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Background: In this study, we aimed to investigate the combined effect of sodium valproate (SV) and lithium (Li) against viability, migration, and invasion of prostate cancer cell line.Method: In this in vitro study, PC3 cells were treated with different concentrations of SV (2.5, 5.0, and 10 μM) and Li (2.5, 5.0, and 10 mM) either alone or in combination. Using the MTT test and annexin V/7ADD flow-cytometry, cell viability and apoptosis were assessed. Transwell chamber test was used to assess PC3 cells' invasion and migration.Results: SV and Li alone had no significant effects on PC3 cell viability. However, the combination of SV and Li in all tested concentrations decreased the viability of PC3 cells in a dose dependent manner (P < 0.001). The combination of SV and Li (5.0 μM + 5.0 mM) increased apoptosis of PC3 cells compared with the control group (P = 0.003). Transwell assay showed that combination of SV with Li (5.0 μM + 5.0 mM) reduced the migration and invasion of PC3 cells significantly. The lack of a significant difference between the predicted and observed fractional inhibition for the effects of SV+Li suggests that SV and Li may have additive effects on lowering PC3 cell viability and invasiveness.Conclusion: These findings show that combined low doses of SV and Li could decrease the viability and invasiveness of the PC3 cells; therefore, it can be considered as a new strategy for the treatment of prostate cancer. However, further in vivo studies are required to confirm the results of this study.

Introduction: Antioxidant defense system, including enzymatic and non-enzymatic antioxidants, protects cells from oxidative damage by neutralizing oxidant compounds. Increasing the production of oxidant species and decrease activity of antioxidant system causes oxidative stress. The role of oxidative stress in the pathogenesis of human diseases and strengthening of human antioxidant defense system in preventing and ameliorating of diseases have been shown in numerous studies. Therefore, identifying reliable oxidative stress markers for evaluating the beneficial effects of antioxidants in human diseases has been the focus of many studies over the past decades. Measuring free radicals and active species by flow cytometry, determining the total antioxidant capacity of body fluids, measuring the oxidation products of macromolecules, determining the activity of antioxidant enzymes, and changing the expression of genes related to the antioxidant system are among these methods. This review discussed the major advantages and limitations of these methods. Conclusion: Due to limitations and potential confounding factors of the current markers of oxidative stress, an appropriate experimental protocol should be used for each study and caution should be taken in the interpretation of results. Furthermore, more than one method should be used to overcome the limitations of each marker.

Introduction: The stimulation of DNA repair mechanisms is an immediate response to radiation-induced damage. Monitoring the expression of DNA-repair-related genes would be a beneficial method to identify bio-dosimeter of radiation exposure, particularly for challenging low-dose radiation. In this study, we aimed to evaluate the effect of different low doses of gamma radiation on the expression of DDB2, XPC, and GADD45A genes involved in DNA-damage repair mechanisms.Material and Methods: Forty-eight male rats were divided into a control group and five exposure groups. The latter groups exposed to various doses of γ-rays (Co-60) ranged from 20 mGy to 1000 mGy. 24 h after irradiation, isolated lymphocytes from collected blood samples were used for evaluating gene expression levels by real-time quantitative polymerase chain reaction (qRT-PCR). Data were expressed as means ± SD and were statistically evaluated using one‑way ANOVA or Kruskal-Wallis test. P value

