Astaxanthin prevents nephrotoxicity through Nrf2/HO-1 pathway.

Renal toxicity is one of the side effects of methotrexate (MTX). Therefore, this study explored the use of astaxanthin (AST), as a natural carotenoid, against MTX-induced nephrotoxicity emphasizing the changes in oxidative stress and the expression of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1). During the 10 days of the experiment, male Wistar rats in different groups received MTX (10 mg/kg) on days 6, 8, and 10 and three doses of AST (25, 50, and 75 mg/kg) during the entire course. Renal failure caused by MTX was observed in significant histopathological changes and a significant increase in serum levels of creatinine, urea, and uric acid (p < 0.05). Oxidative change induced by MTX injection was also observed by remarkably increasing the tissue level of malondialdehyde (MDA) and decreasing the activity of superoxide dismutase (SOD) and catalase (p < 0.001). AST decreases the adverse effects of MTX by upregulating the expression of Nrf2/HO-1 genes (p < 0.01) and decreasing the tissue level of MDA (p < 0.01). Also, AST significantly reduced the amount of creatinine, urea, and uric acid in the serum and improved the activity of SOD and catalase in the kidney tissue (p < 0.05). Thus, AST may protect the kidney against oxidative stress caused by MTX.

Antioxidant effects of astaxanthin and metformin combined therapy in type 2 diabetes mellitus patients: a randomized double-blind controlled clinical trial.

Background and purpose: Since the critical role of oxidative stress in the pathogenesis and complications of type 2 diabetes mellitus (T2DM) has been proven, antioxidant therapy is considered an applicable strategy to control T2DM development. This study aimed at evaluating the effect of astaxanthin (AST) supplementation combined with metformin on oxidative indices and antioxidant defenses in T2DM patients. Experimental approach: In this randomized, double-blind placebo-controlled trial, 50 T2DM subjects receiving metformin were supplemented with 10 mg/day AST or placebo for 12 weeks. Malondialdehyde concentration and serum total antioxidant capacity (TAC) were assessed as oxidative indices. We also evaluated NF-E2-related factor2 (Nrf2) as the most critical transcription factor of antioxidant defense. Moreover, the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase were calculated. Findings/Results: AST supplementation-metformin combination caused a significant increase in SOD and catalase activities, as well as inducing Nrf2 protein expression compared to the placebo group. Significant changes in serum malondialdehyde and TAC between the AST group and placebo group after supplementation were not observed, although a significant increase was observed in TAC within the AST group after supplementation (32.67 ± 6.73) to before (25.86 ± 5.98). These results remained without change after adjustment for potential confounders. Conclusion and implications: Our study demonstrated that AST supplementation controlled oxidative stress through a synergistic effect with metformin and ameliorated overall antioxidant capacity by inducing Nrf2 transcription factor and activating SOD and catalase in T2DM patients. As a result, AST and metformin combination therapy can be considered beneficial in modifying oxidative stress and preventing T2DM complications.

Resistin and prooxidant-antioxidant balance: Markers to discriminate acute coronary syndrome from stable angina.

