Atorvastatin prevents cadmium-induced renal toxicity in a rat model.

In many industrial processes, worker exposure to cadmium causes kidney damage; thus, protection against cadmium toxicity is important in workplace health. Cadmium toxicity involves oxidative stress by increasing the levels of reactive oxygen species. Statins have shown antioxidant effects that might prevent this increase in oxidative stress. We investigated the potential effects of atorvastatin pretreatment in protecting experimental rats against kidney toxicity caused by cadmium. Experiments were performed on 56 adult male Wistar rats (200 ± 20 g), randomly assigned to eight groups. Atorvastatin was administered by oral gavage for 15 days at 20 mg/kg/day, starting 7 days before cadmium chloride intra-peritoneal administration (at 1, 2, and 3 mg/kg) for 8 days. On day 16, blood samples were collected, and kidneys were excised to evaluate the biochemical and histopathological changes. Cadmium chloride significantly increased malondialdehyde, serum creatinine, blood urea nitrogen, and decreased superoxide dismutase, glutathione, and glutathione peroxidase levels. Pre-administration of rats with atorvastatin at a dose of 20 mg/kg decreased blood urea nitrogen, creatinine, and lipid peroxidation, increased the activities of antioxidant enzymes, and prevented changes in physiological variables compared with animals that were not pretreated. Atorvastatin pretreatment prevented kidney damage following exposure to toxic doses of cadmium. In conclusion, atorvastatin pretreatment in rats with cadmium chloride-induced kidney toxicity could reduce oxidative stress by changing biochemical functions and thereby decreasing damage to kidney tissue.

Dataset on biochemical markers and histological alterations in rat kidney intoxicated with cadmium chloride and treated with antioxidant.

This dataset demonstrates the in vivo renal histology and biochemical activity of Atorvastatin (AT) in cadmium-induced nephrotoxic rat model. Fifty-six adult male Wistar rats assigned to eight groups. Rats were treated with physiologic saline at a volume of 4 mg/kg, contained Atorvastatin at a dose of 20 mg/kg body weight for 15 days. The intraperitoneal administration of cadmium chloride at doses of 1, 2, 1 and 3 mg/kg started on day 8. On day 16, samples were collected for biochemical and histological analyses. Data of renal function were estimated in the serum and organ. Cadmium chloride increased malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine (Cr) serum level and decreased superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) levels. Administration of Atorvastatin significantly increased lipid peroxidation and renal decreased glutathione and antioxidant enzymes activity and significantly decreased BUN and Creatinine levels. Data were supported by histological examination indicated improved changes and kidney protective potential following cadmium chloride-induced oxidative stress.

Chrysin-Enhanced Cytotoxicity of 5-Fluorouracil-Based Chemotherapy for Colorectal Cancer in Mice: Investigating its Effects on Cyclooxygenase-2 Expression

Abstract 5-fluorouracil (5-FU) has been recognized as an effective medication used to treat colorectal cancer (CRC); however, its administration is facing limitations due to some complications reported. It is also generally accepted that combination therapy is among strategies to improve chemotherapy efficiency. Therefore, chrysin, with its anticancer effects, in combination with 5-FU was investigated in the present study. Azoxymethane (AOM) as a carcinogenic substance along with dextran sodium sulfate (DSS) was additionally utilized to induce CRC in mice. The anticancer effects of chrysin were then evaluated using aberrant crypt foci (ACF) counting and percentage of pathologic lesions in epithelial tissues from distal colon. In this study, cyclooxygenase (COX-2) protein expression was correspondingly explored through immunohistochemistry (IHC). The results revealed that chrysin alone or in combination with 5-FU could decrease ACF counting and percentage of pathologic lesions in comparison with AOM (p<0.05). Moreover, the combination of chrysin (at a dose of 50 mg/kg) with 5-FU reduced COX-2 expression compared with 5-FU alone (p<0.001) or 5-FU in combination with chrysin at a dose of 100 mg/kg (p<0.05). Furthermore, the combined chrysin boosted 5-FU efficiency, so it was suggested as an auxiliary therapy for CRC.

