Effects of melatonin supplementation on serum oxidative stress markers and disease activity in systemic lupus erythematosus patients: A randomised, double-blind, placebo-controlled trial.

BACKGROUND: Considering pathological significance of oxidative stress in systemic lupus erythematosus (SLE), current research aimed to evaluate the effects of melatonin supplementation on oxidative stress markers and disease activity in SLE. METHOD: In this randomised double-blind, placebo-controlled trial, 32 SLE females were selected and randomly assigned into two groups to take 10 mg/day melatonin or placebo for 12 weeks. Before and after trial, serum malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured and disease activity was determined by Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K). RESULTS: Twenty-five patients (13 in the melatonin and 12 in the placebo groups) completed the trial. Melatonin supplementation caused significant reduction in serum MDA compared with baseline (P = .003) and placebo group (P = .004). Serum TAC level did not change significantly in the melatonin group compared with baseline and placebo group (P > .05). Furthermore, melatonin supplementation did not cause significant change in disease activity compared to baseline and placebo group (P > .05). CONCLUSION: This study demonstrated affirmative effects of melatonin in decreasing oxidative stress in SLE patients without any effect on disease activity. Further investigations are required to affirm these primitive findings and to achieve concise conclusions.What's known Free radical damage and oxidative stress has a remarkable function in systemic lupus erythematosus (SLE) pathogenesis. Products derived from oxidative modification cascades are found in biological fluids and their redundancy has a correlation with disease activity and organ damage in SLE. Dietary supplements, which decrease oxidative stress, would be useful in managing SLE. Melatonin is a potent antioxidant and has anti-inflammatory and immunomodulatory characteristics. Limited in vitro and animal studies are available indicating desirable effects of melatonin in preventing from SLE organ damage, thereby opening a new area of investigation that can contribute to using melatonin as a therapy or co-therapy for SLE. What's new Melatonin supplementation caused significant reduction in serum MDA compared with baseline and placebo group. Serum TAC level did not change significantly in the melatonin group compared with baseline and placebo group. Furthermore, melatonin supplementation did not cause significant change in disease activity compared to baseline and placebo group.

Zinc and Selenium in Inflammatory Bowel Disease: Trace Elements with Key Roles?

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that may emerge at a young age and often lasts for life. It often goes through phases of recurrence and remission and has a devastating effect on quality of life. The exact etiology of the disease is still unclear, but it appears that an inappropriate immune response to intestinal flora bacteria in people with a genetic predisposition may cause the disease. Managing inflammatory bowel disease is still a serious challenge. Oxidative stress and free radicals appear to be involved in the pathogenesis of this disease, and a number of studies have suggested the use of antioxidants as a therapeutic approach. The antioxidant and anti-inflammatory properties of some trace elements have led some of the research to focus on studying these trace elements in inflammatory bowel disease. Zinc and selenium are among the most important trace elements that have significant anti-inflammatory and antioxidant properties. Some studies have shown the importance of these trace elements in inflammatory bowel disease. In this review, we have attempted to provide a comprehensive overview of the findings of these studies and to gather current knowledge about the association of these trace elements with the inflammatory process and inflammatory bowel disease.

Effects of High and Low Doses of Folic Acid on the Soluble Receptor Activator of Nuclear Factor-kappa B Ligand/Osteoprotegerin Ratio during Pregnancy.