Objective(s): Adrenomedullin (AM) has high expression in the spinal cord. In this study, we investigated the expression of AM and its receptor components, including calcitonin receptor-like receptor (CLR) and receptor activity modifying proteins (RAMPs) in dorsal root ganglion (DRG) and spinal motor (SM) neurons. Furthermore, the effects of AM on cAMP/cAMP response element-binding protein (CREB), AKT/glycogen synthase kinase-3 beta (GSK-3β) signaling pathways, and expressions of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) were evaluated. Materials and Methods: Rat embryonic DRG and SM neurons were isolated, purified, and cultured. Real-time PCR was used to assess expressions of AM, CLR, and RAMPs. cAMP levels, p-CREB, BDNF, and NT-3 were determined using an enzyme-linked immunosorbent assay. p-AKT and p-GSK-3β levels were determined by western blotting. Real-time PCR showed expressions of AM, CLR, RAMP2, and RAMP3 in both DRG and SM neurons. Results: AM increased cAMP accumulation and p-CREB levels in DRG and SM neurons. AM increased p-AKT and p-GSK-3β in DRG, but not SM neurons. AM significantly increased BDNF expression in both DRG and SM neurons. There was also an increase in NT-3 level in both DRG and SM neurons, which is statistically significant in SM neurons. Conclusion: These results showed both DRG and SM neurons are targets of AM actions in the spinal cord. An increase in BDNF expression by AM in both DRG and SM neurons suggests the possible beneficial role of AM in protecting, survival, and regeneration of sensory and motor neurons.

Objective(s): Despite effective anticancer effects, the use of doxorubicin (DOX) is hindered due to its cardio and neurotoxicity. The neuroprotective effect of adrenomedullin (AM) was shown in several studies. The present study aimed to evaluate the possible protective effects of AM against DOX-induced toxicity in dorsal root ganglia (DRGs) neurons. Materials and Methods: Rat embryonic DRG neurons were isolated and cultured. The effect of various concentrations of DOX (0.0 to 100 µM) in the absence or presence of AM (3.125 -100 nM) on cell death, apoptosis, oxidative stress, expression of tumor necrosis-α (TNF-α), interleukin1- β (IL-1β), inducible nitric oxide synthase (iNOS), matrix metalloproteinase (MMP) 3 and 13, and SRY-related protein 9 (SOX9) were examined. Results: Based on MTT assay data, DOX decreased the viability of DRG neurons in a dose and time-dependent manner (IC50=6.88 µm) while dose-dependently, AM protected DRG neurons against DOX-induced cell death. Furthermore, results of annexin V apoptosis assay revealed the protective effects of AM (25 nm) against DOX (6.88 µM)-induced apoptosis and necrosis of DRG neurons. Also, AM significantly ameliorated DOX-induced oxidative stress in DRG neurons. Real-time PCR results showed a significant increase in the expression of TNF-α, IL-1β, iNOS, MMP 3, and MMP 13, and a decrease in the expression of SOX9 following treatment with DOX. Treatment with AM (25 nM) significantly reversed the effects of DOX on the above-mentioned genes expression.Conclusion: Our findings suggest that AM can be considered a novel ameliorating drug against DOX-induced neurotoxicity.

Background: Aluminum (Al) exposure is among the environmental risk factors that may involve in the pathogenesis of neurodegenerative diseases. Oxidative stress has a critical role in the Al-induced toxicity. Saffron is a plant with potent radical scavenging and anti-oxidative properties. This investigation was designed to evaluate the possible protective effects of saffron extract (SE) on aluminum maltolate (Almal)-induced oxidative stress and apoptosis in PC12 cell line. Methods: In this in vitro study, PC12 cells were divided into four groups including control, Almal (500 µM), Almal+SE (50 μg/ml), and Almal+SE (100 μg/ml). After 48 hours of treatment with Almal in the absence and presence of SE, cell viability and apoptosis were determined using MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay and Annexin V flow cytometry, respectively. Catalase activity was determined as an index of oxidative stress. Statistical analyses were performed using one-way ANOVA (SPSS version 16.0). PResults: Almal decreased the PC12 cells viability dose-dependently (IC50=500µM). Co-treatment of 50 and 100 μg/ml of SE with 500 µM of Al increased cell viability to 79% (P=0.04) and 86% (P=0.02) of the control group, respectively. Al also increased PC12 cells apoptosis and catalase activity to 37 and 2.7 folds of those of the control group (PConclusion: SE has protective effects against Al-induced apoptosis and oxidative stress and may possess therapeutic values in the treatment of Al-neurotoxicity.

