Betaine attenuates oxidative stress and cognitive dysfunction in an amyloid ß-induced rat model of Alzheimer's disease.

Background and purpose: Increasing evidence indicates that oxidative stress is an important factor in the pathogenesis and progression of Alzheimer's disease (AD). Betaine is trimethylglycine with antioxidant and neuroprotective properties. The present study aimed to evaluate the possible beneficial effects of betaine on oxidative stress and memory deficits induced by intrahippocampal injection of amyloid beta (Aß) in an AD model. Experimental approach: Forty adult male Wistar rats were divided into 5 equal groups: the control and Aß groups which received oral gavage of saline (1 mL daily) for 14 days. The other 3 groups (betaine + Aß) received betaine (5, 10, and 15 mg/kg, orally) for 14 consecutive days. On the 15th day, all of the groups were injected bilaterallyintrahippocampal of Aß (5 µg/µL), except controls that were injected with normal saline as a vehicle. Seven days after the Aß injection, memory was assessed in a passive avoidance test. Changes in catalase activities and glutathione peroxidase, glutathione, and malondialdehyde concentrations were investigated to determine the antioxidant activity in the rat hippocampus. Findings/Results: Data showed that betaine pretreatment of Aß-injected rats improved memory in avoidance tasks. In addition, betaine pretreatment attenuated oxidative stress. Conclusion and implications: The current findings showed that oral administration of betaine could prevent Aß-induced impairment of memory possibly through suppression of oxidative stress in the hippocampus area of rats.

Curcumin neuroprotective effects in Parkinson disease during pregnancy.

BACKGROUND: Young onset Parkinson disease (YOPD) accounts for about 10% of PD patients, with the onset of symptoms between the ages of 21 and 40. At this age, the probability of pregnancy is high and there is a concern that the disease affects the fetuses. Therefore, in the present study, the effects of rotenone-induced PD on female mice as well as their fetuses and curcumin supplementation on the cerebral tissue of both female mice and their resulted fetuses were studied. METHODS: The rotenone was injected subcutaneously to induce PD model of female mice. The different concentrations of curcumin were administrated every day i.p. for 3 weeks and the rotarod test was done on day 1 and 19. Cell viability was measured by MTT test and apoptosis and necrosis of cells were evaluate using flow cytometry technique. After primer design, the expressions of bax, bcl-2, miR-211 and circRNA 0001518 genes were measured using RT-PCR technique. RESULTS: Curcumin administration were improved cerebral cell viability of both female PD mice and resulted fetuses by preventing cell apoptosis and necrosis. bax, miR-211 and circRNA 0001518 were downregulated and bcl-2 overexpressed in cerebral neurons of PD mice and their fetuses. CONCLUSION: PD induction in mice affects their fetal brain, and curcumin can partially reduce the negative effects of PD on fetal brain cells by overexpressing bcl-2 and decreasing bax expression genes.

Negative effect of varicocele on sperm mitochondrial dysfunction: A cross-sectional study.

Background: Varicocele is an abnormal dilation and enlargement of the scrotal venous pampiniform plexus that impairs normal blood drainage and finally leads to infertility if not treated. Objective: This study aimed to figure out the impact of mitochondria status through the mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) assessment and its correlation with semen parameters to illuminate the impact of sperm mitochondria healthiness on normal sperm functionality. Materials and Methods: This analytical cross-sectional study was conducted with 100 men including 50 cases in the normozoospermic group (normal) and 50 in an infertile group with the non-varicocelectomy operation (varicocele) referring to Infertility Research and Treatment Center, ACECR Khuzestan, Iran. Routine semen analysis was performed according to World Health Organization guidelines, DNA fragmentation index, the MMP assay, ATP content, and apoptosis were carried out for all samples. Results: The results showed that the concentration, progressive motility, normal morphology, MMP, and ATP contents of sperm in varicocele were significantly lower than the normal group. In addition, the sperm DNA fragmentation index was significantly higher in the varicocele group in comparison with the normal group. Conclusion: Reduction in MMP and ATP contents, besides the loss of sperm parameters quality and increase in sperm DNA fragmentation, were seriously implicating sperm mitochondria dysfunctionality in varicocele men.

Co-Administration of Vitamins B12 and D During Pregnancy Have Strong Neuroprotective Effects in Parkinson Disease.

