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عضویت
فهرست مطالب نویسنده:

mohammad soukhtanloo

  • Malihe Mehrparvar Tajoddini, Elaheh Gheybi, Mehdi Rostami, Seyed Hadi Mousavi, Seyed Isaac Hashemy, Roghayeh Rashidi, Mohammad Soukhtanloo *
    Objective

    Destruction of dopaminergic neurons causes diseases. Various compounds with neuroprotective and antioxidant properties have been identified, including Hesperidin (HES) and Auraptene (AUR). We aimed in this study to evaluate the in vitro protective effects of these compounds in SH-SY5Y neuroblastoma cell line against the induced neurotoxicity of 6-hydroxydopamine (6-OHDA).

    Materials and Methods

    The MTT test to assess cell viability was used. Flow cytometry was conducted for the cell cycle analysis using propidium iodide (PI) stain. The intracellular production of reactive oxygen species (ROS) was assessed using 2, 7′-dichlorofluorescein diacetate (DCFDA) probe and fluorimetry.

    Results

    Following 6-OHDA treatment, cell viability decreased, and G2/M arrest and ROS levels increased. Our intervention demonstrated that only HES has neuroprotective effects against 6-OHDA-induced toxicity.

    Conclusion

    HES protects SH-SY5Y cells against 6-OHDA-induced neural damage via inhibiting G2/M arrest, reducing the amount of ROS, and increasing cell viability. However, the different effects and more precise mechanisms are still unknown, and requires new research on animal and human models.

    Keywords: Hesperidin Auraptene ROS 6, Hydroxydopamine SH, SY5Y Cells
  • Seyed Hadi Mousavi, Mohammad Jalili-Nik, Mohammad Soukhtanloo, Arash Soltani, Farzaneh Abbasinezhad-Moud, Hamid Mollazadeh, Farzaneh Shakeri, Bahram Bibak, Amirhossein Sahebkar *, Amir R. Afshari
    Objective
    The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells.
    Materials and Methods
    To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot analysis were conducted.
    Results
    At sublethal concentrations of 12.5 and 25 µg/ml, auraptene exhibited a significant reduction in cell invasion and migration of U87 cells, as assessed using scratch wound healing and Transwell tests, respectively. The qRT-PCR and zymography experiments demonstrated a significant decrease in both mRNA expression and activities of MMP-2 and MMP-9 following auraptene treatment. Western blot analysis also showed that the total protein level of MMP-2 as well as phosphorylation of crucial metastasis-related proteins, including p-JNK and p-mTOR, decreased in auraptene-treated cells. The molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-2/-9, the ATP binding site of mTOR and JNK1/2/3.
    Conclusion
    Auraptene effectively inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities. Auraptene might serve as a potential anti-metastatic agent against malignant GBM.
    Keywords: Auraptene, Glioblastoma multiforme, Migration, Invasion, Metastasis
  • Farzaneh Abbasinezhad-Moud, Emad Azimi, Mehdi Rostami, Elaheh Gheybi, Mohammad Soukhtanloo *
    Background and objectives

    In some neurodegenerative diseases, an aberrant accumulation of quinolinic acid is frequently associated with the loss of nerve cells and a condition known as neuritis. This is typically caused by an excessive production of free radicals. Studies have shown that hesperidin has potent antioxidant effects, but nothing is known about how it protects against the neurotoxicity induced by quinolinic acid. This study aimed to evaluate the protective effect of hesperidin against quinolinic acid-induced neurotoxicity in the SH-SY5Y neuroblastoma cell line.

    Methods

    The MTT test was used to determine cell viability and protective dosage of hesperidin. Flow cytometry using propidium iodide (PI) staining was used to determine the cell cycle of SHSY5Y cells after exposure to quinolinic acid in combination with hesperidin. Reactive oxygen species (ROS) levels within cells were also measured using 2', 7'-dichlorodihydrofluorescein diacetate (H2DCFDA) in the mentioned groups.

    Results

    Our results demonstrated that hesperidin had a protective effect against quinolinic acid-induced toxicity at nontoxic concentrations (p<0.001). Moreover, the percentage of apoptotic cells in the sub-G1 phase increased significantly (p<0.001). Hesperidin pretreatment significantly decreased sub-G1 arrest that was induced by quinolinic acid (p<0.001). Hesperidin significantly decreased ROS levels generated by quinolinic acid (p<0.001).

    Conclusion

    The current study showed that hesperidin exerts its effect through antioxidant activity and can be considered a promising neuroprotectant agent against quinolinic acid-induced neurotoxicity in neurodegenerative disorders; however, more research is necessary in this area for the treatment.

