The Oxidative Status and Na+/K+-ATPase Activity in Obsessive-Compulsive Disorder: A Case Control Study.

Background: Oxidative stress is involved in pathogenesis of some psychiatric disorders. To examine the role of oxidative stress in the etiopathogenesis of obsessive-compulsive disorder (OCD), we aimed to determine oxidative stress indices, including malondialdehyde (MDA) levels in serum and red blood cells (RBC) membrane, total antioxidant capacity (TAC), serum glutathione (GSH) levels, serum antioxidant vitamins (A and E), and Na+/K+-ATPase activity, in patients with the mentioned disorder vs. healthy controls. Method: 39 OCD patients diagnosed based on Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and 39 volunteer healthy subjects were included in this study. MDA levels in serum and RBC membrane were measured using fluorometric method. Serum TAC level, serum GSH level, and Na+/K+-ATPase activity were also measured using spectrophotometric methods. Serum levels of vitamins were calculated by reversed-phase high-performance liquid chromatography (RP-HPLC). Result: There was a significantly higher MDA level in serum (p < 0.0001) and RBC membrane (p = 0.002) of OCD patients compared with those in controls. A significant reduction in vitamin A (p = 0.001) and vitamin E (p = 0.024) levels was found in OCD patients vs. controls. There was significantly lower activity of erythrocyte membrane Na+/K+-ATPase in RBC membrane of OCD patients vs. controls (p < 0.0001). Conclusion: Our findings indicate significantly higher levels MDA in both serum and RBC membrane, lower levels of serum vitamins A and E, and lower activity of membrane Na+/K+-ATPase in OCD patients compared to controls. These suggest an imbalance between oxidant and antioxidant factors in OCD patients that might play a fundamental role in the etiopathogenesis of OCD.

Evaluating the Effects of Probiotic Supplementation on Neuropathic Pain and Oxidative Stress Factors in an Animal Model of Chronic Constriction Injury of the Sciatic Nerve.

Introduction: Neuropathic pain is a common and painful somatosensory nervous system disease, and its treatment remains a medical challenge. Evidence demonstrates that gut microbiota alters in neuropathic pain and, therefore, improvement of the gut flora may affect the disease. The present study aimed to evaluate the antinociceptive effect of probiotics in neuropathic pain and oxidative biomarkers' responsiveness to the probiotic treatment. Methods: Using chronic constriction injury (CCI) of the rats' sciatic nerve, neuropathic pain was induced. Investigating the analgesic effect of the probiotics mixture, 40 male rats were randomly assigned to 4 groups (n=10 for each): Sham-operated (SM), and CCI model rats orally received 1 mL saline (CS), or 100 mg/kg gabapentin (CG) or 1 mL probiotics mixture (CP) Lactobacillus plantarum, Lactobacillus delbrueckii, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Bifidobacterium bifidum (109 CFU of each) daily. Using behavioral tests, the pain was assessed on days 1, 4, 7, 14, and 21 of the study. Finally, the biochemical evaluation of sciatic nerve tissue was done. Results: Probiotics decreased cold and mechanic allodynia and thermal hyperalgesia. Reducing lipid peroxidation levels and increasing total antioxidant capacity, superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were also significant in the probiotics group. Conclusion: These findings suggest that probiotics have analgesic effects on the CCI model of neuropathic pain via increasing the antioxidant capacity of the rats' sciatic nerve. Highlights: Oral probiotics mixture diminishes cold and mechanical allodynia in chronic constriction injury (CCI) rats.Probiotics mixture reduces thermal hyperalgesia in CCI rats as well as gabapentine.Balancing in oxidant/anti-oxidant system is key pathway in neuropathic pain reduction. Plain Language Summary: Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide. Neuropathic pain occurs when a health condition affects the nerves that carry sensations to the brain. With neuropathic pain, the pain isn't typically triggered by an event or injury. Instead, the body sends pain signals to the brain unprompted. Neuropathic pain tends to get worse over time. As neuropathic pain could result from an imbalance in the oxidative/antioxidative system, antioxidant supplementation may be a treatment option. Oxidative stress is known to result in the occurrence of molecular mechanisms of diabetes, atherosclerosis, inflammatory bowel disease, and damage to the heart, brain, or transplanted organs. Probiotics are made of good live bacteria and/or yeasts that naturally live in the body and have various health benefits. Consumption of probiotics alone or foods supplemented with probiotics may reduce cell oxidative damage. Incorporating probiotics in foods can provide an excellent strategy to supply dietary antioxidants. This study subjected rats to sciatic nerve ligation to induce neuropathic pain. The oral probiotics mixture was administered for 21 days post-surgery. The result showed that the probiotics mixture administration could reduce oxidative stress and pain in neuropathic pain rats. Therefore, probiotics can prevent and treat many systemic diseases in animal and human studies.

