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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: oxidative stress,Apoptosis,PC12,High glucose toxicity,Renin-angiotensin system
- چکیده:
- چکیده انگلیسی: Objective(s): Hyperglycemia, oxidative stress and apoptosis have key roles in pathogenesis of diabetic neuropathy. There are local renin-angiotensin systems (RASs) in different tissues such as neural tissue. Local RASs are involved in physiological and pathophysiological processes such as inflammation, proliferation and apoptosis. This study aimed to investigate the role of local renin-angiotensin system on high glucose-induced cell toxicity, apoptosis and reactive oxygen species (ROS) production in PC12 cells, as a cell model of diabetic neuropathy.
Materials and Methods: PC12 cells were exposed to a high glucose concentration (27 mg/ml), captopril (ACE inhibitor), telmisartan and losartan (AT1 antagonists), and also PD123319 (AT2 antagonist) were administered before and after induction of high glucose toxicity. Then cell viability was assessed by MTT assay and apoptotic cells and intracellular ROS production were detected by annexin V-propidium iodide and DCFDA, respectively, using flow cytometry.
Results: High glucose concentration decreased cell viability, and increased apoptotic cells. Intracellular ROS production was also increased. In PC12 cells pretreatment and treatment by the drugs showed a significant improvement in cell viability and reduced apoptosis in captopril, telmisartan and PD123319 but only captopril and telmisartan were able to reduce ROS production. Losrtan significantly lowered ROS but didn’t show any improvements in cell viability and apoptotic cells.
Conclusion: The results of the present study showed that RAS inhibitors reduced cell toxicity and apoptosis and ROS production was induced by high glucose. It may be suggested that local RAS has a role in high glucose toxicity.- انتشار مقاله: 05-06-1393
- نویسندگان: Kaveh Shahveisi,Seyed Hadi Mousavi,Mahmoud Hosseini,Abolfazl Khajavi Rad,Seyed Amir Jalali,Ziba Rajaei,Hamid Reza Sadeghnia,Mousa-Al-Reza Hadjzadeh
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: oxidative stress,Crocus sativus,Safranal,Hippocampus,Neurodegenerative disorders,Quinolinic acid
- چکیده:
- چکیده انگلیسی: Objective(s): Quinolinic acid (QA)-mediated excitotoxicity has been widely used as a model for studying neurodegenerative disorders. Recent studies suggested that saffron (Crocus sativus) or its active metabolite, i.e. safranal, exerts pharmacological actions on central nervous system including anxiolytic, anticonvulsant, and neuroprotective properties. The present study aimed to investigate the effect safranal pretreatment on QA-induced oxidative damage in rat hippocampus.
Materials and Methods: Under anesthesia, a guide cannula was stereotaxically inserted into left ventral hippocampus of rats. The rats were then given either saline or safranal (72.75, 145.5, and 291 mg/kg, IP) 30 min before administration of QA (300 nmol, intrahippocampal injection). The markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, as an index of lipid preoxidation), total sulfhydryl groups, antioxidant capacity of hippocampus (using FRAP assay), and oxidative DNA damage (%tail DNA, using comet assay) were measured in hippocampus.
Results: The QA induced a significant increase in TBARS levels and %tail DNA and remarkable decrease in antioxidant power (FRAP value) and total sulfhydryl content of hippocampus, in comparison with control animals. Systemic administration of safranal (291 mg/kg, IP), effectively and dose-dependently decreased the QA-induced lipid peroxidation (P<0.001) and oxidative DNA damage (P<0.001). Safranal also prevented the decrease of hippocampal thiol redox and antioxidant status (P<0.001) produced by QA.
Conclusion: Safranal have protective effects on different markers of oxidative damage in hippocampal tissue following QA administration. Our findings might raise a possibility of potential therapeutic application of safranal for preventing and treating neurodegenerative disorders such as Alzheimer’s disease.- انتشار مقاله: 25-11-1391
- نویسندگان: Hamid Reza Sadeghnia,Mina Kamkar,Elham Assadpour,Mohammad Taher Boroushaki,Ahmad Ghorbani
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Salvia leriifolia,Nuruozak, Lamiaceae, Herbal medicine
- چکیده:
- چکیده انگلیسی: Salvia leriifolia Benth. (vernacular names such as Nuruozak and Jobleh) is a perennial herbaceous plant that grows exclusively in south and tropical regions of Khorasan and Semnan provinces, I. R. Iran. Unlike other species of Salvia genus, the chemical constituents of S. leriifolia are not well recognized. The stem oil of the plant consisted mainly both monoterpenes and sesquiterpenes, while in leaf and flower oils monoterpenes predominated over sesquiterpenes. In recent years, the different properties of this plant such as the attenuation of morphine dependence, hypoglycemic, antinociceptive and antiinflammatory, antioxidant, antiischemia, anticonvulsant, antiulcer effects, antibacterial activities and antimutagenic effects were evaluated. These effects introduce this plant for more toxicological and clinical trials evaluations as a herbal medicine.