    Keywords: hesperidin, oxidative stress, quinolinic acid, SH-SY5Y neuroblastoma cell line
  • Roghayeh Rashidi, Ala Montazeri, Mohammad Soukhtanloo, Shirin Ghasemian, MohammadSadegh Amiri, Maede Hasanpour, Elham Einafshar, Ahmad Ghorbani *
    Objective (s)

    Experimental studies reported that some plants in the genus of Moraea (Iridaceae family) show anticancer potential. This study aimed to evaluate the effects of Moraea sisyrinchium on U87 glioblastoma multiforme and HepG2 liver cancer cells.

    Materials and Methods

    The cells were incubated for 24 hr with hydroalcoholic extract of the stem, flower, and bulb of M. sisyrinchium. Then, the cell proliferation (MTT) assay, cell cycle analysis (propidium iodide staining), cell migration test (scratch), Western blotting (Bax and Bcl-2 expression), and gelatin zymography (for matrix metalloproteinases, MMPs) were performed. Oxidative stress was evaluated by determining the levels of reactive oxygen species and lipid peroxidation. Angiogenesis was evaluated on chick embryo chorioallantoic membrane.

    Results

    The extracts of the flower, stem, and bulb significantly decreased the proliferation of HepG2 and U87 cells. This effect was more for U87 than HepG2 and for the bulb and stem than the flower. In U87 cells, the bulb extract increased oxidative stress, cell cycle arrest, and the Bax/Bcl-2 ratio. Also, this extract suppressed the migration ability of HepG2 and U87 cells, which was associated with the inhibition of MMP2 activity. In addition, it significantly reduced the number and diameter of vessels in the chorioallantoic membrane. Liquid chromatography-mass spectrometry revealed the presence of xanthones (bellidifolin and mangiferin), flavonoids (quercetin and luteolin), isoflavones (iridin and tectorigenin), and phytosterols (e.g., stigmasterol) in the bulb.

    Conclusion

    M. sisyrinchium bulb decreased the proliferation and survival of cancer cells by inducing oxidative stress. It also reduced the migration ability of the cells and inhibited angiogenesis.

    Keywords: Glioblastoma, Hepatocellular carcinoma, HepG2, Iridaceae, U87
  • Abolfazl Bemidinezhad, Farshad Mirzavi, Hamid Gholamhosseinian, Fatemeh Gheybi, Mohammad Soukhtanloo *
    Objective (s)

    Surgery and radiation therapy are the most important known treatments for glioblastoma, which is known as the most malignant tumor of the central nervous system. Numerous studies have proven the effect of different gold nanoparticles in improving radiation sensitivity. But there is still a need for nanoparticles with suitable size and higher sensitivity. Hence, the present study aimed to prepare optimized glucose-coated gold nanoparticles (Glu-GNPs) for improving radiosensitivity against U87 glioblastoma cells.

    Materials and Methods

    Firstly, Glu-GNPs were synthesized and then their physiochemical characterizations were assessed using dynamic light scattering (DLS). The cytotoxicity of Glu-GNPs was evaluated by MTT assay in U87 and NIH-3T3 cell lines. Additionally, the colony formation assay, which is known as the gold standard test, was used to evaluate the radiosensitivity effect of Glu-GNPs on U87 cells.

    Results

    The characterization results showed that Glu-GNPs had a size of 50.3 nm and negative zeta potential of -13.8 mV. Cytotoxicity results revealed that treatment with Glu-GNPs significantly inhibited the proliferation of U87 cells. We found that Glu-GNPs at a concentration of 10 μg/ml were not-toxic for U87 cells. Moreover, the colony formation assay results showed that Glu-GNPs significantly increased the effect of radiation and caused U87 cancer cell death at a non-toxic concentration of 10 μg/ml.

    Conclusion

    Taken together, the Glu-GNPs, with a size of 50.3 nm, increased radiosensitivity and caused cell death at a concentration of 10 µg/ml in U87 glioblastoma cells and deserve further in vitro and in vivo investigations.

    Keywords: β-D-glucose, Gold Nanoparticle, Radiosensitizer, U87 glioblastoma cell
  • Mahtab Norouzi, Hossein Saghi, Reza Mohebbati, Farshad Mirzavi, AmirReza Afshari, Mohammad Soukhtanloo *
    Objective

    Type 2 diabetes mellitus (T2DM) is a condition characterized by insufficient insulin production or insulin resistance. The insulin-degrading enzyme (IDE) is responsible for degrading insulin and is a potential drug target for T2DM treatment. Numerous activities have been proposed for plant extracts, but research on the effects of plant extracts on IDE expression and activity is riddled with drawbacks.

    Materials and Methods

    We investigated the effect of Phaseolus vulgaris, Allium cepa, Portulaca oleracea, Cinnamomum verum, and Citrullus colocynthis extracts on the expression and activity of IDE in the Caco-2 cell line.