BACKGROUND: Resistin and oxidative stress may play a role in the pathogenesis of coronary heart disease (CHD) including acute coronary syndrome (ACS). The aim of this study was to investigate the role of serum resistin and prooxidant-antioxidant balance (PAB) in ACS occurrence in order to differentiate it from stable angina. Moreover, we aimed to determine the correlation between resistin and PAB in patients with ACS and its difference from patients with stable CHD. METHODS: This cross-sectional, descriptive study was conducted on 50 patients with ACS and 50 patients with stable CHD who underwent coronary angiography (CAG). Serum resistin level was measured using enzyme-linked immunosorbent assay (ELISA). PAB and other variables were analyzed using standard methods. RESULTS: A significant increase in serum resistin and PAB was observed in patients with ACS (2.55 ± 0.13 ng/ml and 123.5 ± 5.58 HK unit, respectively) compared to patients with stable CHD (1.53 ± 0.12 ng/ml and 95.9 ± 2.7 HK unit, respectively) (P < 0.001). In addition, a significant positive correlation was seen between serum resistin and PAB in patients with ACS (r = 0.39; P = 0.005), but this correlation was not found in patients with stable CHD (r = 0.21; P = 0.140). Resistin (r = 0.52; P < 0.001) and PAB (r = 0.55; P < 0.001) were significantly associated with high-sensitivity C-reactive protein (hs-CRP) in patients with ACS, but this association was not found in patients with stable CHD (resistin: r = 0.24; P = 0.090; PAB: r = -0.02: P = 0.910). CONCLUSION: High serum resistin or PAB levels, and their association with the occurrence of ACS, can be used as a robust discriminating factor to differentiate ACS from stable CHD.

The effect of salusin-ß on expression of pro- and anti-inflammatory cytokines in human umbilical vein endothelial cells (HUVECs).

BACKGROUND: Atherosclerosis is one of the predominant causes of cardiovascular disease (CVD). Several studies indicated the significant pathophysiological role of salusin-ß in atherosclerosis. Cytokines are involved in all stages of atherosclerosis. Therefore, we aimed to assess the effect of salusin-ß on interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18) (as inflammatory cytokines) and interleukin 1Ra (IL-1Ra) (as anti-inflammatory cytokines) levels in human umbilical vein endothelial cells (HUVECs). METHODS: The HUVECs were cultured in HUVEC completed medium and treated with different doses of salusin-ß for 6 and 12 hours. For the investigation of nuclear factor Æ™ß (NF-ƙß) signaling pathway involvement, cells were treated in the presence or absence of Bay 11-7082 (as NF-Æ™ß inhibitor). The mRNA expression and protein level of cytokines were measured by a real-time polymerase chain reaction (PCR) system and enzyme-linked immunosorbent assay (ELISA) method, respectively. RESULTS: Salusin-ß increased mRNA expression and protein level of IL-6, IL-8 and IL-18. This protein decreased mRNA and protein level of IL-1Ra in HUVECs. NF-Æ™ß signaling pathway was involved in the up-regulatory effect of salusin-ß on mRNA expression of pro-inflammatory cytokines. The down-regulatory effect of salusin-ß on IL-1Ra expression could not be influenced by Bay 11-7082 pre-treatment. CONCLUSION: It seems that salusin-ß may participate in a cascade pathway in vascular inflammation. Our findings suggested that salusin-ß has potential use as a therapeutic target for atherosclerosis.

Salusin-α Attenuates Inflammatory Responses in Vascular Endothelial Cells.

Atherosclerosis accounts for numerous cardiovascular diseases, and cytokines have a critical role in acceleration or suppression of disease. Salusin-α presents a new class of bioactive peptides that can have anti-atherogenic properties. Therefore, the effects of salusin-α on the expression of some pro- and anti-inflammatory cytokines and on TNF-α-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs) were examined. The involvement of the NF-κB pathway in effects of salusin-α in HUVECs was checked using Bay 11-7082 as an NF-κB inhibitor. The mRNA expression of pro-inflammatory cytokines including IL-6, IL-8, and IL-18 and anti-inflammatory cytokine IL-1Ra was assessed by real-time PCR. The protein levels of cytokines were measured by the ELISA method. Salusin-α suppressed both mRNA and protein expression of pro-inflammatory cytokines and induced mRNA and protein expression of IL-1Ra in HUVECs. Salusin-α suppressed TNF-α-induced inflammatory responses in HUVECs. The down-regulatory or up-regulatory effects of salusin-α on expression of cytokines could not be influenced by Bay 11-7082 pretreatment. Our findings indicate anti-inflammatory effects of salusin-α and suggest a novel peptide-based therapeutic strategy for atherosclerosis.

