonoid, on the lipid profile of high-dose glucocorticoid treated rats. Methods A total of 32 Sprague-Dawley rats, were randomly distributed among four groups (8 rats per group) and treated for 6 weeks with one of the following: (i) normal saline; (ii) 40 mg/kg methylprednisolone sodium succinate (MP); (iii) MP + 50 mg/kg quercetin; (iv) MP + 150 mg/kg quercetin. MP was injected subcutaneously, and quercetin was administered by oral gavage 3 days a week. At the end of the study, the animals' lipid profile was measured by enzymatic kits. Data were analyzed and statistical significance was set at p<0.05. Results The mean serum total cholesterol (TC), triglyceride (TG) and LDL levels were drastically increased in GC-treated animals compared with the control group. Both doses of quercetin (50 and 150 mg/kg) ameliorated TC (43% and 45%), LDL (56% and 56%) and TG (46% and 55% respectively). Apo B/A1 ratio decreased more than 20% following quercetin intake and the decline in TC/HDL, TG/HL, LDL/HDL ratios were significant. Conclusions These data suggest that quercetin intake with both doses of 50 and 150 mg/kg could be considered as a protective agent for glucocorticoid-induced dyslipidemia. (Arq Bras Cardiol. 2020; 115(1):102-108.)