    Results

    Findings of RT-PCR showed that IDE gene expression was reduced following treatment with P. vulgaris, C. colocynthis, and C. verum extracts. The results of IDE activity with fluorogenic peptide substrate V also indicated that P. vulgaris, C. colocynthis, and P. oleracea extracts reduced IDE activity in a significant and dose-dependent manner.

    Conclusion

    The hydroalcoholic extracts studied, except for A. cepa, can prevent insulin degradation by reducing the expression and activity of the IDE enzyme. This new insight into the effects of herbal medicines on IDE activity can help future studies.

    Keywords: Insulin-degrading enzyme, Phaseolus vulgaris, Allium cepa, Portulaca oleracea, Cinnamomum verum, Citrullus colocynthis
  • Hossein Salmani, Zahra Hakimi, Zohre Arab, Narges Marefati, MohammadReza Mahdinezhad, Abolfazl Rezaeigolestan, Farimah Beheshti, Mohammad Soukhtanloo, Amirali Mahnia, Mahmoud Hosseini *
    Objective

    The beneficial effect of carvacrol on neuroinflammation, oxidative damage of brain tissue, and depressive- and anxiety-like behaviors after lipopolysaccharide (LPS) administration were evaluated in rats.

    Materials and Methods

    Vehicle (1% Tween 80), 1 mg/kg of LPS, and carvacrol (25, 50, or 100 mg/kg administered prior to LPS) were injected and behavioral and biochemical tests were done.

    Results

    The results of forced swim test revealed that carvacrol attenuated immobility time and increased activity and climbing times (p<0.05 to p<0.001). The results of elevated plus maze also revealed that treatment by carvacrol prolonged the open arms time and entries and decreased the time and entries in the closed arms (p<0.05 to p<0.01). Carvacrol enhanced crossing, time, and traveled distance in the central segment of the open field and increased total crossing and distance while attenuating the peripheral zone time (p<0.05 to p<0.001). All doses of carvacrol attenuated TNF- α (tumor necrosis factor α) and NO (nitric oxide) in the brain (p<0.01 to p<0.001). The 50 and the 100 mg/kg doses of carvacrol decreased malondialdehyde (p<0.001 for both), and the 100 mg/kg dose of carvacrol increased the content of the thiol (p<0.001).

    Conclusion

    In conclusion, carvacrol improved the behavioral consequences of LPS challenge and attenuated neuroinflammation and brain tissue oxidative stress in rats.

    Keywords: Inflammation, Anxiety, Depression, Carvacrol, Oxidative stress
  • Soleyman Bafadam, Maryam Mahmoudabady *, Saeed Niazmand, Seyed Abdolrahim Rezaee, Mohammad Soukhtanloo
    Introduction

    Inadequate control of diabetes mellitus (DM) leads to considerable cardiovascular implications like diabetic cardiomyopathy (DCM). Cardiomyocyte apoptosis is one of the main mechanisms of DCM pathogenesis associated with hyperglycemia, oxidative stress, inflammation, hyperlipidemia and several other factors. Trigonella foenum-graecum (Fenugreek) has been long used as a traditional medicine and has many therapeutic effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory and anti-oxidant properties. The current study aimed to investigate cardioprotective effects of fenugreek seed on diabetic rats.

    Methods

    Diabetes was induced in forty-two male rats by injection of streptozotocin (STZ) (60 mg/ kg). Diabetic animals were treated with three different doses of fenugreek seed extract (50, 100 and 200 mg/kg) or metformin (300 mg/kg) for six weeks by gavage. Nondiabetic rats served as controls. Glucose, cholesterol, and triglycerides levels were measured in the blood samples, and oxidative stress markers as well as gene expression of ICAM1, Bax and Bcl2 were assessed in the cardiac tissues of the experimental groups.

    Results

    Diabetic rats exhibited increased serum glucose, cholesterol and triglycerides levels, elevated markers of oxidative stress thiobarbituric acid–reacting substances (TBARS) levels , total thiol groups (SH), catalase (CAT) and superoxide dismutase (SOD) activity, and enhanced apoptosis cell death (ratio of Bax/Bcl2). Fenugreek seed extract considerably improved metabolism abnormalities, attenuated oxidative stress and diminished apoptosis index.

    Conclusion

    Our study suggests that fenugreek seed may protect the cardiac structure in STZ-induced diabetic rats by attenuating oxidative stress and apoptosis.

    Keywords: Diabetes, Fenugreek Seed, Cardiomyopathy, Oxidative Stress, Apoptosis
  • Mohammad Reza Mahdinezhad, Sara Hooshmand, Mohammad Soukhtanloo, Shirin Taraz Jamshidi, Sajad Ehtiati, Ahmad Ghorbani*
    Background and purpose

    Previous studies have shown the antioxidant, anti-inflammatory, immunomodulatory, and hypolipidemic activities of Iris germanica. The aim of the present study was to evaluate the protective effects of hydroalcoholic extract of Iris germanica rhizomes on streptozotocin-induced diabetic rats.