Parkinson's disease (PD) is a common disease whose pathophysiological mechanism is not well understood. Recent research studies have shown that PD patients have low serum levels of vitamins B12 and D. Therefore, in this study, the effects of supplementation with vitamins B12 and D on PD female mice as well as their fetuses were studied. After preparation of female mice and induction of Parkinson's by rotenone administration for 19 days, rotarod test was used to confirm PD induction. During this time, supplementations with vitamins B12 and D were performed. On day 19, after confirmation of PD induction, half of the mice were killed and the other half were allowed to mate with males. Viability was measured by the MTT method, and apoptosis and necrosis of cerebellar neurons were measured by flow cytometry. The RT-PCR technique was used to evaluate the relative expressions of the bax, bcl-2, miR-211, and circRNA 0,001,518 genes. Data analysis was performed by the GraphPad Prism V.8 software. Co-administration of vitamins B12 and D resulted in highest viability percentage and greatest reduction in apoptosis and necrosis of cerebellar neurons in the female mice as well as their fetuses compared to the PD females. A decrease in the relative expression of the bax and miR-211 genes and an increase in bcl-2 expression were observed in the cerebellar tissue of PD mice receiving both vitamins. Vitamins B12 and D have neuroprotective effects on PD conditions. Therefore, co-administration of these two vitamins is recommended in PD patients during pregnancy.

Histopathologic evaluation of the inflammatory factors and stromal cells in the endometriosis lesions: A case-control study.

Background: Endometriosis is a multifaceted gynecological disorder defined as a benign estrogen-dependent chronic inflammatory process in which endometrial glands and stroma-like tissues are located outside the uterine cavity. It affects around 2-10% of all women during their reproductive years. Objective: This study aimed to evaluate the traffic of mesenchymal stem cells and inflammatory factors toward the lesions. Materials and Methods: Ten samples of normal endometrium and eutopic endometrium were studied as a control group and 10 ectopic samples were considered as a case group. Hematoxylin and eosin staining was used to evaluate stromal cells and inflammatory cells. Immunohistochemical staining was performed to show the presence of proliferating cell nuclear antigen in the lesions. The cells were digested and cultured in the laboratory to study cell proliferation. The number of cells and vessels were counted with Image J software, and data analysis was performed with Prism software. Results: Data analysis showed that the number of stromal cells and vessels in ectopic tissue were significantly higher than the control group (p < 0.001). Also, the number of inflammatory cells, including neutrophils, monocytes, lymphocytes, and macrophages, in the ectopic group was much higher than in the control group (p < 0.005). Conclusion: By expanding the number of blood vessels, blood flow increases, and cell migration to tissues is facilitated. The accumulation of inflammatory cells, especially macrophages, stimulates the growth of stem cells and helps implant cells by creating an inflammatory process.

Effect of the Non-N-Methyl-D-aspartate Receptor of the Glutamatergic System of the Pedunculopontine Tegmental Nucleus on Cardiovascular Responses in Normotensive and Hydralazine-Induced Hypotensive Rats.

Background: Glutamate is an important excitatory neurotransmitter in the pedunculopontine tegmental (PPT) nucleus. The cardiovascular effect of glutamate and its non-N-methyl-D-aspartate (NMDA) receptor in the PPT is unknown; therefore, we evaluated glutamate and its non-NMDA receptor on cardiovascular parameters in normotensive and hypotensive induced by hydralazine (HLZ) in rat. Materials and Methods: After anesthesia, the femoral artery was cannulated for recording of cardiovascular parameters. Microinjection of drugs was done stereotaxically. L-Glutamate (L-Glu) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (an antagonist of nonNMDA receptor) were microinjected into the PPT in normotensive and HLZ hypotensive rats. Changes (Δ) of mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) were obtained and compared with the control group. Results: In normotensive rats, L-Glu significantly increased SBP and MAP (P < 0.001) and decreased HR (P < 0.01), whereas CNQX alone did not significantly effect. Coinjection L-Glu + CNQX significantly attenuates the cardiovascular effect of L-Glu (P < 0.05 to P < 0.01). In hypotension induced by HLZ, SBP and MAP significantly decrease but HR did not change. In HLZ groups, L-Glu significantly improves (P < 0.05) and CNQX deteriorated hypotension induced by HLZ (P < 0.05). Coinjection of L-Glu + CNQX also attenuates the effect of L-Glu on Δ MAP and Δ SBP. In hypotension, ΔHR induced by L-Glu was significantly higher than CNQX (P < 0.01). In L-Glu + CNQX group, ΔHR also was lower than L-Glu (P < 0.05). Conclusion: Our findings revealed that glutamatergic system of the PPT in both normotensive and hypotension induced by HLZ plays a pressor with bradycardic responses that partly mediated by non-NMDA receptor.