Objective(s): According to recent studies, valproate shows some protection against oxidative stress (OS) induced by neurotoxins. Current investigation tried to determine the possible ameliorating effects of sodium valproate (SV) against aluminum (Al)-induced cell death, apoptosis, mitochondrial membrane potential (MMP), and OS in PC12 cells.Materials and Methods: In this in vitro study, PC12 cells were treated with different concentrations of aluminum maltolate (Almal) with and without SV (50–400 µM). Cell viability was assessed by MTT assay. To measure quantitatively the effects of SV on Al-induced apoptosis and reactive oxygen species (ROS), flowcytometry using 7AAD/annexin-V and 2’, 7’-dichlorofluorescein diacetate staining were employed, respectively. MMP was monitored using the retention of rhodamine 123. Catalase (CAT) activity was assayed by the rate of decomposition of hydrogen peroxide. Results: Exposure of PC12 cells for 48 hr to Almal (125–2000 µM) significantly reduced cell viability (IC50=1090 μM), increased ROS generation and apoptosis, and reduced MMP and CAT activity. SV reduced the Almal-induced cell death and apoptosis. Furthermore, the effects of Almal on ROS generation, catalase activity, and MMP reduction were significantly diminished by SV. Conclusion: Data from this study suggest that SV can inhibit Al-induced cell death and apoptosis of PC12 cells via ameliorating OS.

Background: Metastasis is the main cause of prostate cancer (PCa) death. The inhibitory effect of N-myc downstream-regulated gene 2 (NDRG2) on the invasiveness properties of PCa cells has been demonstrated previously. However, its underlying mechanisms have not yet been investigated. The present study aimed to investigate the effects of NDRG2 overexpression on the expression of genes involved in epithelial-mesenchymal transition (EMT) including E-cadherin (E-CAD), α- and β-catenins, Slug and Snail, transforming growth factor (TGF)-α and -β, and vascular endothelial growth factor (VEGF). Methods: In the present in vitro study, LNCaP cells were divided into three groups, namely NDRG2 group (transfected with PSES-pAdenoVator-PSA-NDRG2-IRES-GFP plasmid), mock group (transfected with mock plasmid), and control group (without transfection). The effect of NDRG2 overexpression on the migration and invasion of LNCaP cells were investigated using the transwell assay. Real-time PCR was used for the evaluation of gene expression. For the statistical analyses, one-way ANOVA, student t test or Mann-Whitney U test were applied using the SPSS software (version 15.0). P values

Background & Objective: Cancer metastasis is the primary cause of cancer morbidity and mortality, it accounts for about 90% of cancer deaths. Cancer treatment has improved significantly, due to early detection and inhibition of cancer growth. The ability to invade and migrate is important in malignant tumor cells. The study of cell migration is valuable in cancer diagnosis, prognosis, drug development and treatment. New methods are available to investigate the invasion, migration and the activity of enzymes involved in the invasion process in the laboratory. The effectiveness and efficacy of various anti-cancer drugs and compounds can be studied using these methods in laboratory and animal models. Conclusion: In this paper, we offer a summary of in-vitro migration assays, including the transwell migration assay, scratch wound assay, microfluidic chamber assay, exclusion zone assay, fence assay, micro carrier bead assay, spheroid migration assay and in-vivo approach, Chick chorioallantoic membrane (CAM) assay. This review also provides an overview of methods, In situ Zymography, ELISA, and FRET based measurement of MMP activity and Substrate Zymography for measuring the level of metalloproteinase enzyme as the major enzyme in the degradation of extracellular matrix.