    Experimental approach

    Twenty-four male Wistar rats were randomly assigned into four groups including a normal control group, diabetic control group, diabetic groups treated for 4 weeks with 100 and 200 mg/kg/day of the Iris germanica extract (IGE).

    Findings/Results

    Induction of diabetes significantly decreased the body weight gain and considerably increased the serum levels of glucose, triglyceride, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Diabetes also diminished the antioxidant capacity of the liver (decrease of thiol groups) and significantly degenerated pancreatic islands. The IGE at both doses of 100 and 200 mg/kg significantly reduced the levels of glucose, triglyceride, AST, ALT, and ALP. Moreover, IGE increased the total antioxidant capacity of the liver and ameliorated pancreatic island morphology. The extract had no significant effect on body weight and BUN level.

    Conclusion and implication

    These findings suggest that Iris germanica rhizomes inhibits the progression of hyperglycemia and hypertriglyceridemia and has protective effects against diabetes-induced injury of the liver and pancreas. Therefore, this plant has the potential to be used as a natural product for controlling diabetes.

    Keywords: Diabetes, Glucose, Iris germanica, Lipids, Oxidative stress
  • Javad Sargolzaei, Hamid Sadeghian, Sanaz Golahmadi, Mohammad Soukhtanloo *
    Neuroblastoma is one of the nervous system cancers, which approximately consists of 9% of childhood cancers. In this study, we evaluated the toxic effects of prenyl hydroxy coumarin derivatives on apoptosis of the neuroblastoma cell line N2A. N2a cells were cultured in DMEM medium, then the effects of different concentrations (0.75–200 μg/mL) of prenyl hydroxy coumarin derivatives during 24, 48, and 72 h were studied. Cell viability was quantified by MTT assay; apoptotic cells were determined using PI staining of DNA fragmentation by Flow cytometry (sub-G1 peak). The toxic effect of 3- farnesyl oxi coumarin in the N2A cell starts at 6.25 μg/ml and increases relatively depending on rising in concentration and time. The toxicity and apoptosis in 3- farnesyl and 6- farnesyl oxi coumarin is more than 3- Geranyl and 6-Geranyl oxi coumarin. Prenyl hydroxy coumarin induces peak sub-G1in flow cytometry compared to the control group, indicating prenyl hydroxy coumarin-induced toxicity, which is involved in apoptotic cell death. Different concentration of hydroxy coumarin derivatives (0.75-200) µg/mL in lymphocytes, did not induce any anti-proliferative effect in 24 h. In conclusion, prenyl hydroxy coumarin derivatives induce apoptotic effects in the N2A cell line. Thus prenyl hydroxy coumarin derivatives sound to be chemotherapeutic agents for the neuroblastoma cancer cells.
    Keywords: N2A cell line, Cancer, Apoptosis, cytotoxic, normal cells, Prenyl hydroxy coumarin derivatives
  • Azar Hosseini, Sahar Sheikh, Mohammad Soukhtanloo, Bizhan MalaekehNikouei, Arezoo Rajabian*
    Introduction

    Cardiovascular disorders (CVD) are a common cause of mortality worldwide. Oxidativestress is thought to be a major factor leading to CVD. Anti‑oxidants such as medicinal plants mayhave a role in the mitigation of vascular problems through free radicals scavenging. In this study, weevaluated the protective effects of Rheum turkestanicum against hydrogen peroxide (H2O2)‑inducedtoxicity in endothelial cells (BAE‑1).

    Methods

    To evaluate the protective effect of R. turkestanicumagainst H2O2 toxicity, four groups comprised of control group (the cells without any treatment),H2O2 group (the cells incubated with H2O2 (200 μM)), and treatment groups (the cells treated withR. turkestanicum (12200 μg/ml) alone or 24h before exposure to H2O2). Quercetin (30.23 μg/ml)was used as a bioactive ingredient of the extract. Then the cell viability, reactive oxygen species,lipid peroxidation, and apoptosis were evaluated.

    Results

    H 2O2 exposure reduced cell viability to13.6 ± 1.6%, enhanced ROS generation to 1445 ± 80.7%, lipid peroxidation (LPO, 290 ± 13% ofcontrol), and apoptotic cells (P < 0.001). In contrast, compared with H2O2 group, R. turkestanicumand quercetin significantly restored the cell viability to 80.3 ± 1.6 and 87.2 ± 2.1%, ROSformation to 186 ± 10 and 129 ± 1%, as well as LPO to 130.7 ± 7.7 and 116 ± 2.5 of control,respectively (P < 0.001). Therefore, the extract reduced H2O2‑induced toxicity in BAE‑1 cells byscavenging of free radicals.

    Conclusion

    Our findings demonstrated that the extract might reducetoxicity of endothelial cells by attenuation of oxidative stress, which can be related to the presenceof active ingredients including quercetin.