Regulatory effect of vitamin D on pro-inflammatory cytokines and anti-oxidative enzymes dysregulations due to chronic mild stress in the rat hippocampus and prefrontal cortical area.

BACKGROUND: Chronic stress increases the production of pro-inflammatory cytokines and oxidative stress in the brain, which underlay cognitive and psychological problems. In addition to the anti-depressants, vitamin D is known to act as an anti-inflammatory and anti-oxidative agent. This study investigates the specific effects of vitamin D in protecting hippocampus and pre-frontal cortex (PFC) against chronic mild stress (CMS)-induced activation of pro-inflammatory cytokines IL-6 and TNF-α and decreasing the activation of anti-oxidative enzymes super oxide dismutase (SOD) and glutathione peroxidase (GPx). METHODS AND RESULTS: Rats were exposed to CMS for 3 weeks. Two groups of rats received vitamin D (5 and 10 µg/kg) and another received fluoxetine (5 mg/kg) along with CMS. Control groups were not exposed to CMS, but received treatments similar to CMS groups. Serum corticosterone and IL-6, TNF-α and SOD and GPx levels in the hippocampus and PFC were measured at the end of three weeks. CMS significantly increased corticosterone, IL-6, TNF-α and decreased SOD and GPx levels (P < 0.0001) in hippocampus and PFC. Vitamin D treatment reduced corticosterone levels (P < 0.01), increased SOD (P < 0.0001) and GPx (P < 0.01) and decreased IL-6 and TNF-α (P < 0.0001) levels in the hippocampus and PFC compared to rats treated with vitamin D vehicle. Vitamin D-10 regulation of SOD and IL-6 levels was more effective than fluoxetine (P < 0.0001 and P < 0.01, respectively, in hippocampus). CONCLUSION: This study suggests that vitamin D effectively protects the key regions of the brain related to cognition and affective behavior, against the inflammation and oxidative stress caused by the chronic stress.

Circulating levels of FAM19A5 are inversely associated with subclinical atherosclerosis in non-alcoholic fatty liver disease.

BACKGROUND: Family with sequence similarity 19 (chemokine (C-C motif)-like) member A5 (FAM19A5) is a newly identified adipokine. There is a limited number of studies linking FAM19A5 to metabolic disorders. In the current study, we aimed to explore if FAM19A5 is associated with nonalcoholic fatty liver disease (NAFLD). We also sought to determine the possibility of FAM19A5 association with subclinical atherosclerosis in NAFLD patients. METHODS: A total of 69 subjects including 37 NAFLD and 32 control subjects were included in this cross-sectional study. Plasma concentration of FAM19A5 was measured with the ELISA method. Carotid artery intima-media thickness (cIMT) was assessed by the ultrasonography. RESULTS: Plasma concentration of FAM19A5 in patients with NAFLD was significantly lower in NAFLD patients than controls. Moreover, we observed significant negative correlations between plasma level of FAM19A5 and body mass index (BMI), visceral fat, alanine amino transferase (ALT), aspartate amino transferase (AST), liver stiffness (LS), and cIMT. Following stepwise multiple linear regression analysis, ALT and cIMT were the only determinants of FAM19A5 level. CONCLUSIONS: This is the first report to describe association of circulating FAM19A5 levels with NAFLD. Our findings provide further evidence showing relation of FAM19A5 with the risk of atherosclerosis. However, more studies are necessary to unravel the contribution of lower FAM19A5 levels to the NAFLD pathogenesis and the higher risk of atherosclerosis in these patients.

Neuroprotective Effects of Chemerin on a Mouse Stroke Model: Behavioral and Molecular Dimensions.