Dihydroartemisinin Induces Apoptosis in Human Bladder Cancer Cell Lines Through Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cytochrome C Pathway.

BACKGROUND: Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and has antiproliferative effect. However, such effects of DHA have not yet been revealed for bladder cancer cells. METHODS: We used as bladder cancer cell lines to examine the effect of DHA on the cell viability, cell apoptosis, and monitoring of mitochondrial membrane potential (ΔΨm) changes. Furthermore, the effect of DHA on the reactive oxygen species (ROS) production and cytochrome c release were also detected. We employed MTT assay to investigate the cell proliferation effect of DHA on the EJ-138 and HTB-9 human bladder cancer cells. Annexin/PI staining, caspase-3 activity assay, Bcl-2/Bax protein expression, mitochondrial membrane potential assay, cytochrome c release, and ROS analysis were used for apoptosis detection. RESULTS: DHA significantly reduced cell viability in a dose-dependent manner. Cytotoxicity of DHA was suppressed by N-acetylcysteine. The growth inhibition effect of DHA was related to the induction of cell apoptosis, which were manifested by annexin V-FITC staining, activation of caspase-3. DHA also increased ROS generation, cytochrome c release, and loss of mitochondrial transmembrane potential (ΔΨm) in cells. In addition, the downregulation of regulatory protein Bcl-2 and upregulation of Bax protein by DHA were also observed. CONCLUSIONS: These findings demonstrated that DHA induces apoptosis through mitochondrial signaling pathway. These suggest that DHA may be a potential agent for induction of apoptosis in human bladder cancer cells.

Serum levels of lead, mercury and cadmium in relation to coronary artery disease in the elderly: A cross-sectional study.

BACKGROUND: There is a continuing attempt to identify novel factors that can predict the risk of cardiovascular disease beyond the established coronary risk factors. It has been suggested that serum levels of lead, mercury and cadmium are associated with the risk of coronary artery disease (CAD). In the present study, we aimed to evaluate serum concentrations of lead (s-Pb), mercury (s-Hg) and cadmium (s-Cd) in patients with CAD in comparison with those of healthy individuals. The correlation between serum levels of these heavy metals and lipid profile parameters was also investigated. METHODS: In this case-control study, we included 65 patients (35 females) aged 50-70 years with angiographically-documented CAD and 65 healthy controls (43 female) matched for sex, age and place of residence. Serum concentrations of heavy metals were determined using graphite furnace atomic absorption (GFAA). Serum lipids were measured using routine enzymatic methods. RESULTS: It was observed that the mean concentration of s-Pb (12.54 ± 8.41 vs. 5.89 ± 4.44 µg/L, p < 0.05) and s-Cd (0.938 ± 0.72 vs. 0.448 ± 0.30, p < 0.05; CI: 95%) and s-Hg (10.14 ± 5.06 vs. 6.11 ± 5.66, p < 0.05) were significantly higher in CAD patients compared with control subjects. The same result was also obtained after adjustment for cardiovascular risk factors including age, dyslipidemia, diabetes mellitus and hypertension (p < 0.05). The mean concentration of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and TC:HDL-C ratio were significantly higher in CAD patients (p < 0.05). There was no significant association between serum metal concentrations with TC, HDL-C and TC:HDL-C ratio (p > 0.05). CONCLUSIONS: The present results showed that serum levels of heavy metals are associated with the presence of CAD. Long-term exposure to trace levels of Pb, Cd and Hg may play a role in the development of coronary atherosclerotic plaques.

Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy.