Purpose. The role of oxidative stress in Aluminum (Al)-induced apoptotic effects has been investigated and suicidal death of erythrocytes, eryptosis, is characterized by cell shrinkage and phosphatidylserine externalization (PSE) at the surface of the erythrocyte cell membrane. Eryptosis is stimulated by an increase in cytosolic Ca2+ concentration and reactive oxygen species (ROS). This ex vivo study was conducted to evaluate the effect of well-known antioxidants including vitamin C (vit C) and N-acetylcysteine (NAC), against Al-induced hemolysis and eryptosis. Methods. Isolated erythrocytes from the healthy volunteers were partitioned into various groups (6 replicates/group) and treated by various concentrations of Al (3–100 µM) in the presence and absence of vit C (0.6 mM) and NAC (1 mM). After 24 hours of treatment, hemolysis was determined from hemoglobin levels in the supernatant. Flowcytometric methods were applied to measure PSE, cell shrinkage, Ca2+ content, and ROS abundance using annexin V-binding, forward scatter, Fluo3-fluorescence, and DCFDA dependent fluorescence, respectively. Reduced glutathione (GSH) was measured by the ELISA method. Results. The results showed that a 24 hours’ exposure of the erythrocytes to Al (10–100 µM) significantly increased hemolysis in a dose and Ca2+dependent manner. Al also dramatically decreased forward scatter. The percentage of PSE cells, Fluo3-fluorescence, and DCFDA fluorescence were increased by Al. Furthermore, cotreatment with NAC inhibited the effect of Al on hemolysis, eryptosis, and ROS production. Vit C decreased Al-induced ROS production. However, increased Al-induced eryptosis. There were no significant changes in glutathione after the ALCL3 treatment. Conclusions. Al-induced eryptosis and hemolysis through triggering oxidative stress, while NAC could diverse this effect. In contrast, vit C might intensify Al-induced eryptosis at particular doses through a less known mechanism.

Background: The synergistic effects of valproic acid (VPA), lithium (Li), and celecoxib (CX) have been shown in combination therapy against the proliferation and metastasis of numerous cancers. Angiogenesis plays a critical role in the pathogenesis of tumor growth and metastasis. The aim of the present study was to evaluate the antiangiogenic effects of VPA, lithium chloride (LiCl), and CX, alone or in 2-by-2 combinations, using the chicken chorioallantoic membrane (CAM) assay. Methods: Fertilized chicken eggs were randomly divided into 10 groups: control, VPA (1.8 and 3.6 µmol/CAM), Li (0.15 and 0.60 µmol/CAM), CX (0.02 and 0.08 µmol/CAM), VPA+Li, VPA+CX, and CX+Li (n=10 per group). A window was made on the eggshells and the CAMs were exposed to a filter disk containing VPA, LiCl, and CX, alone or in 2-by-2 combinations. The control CAMs were treated with distilled water (vehicle). Three days after the treatment, the number of vessel branch points was counted in each CAM. The data were analyzed using SPSS, version 15.One-way ANOVA, followed by the Tukey tests, was used to compare the groups. A P

Objective(s): Apoptotic effect of apoptin has been demonstrated in numerous studies. However, its tumor specificity has been questioned by some reports. The aim of this study was to confine the expression of apoptin in the prostate tumor cells by inducing its gene expression under the control of a chimeric enhancer composing of prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) regulatory elements (PSES). Furthermore, we investigated the effects of apoptin expression on LNCaP prostate carcinoma cell survival and apoptosis using MTT assay and annexinV/7-AAD flow cytometry assay. Materials and Methods: Recombinant plasmids containing apoptin gene under the control of PSES/PSA promoter or Cytomegalovirus (CMV) promoter were constructed. Tumor cell lines including LNCaP cells and HeLa cells, and LX-2 cells (as a normal control) were transfected with the plasmids and the expression of apoptin was evaluated by real time-PCR and western blot analyses. The effects of apoptin expression on cell survival and apoptosis were then investigated using MTT and annexinV/7-AAD flow cytometry assay, respectively. Results: Western blot and real time PCR analyses confirmed the specific expression of apoptin under the control of PSES/PSA regulatory element in the LNCaP cells, while CMV promoter caused apoptin expression in both tumor and normal cell lines. Apoptin expression significantly increased cell death and apoptosis in tumor cells when compared with the normal cells (P