BACKGROUND: Pregnancy Associated Osteoporosis (PAO) can lead to serious difficulties such as fragility fractures, elongated back pain and height loss in affected women. Soluble Receptor Activator of Nuclear Factor-Kappa B ligand (sRANKL) to Osteoprotegerin (OPG) ratio is chosen as a bone metabolism equation in many bone diseases characterized by bone resorption, such as post-menopausal osteoporosis and would be modified with folic acid supplementation. This study was done to compare the effects of high dose (5mg/day) and low dose (0.5 mg/day) folic acid in the RANKL/OPG ratio and Tumor Necrosis Factorα (TNFα) concentration during pregnancy. METHODS: Forty-five pregnant women who visited the AL-Zahra Hospital, Tabriz Iran, from September 2013 to November 2014 were assigned into two groups in this randomized, double-blind, clinical trial, included women who took 5 mg/day (group1) and who took 0.5 mg/day (Group 2) folic acid supplementation before pregnancy until 36th pregnancy. The biochemical variables in serum of pregnant women were measured before and at the end of the study. The study was registered in the Iranian Registry of Clinical Trials (IRCT) as ID, IRCT2013122315903N1. RESULTS: OPG levels were significantly higher compared with the baseline value (P=0.008), although sRANKL (P<0.001), TNFα (P=0.005) and sRANKL/OPG ratio (P<0.001) reduced significantly with high dose of folic acid supplementation. A significant positive correlation was observed between the decreased RANKL and TNFα levels (r=0.451, P=0.031) at the end of study in high dose group. CONCLUSION: High dose of folic acid supplementation could decrease bone resorptive biomarkers and may prevent PAO in pregnant women by increasing OPG and decreasing sRANKL and TNFα.

The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia / O efeito do extrato de semente de uva vermelha na atividade do soro paraoxonase em doentes com hiperlipidemia leve a moderada

ABSTRACT: CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

RESUMO: CONTEXTO E OBJETIVO: Extrato de semente de uva vermelha (RGSE) contém complexos de proantocianidinas oligoméricas como classe de flavonoides. Estes compostos são antioxidantes potentes e exercem muitos efeitos de promoção da saúde. Este estudo visou determinar os efeitos de RGSE nos níveis séricos de triglicérides (TG), colesterol total (TC), colesterol de lipoproteína alta-densidade (HDL-C), colesterol de lipoproteína baixa-densidade (LDL-C), apolipoproteína AI (apo-AI) e atividade de paraoxonase (PON) em pacientes com hiperlipidemia leve a moderada (MMH). DESENHO E LOCAL: Estudo clínico randomizado duplo-cego controlado com placebo, realizado no Hospital Shahid-Modarres (Teerã, Irã) e na Universidade de Ciências Médicas de Tabriz. Setenta pacientes com MMH foram aleatoriamente designados para receber tratamento (200 mg/dia de RGSE) ou placebo durante oito semanas. RESULTADOS: Elevação significativa nos níveis séricos de apo-AI (P = 0,001), HDL-C (P = 0,001) e atividade de PON (P = 0,001) e diminuição marcada nas concentrações de TC (P = 0,015), TG (P = 0,011) e LDL-C (P = 0,014) foram encontradas nos casos. Atividade de PON mostrou correlação significativa com apo-AI (r = 0,270; P < 0,01) e HDL-C (r = 0,45; P < 0,001). Diferenças significativas entre os grupos RGSE e controle (antes e após tratamento) para TC (P = 0,001), TG (P = 0,001), PON (P = 0,03), apo-AI (P = 0,001) e LDL-C (P = 0,002) foram observadas. CONCLUSÃO: É possível que RGSE aumente atividade de PON principalmente através da elevação dos níveis de HDL-C e apo-AI em pacientes MMH. Ele pode, assim, ter efeitos benéficos potenciais na prevenção de estresse oxidativo e aterosclerose nesses pacientes.

The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidemia.

CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial.

UNLABELLED: Pre-eclampsia is a pregnancy-related multi-systemic hypertensive disorder and affects at least 5% of pregnancies. This randomized clinical trial aimed at assessing the effect of low doses and high doses of folic acid on homocysteine (Hcy) levels, blood pressure, urea, creatinine and neonatal outcome. A randomized clinical trial was done at Alzahra Teaching Hospital, Tabriz University of Medical Sciences from April 2008 to March 2013. Four-hundred and sixty nulliparous pregnant women were randomly assigned into two groups. Group 1 (n = 230) received 0.5 mg of folic acid and group 2 (n = 230) received 5 mg of folic acid per daily. They were followed until delivery. Blood pressure and laboratory changes, including plasma Hcy levels, were measured and compared between the groups. Homocysteine concentrations were significantly higher at the time of delivery in group 1 (13.17±3.89 µmol/l) than in group 2 (10.31±3.54, µmol/l) (p<0.001). No statistically significant differences were observed in systolic and diastolic blood pressure (p = 0.84 and 0.15, respectively). Birth weight was significantly higher in group 2 (p = 0.031) and early abortion was significantly higher in group 1 than group 2 (p = 0.001). This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT201402175283N9.