Effect of MK-801, an antagonist of NMDA receptor in the pedunculopontine tegmental nucleus, on cardiovascular parameters in normotensive and hydralazine hypotensive rats.

Objectives: In the present study, the cardiovascular effects of glutamate NMDA receptor of the pedunculopontine tegmental nucleus (PPT) in normotensive and hydralazine (HLZ) hypotensive rats were evaluated. Materials and Methods: In the normotensive condition, MK-801(1 nmol; an NMDA receptor antagonist) and L-glutamate (L-Glu, 50 nmol an agonist) alone and together were microinjected into the nucleus using a stereotaxic device. In hypotensive condition, 2 min after induction of hypotension by HLZ (10 mg/kg, intravenous), drugs, same as in normotensive condition, were microinjected into the PPT. Recorded mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) were recorded throughout the experiment by a Power lab apparatus that was connected to a catheter inserted into the femoral arty. The cardiovascular changes (Δ) induced by microinjection drugs were computed and statistically analyzed. Results: In the normotensive condition, L-Glu significantly increased ΔMAP and ΔSBP (P<0.001) and decreased ΔHR (P<0.01) compared with the control. MK-801 alone significantly increased HR (P<0.05) while co-injected with L-Glu + MK-801 it significantly attenuated the L-Glu effect on ΔMAP and ΔSBP but augmented ΔHR (P<0.01). In the hydralazine hypotension condition, L-Glu significantly improved hypotension (P<0.01) and deteriorated bradycardia induced by HLZ (P<0.05). MK-801 alone did not significantly affect ΔMAP, ΔSBP, and ΔHR but when co-injected with L-Glu (L-Glu + MK-801) it could significantly attenuate the cardiovascular effect of L-Glu in the PPT. Conclusion: We found that activation of NMDA receptors of the glutamatergic system in the PPT evoked blood pressure and inhibited HR in both normotensive and hypotensive conditions in rats.

Ursolic Acid Enhances Myelin Repair in Adult Mice Brains and Stimulates Exhausted Oligodendrocyte Progenitors to Remyelinate.

In multiple sclerosis patients, long-term inflammation makes the oligodendrocyte progenitor cells (OPCs) exhausted; therefore, a new therapy that makes them responsive to insults to participate in remyelination is highly in demand. Here, we investigated the effect of ursolic acid (UA) on myelin repair after mid-term and long-term demyelination periods induced by 6 or 12 weeks of cuprizone treatment followed by 2 weeks of recovery with or without UA. Immunohistochemistry studies and myelin genes expression assessment were used to evaluate the myelination status of mouse corpora callosa and the cellular mechanisms of myelin repair. Results showed that UA significantly promoted recovery from myelin loss after discontinuing 6 or 12 weeks of cuprizone feeding, as measured by luxol fast blue (LFB), fluoroMyelin (FM), anti-myelin basic protein (MBP) staining, and oligodendrocyte progenitor cell counts. It led to reduced inflammation and gliosis as evaluated by glial fibrillary acidic protein (GFAP), Iba1, or other marker gene transcripts. Following long-term demyelination, gliosis and TNF-α were observed as potential players in lesion pathology, which were restored by UA. An increased IL-10 may contribute to UA anti-inflammatory effect and making responsive the exhausted OPCs. UA increased the number of new oligodendrocyte lineage cells and myelination. Our findings indicated that UA can enhance myelin repair after cuprizone challenge through the prevention of gliosis and increasing the newly generated myelin.

Comparison of antithyroid effects and hepatic complications of methimazole with catechin and its nanoencapsulation form in adult male rats.