Background: Glucose-induced protein glycation has been implicated in the progression of diabetic complications and age-related diseases. The anti-glycation potential of polyphenol-rich plant extracts has been shown previously. Bunium Persicum has been demonstrated to possess a high level of polyphenols. The aim of current in vitro study was to determine the possible inhibitory effect of Bunium Persicum hydroalcoholic extract (BPE) on glucose-induced bovine serum albumin (BSA) glycation, oxidation, and aggregation. Methods: Folin-Ciocalteu assay was used to measure the content of total phenolic compounds of BPE. To test the in vitro effect of BPE on the formation of glycated BSA, thiol group oxidation, and protein aggregation of BSA, various concentrations of BPE were incubated with BSA and glucose at 37 °C for 72 hr. Glycation, thiol group oxidation, and aggregation of BSA were then measured using thiobarbituric acid, 2, 4-dinitrophenylhydrazine, and Congo red colorimetric methods, respectively. Data were analyzed using the SPSS software (version 16.0). One-way ANOVA followed by Tukey’s post hoc test was used to compare group means. P

Objective(s): The role of aluminum (Al) in the pathogenesis of neurodegenerative diseases has been implicated in several studies. However, the exact mechanisms of cytotoxic effects of Al have not been elucidated yet. The aim of this study was to investigate the effect of L-type calcium channel antagonist, nimodipine (NM), and lithium chloride (LiCl) on Al-induced toxicity in PC12 cells. Materials and Methods: PC12 cells were treated with Al-maltolate (Almal) in the presence and absence of different concentrations of NM (50-150 μm) and/or LiCl (0.5-1.0 mm) for 48 hr. Cell viability, apoptosis, and catalase (CAT) activity, a marker of oxidative stress, were then measured using MTT, flow cytometry and enzyme assay, respectively. Results: The results showed that Almal, dose dependently induced cell death, apoptosis and CAT activity in the PC12 cells. NM significantly increased cell viability and decreased apoptosis and CAT activity of Almal-treated cells in a dose dependent mode. LiCl reduced CAT activity and increased cell viability in Almal-treated cells, without significant effect on apoptosis (P=0.74). Conclusion: These findings suggest that NM and Li may have benefits in the prevention of Al-induced cytotoxicity through decreasing oxidative stress.

Objective: The out-of-field/non-target effect is one of the most important phenomena of ionizing radiation that leads to molecular and cellular damage to distant non-irradiated tissues. The most important concern about this phenomenon is carcinogenesis many years after radiation treatment. In vivo mechanisms and consequences of this phenomenon are not known completely. Therefore, this study aimed to evaluate the oxidative damages to out-of-field lung tissues 24 and 72 hours after pelvic irradiation in rats. Materials and Methods: In this experimental- interventional study, Sprague-Dawleymale rats (n=49) were divided into seven groups (n=7/each group), including two groups of pelvisexposed rats (out-of-field groups), two groups of whole body- exposed rats (scatter groups), two groups of lung-exposed rats (direct irradiation groups), and one control sham group. Outof- field groups were irradiated at a 2×2 cm area in the pelvis region with 3 Gy using 1.25 MeV cobalt-60 gamma-ray source, and subsequently, malondialdehyde (MDA) and glutathione (GSH) levels as well as superoxide dismutase (SOD) activity in out-of-field lung tissues were measured. Results were compared to direct irradiation, control and scatter groups at 24 and 72 hours after exposure. Data were analyzed using Mann-Whitney U test. Results: SOD activity decreased in out-of-field lung tissue 24 and 72 hours after irradiation as compared with the controls and scatter groups. GSH level decreased 24 hours after exposure and increased 72 hours after exposure in the out-of-field groups as compared with the scatter groups. MDA level in out-of-field groups only increased 24 hours after irradiation. Conclusion: Pelvis irradiation induced oxidative damage in distant lung tissue that led to a dramatic decrease in SOD activity. This oxidative stress was remarkable, but it was less durable as compared to direct irradiation.