Effects of folic acid supplementation on serum homocysteine and lipoprotein (a) levels during pregnancy.

INTRODUCTION: There are many ideas concerning the etiology and pathogenesis of preeclampsia including endothelial dysfunction, inflammation and angiogenesis. Elevated levels of total homocysteine (Hcy) and lipoprotein (a) [Lp(a)] are risk factors for endothelial dysfunction. This study aimed to evaluate the effect of high dose folic acid (FA) on serum Hcy and Lp(a) concentrations with respect to methylenetetrahydrofolate reductase (MTHFR) polymorphisms 677C→T during pregnancy. METHODS: In a prospective uncontrolled intervention, 90 pregnant women received 5 mg FA supplementation before pregnancy till 36th week of pregnancy. The MTHFR polymorphisms 677C→T, serum lactate dehydrogenase activity, urine protein and creatinine concentrations were measured before starting folic acid administration. Serum levels of Hcy and Lp(a) were determined before and after completion of folic acid supplementation period. RESULTS: Supplementation of the patients with FA for 36 week decreased the median (minimum- maximum) levels of serum Hcy from 11.40 µmol/L (4.40-28.70) to 9.70 (1.60-20.80) µmol/L (p=0.001). There was no significant change in serum Lp(a) after FA supplementation (p=0.17). The overall prevalence of genotypes in pregnant women that were under study for MTHFR C677T polymorphism was 53.3% CC, 26.7% CT and 20.0% TT. There was no correlation between decreasing level of serum Hcy in the patients receiving FA and MTHFR polymorphisms. CONCLUSION: Although FA supplementation decreased serum levels of Hcy in different MTHFR genotypes, serum Lp(a) was not changed by FA supplements. Our data suggests that FA supplementation effects on serum Hcy is MTHFR genotype independent in pregnant women.

Relationship between vitamin D receptor gene FokI and ApaI polymorphisms and serum levels of fetuin-A, vitamin D, and parathyroid hormone in patients on hemodialysis.

INTRODUCTION: Low fetuin-A and 1,25-hydroxyvitamin D3 (vitamin D) levels accompanied with high intact parathyroid hormone (PTH) contents are associated with cardiovascular disease in dialysis patients. The aim of present study was to evaluate the relationship between vitamin D receptor (VDR) gene FokI and ApaI polymorphisms with serum levels of fetuin-A, vitamin D, and intact PTH in hemodialysis patients. MATERIALS AND METHODS: Serum was obtained from 46 stable chronic hemodialysis patients and 43 healthy controls. Serum levels of intact PTH, fetuin-A, vitamin D, calcium, and phosphorus were measured. Genotyping of the VDR gene was performed using standard methods. RESULTS: Serum fetuin-A and vitamin D levels were significantly lower, whereas serum levels of PTH, calcium, and Phosphorus were higher in the hemodialysis patients than in the healthy controls. The FokI genotypes were more frequent in the hemodialysis patients than the control group (P = .004). With respect to FokI genotypes, intact PTH level was higher among the hemodialysis patients compared to the controls (P = .02). In contrast, vitamin D level was lower in the hemodialysis patients with ApaI genotypes compared to the control group (P = .04). CONCLUSIONS: Our study shows that increased serum level of PTH and decreased fetuin-A and vitamin D levels may increase susceptibility of atherosclerosis in patients with hemodialysis through VDR gene FokI and ApaI polymorphisms.

Protective effect of fish oil supplementation on DNA damage induced by cigarette smoking.

