فهرست مطالب

Physiology and Pharmacology - Volume:23 Issue:3, 2019
  • Volume:23 Issue:3, 2019
  • تاریخ انتشار: 1398/07/09
  • تعداد عناوین: 10
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  • Majid Reza Farrokhi, Masoumeh Emamghoreishi, Atena Amiri, Mojtaba Keshavarz* Pages 150-153
    Introduction

    The reduction of glycogen synthase kinase-3β protein level may correlate to the neuroprotective effects of antioxidant agents like caffeine. Therefore, we aimed to evaluate the impact of GSK-3β protein on neuroprotective effects of caffeine in the SHSY5Y cells exposed to beta-amyloid.

    Methods

    We incubated SHSY5Ycells with beta-amyloid 25–35 and caffeine (0.6 and 1mM) for 24h. Cell viability was determined using MTT test. We used the western blotting technique to measure the glycogen synthase kinase-3β and phosphorylated glycogen synthase kinase-3β protein levels.

    Results

    Caffeine (0.6 and 1mM) diminished beta-amyloid neurotoxicity and attenuated the beta-amyloid effects on the glycogen synthase kinase-3β protein level in a neuronal culture.

    Conclusion

    Caffeine neuroprotective effects against beta-amyloid may correlate to glycogen synthase kinase-3β protein.</div>

    Keywords: Caffeine, Amyloid-beta peptide, Glycogen synthase kinase, Neuroprotection
  • Parisa Sarkoohi, Hadi Aligholi, Atena Amiri, Marzieh Mahdavipour, Zahra Zeraatpisheh, Masoumeh Emamghoreishi* Pages 154-165
    Introduction

    Quercetin, a natural flavonoid, has been suggested as a stimulant of endogenous neural stem cell proliferation; but, its underlying mechanism is unclear. Considering that Nrf2 and proteasome pathways have important role in cell proliferation, the objective of this study was to evaluate the effects of different concentrations of quercetin on Nrf2 protein levels and proteasomal activity in neural stem/progenitor cells (NS/PCs) in relation to NS/PCs viability and proliferation.

    Methods

    NS/PCs of rat fetal ganglionic eminence were cultured and exposed to different concentrations of quercetin (1, 5 and 15μM) or DMSO for 7 days. The size and number of neurospheres and percentage of BrdU positive cells were measured as indexes of cell proliferation. MTT assay was used for evaluating the cell viability. Proteasomal activity and Nrf2 protein levels were determined using proteasomal activity kit and western immunoblotting, respectively.

    Results

    Quercetin increased the percentage of BrdU positive cells, size and number of neurospheres and viability of NS/PCs and increased Nrf2 protein levels and 20S proteasome activity in comparison to DMSO. The effects of quercetin on NS/PCs proliferation, Nrf2 levels and proteasome activity were concentration-dependent.

    Conclusion

    The results of this study indicated that quercetin increased Nrf2 levels and proteasome activity in parallel to enhanced NS/PCs proliferation in a concentration-dependent manner. These findings suggest that quercetin may exert its stimulatory effect on NS/PCs proliferation through the enhancement of Nrf2-proteasome pathway. Quercetin as activators of Nrf2 and proteasome can be suggested as a potential treatment for neurodegenerative conditions to promote endogenous cell proliferation.</div>

    Keywords: Quercetin, Nrf2, Proteasome, Neural stem cells, Proliferation
  • Anahita Mehdizadeh, Bibi Shahnaz Aali, Zahra Hajializadeh, Shima Torkzadeh, Mahani, Saeed Esmaeili, Mahani* Pages 166-173
    Introduction

    Parkinson’s disease is a progressive neurodegenerative disorder characterized by progressive death of midbrain dopaminergic neurons. Neurosteroid dehydroepiandrosteone (DHEA) is synthesized de novo in brain glial cells and its concentration is particularly high in the brain, which dramatically decreases by aging. DHEA has neuroprotective activity against different types of neural injuries. In this study, we investigated the effects of DHEA on 6-hydroxydopamine (6-OHDA)-induced toxicity in rat pheochromocytoma (PC12) cells as an in vitro model of Parkinson’s disease.