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-related death in the world. The expression of N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in CRC. The aim of this study was to investigate the effect of NDRG2 overexpression on cell proliferation and invasive potential of SW48 cells. Methods: SW48 cells were transfected with a plasmid overexpressing NDRG2. After stable transfection, the effect of NDRG2 overexpression on cell proliferation was evaluated by MTT assay. The effects of NDRG2 overexpression on cell migration, invasion and cell motility and matrix metalloproteinase 9 (MMP9) activities were also investigated using matrigel transwell assay, wound healing assay and gelatin zymography, respectively. Results: MTT assay showed that overexpression of NDRG2 caused attenuation of SW48 cell proliferation. Transwell and wound healing assay revealed that NDRG2 overexpression led to inhibition of migration, invasion, and motility of SW48 cells. The overexpression of NDRG2 also reduced the activity of secreted MMP-9. Conclusions: The results of this study suggest that NDRG2 overexpression inhibits proliferation and invasive potential of SW48 cells, which likely occurs via suppression of MMP-9 activity.

Objective(s):N-myc downstream regulated gene 2 (NDRG2) is a candidate gene for tumor suppression. The expression of NDRG2 is down-regulated in several tumors including lung cancer. The aim of this study was to explore the effect of NDRG2 overexpression on invasion, migration, and enzymatic activity of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in human lung adenocarcinoma A549 cells. Materials and Methods: A recombinant plasmid encoding green fluorescent protein (GFP)-tagged NDRG2 (pCMV6-AC-NDRG2-GFP) was used to overexpress GFP-tagged NDRG2 in A549 cells. The cells in the experimental group and those in the control group were transfected with pCMV6-AC-NDRG2-GFP and a control plasmid without NDRG2 (pCMV6-AC-GFP), respectively. Fluorescent microscopy and flowcytometry analysis of GFP expression were used to evaluate the cellular expression of GFP-tagged NDRG2 and the efficiency of transfection. The effects of NDRG2 expression on cell invasion and migration were evaluated using transwell filter migration assay. The gelatinase activity of secreted MMP-2 and MMP-9 was measured by gelatin zymography. Results:Our results demonstrated the expression of GFP-tagged NDRG2 in the cytoplasm and nucleus of A549 cells. The findings of transwell assay showed that NDRG2 overexpression reduced migration and invasion of A549 cells compared to control cells. Gelatin zymography analyses revealed that NDRG2 overexpression decreased the gelatinase activity of secreted MMP-2 and MMP-9. Conclusion: These findings suggest that NDRG2 may be a new anti-invasion factor in lung cancer that inhibits MMPs activities.

Adenosine deaminase (ADA) is an important regulator of insulin action. The single nucleotide polymorphism (SNP) G22A in the ADA gene decreases enzymatic activity of ADA. The aim of this study was to investigate the relationship between the SNP G22A and blood glycemic control, insulin resistance, and obesity of gestational diabetes mellitus (GDM) patients in an Iranian population. SNP G22A was determined in women with GDM (N=70) and healthy pregnant women (control, N=70) using polymerase chain reaction-restriction fragment length polymorphism. Fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), plasma insulin levels and plasma lipids were measured using commercial kits. Homeostasis model of assessment for insulin resistance (HOMA-IR) was calculated. The distribution of genotypes and alleles among GDM patients was similar to that of the control group. FPG and HbA1c were significantly higher in GDM patients with GG genotype compared with GDM patients with GA+AA genotype and non-GDM patients. The frequency of GG genotype was significantly higher in obese GDM patients compared to lean GDM patients. The SNP G22A in the ADA gene was not associated with the risk of GDM in our population. GG genotype was associated with poor glycemic control and obesity in GDM patients.