The study examined the influence of fish oil (FO) supplementation on serum 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels as indicated by DNA damage markers and total antioxidant capacity (TAC) among male cigarette smokers. This double-blind, placebo-controlled randomized study was conducted among healthy cigarette smokers (n=40) who were part of a larger prospective cohort study. Twenty smokers were randomly selected to receive FO for 3 months (1 g/day), and another 20 smokers received a placebo for 3 months; 8-OHdG and TAC levels were measured in blood samples before and after the intervention. Serum 8-OHdG significantly decreased (p=0.001) and TAC increased (p<0.001) after 3 months of treatment with FO. Between baseline and endline, the difference in 8-OHdG significantly correlated with the difference in TAC among smokers who received FO (r=-0.540, p=0.014). The study provides evidence that FO supplementation can modify decreased antioxidants and increased oxidative DNA damage in cigarette smokers.

Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia.

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

Effects of zinc supplementation on antioxidant status and lipid peroxidation in hemodialysis patients.

OBJECTIVES: This study was designed to determine the effects of zinc supplementation on oxidative stress in hemodialysis (HD) patients through evaluating total antioxidant capacity (TAC), whole blood glutathione peroxidase (GSH) level, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) level. DESIGN AND SETTING: Double-blinded randomized controlled trialfrom October 2006 to December 2007 at Tabriz Imam Khomeini Hospital. SUBJECTS: Sixty-five HD patients were randomly enrolled into 2 groups. INTERVENTION: Patients received placebo in group A and zinc (100 mg/day) in group B for 2 months. After a washout period for 2 months, the groups were crossed over and the study was continued for an additional 2 months. MAIN OUTCOME MEASURES: Serum zinc concentration was measured using atomic absorption spectrophotometry. TAC, GSH level, and SOD activity were determined by commercial enzyme-linked immunosorbent assay kits. MDA level was measured using a thiobarbituric acid method. RESULTS: The levels of serum zinc, TAC, GSH (P < .001 for all), and SOD activity (P < .001 for group A and P = .003 for group B) significantly increased after zinc supplementation whereas the serum level of MDA decreased after the same period (P = .003 for group A and P < .001 for group B). CONCLUSIONS: Zinc supplementation for 2 months improved the serum levels of zinc, antioxidant status, and lipid peroxidation in HD patients.

Serum receptor activator of nuclear factor-κ B ligand, osteoprotegrin, and intact parathyroid hormone in hemodialysis and renal transplant patients.

Serum receptor activator of nuclear factor-κ B ligand and osteoprotegrin are mediated to vascular calcification in the general population. Our knowledge is very sparse in hemodialysis and renal transplant patients. Receptor activator of nuclear factor-κ B ligand, osteoprotegrin, intact parathyroid hormone, calcium, and phosphorus were measured in blood samples of 45 hemodialysis and 45 age-matched renal transplant patients. Osteoprotegrin (P = 0.001) and intact parathyroid hormone (P = 0.001) levels in the hemodialysis patients were higher than the renal transplant recipients. Osteoprotegrin had positive correlation with duration of dialysis and age in the hemodialysis (r = 0.88, P = 0.001 and r = 0.34, P = 0.02, respectively) and renal transplant patients (r = 0.92, P = 0.001 and r = 0.46, P = 0.001, respectively). Hemodialysis patients have higher osteoprotegrin levels than the renal transplant recipients. It may act as a protective factor for renal osteodystrophy or only as a secondary phenomenon of advanced renal failure.

Paraoxonase enzyme activity is enhanced by zinc supplementation in hemodialysis patients.

BACKGROUND AND AIMS: Patients on maintenance hemodialysis (HD) face an increased risk of atherosclerosis, a crucial problem and the leading cause of cardiovascular morbidity and mortality. This study was designed to evaluate the effects of zinc supplementation on paraoxonase (PON) enzyme activity in patients on HD. METHODS: This double-blind randomized controlled trial was conducted from June 2005 to June 2007. Sixty HD patients were enrolled and divided into two groups: treatment (case) and control. The treatment and control groups were treated with 100 mg/day zinc or placebo, respectively, for 2 months. Serum zinc concentration was measured by atomic absorption spectrophotometry. PON activity was evaluated by spectrophotometric method. Lipid profile was determined using commercial kits, and apolipoprotein AI (Apo-AI) and B (Apo-B) levels were measured by commercial immunoturbidimetric kits. RESULTS: In the case group, there was no significant change in the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and Apo-B levels, while the serum levels of high-density lipoprotein (HDL), Apo-AI, and PON activity were significantly increased (p = 0.02). In the control group, although significant increases were observed in the serum levels of TC, TG, and Apo-B (p = 0.009, 0.019, and 0.001, respectively), the serum PON activity was significantly decreased (p = 0.025) and the serum levels of HDL, LDL, and Apo-AI were not changed. At the end of intervention period, the serum level of Apo-AI and PON activity were significantly higher in the case group. CONCLUSIONS: Zinc supplementation increased both the activity of PON and the serum level of Apo-AI in the HD patients.