OBJECTIVE: Gastric cancer is the fourth most common cancer and the second cause of death in the world. According to the studies, the gastric cancer is relatively sensitive to chemotherapy. The aim of this study was to investigate the association of oral administer PUFAs with Caspase enzymes in patients with gastric cancer under chemotherapy. METHODS: This study was a Clinical Trial in which the target group consisted of the patients recognized with gastric cancer for the first time and cured under chemotherapy. Thirty-four patients were selected and categorized randomly into two groups. The case group included the patients taking PUFAs along with chemotherapeutic agent. In these patients, chemotherapy started with Cis-Platin plus PUFAs supplement in the scale of 3600 mg daily and in three courses. In control group, the individuals were under the same chemotherapy protocol without PUFAs. Biopsy samples from tumor were taken from the patients before and after chemotherapy. Levels of mRNA and protein expression of caspase 3, 8, 9 were measured in biopsy samples by Real-Time PCR and Frozen Section methods. The levels of apoptosis were determined using DNA-damage colorimetric assay. RESULTS: In the case group, caspase 3 showed a significant increase in both gene and protein expression levels after administration of PUFAs supplement in comparison with those of the control group (p=0.006 for gene, p=0.001 for protein). PUFAs induced caspase-9 gene expression level in these patients (p<0.0001). Caspase-9 protein level also revealed a marked elevation when PUFAs were administered along with chemotherapeutic agent (p<0.0001). DNA damage in gastric tissue from the patients under PUFAs treatment plus Cis-Platin was significantly higher than that of control group (p=0.003). PUFAs showed no significant changes in caspase-8 both at the gene and protein levels in the patients. CONCLUSION: According to the results of present study, it appears that oral administration of PUFAs can elevate the efficacy of chemotherapy agent in individuals' mitochondria-dependent apoptosis. As PUFAs enhances caspase-3 and 9 genes expression levels, which is an important induce the mitochondrial dependent apoptosis process. The study was registered in Iran clinical trials registry center under No. IRCT2014031016922N1.

Association of serum microRNA-21 levels with Visfatin, inflammation, and acute coronary syndromes.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression. It seems that microRNA-21 (miR-21) and Visfatin, a novel adipocytokine, play roles in inflammation and atherosclerosis. The aim of this study was to investigate the association of miR-21 with Visfatin, inflammation, atherosclerosis and acute coronary syndrome (ACS). Based on coronary angiography and electrocardiogram (ECG), 53 patients with ACS and 52 patients with stable CAD were enrolled in this study. We assayed serum miR-21, Visfatin, and routine chemistries using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR), enzyme-linked immunosorbent assay (ELISA) and automated analyzer, respectively. We used a regression analysis to describe the relationship between the variables. Serum miR-21 level in 2-ΔCt value was significantly higher in ACS patients (10.52 ± 1.01-fold) than the stable CAD patients (4.4 ± 0.79-fold) (F = 4.59, p < 0.001). In addition, serum Visfatin was significantly higher in ACS patients (17.5 ± 0.61 ng/ml) than the stable CAD patients (12.7 ± 0.49 ng/ml) (F = 2.62, p < 0.001). Furthermore, the serum miR-21 level correlated positively with serum Visfatin level (r = 0.26, p = 0.008), hs-CRP (r = 0.29, p = 0.003), age (r = 0.21, p = 0.034) and negatively with HDL-cholesterol (r = -0.28, p = 0.004). We concluded that the increased serum miR-21 and Visfatin may be involved in the pathogenesis of ACS through promoting inflammation or may result from inflammatory responses to ACS. Furthermore, the potential role of miR-21 and Visfatin in plaque instability and inflammation warrants further investigations.

The effect of ω-fatty acids on the expression of phospholipase A2 group 2A in human gastric cancer patients.