The present study was conducted to investigate the effects of different doses of recombinant human Chemerin (rhChemerin) on brain damage, spatial memory, blood-brain barrier (BBB) disruption and cellular and molecular mechanisms in a mouse stroke model. The mouse stroke model was developed by blocking the middle cerebral artery for 1 h and performing reperfusion for 23 h. Immediately, one and three hours after the stroke, 200, 400 and 800 ng/mouse of intranasal rhChemerin was administered. Neuronal and BBB damage, spatial memory and neurological performance were examined 24 h after the stroke. Western blotting and immunofluorescence were utilized to determine the effects of rhChemerin on the expressions of nuclear factor kappa B (NF-κB), pro-inflammatory cytokines such as TNF-α and IL-1ß, anti-inflammatory cytokines such as IL-10 and TGF-ß and vascular endothelial growth factor (VEGF). Administering 400 and 800 ng/mouse of rhChemerin in the mice immediately and one hour after ischemia minimized the infarct size, BBB opening, spatial memory and neurological impairment (P < 0.001). Furthermore, 800 ng/mouse of rhChemerin significantly diminished terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive (apoptotic) cells, suppressed the expressions of NF-kB, TNF-α and IL-1ß and upregulated IL-10 and VEGF in the cortex and hippocampus of the mice. The present findings showed that rhChemerin administered immediately and one hour after stroke alleviates neuronal and BBB injures and improves spatial memory. These effects of rhChemerin may be mediated by inhibiting inflammatory pathways and apoptotic machinery.

Co-administration of 5FU and propolis on AOM/DSS induced colorectal cancer in BALB-c mice.

AIMS: Currently, the main problems with chemotherapy are its side effects, toxicity, and drug resistance. Propolis has biological activities, such as anti-inflammatory and anti-cancer properties. This study aims to examine the combined effects of 5-fluorouracil (5FU) and propolis on colorectal cancer (CRC) in mouse models. MATERIALS AND METHODS: The chemical composition of ethanolic extract of propolis was determined by gas chromatography-mass spectrometry (GC-MS). In this study, 49 male Balb/c mice (16-20 g) were divided in seven groups as a control group and experimental groups (treated and untreated CRC model [azoxymethane + dextran sodium sulfate]). This study was conducted in 8 weeks. To examine the anti-cancer effects of propolis, the number of aberrant crypt foci (ACF) was counted and the pathological lesions in the distal colonic epithelial tissue were diagnosed. In this study, the expression of beta-catenin (ß-catenin), induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) proteins, which play a major role in the incidence and progression of cancer, were determined. KEY FINDINGS: GC-MS analysis of propolis showed the presence of hydrocarbons, alcohols, ketones, terpenes, phenols, and flavonoids. Administering propolis in combination with 5FU reduced the number of ACFs and pathological lesions in comparison with cancer control groups (p < 0.0001) and 5FU-alone treatment (p < 0.05). The propolis combined with 5FU reduced the expression of Cox-2, iNOS, and ß-catenin proteins. SIGNIFICANCE: The results showed that propolis increased the efficiency of 5FU and could be taken into account as the adjunct therapy for colorectal cancer.

Microinjection of the BDNF receptor antagonist ANA-12 into the nucleus accumbens and medial-prefrontal cortex attenuates morphine-induced reward memory, and alterations of BDNF levels and apoptotic cells in rats.