Influence of chemotherapy on the lipid peroxidation and antioxidant status in patients with acute myeloid leukemia.

Chemotherapeutic agents used in patients with cancer cause to generate the enormous amounts of free radicals associated with cell injury. In this study we assess the effects of chemotherapy regimen on oxidant/antioxidant status in patients with acute myeloid leukemia (AML). 38 newly diagnosed patients with acute myeloid leukemia were recruited in this study. All patients received cytarabine and daunorubicin as chemotherapy regimen. Plasma levels of malondialdehyde (MDA), total antioxidant status (TAS), and the levels of erythrocyte activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were determined before chemotherapy and 14 days after chemotherapy with cytarabine and daunorubicin. Plasma MDA concentrations increased significantly (from 2.68 ± 0.89 nmol/L to 3.14 ± 1.29 nmol/L) during the 14 days post-chemotherapy period (P=0.04). Plasma TAS concentrations changed with chemotherapy from 1.09 ± 0.15 mmol/L to 1.02 ± 0.14 mmol/L with P=0.005. Erythrocyte SOD and GPX activity decreased overtime from 1157.24 ± 543.61 U/g Hb to 984.01 ± 419.09 U/g Hb (P=0.04) and 46.96 ± 13.70 U/g Hb to 41.40 ± 6.44 U/g Hb (P=0.02) respectively. We report here that there is an increase in malondialdehyde levels and a decrease in the levels of antioxidant enzymes and total antioxidant status. This suggests that chemotherapy causes these changes as a result of enormous production of reactive oxygen species in the patients with AML. Antioxidant supplementation must be approached with caution because of the probability of reduction the therapeutic efficacy of these cytotoxic drugs.

Effect of fish oil supplements on serum paraoxonase activity in female patients with rheumatoid arthritis: a double-blind randomized controlled trial.

BACKGROUND: This study was conducted to determine the effect of fish oil (FO) supplements on high density lipoprotein cholesterol (HDL-C), apolipoprotein-AI (Apo-AI), malondialdehyde (MDA), arylesterase (Aryl), and paraoxonase-1 (PON1) activity in female patients with rheumatoid arthritis (RA). METHODS: A total of 90 RA patients were randomly allocated into two groups that were treated with one FO pearl (1 gr) daily or placebo for three months in addition to conventional treatment. HDL-C, Apo-AI, and MDA levels as well as PON1 and Aryl activities were measured before and after treatment. Independent t-test was used to match basal parameters of case and control groups. Paired t-test was used to assess significance of the differences. Correlation was evaluated by Pearsons test and the statistical significance was set at P < 0.05. RESULTS: No significant differences were noted between FO and placebo patients with regards to age, disease duration, post-menopausal status, conventional therapy, body mass index (BMI), and numbers of swollen and tender joints at the beginning of the study. There were 83 patients who completed the three-month follow up. Serum levels of HDL-C (P = 0.018), Apo-AI (P = 0.165), Aryl (P = 0.026), and PON1 (P = 0.049) activity increased, whereas MDA levels decreased significantly with FO supplementation (P = 0.077). Significant correlations between increased PON1 activity and both HDL-C (P = 0.007, r = 0.419) and Apo-AI (P < 0.001, r = 0.742) concentrations as well as between HDL-C and Apo AI levels (P = 0.01, r = 0.403) were found. CONCLUSION: According to the results of this study, FO could increase serum HDL-C and PON1 levels and Aryl activity in female patients with RA.