OBJECTIVES: Methimazole is an antithyroid drug and is used clinically in hyperthyroidism. Liver dysfunction is one of the side effects of methimazole. Catechins are natural flavonoids and have antioxidant, antithyroid, and liver protection effects. Despite the wide range of biological properties of catechins, their effective use is limited due to poor water solubility, low stability, and low bioavailability. Catechin niosomal nanoencapsulation improves the properties of catechin and increases its antioxidant activities. METHODS: Niosomal vesicles were synthesized by the Thin Film Hydration method and their physicochemical characteristics, morphology, and percentage of trapped catechin in them were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), and spectrophotometry, respectively. In this study, 32 adult male rats were divided into 4 groups: control, 50 mg/kg methimazole, 100 mg/kg catechin, and 100 mg/kg nanocapsule niosomal form of catechin. The drugs were administered orally and the duration of treatment was 8 weeks. Then, the serum concentration of thyroid hormones and thyroid stimulating hormone (TSH) by enzyme-linked immunosorbent assay (ELISA) method, and serum liver function tests were performed using an autoanalyzer. The activities of hepatic oxidative enzymes were measured spectrophotometrically. RESULTS: Our study showed that the percentage of catechin encapsulation in the niosome was calculated to be 51%. A significant difference was observed in the catechin and encapsulated catechin treatment groups compared to the methimazole group (p <0.0001). In all three treatment groups of methimazole, catechin, and niosomal nanocapsule catechin, serum levels of TT3, TT4, FT3, FT4, body weight and daily consumption of water and food were significantly reduced compared to the control group (p <0.0001). CONCLUSIONS: The antithyroid effects of catechin and its encapsulated form were comparable to methimazole. Also, the encapsulation improved the hepatoprotective effects of catechin.

Intensity Dependent Effects of Interval Resistance Training on Myokines and Cardiovascular Risk Factors in Males With Obesity.

Objective: To determine the effects of different intensities of interval resistance training (IRT) protocols on the levels of select myokines (decorin, follistatin, myostatin, activin A, transforming growth factor beta-1 [TGF-ß1]), and cardiometabolic and anthropometric measures in males with obesity. Methods: Forty-four obese males (age: 27.5 ± 9.4 yr.; height: 165.4 ± 2.8 cm; weight: 97.9 ± 2.6 kg and BMI: 35.7 ± 4.3 kg/m2) were randomly assigned to one of four groups (n=11 per group): low-intensity interval resistance training (LIIRT), moderate-intensity interval resistance training (MIIRT), high-intensity interval resistance training (HIIRT) or control (C). The LIIRT group performed 10 exercises in 3 sets of 40% (20 repetitions), the MIIRT group performed 10 exercises in three sets of 60% (13 repetitions), and the HIIRT group performed 10 exercises in three sets of 80% (10 repetitions) of one maximum repetition (1RM), which were followed with active rest of 20% of 1RM and 15 repetitions. The resistance training groups exercised ~70 min per session, 3 days per week, for 12 weeks. Measurements were taken at baseline and after 12 weeks of exercise training. Results: Baseline levels of myokines, cardiovascular risk factors, anthropometry, body composition, and cardio-respiratory fitness were not different between the four groups (p>0.05). The group x time interactions for decorin, activin A, follistatin, myostatin, and TGF-ß1, total cholesterol (TC), triglyceride (TG), high-density cholesterol (HDL), low-density cholesterol (LDL), anthropometry, body composition, and cardio-respiratory fitness were statistically significant (p<0.05). There were increases in post-test values for decorin, follistatin, HDL (p<0.05) and decreases in TC, TG, TGF-ß1, LDL, and myostatin levels in the LIIRT, MIIRT, and HIIRT groups compared to pretest values (p<0.05). Changes in fat mass, VO2peak, HDL, TG, glucose, activin A, decorin were not significant in LIIRT compared to the control group, while changes in activin A, follistatin, and TFG-ß1 levels were greater in HIIRT and MIIRT groups compared to the LIIRT group (p<0.05). Conclusion: The LIIRT, MIIRT, and HIIRT protocols all produced beneficial changes in decorin, activin A, follistatin, myostatin, and TGF-ß1 levels, and cardiometabolic risk factors, with greater effects from the MIIRT and HIIRT protocols compared to LIIRT.

Neuroprotective Effects of Crocin Against Ethanol Neurotoxicity in the Animal Model of Fetal Alcohol Spectrum Disorders.