- انتشار مقاله: 07-07-1394
- نویسندگان: Hossein Hosseinzadeh,Hamid Reza Sadeghnia,Mohsen Imenshahidi,Bibi Sedigheh Fazly Bazzaz
- مشاهده
- جایگاه : پژوهشی
- مجله: Avicenna Journal of Phytomedicine
- نوع مقاله: Journal Article
- کلمات کلیدی: oxidative stress,Seizures,Coriandrum sativum,Pentylenetetrazole,Frakshens
- چکیده:
- چکیده انگلیسی: Objective: In the present work, the effects of different fractions of Coriandrum sativum (C. sativum), on pentylenetetrazole (PTZ)-induced seizures and brain tissues oxidative damage were investigated in rats.
Materials and Methods: The rats were divided into the following groups: (1) vehicle, (2) PTZ (90 mg/kg), (3) water fraction (WF) of C. sativum (25 and 100 mg/kg), (4) n-butanol fraction (NBF) of C. sativum (25 and 100 mg/kg), and (5) ethyl acetate fraction (EAF) of C. sativum (25 and 100 mg/kg).
Results: The first generalized tonic-clonic seizures (GTCS) latency in groups treated with 100 mg /kg of WF or EAF was significantly higher than that of PTZ group (p< 0.01). In contrast to WF, the EAF and NBF were not effective in increasing the first minimal clonic seizure (MCS) latency. Malondialdehyde (MDA) levels in both cortical and hippocampal tissues of PTZ group were significantly higher than those of control animals (p< 0.001). Pretreatment with WF, NBF, or EAF resulted in a significant reduction in the MDA levels of hippocampi (pConclusion: The present study showed that different fractions of C. sativum possess antioxidant activity in the brain and WF and EAF of this plant have anticonvulsant effects.- انتشار مقاله: 17-01-1394
- نویسندگان: Akbar Anaeigoudari,Mahmoud Hosseini,Reza Karami,Farzaneh Vafaee,Toktam Mohammadpour,Ahmad Ghorbani,Hamid Reza Sadeghnia
- مشاهده
- جایگاه : پژوهشی
- مجله: Avicenna Journal of Phytomedicine
- نوع مقاله: Journal Article
- کلمات کلیدی: Curcumin,PC12,Thymoquinone,Linalool,Rutin,Safranal
- چکیده:
- چکیده انگلیسی: Objective: Several phytochemical agents have been known to exhibit a neuroprotective effect. Among them, curcumin, linalool, rutin, safranal, and thymoquinonewere widely investigated and neuroprotective activity of each of them was shown by several studies. This work was planned to investigate whether different combinations of them could induce better neuroprotective effect against glucose/serum deprivation (GSD)-induced cytotoxicity.
Materials and Methods: PC12 cells were cultivated for 8 h in GSD condition in both the absence and presence of curcumin, linalool, rutin, safranal, thymoquinone, or combinations of them. At the end of the experiment, the cell viability was determined using MTT assay.
Results: The cells cultured in GSD condition showed a significant decrease in viability (28±1%) as compared with those cultured in standard condition (100±2%). In the presence of curcumin (10 µg/ml), linalool (16 µg/ml), rutin (200 µg/ml), safranal (50 µg/ml), and thymoquinone (1 µg/ml), the cell viability increased to 69±3.4% (p<0.001), 44±1.4% (p<0.01), 64±0.5% (p<0.001), 49±2% (p<0.001), and 70±3.2% (p<0.001), respectively. When different combinations of the agents were tested, the best cytoprotective activity was obtained from safranal + curcumin + thymoquinone (97±5%, pvs. untreated cells).
Conclusions: The present study demonstrated that a combination of safranal + curcumin + thymoquinone can block GSD-induced cell death and has the potential to be considered for management of cerebral ischemia and neurodegenerative diseases.- انتشار مقاله: 05-11-1391
- نویسندگان: Bagher Alinejad,Ahmad Ghorbani,Hamid Reza Sadeghnia
- مشاهده
- جایگاه : پژوهشی
- مجله: Avicenna Journal of Phytomedicine
- نوع مقاله: Journal Article
- کلمات کلیدی: Nigella sativa,DNA damage,Serum/glucose deprivation,PC12 cells,Thymoquinone
- چکیده:
- چکیده انگلیسی: Objective: The discovery and development of natural products with potent antioxidant properties has been one of the most interesting and promising approaches in the search for treatment of CNS injuries. The most significant consequence of the oxidative stress is thought to be the DNA modifications, which can become permanent via the formation of mutations and other types of genomic instability resulting cellular dysfunction. Serum/glucose deprivation (SGD) has served as an excellent in vitro model for the understanding of the molecular mechanisms of neuronal damage during ischemia and for the development of neuroprotective drugs against ischemia-induced brain injury. Nigella sativa (N. sativa) seeds and thymoquinone (TQ), its most abundant constituent, have been shown to possess anti-inflammatory, antioxidant, chemopreventive and anti-neoplastic effects both in vitro and in vivo. Therefore, in this study we investigated genoprotective effects of N. sativa and TQ on DNA damage of PC12 cells under SGD condition.