Effects of Folic Acid Supplementation on Liver Enzymes, Lipid Profile, and Insulin Resistance in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial.

Background: Previous evidence revealed an association between folate deficiency and non-alcoholic fatty liver disease (NAFLD). This study is the first one investigating the effects of folic acid on hepatic steatosis grade, liver enzymes, insulin resistance, and lipid profile in NAFLD cases. Materials and Methods: Sixty-six participants with NAFLD were allocated randomly to take either a placebo or one oral tablet of folic acid (1 mg) on a daily basis within eight weeks. Serum folate, homocysteine, glucose, aminotransferases, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and lipids were assessed. Ultrasonography was used for assessing the liver steatosis grade. Results: The serum alanine transaminase, grade of hepatic steatosis, and aspartate transaminase significantly were decreased within both study groups; however, the between-group comparison was not statistically significant. Of note, the decrease in ALT was more pronounced in folic acid compared with the placebo group (-5.45 ± 7.45 vs. -2.19 ± 8.6 IU/L). The serum homocysteine was decreased after receiving folic acid compared to the placebo (-0.58 ± 3.41 vs. +0.4 ± 3.56 µmol/L; adjusted P = 0.054). Other outcomes did not significantly change. Conclusion: Supplementation with folic acid (1 mg/d) for eight weeks among cases with NAFLD did not change significantly the serum levels of liver enzymes, the hepatic steatosis grade, insulin resistance and lipid profile. However, it was able to prevent the increase in homocysteine in comparison with the placebo. Conducting further research is suggested with the longer duration and different doses of folic acid, adjusted to the genotypes of methylenetetrahydrofolate reductase polymorphism, among NAFLD patients.

Relationship Between Red Cell Distribution Width and Oxidative Stress Indexes in Patients with Coronary Artery Disease.

Background: Red blood cell distribution (RDW), an index of the size variability of erythrocytes, is significantly associated with coronary stenosis and can strongly predict the mortality risk in coronary artery disease (CAD). The biological mechanisms involved are not fully understood but may include oxidative stress. We sought to investigate the relationship between RDW and markers of oxidative stress in patients with CAD. Methods: Participants were 112 consecutive patients referred to department of cardiac surgery for evaluation of chest pain. 32 patients had stable CAD, 40 patients had unstable CAD and 40 subjects were diagnosed as non-CAD. The levels of lipid peroxidation (TBARS) were measured in plasma and membrane samples by a fluorometric method. The plasma levels of glutathione (GSH) and total antioxidant capacity (TAC) were determined using spectrophotometric methods. Results: Lipid peroxidation levels were significantly higher in the erythrocyte membrane of stable CAD patients than non-CAD patients. The levels of TAC were significantly lower in both stable and unstable groups when compared to that of the control group (P< 0.019 and P< 0.001, respectively), but did not differ between stable and unstable CAD. In addition, there was no significant difference in the serum GSH levels among the study groups. Membrane TBARS was directly associated with RDW in three groups of study. Conclusions: We found an independent association between RDW levels and membrane lipid peroxidation in patients with CAD. This finding suggests that oxidative stress may be a potential underlying biological mechanism for increased RDW in CAD patients.

The effects of vitamin B12 supplementation on metabolic profile of patients with non-alcoholic fatty liver disease: a randomized controlled trial.