Several experimental and clinical findings suggest that ethanol consumption during pregnancy activates an oxidative-inflammatory cascade followed by wide apoptotic neurodegeneration within several brain areas, including the hippocampus. Crocin can protect neurons because of its antioxidant, anti-inflammatory, and antiapoptotic effects. This study evaluated the crocin protective impact on ethanol-related neuroinflammation and neuronal apoptosis in the hippocampus of rat pups exposed to alcohol over postnatal days. Ethanol (5.25 g/kg) was administrated in milk solution (27.8 ml/kg) by intragastric intubation 2-10 days after birth. The animals received crocin (15, 30, and 45 mg/kg) 2-10 days after birth. The hippocampus-dependent memory and spatial learning were evaluated 36 days after birth using the Morris water maze task. Further, the concentrations of TNF-α and antioxidant enzymes were determined using ELISA assay to examine the antioxidant and anti-inflammatory activities. Also, immunohistochemical staining was performed to evaluate the glial fibrillary acidic protein (GFAP), Ionized calcium binding adaptor molecule 1(Iba-1), and caspase-3 expression. The administration of crocin significantly attenuated spatial memory impairment (P < 0.01) after ethanol neurotoxicity. Also, crocin led to a significant enhancement in SOD (P < 0.05) and GSH-PX (P < 0.01), whereas it caused a reduction in the TNF-α and MDA concentrations compared to the ethanol group (P < 0.01). Moreover, the hippocampal level of caspase-3 (P < 0.01) and the number of GFAP and Iba-1-positive cells decreased in the crocin group (P < 0.001). Crocin suppresses apoptotic signaling mediated by the oxidative-inflammatory cascade in rat pups exposed to ethanol after birth.

The Effect of 6-gingerol on Growth Factors and Apoptosis Indices in Rats Exposed to Gold Nanoparticles.

INTRODUCTION: Research has shown that gold nanoparticles (AuNPs) can damage the physiological processes of brain tissue. Given the antioxidant properties of Gingerol (GING), this study aimed to determine the protective effect of 6-gingerol on hippocampal levels of Brain-Derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), DNA oxidative damage, and the amount of Bax and Bcl2 apoptosis indices of rats exposed to AuNPs. METHODS: A total of 42 male Wistar rats were divided into four groups: control (30 days 0.5 mL saline), AuNPs (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL saline), AuNPs+GING 50 (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL density of gingerol 50 mg/kg), and AuNPs+GING100 (one time injection of 0.5 mL AuNPs, 200 ppm and 60 Nm + 30 days 0.5 mL density of gingerol 100 mg/kg). At the end of the treatment period, the hippocampal levels of NGF, BDNF, 8-hydroxy-desoxyguanosine (8-HOdG), and apoptotic indices of Bax and Bcl-2 were assessed with the ELISA method. RESULTS: Compared with the AuNPs group, hippocampal levels of BDNF, NGF, and Bcl-2 in rats in the AuNPs+GING 50 and AuNPs+GING 100 groups significantly increased dose-dependently. However, the hippocampal levels of Bax and 8-HOdG significantly decreased dose-dependently (P<0.05). CONCLUSION: According to obtained results, gingerol may improve hippocampal BDNF and NGF levels in rats exposed to AuNPs, probably by reducing apoptosis and oxidative DNA damage.

The role of interaction between orexin receptors and ß2 adrenergic receptors in basolateral amygdala in dentate gyrus synaptic plasticity in male rats.