    Methods

    Cell damage was induced by 150μM 6-OHDA and the cell survival rate was examined by MTT assay. The level of intracellular reactive oxygen species (ROS) was determined with a 2,7-dichlorofluorescein diacetate probe. Immunoblotting was also employed to determine the level of biochemical markers of neural apoptosis in PC12 cells.

    Results

    The data demonstrated toxic effect of 6-OHDA by reducing cell viability in a dose-dependent manner. Furthermore, activated caspase-3 and Bax/Bcl2 ratio were significantly increased in 6-OHDA-treated cells. Incubation of cells with DHEA (400 and 600μg/ml) decreased cell damage.

    Conclusion

    Our results suggest that DHEA has protective effects against 6-OHDA-induced neural damage. The mechanisms of these effects may be due to the attenuation of neural apoptosis and suggest therapeutic potential of this neurosteroid in the treatment of Parkinson’s disease.</div>

    Keywords: Dehydroepiandrosterone, Parkinson’s disease, 6-hydroxydopamine, Apoptosis, PC12 cells
  • Soodeh Rowhani Rad, Mahnaz Taherianfard* Pages 174-182
    Introduction

    Brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNFα) are two critical factors in multiple sclerosis (MS). The aim of the present study is comparing the crosstalk between BDNF and TNFα in the brain versus serum and their effects on recovery of C57BL/6 mice demyelination in cuprizone model.

    Methods

    Fifteen C57BL/6 mice 6-week-old in three different groups were used: control (standard rodent chow), cuprizone-exposed1 (CPZ1; 0.2% cuprizone feeding for 5 weeks) and cuprizone-exposed2 (CPZ2; 0.2% cuprizone feeding for 5 weeks followed by 2 weeks of cuprizone withdrawal). To prove MS induction and cognitive behavioral impairment, Y-maze test and histological studies with luxol fast blue staining were done. The levels of BDNF and TNFα in the brain and serum were measured by ELIZA kits.

    Results

    In the present study, Y-maze test demonstrated that MS significantly impaired the cognitive behavior in both CPZ groups compared to control group. Demyelination in corpus callosum (CC) significantly was higher in the two CPZ groups relative to control group. The brain levels of BDNF significantly decreased while the brain levels of TNFα significantly increased in both CPZ groups compared to control group. Serum levels of BDNF and TNFα significantly increased in CPZ1 group compared to control group.

    Conclusion

    According to the present results, cuprizone-induced MS caused to an extensive demyelination in CC, which led to impaired cognitive behavior. Moreover, brain and serum levels of BDNF and TNFα as well as their crosstalk were affected by cuprizone exposure.</div>

    Keywords: BDNF, TNFα, Multiple sclerosis, de, re-myelination, Cuprizone
  • Alireza Gharebaghi, Akram Ranjbar, Tayebe Artimani, Banafsheh Mirzaeiseresht, Sara Soleimani Asl* Pages 183-188
    Introduction

    Diabetes mellitus is a major chronic metabolic disorder that induces memory and learning impairment. Herein, we investigated the protective effects of cerium oxide nanoparticles (CeO2) against streptozotocin (STZ)-induced memory impairment and antioxidant capacity in the diabetic rats.

    Methods

    Adult male Wistar rats were assigned into the control, STZ, CeO2 and STZ plus CeO2 groups. Diabetes was induced using STZ and next CeNPs (60mg/kg) was administered for 14 constitutive days. The day after the last administration, spatial memory was assessed using the Morris water maze (MWM). Ultimately, the level of total antioxidant capacity (TAC) was investigated.

    Results

    Our results showed that STZ significantly decreased the spatial memory and CeO2 could compensate for these changes. Furthermore, TAC increased following administration of CeO2 in the diabetic rats.

    Conclusion

    The results of this study suggest that CeO2 seems to be able to improve STZ-induced neurotoxicity in the rats.</div>

    Keywords: Streptozotocin, Cerium oxide nanoparticles, Spatial memory, antioxidant capacity
  • Alireza Halabian, Nasrin Mehranfard, Maryam Radahmadi, Maedeh Ghasemi* Pages 189-196
    Introduction

    Effects of chronic scheduled dietary on plasma ghrelin and food intake in adult male rats were assessed.