BACKGROUND: Studies show that polyunsaturated fatty acids (PUFAs) may have an inhibitory role in carcinogenesis. It was previously shown that PLA2 group 2A (PLA2G2A) messenger RNA (mRNA) expression is associated with less frequent metastasis and longer survival in gastric adenocarcinoma. This study intends to investigate the effect of PUFAs on the expression of PLA2G2A in patients with gastric cancer. MATERIALS AND METHODS: Thirty-four patients with gastric cancer (GC) were randomly divided into two groups. The first group received cisplatin medication. The second group received cisplatin medication and supplements of ω-fatty acids for three courses. The total RNA was extracted from the tissues and cDNA was synthesized. The gene expression of PLA2G2A was evaluated by the real-time polymerase chain reaction (PCR) method. To confirm the changes in gene expression, frozen section was utilized. The frozen tissue samples were sectioned and stained using the immunohistochemistry technique. RESULTS: After chemotherapy and chemotherapy plus supplement, the relative mean of PLA2G2A gene expression increased 1.5 ± 0.5-fold and 7.4 ± 2.6-fold, respectively (P = 0.006). The relative mean of gene expression in patients who received cisplatin and ω-fatty acids supplement increased more significantly (7.5 ± 3.3-fold) than in patients who received only cisplatin (P = 0.016). CONCLUSION: It was found that PUFAs increased the gene and protein expression of PLA2G2A in gastric cancer. Concerning the fact that studies reveal protective function of PLA2G2A in gastric cancer, it is suggested that increased expression of PLA2G2A is helpful. Furthermore, PUFAs can be considered as a useful therapeutic supplement for patients with gastric cancer.

Antioxidant effects of hydroalcoholic and polyphenolic extracts of Peucedanum pastinacifolium Boiss. & Hausskn.

Antioxidant activity of Peucedanum pastinacifolium Boiss. & Hausskn aerial part hydroalcoholic extract (HAE) and polyphenolic extract (PPE) as well as their total phenolic and flavonoid contents were studied. Phenolic and flavonoid contents were respectively estimated as gallic acid and quercetin equivalents. The in vitro antioxidant activity of two extracts of P. pastinacifolium were evaluated by radical scavenging of 1,1-diphenyl-2-picryl hydrazyl radical (DPPH), chelating activity on ferrous ions, or ferric reducing antioxidant power (FRAP) assay. In addition, the in vivo antioxidant activity of hydroalcoholic extract was measured by FRAP assay. Total phenolic contents of PPE and HAE were 117.1 ± 6.2 and 44.3 ± 1.7 mg/g, respectively. Total flavonoid content of PPE (43.4 ± 2.1 mg/g) was found to be higher than that of HAE (8.0 ± 1.5 mg/g). In DPPH radical scavenging assay, HAE and PPE showed fifty percent inhibitory concentration (IC50) values of 469.4 ± 9.3 µg/mL and 128.2 ± 5.5 µg/mL, respectively. Iron chelating activity assays indicated IC50 values of 657.5 ± 13.2 µg/mL and 735.4 ± 16.1 µg/mL for HAE and PPE as opposed to ethylenediamine tetra-acetic acid (EDTA) being 16.5 ± 0.8 µg/mL. PPE exhibited greater FRAP value (154.0 ± 1.8 µM) as compared with that of HAE being 69.3 ± 1.4 µM. In animal study, HAE showed a significant (p < 0.05) increase in FRAP level when compared with that of control group. Our results showed that P. pastinacifolium possess antioxidant properties which most likely are exerted through free radical scavenging, chelating activity, and reducing power.

The role of serum levels of microRNA-21 and matrix metalloproteinase-9 in patients with acute coronary syndrome.