Orexin receptors expressed in basolateral amygdala (BLA) have been proposed for memory processing and hippocampal plasticity. There are several investigations about the effect of the adrenergic system in BLA on memory enhancement. However, there is no information about the molecular basis of this effect. Adrenergic and orexinergic fibers are found in BLA. In this study, the effects of both adrenergic and orexinergic systems were investigated on the amygdala function. To this end, the selective beta 2 adrenergic agonist (clenbuterol) and orexin receptors' antagonists (OX1R and OX2R, SB-334867-A and TCS-OX2-29, respectively) were administered into the BLA, then the high frequency stimulation (200-Hz) was applied to the perforant pathway and the synaptic plasticity of the dentate granular cells was studied in anaesthetized rats. Clenbuterol injection into the BLA enhanced the population spike (PS) component of LTP in the dentate gyrus (DG), as compared to that observed after dimethyl sulfoxide treatment. In addition, after orexin 1 or 2 receptor antagonists (SB-334867-A and TCS-OX2-29, respectively) injecting into the BLA, the enhancing effect of clenbuterol on PS was reduced. Moreover, the population excitatory post-synaptic potential also decreased in the SB-clenbuterol and TCS- clenbuterol experimental groups. However, the PS amplitude was also decreased in the group treated only by SB or TCS relative to the clenbuterol treated group. The PS amplitude or EPSP slope in the groups treated by both application of orexin receptors' antagonists and clenbuterol was considerably lower relative to the groups treated only by orexin receptors' antagonists. It is concluded that the BLA orexinergic system modulates hippocampal plasticity in relation with the adrenergic system.

Protective effects of the fruit extract of raspberry (Rubus fruticosus L.) on pituitary-gonadal axis and testicular histopathology in streptozotocin induced diabetic male rats.

OBJECTIVE: Protective effects of raspberry (Rubus fruticosus L.) fruit extract on pituitary-gonadal axis and testicular tissue in diabetic male rats, were investigated. MATERIALS AND METHODS: Sixty male rats were divided into control, sham (saline treated), streptozotocin (STZ)-diabetic, and STZ-diabetic animals treated with 50, 100 and 200 mg/kg/day of raspberry extract. After 4 weeks, blood samples were obtained and left testes were removed and prepared for histopathological studies. Serum levels of Luteinizing hormone (LH), Follicle stimulating hormone (FSH), testosterone, Nitric oxide (NO), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) and catalase (CAT) activity level were assayed. Sperm number and motility in the epididymis samples were measured. Data were analyzed using ANOVA (one-way analysis of variance). RESULTS: Serum levels of LH, FSH and MDA significantly increased in diabetic rats, however, treatment with the extract significantly reversed the alterations. Serum levels of testosterone and NO, activity of SOD and CAT, and sperm number and motility significantly decreased and severe destruction of testicular histology was observed in diabetic animals while treatment with the extract significantly reversed the pathologic alterations observed in diabetic rats. According to the results, 100 and 200 mg/kg of the extract were able to effectively reverse the diabetes complications. CONCLUSION: Our findings demonstrated that the fruit extract of raspberry has protective effects on male reproductive system in diabetic rats partially due to its improving effects on NO system, and SOD and CAT activity.

Curcumin attenuates spatial memory impairment by anti-oxidative, anti-apoptosis, and anti-inflammatory mechanism against methamphetamine neurotoxicity in male Wistar rats: Histological and biochemical changes.

OBJECTIVE: Methamphetamine is used extensively around the world as a psychostimulant. The complications related to methamphetamine include methamphetamine-induced neurotoxicity, mainly involving intraneuronal processes, such as oxidative stress and excitotoxicity. Curcumin is effective against neuronal injury due to its antioxidant, anti-inflammatory effects. In this study, we examined the protective effects of curcumin against methamphetamine neurotoxicity. METHODS: Sixty male Wistar rats were divided into the following groups: control (n = 12), DMSO (n = 12), methamphetamine (n = 12), and methamphetamine + curcumin (100 and 200 mg/kg, respectively, intraperitoneal [IP]; n = 12). Neurotoxicity was induced by 40 mg/kg of methamphetamine administrated through 4 injections (4 × 10 mg/kg, q2h, IP). Curcumin (100 and 200 mg/kg) was administered at 7 days after the last methamphetamine injection. By using a Morris water maze task, the hippocampus-dependent memory and spatial learning were evaluated 1 day after the last curcumin injection. Then, the animal brains were isolated for biochemical measurements, as well as glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1(Iba-1) and caspase-3 immunohistochemical staining. RESULTS: The current study demonstrated that administration of curcumin significantly attenuates spatial memory impairment (P < 0.01) following methamphetamine neurotoxicity. Curcumin caused a significant increase in the levels of superoxide dismutase and glutathione peroxidase (P < 0.05). However, it decreased tumor necrosis factor (TNF-α) (P < 0.05) and malondialdehyde (P < 0.01) levels as compared to the methamphetamine group. Also, curcumin significantly reduced Iba-1 (P < 0. 01), GFAP and caspase-3 positive cells in the hippocampus (P < 0.001). CONCLUSION: Curcumin exerted neuroprotective effects on methamphetamine neurotoxicity because of its antioxidant and anti-inflammatory effect.