Protective effect of grape seed extract on gentamicin-induced acute kidney injury.

INTRODUCTION. This study was designed to determine the protective effect of red grape seed extract (RGSE) on gentamicin-induced nephrotoxicity in rats. MATERIALS AND METHODS. Thirty male Wistar rats were divided into 3 groups to receive RGSE, for 60 days followed by intraperitoneal injection of saline solution (as placebo) for 8 days (group 1); RGSE followed by gentamicin for 8 days (group 2); and gentamicin without pre-medication of RGSE (group 3). Oral RGSE, 40 mg/kg/d, and intraperitoneal injection of gentamicin, 100 mg/kg/d, were administered in these groups of rats. Blood and urine samples were collected on days 0 and 68 of the study. Then, the kidneys were removed for pathologic examination. RESULTS. On day 68, serum creatinine and blood urea nitrogen concentrations were highest in group 3, which was significantly higher than in group 1 (P = .001 and P = .004, respectively), while slightly higher than in group 2 (P = .30 and P = .50, respectively). Fractional excretion of sodium was not significantly different between the three groups. Histopathological evaluation showed that rats in group 3 had significantly higher degrees of severe acute tubular necrosis and interstitial mononuclear cell infiltration than the rats in groups 1 and 2 (P < .001). CONCLUSIONS. This animal study suggests that pretreatment with RGSE protects against gentamicin-induced acute kidney injury as evident on tissue histology. However, this was not accompanied with significant improvement in biochemical markers of kidney injury.

Fish oil supplementation decreases serum soluble receptor activator of nuclear factor-kappa B ligand/osteoprotegerin ratio in female patients with rheumatoid arthritis.

OBJECTIVE: Soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) to osteoprotegerin ratio is designated as a bone metabolism equation in many rheumatologic disorders and would be modified with fish oil (FO) supplementation. DESIGN AND METHODS: Eighty-three females with rheumatoid arthritis were divided randomly to 40 and 43 patients treated with (1 g/day) or without FO for 3 months accompanied with conventional drugs, respectively. Osteoprotegerin, sRANKL, tumor necrosis factor alpha (TNFalpha) serum levels were measured before and after treatment. RESULTS: Serum levels of osteoprotegerin increased, although sRANKL, TNFalpha and sRANKL/osteoprotegerin ratio decreased with FO therapy. A significant positive correlation was observed between sRANKL/osteoprotegerin ratio and TNFalpha levels (r=0.327, p=0.040) in the FO-treated group. CONCLUSIONS: FO could decrease the inflammatory response by lowering of serum TNFalpha levels and sRANKL/osteoprotegerin ratio.

Prevention of selenite-induced cataractogenesis in Wistar albino rats by aqueous extract of garlic.

PURPOSE: The main aim of this study was to evaluate the inhibitory impacts of the aqueous extract of garlic (Ga) on the formation of cataract induced by sodium selenite (Se). METHODS: Thirty-two Wistar albino rat pups (4 equal groups: G1, G2, G3, and G4) were treated as follows: G1, subcutaneous (s.c.) and intraperitoneal (i.p.) injection of normal saline (0.3 mL) on postpartum (day 10); G2, i.p. injection of aqueous extract of garlic (1 mL/kg body weight) and s.c. injection of normal saline (0.3 mL) on postpartum (day 10); G3, s.c. injection of sodium selenite (20 nmol/g body weight) and i.p. injection of normal saline (0.3 mL) on postpartum (day 10); and G4, s.c. injection of sodium selenite (20 nmol/g body weight) and i.p. injection of aqueous extract of garlic (1 mL/kg body weight) on postpartum (day 10). Daily i.p. injections of aqueous extract of garlic (in G2 and G4) and normal saline (in G1 and G3) were continued for 14 days. The development of cataract was assessed over a period of 2 weeks after injection of sodium selenite. For further examination, the rats' lenses were removed and analyzed for glutathione (GSH), malondialdehyde (MDA) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPX) activities. RESULTS: In G3 (Se-treated group), all rats developed grade 3 cataract in both eyes. However, in G1 (untreated control group), G2 (Ga-treated group), and G4 (Ga-Se-treated group), the lenses in both eyes of all rats remained clear (P < 0.0001). This clinical finding was associated with higher GSH level and GPX, SOD activities and lower level of MDA in the Se- and Ga-treated group (G4) compared with SS-treated group (G3) rat lenses (P < 0.003). CONCLUSIONS: Intraperitoneal injection of the Ga in rat model appeared to effectively prevent Se-induced cataract, thus such herbal remedy may be considered for treatment of cataract.