Acute coronary syndrome (ACS) is one of the leading causes of cardiovascular death. It seems that microRNA-21 and matrix metalloproteinase-9 implicated in the pathogenesis of cardiovascular diseases. The aim of this study was to investigate the role of circulating miR-21 and MMP-9 as biomarkers for ACS. Based on coronary angiography and electrocardiography results, 50 patients with ACS and 50 patients with stable coronary artery disease (stable CAD) were enrolled in this study. Samples were collected from patients and stored at -80 °C. Serum miR-21 gene expression was measured by quantitative real-time PCR method. Serum total MMP-9 was measured by enzyme-linked immunosorbent assay kit. Also, the activity of MMP-9 was measured by gelatin zymography. Patients with ACS had a significantly higher miR-21 level compared to the stable CAD ([Formula: see text] = 0.88 ± 0.06 and 0.31 ± 0.08 respectively, P < 0.001). At the same time, the serum levels and activity of MMP-9 were significantly higher in ACS patients compared to those with stable CAD (324.01 ± 17.57 and 204.6 ± 12.39 ng/mL, P < 0.001, and 2524.5 ± 131.3 and 1280.8 ± 19.6 units, P < 0.001, respectively). miR-21 expression levels were correlated positively with MMP-9, hs-CRP, and age and negatively with HDL-cholesterol (r = 0.33, P < 0.001, r = 0.22, P < 0.031, r = 0.26, P < 0.008, r = -0.32, P < 0.001, respectively). We concluded that increased serum expression of miR-21 and higher serum activity of MMP-9 may be useful indicators for ACS. However, we suggest further studies to be performed.

Investigation of membrane fatty acid profiles in erythrocytes of patients with stable coronary artery disease.

BACKGROUND: The association between the erythrocyte membrane fatty acids and the severity of coronary stenosis has not been studied in patients with stable coronary artery disease (CAD). OBJECTIVE: We sought to investigate whether the fatty acid profile of erythrocyte membranes is significantly different in patients with stable CAD compared with patients with nonsignificant coronary stenosis and evaluate a possible relationship between fatty acid profile and the severity of coronary stenosis. METHODS: The population included 144 patients, undergoing clinically indicated coronary angiography. The severity of coronary stenosis was scored after coronary angiography, and patients were divided into 2 groups; the S-stenosis group (CAD patients, n = 82) had a significant stenosis indicated by coronary angiography and the second group, S-stenosis (n = 62), had nonsignificant coronary stenosis. RESULTS: The erythrocyte membranes linoleic acid (LA) levels were lower (P < .001) and the arachidonic acid (AA)-to-LA ratio, a marker of desaturase activity, were higher (P < .001) in CAD patients compared with S-stenosis patients. The CAD scores were correlated negatively with the membrane LA levels (r = -0.338; P < .001) and positively with the AA-to-LA ratio (r = 0.306; P < .001). CONCLUSIONS: This study shows that LA levels of the erythrocyte membrane and AA-to-LA ratio are correlated with the severity of CAD.

Factor V Leiden, factor V Cambridge, factor II GA20210, and methylenetetrahydrofolate reductase in cerebral venous and sinus thrombosis: A case-control study.

BACKGROUND: Factor V G1691A (FV Leiden), FII GA20210, and methylenetetrahydrofolate reductase (MTHFR) C677T mutations are the most common genetic risk factors for thromboembolism in the Western countries. However, there is rare data in Iran about cerebral venous and sinus thrombosis (CVST) patients. The aim of this study was to evaluate the frequency of common genetic thrombophilic factors in CVST patients. MATERIALS AND METHODS: Forty consequently CVST patients from two University Hospital in Isfahan University of Medical Sciences aged more than 15 years from January 2009 to January 2011 were recruited. In parallel, 51 healthy subjects with the same age and race from similar population selected as controls. FV Leiden, FII GA20210, MTHFR C677T, and FV Cambridge gene mutations by polymerase chain reaction technique were evaluated in case and control groups. RESULTS: FV Leiden, FII GA20210, and FV Cambridge gene mutations had very low prevalence in both case (5%, 2%, 0%) and control (2.5%, 0%, 0%) and were not found any significant difference between groups. MTHFR C677T mutations was in 22 (55%) of patients in case group and 18 (35.5%) of control group (P = 0.09). CONCLUSION: This study showed that the prevalence of FV Leiden, FII GA20210, and FV Cambridge were low. Laboratory investigations of these mutations as a routine test for all patients with CVST may not be cost benefit.

Calcium/Calmodulin-dependent Protein Kinase II is a Ubiquitous Molecule in Human Long-term Memory Synaptic Plasticity: A Systematic Review.