The present study is the first effort to evaluate the effects of vitamin B12 supplementation on the serum level of liver enzymes, homocysteine, grade of hepatic steatosis, and metabolic profiles in patients with non-alcoholic fatty liver disease (NAFLD). Forty patients with NAFLD were enrolled in a double-blind placebo-controlled trial to receive either one oral tablet of vitamin B12 (1000 µg cyanocobalamin) or a placebo per day for 12 weeks. We investigated serum levels of homocysteine, aminotransferases, fasting blood glucose (FBG), lipids, malondialdehyde (MDA), and homeostasis model assessment of insulin resistance (HOMA-IR). The grade of liver steatosis and fibrosis was measured by real-time 2-dimensional shear wave elastography. Vitamin B12 supplementation significantly decreased serum levels of homocysteine compared to placebo (medians: - 2.1 vs. - 0.003 µmol/l; P = 0.038). Although serum alanine transaminase (ALT) in the vitamin B12 group decreased significantly, this change did not reach a significant level compared to the placebo group (medians: - 7.0 vs. 0.0 IU/l; P > 0.05). Despite the significant within-group decrease in FBG, MDA, and liver steatosis in the vitamin B12 group, between-group comparisons did not reveal any significant difference. Vitamin B12 supplementation might decrease serum levels of homocysteine in patients with NAFLD. The fasting blood glucose and serum levels of MDA were significantly improved in the trial group who received vitamin B12. However, these changes did not reach a significant level compared to the placebo group. In this respect, further studies with larger sample sizes, different doses, and types of vitamin B12 will reveal additional evidence.Trial Registration: At  http://irct.ir/  as IRCT20120718010333N5 on December 25, 2019.

The effects of selenium administration on carotid intima-media thickness and metabolic status in diabetic hemodialysis patients: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Intake of dietary antioxidants is inversely associated with reduced markers of atherosclerosis development such as carotid intima-media thickness (CIMT). OBJECTIVE: This study was designed to assess the effects of selenium supplementation on CIMT and metabolic profiles of in diabetic hemodialysis (HD) patients. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled trial was performed on 60 diabetic HD patients. Subjects were randomly assigned to receive selenium supplements or placebo (starch). Individuals in the selenium group (n = 30) received 200 µg selenium per day in the placebo group (n = 30) received for 24 weeks. Fasting blood samples were taken at the study baseline and after 24 weeks of intervention. RESULTS: Following the administration of selenium supplements, was observed a significant reduction in serum insulin levels (P = 0.003), insulin resistance (P = 0.003), total cholesterol (P = 0.008), LDL-cholesterol (P < 0.001) and C-reactive protein (CRP) (P < 0.001), and a significant increase in insulin sensitivity (P < 0.001), HDL-cholesterol (P < 0.001) and total glutathione (GSH) (P < 0.001) compared with the placebo. CONCLUSIONS: Selenium supplementation in diabetic HD patients had beneficial effects on markers of insulin metabolism, total-, LDL-, HDL-cholesterol, CRP and GSH levels. This trial was registered at www.irct.ir as http://www.irct.ir: IRCT20170513033941N47.

Metabolic and Anti-inflammatory Response to Melatonin Administration in Patients with Diabetic Nephropathy.

INTRODUCTION: Data on the effects of melatonin administration on metabolic parameters in patients with diabetic nephropathy (DN) is limited and controversial. This study was performed to analyze the effects of melatonin administration on metabolic status in patients with DN. METHODS: This randomized, double blind, placebo-controlled clinical trial was performed on 60 patients with DN. Patients were randomly assigned into two groups to take either 10 mg/d of melatonin (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were taken at baseline and 12 weeks after intervention to quantify metabolic parameters. RESULTS: Melatonin administration significantly reduced plasma fasting glucose (ß = -10.64 mg/dL; 95% CI: -20.37 to -0.90; P < .05), insulin (ß = -2.37 µIU/mL, 95% CI: -3.33 to -1.41; P < .001), insulin resistance (ß = -0.67, 95% CI: -0.98 to -0.35; P < .001), significantly increased insulin sensitivity (ß = 0.01, 95% CI: 0.006 to 0.01; P < .05), and plasma HDL-cholesterol levels (ß = 2.75 mg/dL, 95% CI: 0.75 to 4.75; P < .05) when compared with the placebo. Melatonin also caused a significant increase in total antioxidant capacity (TAC) (ß = 140.45 mmol/L; 95% CI: 80.48 to 200.41; P < .001), and glutathione (GSH) levels (ß = 50.36 µmol/L, 95% CI: 94.08 to 0.02; P < .05) when compared with placebo. Ultimately, melatonin could upregulate gene expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) (P < .05) in comparison with placebo. CONCLUSION: Results of this study indicated that melatonin administration for 12 weeks in DN patients had beneficial effects on glycemic control, HDL-cholesterol, TAC and GSH levels, and gene expression of PPAR-γ, but did not affect other metabolic parameters.