    Keywords: Apoptosis, endothelial cells, oxidative stress, quercetin, Rheum turkestanicum
  • Marzieh Mogharrabi, Hamid Reza Rahimi, Shima Hasanzadeh, Mostafa Dastani, Reza Kazemi-Oskuee, Saeed Akhlaghi, Mohammad Soukhtanloo*
    BACKGROUND

    Coronary artery disease (CAD) is the most common type of cardiovascular disease. Increasing the expression and activity of matrix metalloproteinases (MMPs) facilitates vascular remodeling and cardiovascular complications. Curcumin (the active ingredient of turmeric) is a potent natural anti-inflammatory agent, with cardiovascular protective effects. The present study was a clinical trial for investigating the effects of curcumin on activity and gene expression of MMP-2 and MMP-9 in patients with CAD.

    METHODS

    In this study, 70 patients with CAD (with 40%-50% stenosis) were randomly divided into two groups of curcumin (80 mg nanomicelle per day) and placebo. The intervention lasted 3 months. The activity levels of MMP-2 and MMP-9 in serum samples of patients were measured using gelatin zymography assay before and after the intervention. MMP-2 and MMP9 gene expression in peripheral blood mononuclear cells (PBMCs) was also analyzed using realtime polymerase chain reaction (PCR). Statistical significance was set at P < 0.0500.

    RESULTS

    After 3 months of medication, the expression of MMP-9 produced by PBMCs significantly decreased in the curcumin group (0.811 ± 0.25) in comparison with the placebo group (2.23 ± 0.94) (P < 0.0001). Furthermore, the zymographic analysis showed that the administration of curcumin significantly inhibited the activity levels of MMP-2 (12469.7 ± 5308.64 pixels) and MMP-9 (14007.2 ± 5371.67 pixels) in comparison with that in patients receiving placebo (MMP-2: 17613.8 ± 5250.68 pixels; MMP-9: 20010.1 ± 3259.37 pixels) (P < 0.0500).

    CONCLUSION

    Our results show that curcumin can significantly reduce the expression and activity of MMP-2 and MMP-9. Because of the anti-inflammatory effects of curcumin, this compound can be considered as a new strategy for the prevention of cardiovascular events.

    Keywords: Curcumin, Matrix Metalloproteinases, Coronary Artery Disease
  • Mitra Hosseinpour, Kazem Mashayekhi, Reza Falak, Sirous Jamalzehi, Saeed Mohammadian Haftcheshmeh, MohamadJavad Mousavi, Anvar Soleimani, Khadijeh Koushki, Mojtaba Sankian*, Mohammad Soukhtanloo

    Allergy to non-specific lipidtransfer protein (nsLTP), the major allergen of grape (Vit v1), is considered as one of the most common fruit allergies in Iran. Therefore, a specific monoclonal antibody (mAb) can be used for the characterization and assessment of. Accordingly, this study aimed to generate and characterize a mAb against Vit v1 with a diagnostic purpose. To this end, Vit v1 allergen (9 kDa) was extracted using a modified Bjorksten extraction method. Natural Vit v1-immunized mouse splenocytes were fused with SP2/0Ag-14 myeloma cells for generating hybridoma cells. Specific antibody-secreting Hybridoma cells were selected using ELISA. Finally, anti-Vit v1 mAb was characterized by western blotting, ELISA, and isotyping methods. In the current study, a 9 kDa (Vit v1) protein was attained fromcrude and fresh juice of grape extracts and the isotype of desired anti-Vit v1 mAb was determined as IgM with k light chain. In addition, The ELISA results demonstrated that anti-Vit v1 mAb was specified against natural Vit v1 in the grape cultivar and related LTP allergens, such as Pla or 3 (p<0.0001). In the present study, a specific mAb was produced for detecting the LTP allergen. This mAb with a confirmed specificity can be utilized for evaluating the LTP allergens and their allergenicity in different grape cultivars.

    Keywords: Allergy, Grape, Lipid transfer protein, Monoclonal antibody, Non-specific lipidtransfer protein
  • Maryam Paseban, Saeed Niazmand*, Mohammad Soukhtanloo, Naser Tayyebi Meibodi
    Introduction

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered as one of the most administrated groups of medications worldwide. Due to the role of NSAIDs in inducing gastric ulceration, their clinical applications are still challenging. Nigella sativa seed is widely used as herbal medication against gastrointestinal complications. The present experiment was carried out to investigate the impact of N. sativa seed hydro-alcoholic extract on gastric ulcer induced by indomethacin (IND) and to evaluate its possible mechanisms in rat.

    Methods

    This study was performed on 48 male Wistar rats. Acute gastric ulceration was induced by IND (35 mg/kg). N. sativa seed extract (100, 200, 400 mg/kg) and ranitidine (50 mg/kg) were administered orally for five days before induction ulcer. Ulcer index, gastric acid secretion, gastric mucus content, glutathione (GSH), malondialdehyde (MDA), total hexose, gastric juice protein content were determined on the fifth day.