BACKGROUND: Long-term memory is based on synaptic plasticity, a series of biochemical mechanisms include changes in structure and proteins of brain's neurons. In this article, we systematically reviewed the studies that indicate calcium/calmodulin kinase II (CaMKII) is a ubiquitous molecule among different enzymes involved in human long-term memory and the main downstream signaling pathway of long-term memory. METHODS: All of the observational, case-control and review studies were considered and evaluated by the search engines PubMed, Cochrane Central Register of Controlled Trials and ScienceDirect Scopus between 1990 and February 2015. We did not carry out meta-analysis. RESULTS: At the first search, it was fined 1015 articles which included "synaptic plasticity" OR "neuronal plasticity" OR "synaptic density" AND memory AND "molecular mechanism" AND "calcium/calmodulin-dependent protein kinase II" OR CaMKII as the keywords. A total of 335 articles were duplicates in the databases and eliminated. A total of 680 title articles were evaluated. Finally, 40 articles were selected as reference. CONCLUSIONS: The studies have shown the most important intracellular signal of long-term memory is calcium-dependent signals. Calcium linked calmodulin can activate CaMKII. After receiving information for learning and memory, CaMKII is activated by Glutamate, the most important neurotransmitter for memory-related plasticity. Glutamate activates CaMKII and it plays some important roles in synaptic plasticity modification and long-term memory.

Adiponectin: an adipokine with protective features against metabolic syndrome.

Metabolic syndrome (MetS) as a collection of obesity-associated disorders is associated with inflammation, oxidative stress, pro-thrombotic state, elevated risk of developing cardiovascular disease and type 2 diabetes. Adiponectin is one of the most abundant peptide hormones derived from adipose tissue. This protein plays a major role in glucose and lipid metabolism and prevents development of vascular changes. Anti-oxidative and anti-inflammatory effects are the other features of adiponectin. Hypoadiponectinemia is associated with hypertension and pro-thrombotic state. In this review, we discuss the crucial role of adiponectin in prevention of metabolic syndrome considering its effects on the components of this syndrome. Pharmacological interventions and lifestyle modification may increase plasma adiponectin level or tissue sensitivity which seems to be a promising target for prevention and therapeutic approaches of MetS and related diseases.

Hypocholesterolemic effects of Balangu (Lallemantia royleana) seeds in the rabbits fed on a cholesterol-containing diet.

OBJECTIVES: Lallemantia royleana (Benth. in Wall.) Benth. (Lamiaceae) is a medicinal plant used in Iranian traditional and folklore medicine in the treatment of various nervous, hepatic, and renal diseases. In the present study, whole seeds of the herb were prepared and evaluated for hypolipidemic activities using an animal model. MATERIALS AND METHODS: Animals were fed normal diets or diets supplemented with cholesterol (0.5%) for 12 weeks to evoke hypercholesterolemia. Moreover, hypercholesterolemic animals were treated with different doses of whole seeds of Balangu (0, 5, 10, and 20%) for 12 weeks. RESULTS: Results showed that the serum total cholesterol and triglyceride decreased in all groups treated with Balangu seeds p<0.05. Changes in the distribution of cholesterol in low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were found. LDL-C and HDL-C decreased significantly in all of the groups treated with whole seeds of the herb with respect to hypercholesterolemic group p<0.05. CONCLUSION: Our results showed that L. royleana seeds decreased the serum cholesterol and triglyceride levels in hypercholesterolemic animals but led to the increase of atherogenic index in all treated groups.

Hepatotoxicity effect of some Iranian medicinal herbal formulation on rats.