The effects of zinc supplementation on clinical response and metabolic profiles in pregnant women at risk for intrauterine growth restriction: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This investigation was conducted to assess the effects of zinc supplementation on clinical response and metabolic status among pregnant women at risk for intrauterine growth restriction (IUGR). METHODS: This randomized, double-blind, placebo-controlled, clinical trial was conducted among 52 women at risk for IUGR according to abnormal uterine artery Doppler waveform. Participants were randomly assigned to take either 233 mg zinc gluconate (containing 30 mg zinc) supplements (n = 26) or placebo (n = 26) for 10 weeks from 17 to 27 weeks of gestation. Fasting blood samples were taken at baseline and after the 10-week treatment to quantify related variables. RESULTS: After the 10-week intervention, taking zinc led to a significant reduction in serum high-sensitivity C-reactive protein (hs-CRP) (ß â€’1.17 mg/L; 95% CI, -1.77, -0.57; p < .001) and plasma malondialdehyde (MDA) levels (ß -0.23 µmol/L; 95% CI, -0.45, -0.02; p = .03); also a significant rise in total antioxidant capacity (TAC) (ß 59.22 mmol/L; 95% CI, 25.07, 93.36; p = .001) was observed in comparison to placebo. In addition, zinc supplementation significantly reduced serum insulin (ß -1.33 µIU/mL; 95% CI, -2.00, -0.67; p < .001) and insulin resistance (ß -0.30; 95% CI, -0.44, -0.15; p < .001), and significantly increased insulin sensitivity (ß 0.008; 95% CI, 0.003, 0.01; p < .001) compared with the placebo. Zinc supplementation did not influence pulsatility index (PI) and other metabolic parameters. CONCLUSIONS: Overall, zinc supplementation in pregnant women at risk for IUGR had beneficial effects on TAC, MDA, hs-CRP, and insulin metabolism, but did not affect PI and other metabolic profiles.

The Effects of Nano-curcumin on Metabolic Status in Patients With Diabetes on Hemodialysis, a Randomized, Double Blind, Placebo-controlled Trial.

INTRODUCTION: This study evaluated the effects of nano-curcumin intake on metabolic status in patients with diabetes on hemodialysis (HD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was performed on 60 patients with diabetes on HD. Participants were randomly divided into two groups to take either 80 mg/d nano-curcumin (n = 30) or placebo (n = 30) for 12 weeks. RESULTS: Nano-curcumin significantly decreased fasting plasma glucose (ß = -19.68 mg/dL, 95% CI: -33.48 to -5.88; P < .05) and serum insulin levels (ß = -1.70 µIU/mL, 95% CI: -2.96 to -0.44; P < .05) when compared with patients who received placebo. Nanocurcumin treatment was associated with a significant reduction in triglycerides (ß = -16.13 mg/dL, 95% CI: -31.51 to -0.75; P < .05), VLDL-cholesterol (ß = -3.22 mg/dL, 95% CI: -6.30 to -0.15; P < .05), total cholesterol (ß = -17.83 mg/dL, 95% CI: -29.22 to -6.45; P < .05), LDL-cholesterol (ß = -15.20 mg/dL, 95% CI: -25.53 to -4.87; P < .05), and total-cholesterol/HDL-cholesterol ratio (ß = -1.15, 95% CI: -0.2.10 to -0.21; P < .05) when compared with the placebo. Nanocurcumin also resulted in a significant reduction of serum high sensitivity CRP (ß = -0.78 mg/L, 95% CI: -1.41 to -0.15; P < .05), and plasma malondialdehyde (ß = -0.25 µmol/L, 95% CI: -0.45 to -0.04; P < .05); but also with a significant increase in plasma total antioxidant capacity (ß = 52.43 mmol/L; 95% CI: 4.52 to 100.35; P < .05) and total nitrite levels (ß = 3.62 µmol/L, 95% CI: 2.17 to 5.08; P < .001) when compared with placebo. CONCLUSION: Nano-curcumin intake for 12 weeks had beneficial effects on metabolic profile in patients with diabetes on HD.