This study was designed to examine the effects of intra- nucleus accumbens (NAc) of BDNF receptor antagonist ANA-12 on the acquisition and expression and intra- medial-prefrontal cortex (mPFC) of ANA-12 on the extinction and reinstatement of morphine-induced conditioned place preference (CPP) and also BDNF levels and apoptotic neurons in the NAc and mPFC of rats. In this study, adult male Wistar rats (200-250 g) were used. Two separate cannulas were inserted bilaterally into the NAc and/or mPFC. ANA-12 (3 µg/0.5 µl/side) was injected into the NAc and/or mPFC to evaluate the rewarding effects of morphine using a CPP paradigm. Then, the levels of BDNF and apoptotic in the NAc and mPFC were assessed at the end of each treatment phase using ELISA and TUNEL methods, respectively. All of vehicle-treated rats following morphine CPP showed the increase of BDNF levels and apoptotic neurons in the NAc and mPFC. ANA-12 significantly attenuated the acquisition and expression of morphine-induced CPP, BDNF levels and apoptotic neurons in the NAc during the acquisition, but not the expression phase. Also, ANA-12 significantly facilitated the extinction, but no effect on reinstatement of morphine CPP, and decreased BDNF levels and apoptotic neurons in the mPFC during the extinction, but not the reinstatement. We conclude that blocking TrkB with ANA-12 showed therapeutic effects on morphine-associated reward memory and neuronal death in the NAc and mPFC induced by morphine CPP. Thus, the BDNF-TrkB signaling may be important in the acquisition, expression, extinction, but not the reinstatement of morphine CPP.

Oxytocin Reduces Brain Injury and Maintains Blood-Brain Barrier Integrity After Ischemic Stroke in Mice.

The present study was designed to determine the effect of different doses of oxytocin (OXT) on neuronal injury, spatial memory, blood-brain barrier (BBB) integrity and to explore possible underlying molecular mechanisms in the early stage of stroke in mice. Stroke model was generated by middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion in mice. OXT at doses of 1, 2, 4 and 8 IU/per mouse was administrated intranasally at the beginning of brain ischemia. Brain injury, BBB integrity, and spatial memory were evaluated by standard methods. Changes in the expression of nuclear factor-kappa B (NF-κB), and TUNEL positive cell were detected by immunohistochemistry. The levels of vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4) and brain-derived neurotrophic factor (BDNF) proteins were determined by western blotting and ELISA methods. OXT at doses of 4 and 8 IU/per mouse reduced the infarct size by 42% and 52%, respectively, and improved spatial memory function (p < 0.001). OXT (8 IU/per mouse) significantly reduced brain edema, BBB disruption and upregulated the AQP4 expression (p < 0.001). Finally, OXT significantly diminished the number of apoptotic, NF-κB positive cells and enhanced the expression of BDNF and VEGF proteins in the brain tissue (p < 0.001). These findings provide important evidences that OXT significantly suppresses neuronal damage in the early stage of stroke by inhibiting apoptotic and NF-κB signaling pathway, increasing the expression of VEGF, AQP4 and BDNF proteins and reducing the BBB leakage.

Effects of treadmill exercise and sex hormones on learning, memory and hippocampal brain-derived neurotrophic factor levels in transient congenital hypothyroid rats.

Transient thyroid function abnormalities at birth exhibit intellectual developmental and cognitive disorders in adulthood. Given the well-known effects of physical activity and sex hormones on cognitive functions and brain-derived neurotrophic factor (BDNF), the present study examined the effects of treadmill exercise, sex hormones, and the combined treatment on learning and memory and hippocampal BDNF levels in transient congenital hypothyroid rats. To induce hypothyroidism, 6-propyl-2-thiouracil was added to the drinking water from the 6th day of gestation to the 21st postnatal day (PND). From PNDs 28 to 47, female and male pup rats received 17ß-estradiol and testosterone, respectively, and about 30 min later, they were forced to run on the treadmill for 30 min once a day. On PNDs 48-55, spatial learning and memory of all rats tested in the water maze, which followed by measurement of BDNF in the hippocampus. Results showed that developmental hypothyroidism induced significant deficits in spatial learning and memory and hippocampal BDNF in both male and female rats. In both male and female hypothyroid rats, exercise and exercise plus sex hormones, but not sex hormones alone alleviated learning and memory deficits and all treatments (exercise, sex hormones, and the combined treatment) increased hippocampal BDNF. These disconnects in the effects of exercise, sex hormones and the combined treatment on behavioral and neurochemical outcomes suggest that a neurochemical mechanism other than hippocampal BDNF might contribute in the ameliorating effects of exercise on learning and memory deficits induced by developmental thyroid hormone insufficiency.