Materials and Methods: PC12 cells were cultured in DMEM medium containing 10% (v/v) fetal bovine serum, 100 units/ml penicillin, and 100 µg/ml streptomycin. Initially cells were pretreated with different concentrations of N. sativa extract (NSE), (10, 50, 250 µg/ml) and TQ (1, 5, 10 µg/ml) for 6 h and then deprived of serum/glucose (SGD) for 18 h. The alkaline comet assay was used to evaluate the effect of these compounds on DNA damage following ischemic insult. The amount of DNA in the comet tail (% tail DNA) was measured as an indicator of DNA damage.
Results: A significant increase in the % tail DNA was seen in nuclei of cells following SGD induced DNA damage (p<0.001). In the control groups, no significant difference was found in the % tail DNA between NSE- or TQ-pretreated and vehicle-pretreated PC12 cells (p>0.05). NSE and TQ pretreatment resulted in a significant decrease in DNA damage following ischemic insult (p<0.001). This suppression of DNA damage by NSE and TQ was found to be dose-dependent.
Conclusion: These data indicate that NSE and TQ have a genoprotective property, as revealed by the comet assay, under SGD condition in PC12 cells.- انتشار مقاله: 06-06-1390
- نویسندگان: Beheshteh Babazadeh,Hamid Reza Sadeghnia,Elham Safarpour Kapurchal,Heydar Parsaee,Sima Nasri,Zahra Tayarani-Najaran
- مشاهده
- جایگاه : پژوهشی
- مجله: Avicenna Journal of Phytomedicine
- نوع مقاله: Journal Article
- کلمات کلیدی: Neuroprotective,Coriandrum sativum,Glucose/serum deprivation,PC12
- چکیده:
- چکیده انگلیسی: Objective: This study was planned to investigate whetherCoriandrum sativum (C. sativum) is capable of protecting neurons against glucose/serum deprivation (GSD)-induced cytotoxicity. Material and Methods: The PC12 cells were cultivated for 24 h in standard media (high-glucose DMEM containing Fetal Bovine Serum) or for 6 h in GSD condition (glucose-free DMEM, without serum) in the absence or presence of various concentrations (0.1, 0.2, 0.4, 0.8 and 1.6 mg/ml) of hydro-alcoholic extract (HAE), water fraction (WF), ethyl acetate fraction (EAF) or N-butanol fraction (NBF) of this plant. At the end of the treatments, the cell viability was determined using MTT assay. Results: With the exception of 1.6 mg/ml of EAF or NBF which decreased cell survival, the HAE and its fractions exhibited no cytotoxicity under standard condition. Exposure of the cells to GSD condition showed 52% decrease in the viability. In this condition, the HAE, EAF and NBF not only failed to increase cell viability but also increased the toxicity. On the other hand, WF at 0.4, 0.8 and 1.6 mg/ml significantly attenuated the GSD-induced decrease in cell survival. Conclusion: The present study revealed that C. sativum bearing water-soluble compound(s) could induce neuroprotective activity. Also, we showed that some constituents from this plant may serve as cytotoxic agents under stressful conditions like hypoglycemia and serum limitation.
- انتشار مقاله: 01-02-1390
- نویسندگان: Ahmad Ghorbani,Hassan Rakhshandeh,Elham Asadpour,Hamid Reza Sadeghnia
- مشاهده
- جایگاه : پژوهشی
- مجله: Avicenna Journal of Phytomedicine
- نوع مقاله: Journal Article
- کلمات کلیدی: Seizure,Berberine,Berberis vulgaris,Pentylenetetrazol,Diazepam
- چکیده:
- چکیده انگلیسی: Objective: Antiepileptic drugs (AEDs) that are usually used for treatment of epilepsy have substantial side effects and about 30% of patients continue to have seizures with current AEDs therapy. Some herbs which traditionally used in the management of seizures of many rural areas of the developing countries have shown anticonvulsant activity in modern pharmacological bioassays. The aim of the present study was to evaluate the effects of berberine, an alkaloid from Berberis vulgaris, on seizures induced by pentylenetetrazol (PTZ) in rats. Material and Methods: Rats (n=6-7) received berberine (100, 200 and 400 mg/kg, i.p.), diazepam (4mg/kg, i.p. as positive control), and vehicle (saline) and then 30 min later PTZ (110mg/kg, i.p.) were injected . Behavioral responses of the animals to PTZ administration were evaluated using these criteria: latency to first minimal clonic seizure (MCS), incidence of MCS, latency to the first generalized tonic–clonic seizures (GTCS), incidence of GTCS, protection against GTCS and mortality. Results: Intraperitoneal administration of lower doses of berberine (100 and 200 mg/kg) had no significant effects on minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) latencies, while injection of 400 mg/kg caused significant increase in both MCS and GTCS latencies (p<0.05). In this study diazepam, (4 mg/kg) 30 min prior to PTZ, significantly increased GTCS latency. Berberine at tested doses had no protection against mortality following PTZ administration. Conclusion: It can be concluded that berberine at high doses could be a useful protective agent in PTZ-induced epileptic seizures in rats.
- انتشار مقاله: 02-11-1391
- نویسندگان: Hamid Reza Sadeghnia,Sahar Darbarpanah,Seyed Mahmood Hosseini
- مشاهده