    Methods

    Forty male Wistar rats (180-200g) were distributed into four groups (n=10), freely fed rats (control) and three scheduled-fed groups with different caloric intakes: high fat, standard and restricted diet. Then, plasma ghrelin and food intake were measured on days 0, 7 and 14.

    Results

    Plasma ghrelin was significantly different among all groups, the scheduled-standard rats having the lowest ghrelin on day 7 and the restricted rats having the highest ghrelin on day 14. Noteworthy, fasted ghrelin in controls was as much as that of schedule groups exception restricted diet at the end of experiment. Controls consumed stable food over the time, while schedule groups showed time and caloric-dependency of food intake. Schedule-standard and restricted groups on feeding time consumed high level of food. Schedule-high fat group displayed a time dependent reduction in food intake. A positive correlation was found between plasma ghrelin and food intake in fasting status for freely fed rats and anticipating status for standard and restricted-schedule groups.

    Conclusion

    A component of ghrelin secretion can be entrained or learned for time feeding as well as long last-fasting and more is affected by quantitative and qualitative of caloric intake. Elevated ghrelin levels in restricted model are subjective both by low energy levels and learning. Also, caloric intake amount can be controlled by learning; we observed a reduction in meal size in scheduled–high fat diet.</div>

    Keywords: Ghrelin, Food intake, High fat diet, Caloric restriction
  • Ilham Touiss*, Mohamed Harnafi, Saloua Khatib, Oussama Bekkouch, Khadija Ouguerram, Souliman Amrani, Hicham Harnafi Pages 197-207
    Introduction

    In this study, we investigated the effect of basil rosmarinic acid-rich extract on mice lipid metabolism, low-density lipoprotein oxidation and antiradical property.

    Methods

    The rosmarinic acid rich-extract was used to treat male mice. Mice were divided into four groups of seven mice and treatment was performed daily and orally for 9 weeks. The antihyperlipidemic effect was evidenced by the measurement of plasma and liver lipid profiles. Thiobarbituric acid reactive substances assay was used to measure the antioxidant capacity of the phenolic extract using mice plasma rich in low density lipoprotein (LDL). The antioxidant activity of the extract was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging capacity and the measurement of oxidative β-carotene bleaching.

    Results

    The extract exerts a significant decrease in plasma total cholesterol, triglycerides and LDL-cholesterol. Similar results were observed in liver total cholesterol and triglycerides. The phenolic extract prevents lipoprotein oxidation by 93% at a dose of 25μg/ml. We also note that the extract scavenges DPPH radical in a dose-dependent manner with an IC50= 12.45±0.18 μg/ml. Besides, the extract inhibits the oxidation process of β-carotene, the IC50 was 12.16±0.19 μg/ml. HPLC analysis shows that the extract contains caftaric acid (2.9%), caffeic acid (4.3%), chicoric acid (5.5%) and rosmarinic acid (87.3%) which is the major compound.

    Conclusion

    The results obtained suggest that the extract may be an important source of natural compounds that can be exploited as a substrate to develop new treatment of hyperlipidemia and atherosclerosis.</div>

    Keywords: Ocimum basilicum L., Rosmarinic acid, Lipid metabolism, Lipoprotein oxidation, Free radical scavenging
  • Farzaneh Kianian, Hamid Reza Sadeghipour, Seyed Morteza Karimian, Mehri Kadkhodaee, Behjat Seifi* Pages 208-214
    Introduction

    Comorbidity of anxiety has been reported to aggravate the control of asthma symptoms. Considering the important role of oxidative stress in the pathophysiology of asthma and anxiety, the present study evaluated whether hydrogen sulfide (H2S) as an antioxidant agent, has anxiolytic effects in ovalbumin (OVA)-induced chronic asthma.

    Methods

    BALB/c mice were randomly divided into 4 groups (n=8): control, asthma, NaHS (sodium hydrosulfide, a donor of H2S) and ascorbic acid (as a positive control). All animals except in the control group were sensitized and challenged with ovalbumin. Mice in the NaHS group, intraperitoneally received 14μmol/kg NaHS 30min before each challenge. In the ascorbic acid group, 130mg/kg ascorbic acid was given by gavage 30min before each challenge. On the day of the last challenge, animal body weight and anxiety-related behaviors were examined.