Protective Effects of Spirulina platensis, Voluntary Exercise and Environmental Interventions Against Adolescent Stress-Induced Anxiety and Depressive-Like Symptoms, Oxidative Stress and Alterations of BDNF and 5HT-3 Receptors of the Prefrontal Cortex in Female Rats.

BACKGROUND AND PURPOSE: Ample evidence indicates that chronic adolescence stress is associated with an increased risk of developing neuropsychiatric disorders in adulthood. Given the importance of the effective therapeutic ways to overcome adolescent stress-related deficits, the present study investigated the effects of Spirulina platensis (SP), environmental enrichment (EE), and voluntary exercise (EX) and their combination on anxiety or depression-like behaviors, oxidative stress, and alterations of BDNF and 5HT-3 receptors in the prefrontal cortex (PFC) induced by adolescent stress in adult female rats. METHODS: During the adolescent period (PNDs30-40), rats were subjected to restraint stress. Then, the animals were subjected to SP treatment (200 mg/kg/day), EX, EE, and the combined treatments (SP+EX, and SP+EE) for 15 days between PNDs41-55. Subsequently, anxiety or depression-like behaviors, BDNF levels, oxidative stress markers and mRNA expression of BDNF and 5HT3 in the PFC were assessed. RESULTS: Stressed rats demonstrated enhanced anxiety levels and depression-like behaviors in adulthood. Regarding the oxidative stress markers, stressed rats exhibited significantly higher levels of malondialdehyde, a lipid peroxidation product, higher activities of antioxidant enzymes (glutathione peroxidase and superoxide dismutase) and significantly lower total antioxidant reactivity capacity in the PFC. Additionally, adolescent stress significantly increased 5HT3 receptor mRNA expression and decreased BDNF content and its mRNA expression in the PFC. Treatments with SP, EX, EE, and the combined interventions alleviated these deficits. CONCLUSION: Our findings indicate that appropriate interventions during the adolescent period can protect against adolescent stress-induced behavioral, and biochemical defects and oxidative stress damage in adulthood.

Hepatoprotective effect of atorvastatin on Cadmium chloride induced hepatotoxicity in rats.

AIMS: Cadmium chloride has various industrial applications and considered an industrial and environmental pollutant. The aim of this study was to evaluate the effect of atorvastatin on Cadmium chloride-induced hepatotoxicity in male rats. MATERIALS AND METHODS: Fifty-six adult male rats, randomly were divided into 8 groups. Groups 1-3 were received atorvastatin (20 mg/kg) intragastrically for 15 days during which Cadmium chloride (1, 2, and 3 mg/kg) were given intraperitoneally from days 8 to 15. Groups 4-6 were as first three groups but animals were received vehicle of atorvastatin. Group 7 was received vehicle of atorvastatin and vehicle of Cadmium chloride and Group 8 was received atorvastatin and vehicle of Cadmium chloride according to timeline of other groups. On day 16, under full anesthesia, blood sampling was prepared from heart, and livers were dissected out to analyses the biochemical and histopathology studies. KEY FINDINGS: Cadmium chloride significantly increased aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) in the serum. Malondialdehyde (MDA) significantly increased and superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH) significantly decreased the in the liver following Cadmium chloride administration. Atorvastatin significantly improved the levels of MDA, SOD, GPx, GSH, but not ALT, AST, and ALP in Cadmium chloride-treated rats. In histopathological studies, atorvastatin could not improve injured liver tissues induced by Cadmium chloride. SIGNIFICANCE: Atorvastatin has beneficial effects in improving Cadmium chloride-induced antioxidative enzymes disturbance which may be contribute to improving liver function in male rats.