Preventive effect of onion juice on selenite-induced experimental cataract.

PURPOSE: To evaluate the effects of onion juice on sodium-selenite induced cataract formation. MATERIALS AND METHODS: Thirty-two 10-day-old Wistar-albino rat pups were divided into four equal groups. Group 1 received only subcutaneous saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into the right eye for 14 days; the left eye received no treatment. Group 4 rats were similar to those of Group 3, the only difference being that of undiluted fresh juice of crude onion. The development of cataract was assessed. Rat lenses were analyzed for total antioxidant (TA) level, and for activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD). RESULTS: Both eyes of all rats in Group 1 did not exhibit cataract formation . In Group 2, all rats developed Grade 3 cataract in the lenses of both eyes. The difference in exhibited cataract in the lens of the right eyes in all rats between Group 2 and any eyes of groups 3 or 4 were significant ( P = 0.001). The mean TA level and mean activities of SOD and GPX in Group 2 rat lenses were significantly lower than the values in lenses of all rats in Group 1 ( P = 0.001, 0.003, 0.001), and in the lenses of the right eyes of rats in Groups 3 and 4 ( P = 0.001, 0.020, 0.001). CONCLUSION: Instillation of onion juice into the rat eyes can effectively prevent selenite-induced cataract formation. This effect was associated with increased TA level, SOD and GPX activities in the lens.

Neuroprotective effects of high-dose vs low-dose melatonin after blunt sciatic nerve injury.

INTRODUCTION: Melatonin, the secretory product of the pineal gland, has potent antioxidant properties. The aim of this study was to compare the effects of low-dose (10 mg/kg) vs high-dose (50 mg/kg) melatonin on early lipid peroxidation levels and ultrastructural changes in experimental blunt sciatic nerve injury (SNI). We believe this to be the first study to assess the dose-dependent neuroprotective effects of melatonin after a blunt peripheral nerve injury. MATERIALS AND METHODS: Rats were randomly allocated into 5 groups of 10 animals each. The SNI only rats underwent a nerve injury procedure. The SNI plus vehicle group received SNI and intraperitoneal injection of vehicle (diluted ethanol) as a placebo. The SNI plus low-dose or high-dose melatonin groups received intraperitoneal melatonin at doses of 10 mg/kg or 50 mg/kg, respectively. Controls had no operation, melatonin or vehicle injection. SNI was induced by clamping the sciatic nerve at the upper border of the quadratus femoris for 2 min. RESULTS: Sciatic nerve samples were harvested 6 h after nerve injury and processed for biochemical and ultrastructural analysis. Trauma increased the lipid peroxidation of the sciatic nerve by 3.6-fold (153.85 +/- 18.73 in SNI only vs 41.73 +/- 2.23 in control rats, P < 0.01). Low (P = 0.02) and high (P < 0.01) doses of melatonin attenuated the nerve lipid peroxidation by 25% and 57.25%, respectively (65.76 +/- 2.47 in high-dose vs 115.08 +/- 7.03 in low-dose melatonin groups). DISCUSSION: Although low-dose melatonin reduced trauma-induced myelin breakdown and axonal changes in the sciatic nerve, high-dose melatonin almost entirely neutralized any ultrastructural changes. CONCLUSION: Our results suggest that melatonin, especially at a dose of 50 mg/kg, has a potent neuroprotective effect and can preserve peripheral neural fibers from lipid peroxidative damage after blunt trauma. With further investigations, we hope that these data may prove useful to clinicians who treat patients with nerve injuries.