Simvastatin attenuates spatial memory impairment via inhibiting microgliosis and apoptotic cell death against ethanol induced neurotoxicity in the developing rat hippocampus.

Ethanol is associated with oxidative stress. Exposure to ethanol during childhood may lead to neurological disorders. Congenital disorders induced by alcohol are mainly caused by an oxidative-inflammatory cascade due to extensive apoptotic neurodegeneration in the brain, particularly in the hippocampus. Simvastatin, which acts as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), is widely used to manage cardiovascular diseases. Recently, the neuroprotective effects of simvastatin against nervous system disorders have been introduced. In this study, we examined the protective effects of simvastatin on ethanol-related neurotoxicity in the hippocampus of rat pups. Ethanol (5.27 g/kg) in a milk solution (27.8 mL/kg) was administered to male rat pups via intragastric intubation at 2-10 days after birth. Also, 10 and 20 mg/kg of simvastatin were injected to the animals. By using Morris water maze task, the hippocampus-dependent memory and spatial learning was evaluated 36 days after birth. An ELISA assay was performed to investigate the antioxidant and anti-inflammatory effects of simvastatin by measuring the levels of tumor necrosis factor-α (TNF-α), and antioxidant enzymes. To assess the expression levels of Iba1 immunohistochemical staining and caspase-3 immunofluorescence staining was performed. The current study demonstrated that administration of simvastatin significantly attenuates spatial memory impairment (P < 0.01) after ethanol neurotoxicity. Also simvastatin could considerably increase the total superoxide dismutaseand glutathione levels (P < 0.01). Moreover, it was associated with a greater reduction in malondialdehyde (P < 0.05) and TNF-α levels, compared to the ethanol group (P < 0.01). Furthermore, in the simvastatin group, the hippocampal level of caspase-3 and the level of Iba1-positive cells, reduced (P < 0.01). This study demonstrated that apoptotic signaling, mediated by the oxidative-inflammatory cascade, could be inhibited by simvastatin in rat pups with ethanol exposure in the postnatal period.

Evaluation of IL-3, IL-5, and IL-6 concentration in the follicular fluid of women with endometriosis: A cross-sectional study.

Background: Endometriosis is associated with abnormal immunologic responses and combined inflammatory and anti-inflammatory conditions. Objective: This study aims to investigate follicular fluid (FF) concentration of interleukin (IL)-3, IL-5, and IL-6 in women with and without endometriosis. Materials and Methods: In this cross-sectionalstudy 68 women who were referred to the in vitro fertilization center of Imam Reza hospital in Mashhad during 2018 were selected randomly. Leaves of cytokines in the FF samples were evaluated in the endometriosis and the control group (n = 34/each). The diagnostic accuracy of cytokines and clinical characteristics were evaluated. Results: IL-3 and IL-6 were significantly changed in the FF of the women with endometriosis compared with the control group (p = 0.04, and p < 0.01, respectively), and the mean concentration of IL-5 in the endometriosis group was lower than in the control group (p = 0.5), but this was not significant. There were significant differences in the menstrual cycle, dyspareunia, and dysmenorrhea between the groups (p < 0.01, p = 0.04, and p = 0.02, respectively). The diagnostic accuracy of IL-3 and IL-6 in the FF was low, with the area under the curve of 0.614 and 0.645, respectively. Conclusion: Although none of the cytokines had a predictive value for endometriosis, the decreased levels of IL-3 and increased levels of IL-6 in the FF samples of women with endometriosis, and risk factors, including irregular menstrual cycle, dyspareunia, and dysmenorrhea, could be associated with the pathogenesis of this painful disease.

Protective effect of piperine in ischemia-reperfusion induced acute kidney injury through inhibition of inflammation and oxidative stress.