The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease.

BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (ß - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (ß - 1.37 µIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (ß 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (ß - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (ß 5.13 µmol/L, 95% CI, 1.85, 8.41; P = 0.003) and total antioxidant capacity (TAC) (ß 43.44 mmol/L, 95% CI, 3.39, 83.50; P = 0.03) when compared with placebo. Furthermore, magnesium and zinc significantly reduced the Beck Depression Inventory index (BDI) (ß - 1.66; 95% CI, - 3.32, - 0.009; P = 0.04) and Beck Anxiety Inventory (BAI) (ß - 1.30; 95% CI, - 2.43, - 0.16; P = 0.02) when compared with the placebo. CONCLUSIONS: In patients with T2DM and CHD, the 12-week intake of magnesium plus zinc had beneficial effects on FPG, HDL-cholesterol, CRP, insulin, total nitrite, TAC levels, and BDI and BAI score. This suggests that magnesium and zinc co-supplementation may be beneficial for patients with T2DM and CHD. Further studies on more patients and lasting longer are needed to determine the safety of magnesium and zinc co-supplementation. TRIAL REGISTRATION: Current Controlled Trials http://www.irct.ir: IRCT20130211012438N31 at 11 May 2019 of registration. This study retrospectively registered.

Melatonin supplementation and the effects on clinical and metabolic status in Parkinson's disease: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: This study was performed to evaluate the impact of melatonin supplementation on clinical and metabolic profiles in people with Parkinson's disease (PD). METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted among 60 patients with PD. Participants were randomly divided into two groups to intake either 10 mg melatonin (two melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day, 1 h before bedtime for 12 weeks. RESULTS: Melatonin supplementation significantly reduced the Unified Parkinson's Disease Rating Scale (UPDRS) part I score (ß -2.33; 95% CI, -3.57, -1.09; P < 0.001), Pittsburgh Sleep Quality Index (PSQI) (ß -1.82; 95% CI, -3.36, -0.27; P = 0.02), Beck Depression Inventory (BDI) (ß -3.32; 95% CI, -5.23, -1.41; P = 0.001) and Beck Anxiety Inventory (BAI) (ß -2.22; 95% CI, -3.84, -0.60; P = 0.008) compared with the placebo treatment. Compared with the placebo, melatonin supplementation resulted in a significant reduction in serum high sensitivity C-reactive protein (hs-CRP) (ß -0.94 mg/L; 95% CI, -1.55, -0.32; P = 0.003) and a significant elevation in plasma total antioxidant capacity (TAC) (ß 108.09 mmol/L; 95% CI, 78.21, 137.97; P < 0.001) and total glutathione (GSH) levels (ß 77.08 µmol/L; 95% CI, 44.29, 109.86; P < 0.001). Additionally, consuming melatonin significantly decreased serum insulin levels (ß -1.79 µIU/mL; 95% CI, -3.12, -0.46; P = 0.009), homeostasis model of assessment-insulin resistance (HOMA-IR) (ß -0.47; 95% CI, -0.80, -0.13; P = 0.007), total- (ß -13.16 mg/dL; 95% CI, -25.14, -1.17; P = 0.03) and LDL- (ß -10.44 mg/dL; 95% CI, -20.55, -0.34; P = 0.04) compared with the placebo. CONCLUSIONS: Overall, melatonin supplementation for 12 weeks to patients with PD had favorable effects on the UPDRS part I score, PSQI, BDI, BAI, hs-CRP, TAC, GSH, insulin levels, HOMA-IR, total-, LDL-cholesterol, and gene expression of TNF-α, PPAR-γ and LDLR, but did not affect other metabolic profiles.