Therapeutic Effects of Spirulina platensis Against Adolescent Stress-Induced Oxidative Stress, Brain-Derived Neurotrophic Factor Alterations and Morphological Remodeling in the Amygdala of Adult Female Rats.

OBJECTIVE: The amygdala structural and functional abnormalities have been implicated in numerous neuropsychiatric and neurodevelopmental disorders. Given the important role of the amygdala in stress responses and the susceptibility of the females to adolescent stress, the present study investigated the beneficial effects of Spirulina platensis microalgae (SP) as a neuroprotective supplement against adolescent stress-induced oxidative stress, brain-derived neurotrophic factor (BDNF) alterations, molecular and morphological remodeling in the basolateral amygdala (BLA) of adult female rats. METHODS: During the adolescent period (PNDs 30-40) rats were subjected to restraint stress (2 h/day for 10 days). Then, the animals were subjected to 15 days treatment (PNDs 41-55) with SP (200 mg/kg/day) followed by biochemical (BDNF and stress oxidative markers), molecular (BDNF and its receptor tropomyosin receptor kinase B [TrkB] mRNA expression), and morphological (dendritic length and spines) assessments in the BLA. RESULTS: The study revealed that adolescent stress decreased BDNF levels and reduced apical dendritic length and branch points of pyramidal neurons in the BLA. In addition, chronic stress significantly increased oxidative stress parameters and decreased BDNF and TrkB mRNA expression in the BLA. Treatment with SP alleviated both biochemical, molecular, and neuroanatomical deficits that induced by adolescent stress. CONCLUSION: Our findings provide important evidence that SP as a non-pharmacological intervention during adolescent period can protect against chronic stress-induced neuroanatomical biochemical, and molecular deficits in adulthood, and thus, reduce stress-related disorders.

Effect of crocin on morphine tolerance and serum BDNF levels in a rat model of neuropathic pain.

BACKGROUND: Chronic use of morphine treatment for neuropathic pain leads to morphine-induced analgesic tolerance. Crocin contained in Crocus sativus L., exerts anti-inflammatory and analgesic effects. This study examined the effects of crocin on morphine tolerance and serum BDNF levels on neuropathic pain induced by chronic constriction injury (CCI) in rats. METHODS: CCI model of neuropathic pain was done in male Wistar rats (200-250 g). Rats were treated with crocin (15 or 30 mg/kg, intraperitoneally) alone or simultaneously with morphine (10 mg/kg, subcutaneously) during or after induction of CCI. Pain behavioral responses including mechanical allodynia and thermal hyperalgesia were measured from days of 15-27 after CCI. Then, rats were evaluated for serum BDNF levels on days 14 and/or 27. RESULTS: We found that morphine tolerance developed after the induction of neuropathic pain. The injection of crocin (15 and 30 mg/kg) was able to enhance analgesic effect of morphine by reduction of mechanical allodynia on days 15-27 post-surgery in CCI rats. While preemptive administration of crocin at a lower dose (15 mg/kg) maintained the analgesic effect of morphine. Morphine injection and/or co-administration with crocin (15, 30 mg/kg) decreased serum BDNF levels in CCI rats. CONCLUSION: These findings indicate that crocin may have a therapeutic effect to maintain morphine analgesic efficacy and also to prevent the development of morphine tolerance in neuropathic pain, but probably not through BDNF.

Impact of different intensities of forced exercise on deficits of spatial and aversive memory, anxiety-like behavior, and hippocampal BDNF during morphine abstinence period in male rats.