    Results

    The ulcer index in all groups of N. sativa seed was significantly lower than that of the IND group. N sativa seed considerably decreased MDA and protein content, but increased total thiol, total hexose, and mucus content compared to the IND group. N. sativa seed did not affect gastric acid secretion.

    Conclusion

    These findings were indicative of the gastroprotective effect of N. sativa seed against the IND-induced ulcer, suggesting that it can mainly be exerted through the anti-oxidant activity of the extract as well as its role in stimulating gastric mucus secretion and increasing total hexose in the gastric mucosa.

    Keywords: Gastric ulcer, Indomethacin, Nigella sativa, Rat, Oxidative stress
  • Fereshteh Asgharzadeh, Mahmoud Hosseini, Rahimeh Bargi, Mohammad Soukhtanloo, Farimah Beheshti, Zohreh Mohammady, Akbar Anaeigoudari *
    Background

    Frequent seizure is followed by overproduction of free radicals and brain oxidative stress. Renin angiotensin system (RAS) has some effects on central nervous system. We designed this research to challenge the effect of captopril as an angiotensin converting enzyme (ACE) inhibitor against brain oxidative stress in pentylenetetrazole (PTZ) -induced seizures in mice.

    Methods

    The groups were including (1) Control (saline); (2) PTZ (100 mg/kg, i.p.), (3-5) PTZ- captopril (Capto) that received three doses of Capto 10, 50 and 100 mg/kg 30 min before PTZ injection. Latency time in the onset minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) were recorded. The level of malondialdehyde (MDA) and total thiol, as well as superoxide dismutase (SOD) and catalase (CAT) activity in the hippocampus and cortex were measured.

    Results

    All doses of captopril postponed the onset of MCS and GTCS. Accumulation of MDA in the brain tissues of PTZ group was higher than control group, while total thiol content and CAT activity were lower. Pretreatment with captopril (100 mg/kg) diminished MDA concentration compared with PTZ group. Captopril (50 and 100 mg/kg) also increased the level of total thiol groups versus PTZ group. Captopril injection (50 and 100 mg/kg) elevated the activity of SOD and CAT in the brain tissues. In addition captopril administration diminished mortality rate caused by PTZ.

    Conclusion

    Findings demonstrated that convulsions caused by PTZ were followed by oxidative stress status in the brain tissues. Pretreatment with captopril attenuated the effect of PTZ on brain tissue oxidative damage.