Background:Amylin and Salmon Calcitonin belong to the calcitonin family of peptides and have high affinity binding sites in the rat spinal cord. The aim of this study was to characterize receptors for Amylin and Salmon Calcitonin functionally in the spinal cord of rats. We assessed the expression of c-Fos in response to intraplantar formalin in the lumbar regions of the spinal cord in conscious rats. Methods:Amylin (0.05 nmoles) or Salmon Calcitonin (0.005 nmoles) was administered intrathecally (i.t.) 10 minutes before the start of the formalin test. Antagonists were injected intrathecally 10 minutes before the administration of either of the peptides. Results: Two hours after formalin stimulation, rats pretreated intrathecally by either Amylin or Salmon Calcitonin, showed lower numbers of c-Fos immunoreactive nuclei in their lumbar spinal cord as compared to rats pretreated with saline. These effects were reversed upon co-administration of either of the Amylin antagonists AC187 or rat amylin8-37, but not rat α-CGRP8-37. A few cells with c-Fos immunoreactivity were found in the lumbar spinal cord of rats two hours after i.t. injection of saline, Amylin and/or Salmon Calcitonin. However, Fos-like immunoreactivity was increased in the lumbar spinal cord two hours after i.t. treatment of either of the antagonists AC187 and rat amylin8-37,when compared to saline treated rats. Conclusion:Both Amylin and Salmon Calcitonin inhibit formalin induced c-Fos expression in the rat lumbar spinal cord when administered intrathecally. Effects of the two peptides were possibly produced by undefined receptors.

Serotonin (5-hydroxytriptamine), one of the most important neurotransmitters, is synthesized from amino acid L-tryptophan in some neurons located in the central nervous system and intestine enterochromaffin cells . The role of this neurotransmitter is important and involves control of sexual behaviors, morality, sleep, pain, appetite, aggression, cardiovascular function and regulation of gut function. Serotonin is stored in cells by serotonin transporter; and after release, it binds to its specific receptors so as to perform its function, which is neuronal stimulation. There is a relationship between serotonin concentration changes, serotonin transporter gene alleles, and serotonin receptors and some diseases; consequently, using some drugs which are effective on these factors could be useful in the treatment of these diseases.

Background & Objective: Diabetes mellitus is a metabolic disease and is a multifactorial disorder characterized by chronic hyperglycemia resulting from impaired insulin secretion and insulin factional or both. In this study, the protective role of vitamin E and sodium selenite in preventing the harmful effects of insulin resistance (diabetes type 2) on spermatogenesis was studied. Materials & Methods: Male adults (180-200 g) of Wistar rats were divided into five groups, each containing 7 rats (control, sham, and three experimental groups). The rats were fed daily with water-soluble fructose (10%), mg/kg 200 of vitamin E (gavage), and 5/0 mg/kg of sodium selenite (intraperitoneal injection) or both for 110 days. Subsequently, sperm parameters, levels of testosterone, LH, and daily sperm production (DSP) were checked. Additionally, testicular histopathology and malondialdehyde (MDA) in the testis were examined. Results: Sperm count, sperm motility and viability, and insulin resistance in the rats decreased DSP. A significant decrease was observed in the number of Leydig cells, spermatogonia, spermatogenesis, and spermatozoa in the testis of the insulin-resistant animals, whereas MDA and testosterone rose in the insulin-resistant rats. Vitamin E and sodium selenite intake reduced the levels of MDA and harmful effects of fructose on testicles, as well as sperm parameters and testicular pathology. A simultaneous intake of vitamin E and sodium selenite conferred the highest level of protection. Conclusion: These findings suggest that vitamin E and sodium selenite can have a protective role in the testes of rats against oxidative stress induced by diabetes type 2.

Background &Objectives: Adenosine deaminase (ADA) is a marker of T cell activation. ADA catalyzes the deamination of adenosine and modulates the bioactivity of insulin. The aim of this study was to investigate a possible relationship between ADA activity and various clinical and metabolic parameters, including fasting plasma sugar (FBS) and glycated hemoglobin (HBA1c), in gestational diabetes (GDM). Materials &Methods: Fasting ADA activity, FBS, HBA1c, serum insulin level, and blood lipids were measured in 70 GDM patients and in 70 non-diabetic pregnant subjects. Insulin resistance was measured using a homeostasis model of assessment-insulin resistance ( HOMA-IR). Results: ADA activity was increased in the GDM patients compared with that in the non-diabetic pregnant subjects (mean ± standard error, 13.9 ± 7.1 U/L vs. 9.6 ± 3.8 U/L; p value