    Results

    Asthma caused significant decreases in the percentages of open arm entries and spending time in open arms in the elevated plus maze as well as the spending time in the light side in the light-dark transition. Also, induction of asthma resulted in a significant decrease of the animal body weight. Administration of NaHS as well as ascorbic acid, attenuated anxiety-related behaviors and improved the body weight in asthmatic mice.

    Conclusion

    The current study suggested that NaHS improves anxiety-related behaviors in OVA-induced asthma same as ascorbic acid, a strong antioxidant. Therefore, NaHS appears to be effective for managing the comorbidity of anxiety with asthma.</div>

    Keywords: Asthma, Anxiety, Hydrogen sulfide, Ascorbic acid
  • Leila Hafazeh, Saeed Changizi, Ashtiyani*, Farideh Jalali Mashayekhi, Tina Rahjo, Houshang Najafi, Saeed Babaei Pages 215-223
    Introduction

    Antioxidant and anti-inflammatory features of Centella asiatica (Centella) hydroalcoholic extract is documented in various diseases. This study aimed to investigate the effect of Centella hydroalcoholic extract on gentamicin (GM) induced nephrotoxicity.

    Methods

    In this study, 28 male Wistar rats were studied in 4 groups namely: control, sham, GM+normal saline (NS) and GM+Centella extract. In order to nephrotoxicity induction, gentamicin (100mg/kg) was injected as ip for seven days and then Centella (100 mg/kg/ip) administered for 7 consecutive days. Finally, the blood samples were collected from heart in order to measure the plasma creatinine (Cr) and urea nitrogen levels. Oxidative stress indices were also measured through assessing the malondialdehyde (MDA) and ferric reduction antioxidant power (FRAP) levels in right kidney. Moreover, histological damages were assessed through studying hematoxylin-eosin stained left kidney sections.

    Results

    There was a significant increase in Cr, urea nitrogen and MDA levels, as well as renal tissue damages, while FRAP level reduced in the group received GM+NS compared to the sham one. Treatment with Centella resulted in a significant decrease in plasma Cr, urea nitrogen, MDA and tissue damages in the GM+Centella extract group compared to the GM+NS group. Moreover, FRAP level increased significantly in the GM+Centella group compared to the GM+NS group.

    Conclusion

    Treatment with Centella extract is effective for ameliorating the kidney damages in gentamicin-induced nephrotoxicity in rats.</div>

    Keywords: Centella asiatica, Gentamicin, Nephrotoxicity, Oxidative stress
  • Alexandre Kormanovski, Maria Del Carmen Castillo Hernández*, Gustavo Guevara, Balcázar, Teresa Pérez, Eleazar Lara Padilla Pages 224-234
    Introduction

    Nitric oxide (NO) is an important regulator involved in functional adaptation in all tissues to exercise, as shown in recent studies. The aim of this short-term study was to evaluate the hypothesis that the important factor of higher performance of trained females during exhaustive exercise can be the interaction between physiological effect of nitric oxide and oxidant/antioxidant response.

    Methods

    Males and females of trained mice were divided into three groups: basal, fasting and prolonged exercise. Parameters of oxidant/antioxidant state, including nitric oxide and glutathione were measured in blood, muscle, liver, heart, kidney, brain, small intestine, adipose tissue and thoracic aorta. Females in this animal model had better performance than males during exhaustive exercise.

    Results

    Females showed greater basal levels of nitric oxide, total antioxidant status and glutathione peroxidase in most tissues evaluated. Compared to fasting levels, the net effects of prolonged exercise included lipoperoxidation in liver, brain and kidney, and nitrosative stress in liver, muscle and heart only in males. The decrement of glutathione without significant changes in its grade of oxidation was observed in liver, intestine and adipose tissue only in females, confirmed possible redistribution of reduced glutathione during prolonged exercise.

    Conclusion

    It is possible that the gender difference that existed in the performance of the animals during exhaustive exercise was determined by NO modulation of the oxidant/antioxidant response in tissues, and particularly of the redistribution of glutathione from the liver to other tissues. NO- induced vasodilatation can be beneficial for ischemic tissues during prolonged or exhaustive exercise.</div>

    Keywords: Gender difference, Oxidative stress, Nitric oxide, Antioxidant, Mice