    Keywords: Captopril, Pentylenetetrazole, Seizures, Mice, Oxidative Stress
  • Mahdi Jalali, Mohammad Reza Nikravesh, Mohammad Soukhtanloo, Mahmoud Moghaddam *
    Background
    Evidence shows that chemical fertilizers used for agricultural purposes have high levels of nitrate. These agricultural products consumed by livestock are the most important sources of nitrate. Type-IV collagen, found primarily in the base membrane, is significantly vital for the performance of glomerular base membrane in the kidney.
    Objectives
    The present study aimed to investigate the effect of nitrate and vitamin C on the expression of type-IV collagen in rat kidney.
    Methods
    This empirical research was conducted on 49 Wistar rats in Iran from 2017 to 2018. The sample size was determined using Morgan Table Samples were randomly divided into seven groups: (1) no nitrate (control), (2) nitrate at 10 mg/L, (3) nitrate at 45 mg/L, (4) nitrate at 200 mg/L, (5) nitrate (10 mg/L) + vitamin C (20 mg per 100 g of body weight), (6) nitrate (45 mg/L) + vitamin C (similar amount), and (7) nitrate (200 mg/L) + vitamin C (similar amount). After 91 days, the content of type-IV collagen in the kidney tissue was determined using the immunohistochemistry (IHC) protocol. The expression of type-IV collagen gene was detected by real-time polymerase chain reaction (RT-PCR) in all groups.
    Results
    There was no significant difference among the groups of 1-3 (4.55 ± 0.51, 4.7 ± 0.47, 3.6 ± 0.5, P > 0.05) in terms of type-IV collagen. However, the obtained results of group 4 indicated a significant reduction in the content of type-IV collagen (1.25 ± 0.44), compared to the control group (4.55 ± 0.51, P = 0.000). In terms of vitamin C consumption, the groups of 5 (3.45 ± 0.51) and 6 (3.4 ± 0.5) did not differ significantly from the control group (4.55 ± 0.51, P > 0.05). Nonetheless, the severity of response to anti-type-IV collagen antibody significantly increased in group 7 (3.55 ± 0.6) compared to group 4 (1.25 ± 0.44, P < 0.05).
    Conclusions
    The investigated doses of nitrate in drinking water (up to 45 mg/L) had no significant effect on the content of type-IV collagen. On the other hand, the excessive concentrations of nitrate limited the distribution of type-IV collagen and led to potential side effects on the glomerular base membrane. Moreover, vitamin C had no significant effect on 10 and 45 mg/L doses of nitrate. Nevertheless, 200 mg/L dose of nitrate improved the destructive effects of type-IV collagen on the kidney.
    Keywords: Ascorbic Acid, DrinkingWater, Fertilizers, Immunohistochemistry, Kidney, Livestock, Nitrates, Real-Time PolymeraseChain Reaction, Rats
  • Farimah Beheshti, Mahmoud Hosseini *, Milad Hashemzehi, Mohammad Soukhtanloo, Majid Khazaei, Mohammad Naser Shafei
    Objective(s)
    The aim of current study was to evaluate improving effects of pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), on brain-derived neurotrophic factor (BDNF) and cytokines as well as tissue oxidative damage criteria in the hippocampus in a rat model of lipopolysaccharide (LPS) induced memory impairment.
    Materials and Methods
    The rats were classified and treated as follows (10 rats per group): (1) vehicle, (2) vehicle before LPS (1 mg/kg, 120 min before memory tests), (3-5) pioglitazone 10, 20 or 30 mg/kg 30 min before LPS. Finally, the hippocampal tissues were collected for biomedical analyses.
    Results
    In the Morris water maze test, the LPS group, had a longer latency to find the platform while they spent a shorter time in the target quadrant in the probe trial. In the passive avoidance test, the animals of the LPS group had shorter delay times to enter the dark compartment than those of the control group. Treatment with 20 and 30 mg of pioglitazone corrected these parameters. In the hippocampus of LPS group interleukin-6, tumor necrosis factor-α, nitric oxide metabolites, and malondialdehyde were higher while  thiol, BDNF, and IL-10 concentrations and the activities of catalase (CAT) and superoxide dismutase (SOD) were lower than the control group. Treatment by both doses of 20 and 30 mg of pioglitazone corrected the biochemical parameters in the hippocampus.
    Conclusion
    The current findings revealed that pioglitazone protected the rats from learning and memory impairment induced by LPS. The effects were associated with improvement of cytokines, oxidative stress criteria, and BDNF.
    Keywords: Brain-derived neurotrophic- factor, Cytokines learning, Lipopolysaccharide, Memory, Pioglitazone
  • Amir R. Afshari, Mostafa Karimi Roshan, Mohammad Soukhtanloo, Ahmad Ghorbani, Farzad Rahmani, Mohammad Jalili, Nik, Mohammad Mahdi Vahedi, Azar Hoseini, Hamid R. Sadeghnia, Hamid Mollazadeh, Seyed Hadi Mousavi *
    Objective
    Glioblastoma multiforme (GBM) is the deadliest type of primary brain tumors, and the survival of patients is estimated to be only about one year. This study, for the first time, investigated the cytotoxic effects of auraptene on U87 GBM cell line.
    Materials and Methods
    The cellular toxicity was measured by the MTT assay following 24 and 48-hr treatment with different concentrations of auraptene (0-400μg/ml). Apoptosis was evaluated by sub-G1 peak in cell cycle analysis of propidium-iodide- stained nuclei. Moreover, to determine the Bax, Bcl-2, MCP-1, NF-κB, IL-1β, and p53 genes expression, we used real-time polymerase chain reaction (RT-PCR).