Background: The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats.Methods: Fifty adult male Sprague–Dawley rats were randomly divided into five groups (n=10 each). The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day) alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day), vitamin E (200 mg/kg/day), or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH), plasma testosterone and malondialdehyde (MDA) levels in the testis were determined. Results: Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP) and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan.Conclusion: The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

Background & Objective: Sulfasalazine (SASP) is a drug used for the treatment of inflammatory bowel diseases. SASP causes testicular damage. The aim of this study was to verify whether or not an additional supply of vitamin E or C or together prevent the toxic effect of SASP on the rat spermatogenesis. Materials & methods: Adult male wistar rats (150-200 gr) were divided into five groups (n=8) control and four experimental groups. The experimental groups were treated with SASP (600 mg/kg/day by gavage feeding ) for 14 successive days. Additionally the experimental group 2 were treated with the vitamin C (20 mg/kg/body weight/daily), the experimental group 3 received vitamins E (200 mg/kg body weight/daily) and the experimental group 4 received daily vitamin C and vitamin E 20 and 200 mg/kg body weight, respectively through the same root. At the end of the experimental period the mean body weight growth and the ratio between body and testis weight were calculated and compared with the control groups, Spermatogenesis Parameters such as, daily Sperm count, percent of motility, viability, Daily sperm production (DSP), testicular histopathology, serum testosterone levels and the level of Malondialehyde (MDA) were evaluated. The data were analyzed using Danken and one way variance test and the P≤ 0.05 were considered significant.Results: Sperm count, percent of motility, viability and DSP were decreased in SASP treated animals. A significant decrease in the number of sertoli cells, Leydig cells, spermatogonia and spermatid were seen in the testis of SASP treated animals. The level of MDA was increased in the SASP treated group. However, Co-administration of vitamin E and C with SASP reduced the level of MDA and deleterious effects of SASP on the sperm parameters and testicular histology. Finally, the Co-administration of vitamin E and C had the most protective effects when compared with the control groups. Conclusion: The results suggested that additional supply of vitamin E and C protect against SASP–induced oxidative stress in the rat testis.

Background & Objective: Sulfasalazine (SASP) is a drug used for the treatment of inflammatory bowel diseases. SASP causes testicular damage. The aim of this study was to verify whether or not an additional supply of vitamin E or C or together prevent the toxic effect of SASP on the rat spermatogenesis. Materials & methods: Adult male wistar rats (150-200 gr) were divided into five groups (n=8) control and four experimental groups. The experimental groups were treated with SASP (600 mg/kg/day by gavage feeding ) for 14 successive days. Additionally the experimental group 2 were treated with the vitamin C (20 mg/kg/body weight/daily), the experimental group 3 received vitamins E (200 mg/kg body weight/daily) and the experimental group 4 received daily vitamin C and vitamin E 20 and 200 mg/kg body weight, respectively through the same root. At the end of the experimental period the mean body weight growth and the ratio between body and testis weight were calculated and compared with the control groups, Spermatogenesis Parameters such as, daily Sperm count, percent of motility, viability, Daily sperm production (DSP), testicular histopathology, serum testosterone levels and the level of Malondialehyde (MDA) were evaluated. The data were analyzed using Danken and one way variance test and the P≤ 0.05 were considered significant.Results: Sperm count, percent of motility, viability and DSP were decreased in SASP treated animals. A significant decrease in the number of sertoli cells, Leydig cells, spermatogonia and spermatid were seen in the testis of SASP treated animals. The level of MDA was increased in the SASP treated group. However, Co-administration of vitamin E and C with SASP reduced the level of MDA and deleterious effects of SASP on the sperm parameters and testicular histology. Finally, the Co-administration of vitamin E and C had the most protective effects when compared with the control groups. Conclusion: The results suggested that additional supply of vitamin E and C protect against SASP–induced oxidative stress in the rat testis.