Forced exercise can alleviate cognitive-behavioral deficits in an experimental model of addiction. However, the effects of different intensities of forced exercise in improving behavioral, cognitive and biochemical deficits during morphine abstinence period are not well investigated. Thus, the current work examined the effects of different loads of forced exercise on cognition functions, anxiety behavior and BDNF changes in the hippocampus, and prefrontal cortex (PFC), and also serum levels of BDNF and corticosterone during the abstinent period in male rats. Animals received morphine injections (10 mg/kg, twice a day) for 10 consecutive days. Then, the animals were exposed to a 4-week forced exercise training program under low, moderate or high intensities (30 min per session on 5 days a week), which accompanied by behavioral and biochemical tests. In Experiment 1, anxiety-like behaviors using elevated plus maze (EPM), and light/dark box (L/D box) were examined. In Experiment 2, cognitive functions using T-maze alteration and passive avoidance tasks were tested, which accompanied by BDNF measurements in the hippocampus and PFC. In Experiment 3, serum levels of BDNF and corticosterone following the termination of forced exercise regimen were measured. Morphine-abstinent animals exhibited anxiogenic -like behaviors in the EPM, but not L/D box. They also exhibited impaired T-maze alternation performance and passive avoidance memory, and a decline in hippocampal BDNF, but not PFC. Forced exercise at a moderate intensity alleviated anxiety, cognitive and BDNF defects in morphine-abstinent animals. The high load exercise enhanced serum levels of corticosterone in both saline and morphine groups. Thus, regular moderate forced exercise may be beneficial in preserving cognitive and mood functions in male addicts during the abstinent period and drug rehabilitation.

Hippocampal Up-Regulation of Apolipoprotein D in a Rat Model of Maternal Hypo- and Hyperthyroidism: Implication of Oxidative Stress.

Thyroid disorders impair various functions of the hippocampus where thyroid hormone receptors are localized in the brain. Hyper and hypothyroidism are associated with large changes in brain oxidative stress. Apolipoprotein D (APOD) is a conserved glycoprotein that increased in response to oxidative stress in the brain and has been suggested function as an antioxidant in the brain. Thus, the goal of this work was to explore the effect of maternal hypo- and hyperthyroidism on the Apod expression in the pup's brain regarding changes in oxidative stress. For induction hypo and hyperthyroidism in adult female rats, 100 ppm propylthiouracil (PTU) and 8 ppm levothyroxine administrated 1 month before copulation to the week 3 after delivery in drinking water. The hippocampal region of rat pups was isolated and used for immunohistochemistry and quantitative RT-PCR on postnatal day (PND)5, PND10 and PND20. Results revealed that APOD over-expressed in both hypo- and hyperthyroid groups on PND5, PND10, and PND20. There was a proportional increase between the Apod expression and oxidative stress in the hyperthyroid group but not the hypothyroid in different days. Regarding the wide functions of thyroid hormones, oxidative stress does not suggest to be the only mechanism that involves Apod gene expression in thyroid disturbances.

Probiotic supplementation attenuates hippocampus injury and spatial learning and memory impairments in a cerebral hypoperfusion mouse model.

Probiotics are referred to species of living microscopic organisms may help conserve the normal balance of the digestive system and/or manage diseases. A number of autoimmune, psychiatric, cardiovascular and cerebrovascular disorders may be associated with the imbalance of gut microbiota. This study examines the effect of 21 days consumption of multistrain probiotics on hippocampus injury, spatial and learning memory and some potential molecular mechanisms in a mouse model with cerebral hypoperfusion. Cerebral hypoperfusion was established in the mouse model by bilateral common carotid artery occlusion (BCCAO) for 20 min and 24 h reperfusion. Mixtures of several probiotic bacteria at concentrations of 107, 108 and 109 CFU/day were orally administrated for 3 weeks before the BCCAO. Spatial and learning memory, histological damage and apoptosis were assessed in the CA1, CA3 and dentate gyrus (DG) of the hippocampus 24 h after ischemia. The malondialdehyde (MDA) content and brain-derived neurotrophic factor (BDNF) level were measured by ELISA technique. Prophylactic of probiotic considerably reduced the number of apoptotic cells and neuronal death in the CA1, CA3 and DG of the hippocampus at all three concentrations (P < 0.001). In addition, probiotics reduced spatial memory impairment and neurological dysfunction only at the 109-CFU/day (P < 0.01). Nonetheless, probiotics did not change the levels of BDNF and MDA in the hippocampus (P > 0.05). According to the findings, the daily prophylactic ingestion of probiotics reduced hippocampus damage and prevented the spatial learning and memory deficit by suppressing apoptosis in the mouse model with cerebral hypoperfusion. Probiotic supplementation may be suggested as a useful preventive dietary strategy for groups susceptible to cerebrovascular diseases.