BACKGROUND: The public conviction that 'herbal remedies are safe' has led to an increased consumption of these products. This study was performed in view of the wide distribution of herbal remedies, the risks posed by self-treatment with these products, and the existing reports about the toxic effects of some medicinal herbs. MATERIALS AND METHODS: In this study the effect of some of the most used herbal drops of A, B, C, and D on the liver function of rats was examined at different doses, namely minimum dose, maximum dose, and 2.5 times the maximum dose indicated in the brochures. The rats were administered the said doses via a feeding tube for 50 days. The liver function parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), total serum protein, albumin, and urea were measured using the spectrophotometric method. RESULTS: The animals' liver tissues were examined pathologically. The A drop did not change the liver function parameters significantly. The B drop increased the LDH by 34% compared to the controls, at the maximum administered dose. The C and D drops increased the ALT, AST, and LDH significantly compared to the controls. The histological findings suggest the possible effect of C and D drops on the function of hepatocytes. CONCLUSIONS: We recommend that the herbal formulations available in pharmaceutical markets be more closely controlled in terms of quality, as well as toxicity, especially with regard to the possible effects on the hepatic function.

Further studies on anti-inflammatory activity of maprotiline in carrageenan-induced paw edema in rat.

Antidepressant drugs are commonly used for treatment of different medical disorders besides of psychiatric diseases. Accumulating evidence suggests that antidepressants exhibit anti-inflammatory activity in vivo and in vitro conditions, but the mechanisms of this property are not clear very well. In our earlier work, we demonstrated that i.c.v. and i.p. injection of maprotiline, as an antidepressant, decreased paw edema at the fourth hour after subplantar injection of carrageenan. Therefore, this work was undertaken to investigate anti-inflammatory effects of maprotiline in more details. Our results verified that i.p. (25 and 50 mg/kg) and i.c.v. (100 µg/rat) application of maprotiline significantly reduced paw edema at 1, 2, 3 and 4 h intervals after carrageenan challenge. Pathological examinations and MPO activity also showed that both i.p. and i.c.v. maprotiline considerably inhibited infiltration of PMN leucocytes into the inflamed paws. Additionally, i.p. and i.c.v. maprotiline at all applied doses noticeably declined levels of IL-1ß into the site of inflammation, while only i.p. maprotiline at a dose of 50 mg/kg significantly decreased TNF-α levels in the carrageenan-injected paws. These results confirmed anti-edematogenic activity of i.p. and i.c.v. maprotiline in the carrageenan induced paw edema model and showed that these properties of maprotiline might be mediated through inhibition of PMN infiltration and release of IL-1ß and TNF-α.

Glutathione S-transferase mu gene variants and colorectal cancer development--use of sequence-specific probes for an Iranian population.

BACKGROUND: Enzymes of the glutathione S-transferase (GST) family are encoded by a set of polymorphic genes as an important part of cellular chemical defense. The aim of this study was to investigate the possible effect of GSTM1 deletion on susceptibility to developing clinical outcome of colorectal cancer in a group of CRC patients from Isfahan province, Iran, in comparison to age and gender matched control group. METHODS: DNA was extracted from blood of 140 CRC patients and 90 healthy individuals and a set of sequence specific hybridization probes was used for GSTM1 genotyping by real-time PCR in Light-Cycler instrument. Chi-squared test was used to assess the statistical significance of observed differences between the patient and control subjects of different genders and ages. To estimate the risk for overall and stratified analyses, odds ratios (OR) with 95% confidence intervals (CI) computed with logistic regression. RESULTS: No difference in GSTM1 null genotype frequency was found in CRC patients and controls stratified by gender (p value=0.14). The data were suggested a trend of increasing risk for GSTM1 null genotype in patients over 60 years old compared with controls (p value=0.05). GSTM1 null genotype carried an increase of the odds of developing CRC in patients over 60 years old (OR=2.7; 95% CI: 1.03-7.05). No significant association was found (P>0.05) between the GSTM1 null genotype with tumor site (right, left, rectum) or tumor differentiation (well, moderately). CONCLUSION: Our findings suggest that the GSTM1 null genotype may contribute to colorectal cancer development in people over 60 years old.