BACKGROUND AND AIM: Renal ischemia-reperfusion is associated with inflammation and oxidative stress. As a major compound in black pepper, piperine has anti-inflammatory and anti-oxidative properties. In present study, the protective effects of oral administration of piperine in renal ischemia-reperfusion (IR) induced acute kidney injuries (AKI) were investigated. EXPERIMENTAL PROCEDURE: Male Wistar rats received piperine (10 or 20 mg/kg.bw) or vehicle for 10 days. The artery and vein of both kidneys were then clamped for 30 min, followed by a 24-h reperfusion period. Concentrations of creatinine and urea-nitrogen in descending aorta blood were measured, and malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) levels were measured in kidney tissue to evaluate the oxidative stress. Inflammation was evaluated by measuring the TNF-α and ICAM-1 mRNA expression levels in renal cortical tissue using Real Time PCR method and counting leukocytes infiltration to interstitium. Further measured were tissue damages in H & E stained sections. RESULTS: Renal IR reduced FRAP, while increasing the plasma concentrations of creatinine and urea-nitrogen, tissue MDA level, TNF-α and ICAM-1 mRNA expressions, leukocyte infiltration and histopathologic injuries. Piperine administration significantly reduced the plasma concentrations of creatinine and urea-nitrogen, expression of pro-inflammatory factors, oxidative stress and renal histopathologic injuries. It is to be noted that 20 mg/kg dose was more effective. CONCLUSION: Our results suggest piperine protects the kidney against ischemia-reperfusion induced acute kidney injuries by its anti-inflammatory and anti-oxidative properties.

The role of Artemisia turanica extract on renal oxidative and biochemical markers in STZ-induced diabetes in rat.

OBJECTIVE: The aim of the current study was to investigate the protective effect of Artemisia turanica (AT) against diabetes- induced renal oxidative stress in rats. MATERIALS AND METHODS: Fifty male Wistar rats were randomly divided into five groups: control, STZ-induced diabetic rats, diabetic rats+ metformin, diabetic rats + AT extract, diabetic rats+ metformin+ AT extract. In the present study, diabetes was induced by a single-dose (55 mg/kg, ip) injection of streptozotocin (STZ). Diabetic rats were daily treated with metformin (300 mg/kg), AT extract (70 mg/kg) and metformin+ AT extract for 4 consecutive weeks. Tissue activities of superoxide dismutase (SOD) and catalase and the levels of malondialdehyde (MDA) and total thiol content were measured in kidney tissue. Serum concentrations of glucose, creatinine, and urea, as well as, lipid profile were also measured. RESULTS: STZ significantly increased the levels of glucose, triglyceride, urea and MDA compared to the control group. Total thiol content, as well as, catalase and SOD activities showed significant decreases in diabetic group when compared with the control animals. Serum glucose, triglyceride, cholesterol and renal MDA showed a significant decrease and renal total thiol and the activities of antioxidant enzymes showed significant increases in AT+STZ group compared with the diabetic group. In diabetic rats received AT+ metformin, serum LDL and HDL, renal MDA and SOD and catalase activities significantly improved compared with the diabetic rats. CONCLUSION: These findings suggested that AT extract has therapeutic effects on renal oxidative damage and lipid profile in diabetes, that possibly may be due to its antioxidant and hypolipidemic effects.

Modulation of long-term and short-term plasticity in the dentate gyrus granule cells by activating the ß-adrenergic receptors of the basolateral amygdala.

The beta-adrenergic receptors of the basolateral amygdala (BLA) are involved in modulating emotional memory formation in the hippocampus. The molecular mechanisms of this involvement are still unclear. In this study, we investigate the effects of the beta-adrenergic receptors of the BLA involvements during the major cellular mechanisms that underlie memory formation in hippocampal sub-regions. Wistar rats were injected with the selective beta receptor agonist, clenbuterol (15 ng/0.5 µl) bilaterally into the BLA. Then, the long-term potentiation (LTP) and the paired-pulse responses were recorded. Control rats were injected by saline at the same volume. Our data indicated that the injection of clenbuterol into the BLA area enhanced the amplitude of the population spike (PS) but not the slope of the excitatory postsynaptic potential (EPSP). In addition, short-term plasticity in the dentate gyrus (DG) region was significantly changed at 500 ms inter-pulse interval. These results suggest that the activation of the beta-adrenergic receptors of the BLA can improve LTP induction, which depends on the short-term plasticity with a mechanism related to the GABAergic transmission. Thus, it can be concluded that the adrenergic system of the BLA engages with long-term and short-term plasticity.