Beneficial effects of Spirulina platensis, voluntary exercise and environmental enrichment against adolescent stress induced deficits in cognitive functions, hippocampal BDNF and morphological remolding in adult female rats.

Chronic exposure to stress during adolescent period has been demonstrated to impair cognitive functions and the dendritic morphology of pyramidal neurons in the rat hippocampal CA3 area. The present study investigated the combined protective effects of Spirulina platensis (SP), a supplement made from blue-green algae with neuroprotective properties, voluntary exercise (EX) and environmental enrichment (EE) against cognitive deficits, alternations in hippocampal BDNF levels, and abnormal neuronal remodeling in adult female rats (PND 60) induced by exposure to chronic restraint stress during adolescent period (PND 30-40). Rats were exposed to restraint stress (2 h/day for 10 days, PND 30-40). Then, the animals were subjected to treatment with SP (200 mg/kg/day), EX, EE and the combined treatments (SP + EX, and SP + EE) between PND 41 and 55 of age. Following the interventions, spatial learning and memory, passive avoidance performance, hippocampal dendritic morphology and BDNF levels were assessed. Results showed that plasma corticosterone levels increased at PND 40 and remained elevated at PND 55 and 70 in the stressed rats. Stressed rats showed deficits in spatial learning and memory and passive avoidance performance, decreased BDNF levels in the hippocampus, and reduced apical dendritic length and branch points of the CA3 pyramidal neurons. These deficits were alleviated by the SP, EX and EE, and the combined treatments, which accompanied with a decline in serum corticosterone in stressed animals. Some treatments even enhanced cognitive functions, and BDNF levels and neuroanatomical remodeling in the hippocampus of non-stressed animals. Our findings provide important evidences that physical activity, exposure to EE, and the SP treatment during adolescent period can protect against adolescent stress induced behavioral, biochemical and neuroanatomical impairments in adulthood.

Fluctuations of epigenetic regulations in human gastric Adenocarcinoma: How does it affect?

Gastric cancer (GC) or human gastric adenocarcinoma is one of the most commonplace type of serious cancers and also the most common cause of cancer-related mortality in the world. Relatively, many studies have acknowledged that GC is a multi-factorial pathological situation that environmental factors, particularly dietary ones and H.pylori infection are considered to have a strong key role in the etiology of GC. Inappropriate dietary habits are the first cause as they affect main molecular functions related with the onset of the GC tumorigenesis and carcinogenesis. Correspondingly, cancer investigation has impressively zoomed on the different genetic markers and also molecular mechanisms pathways responsible for the progression of the GC. Various molecular signaling pathways such as WNT, NOTCH, SHH, MYC have different functions and analyzing their role in the GC is of great importance particularly for the treatment modalities. Proportionately, fluctuations of epigenetic alterations including DNA methylation, histone modification, histone acetylation and also histone phosphorylation's are involved in all cancers specially the GC. Conspicuously, novel developments in cancer epigenetic have indicated immense reprogramming of every structure of the epigenetic mechanism in cancer, comprising microRNAs, nucleosome positioning, DNA methylation, noncoding RNAs, and histone modifications. In this account, aberrant DNA methylation mechanism in the promoter regions of certain genes, which leads to silencing of some particular genes such as tumor suppressor and other cancer-related genes in carcinogenesis, is the most important epigenetic hallmark in human GC especially as a target for detection and diagnosis in cancer treatment. Here, we review the importance of epigenetic fluctuations alongside with their molecular signaling mechanism in the GC.