    Results
    The results revealed that auraptene reduced the viability of U87 cells concentration- and time-dependently with IC50 values of 108.9 and 79.17μg/ml obtained for 24 and 48-hr treatments, respectively. Also, sub-G1 population was significantly increased following 24 (p real-time RT-PCR showed an up-regulation in Bax, NF-κB, IL-1β, and p53 but a down-regulation in MCP-1 and Bcl-2 genes expression.
    Conclusion
    This study showed that auraptene triggered apoptosis probably through Bax/Bcl-2 regulation, blocked cell cycle progression and inhibited proliferation in U87 GBM cells. Taken together, auraptene can be utilized as an effective natural medicine against GBM, after complementary studies.
    Keywords: Brain tumors, Glioblastoma multiforme, Auraptene, Cytotoxicity, Apoptosis
  • فاطمه رحیمی عنبرکه، راهله برادران، نسیبه قندی، مهدی جلالی*، محمد سوختانلو، محمدرضا نیک روش
    مقدمه
    مونوسدیم گلوتامات به عنوان طعم دهنده و چاشنی غذایی مورد استفاده قرار می گیرد. بعضی از مطالعات اثرات اکسیداتیو استفاده از این ماده را بر روی بافت های مختلف گزارش کردند.
    هدف
    این مطالعه به منظور بررسی اثر مونوسدیم گلوتامات بر آپوپتوز سلول های زایای بیضه و فاکتورهای بیوشیمیایی آن و اثر محافظتی ویتامین C بر روی بیضه انجام شد.
    موارد و روش ها
    در این مطالعه تجربی، تعداد 24 سر رت نر بالغ به طور تصادفی به 4 گروه کنترل، گروه ویتامینC   mg/kg) 150(، گروه تجربی 1  (مونوسدیم گلوتامات gr/kg 3)، گروه تجربی 2 (مونوسدیم گلوتامات gr/kg 3 + ویتامین C  mg/kg150) تقسیم شدند. رت ها به مدت 30 روز گاواژ و سپس قربانی شده و بیضه راست برای انجام آزمایشات بیوشیمیایی GSH و MDA و بیضه چپ برای بررسی های بافت شناسی جدا شد. برای بررسی تعداد سلول های آپوپتوتیک از رنگ آمیزی تانل و جهت آنالیز آماری نیز از تست One way ANOVA استفاده شد.
    نتایج
    در نتایج بدست آمده دیده شد که سلول های آپوپتوتیک در گروه MSG درمقایسه با گروه کنترل افزایش معنی داری داشت (0/001 p=)، اما تعداد این سلول ها در گروه MSG+Vit C و Vit C کاهش چشمگیری نسبت به گروه MSG نشان داد. ضخامت اپیتلیوم ژرمینال نیز در گروه MSG نسبت به گروه کنترل کاهش داشت.
    نتیجه گیری
    مونوسدیم گلوتامات می تواند منجر به تغییرات آپوپتوتیک در اپیتلیوم ژرمینال بیضه شود همچنین ویتامین C به عنوان یک آنتی اکسیدان می تواند تغییرات پاتولوژی و بیوشیمیایی ایجاد شده توسط MSG را تعدیل کند.
    کلید واژگان: آپوپتوز، مونوسدیم گلوتامات، رت، بیضه، ویتامین C
    Fatemeh Anbarkeh Rahimi, Raheleh Baradaran, Nasibeh Ghandy, Mehdi Jalali*, Mohammad Reza Nikravesh, Mohammad Soukhtanloo
    Background
    Monosodium glutamate (MSG) is used as a flavoring and food seasoning. Some studies have reported the oxidative effects of using this substance on various tissues.
    Objective
    This study has investigated the effects of MSG and the protective effect of vitamin C (vit C) on apoptosis of testicular germ cells and biochemical factors.
    Materials and Methods
    In this experimental study, 24 adult male Wistar rats were randomly divided into four groups: control (received distilled water), vit C group (150 mg/kg), experimental group 1 (MSG 3 gr/kg), experimental group 2 (MSG 3 gr/kg + vit C 150 mg/kg). The rats were gavaged for 30 days, and then were sacrificed, the right testis was isolated for biochemical examinations for the glutathione, malondialdehyde, and left testis used in histological experiments. Tunnel staining was used to determine the number of apoptotic cells.
    Results
    The results showed that apoptotic cells in the MSG group had a significant increase compared to the control group (P = 0.001), but the number of these cells in the MSG co-administered with vit C and vit C groups were significantly lower than the MSG group. Germinal epithelial thickness also decreased in MSG group compared to the control group.
    Conclusion
    MSG can lead to increase apoptotic changes in the germinal epithelial of the testicle, and vit C as an antioxidant can modify the pathological and biochemical changes induced by MSG.
    Keywords: Apoptosis, Monosodium glutamate, Rat, Testis, Vitamin C
  • Mohammad Jalili, Nik, Mohammad Soukhtanloo, Sajad Javanshir, Amirali Jahani Yazdi, Mahdi Esmaeilizadeh, Amir Hossein Jafarian, Ahmad Ghorbani *
    Previous studies have shown that some plants in the genus of Ferula (Apiaceae) have antidiabetic effects. The present work was aimed to evaluate effects of Ferula gummosa oleo-resin in a rat model of streptozotocin-induced diabetes. Male Wistar rats were randomized into five groups (n = 6): normal control, diabetic control, diabetic rats treated with insulin (3 IU/day), and diabetic rats treated with 100 or 400 mg/kg/day of an ethanolic extract of the oleo-resin. After 4 weeks, blood samples were collected for measuring fasting blood glucose (FBG), lipid profile, aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, blood urea nitrogen, and creatinine. In addition, levels of lipid peroxidation, thiol groups, and superoxide dismutase (SOD) activity were evaluated in the liver and kidney. At the end of the fourth week, the level of FBG in rats treated with 100 mg/kg of the extract was lower than that in diabetic control rats (273 ± 39 mg/dL vs 471 ± 32 mg/dL). Administration of insulin and the extract had no significant effects on the serum lipids. Insulin and both doses of the extract significantly reduced the activity of ALT. In addition, the extract inhibited lipid peroxidation in the kidney and restored the elevated level of SOD in the liver and kidneys. Ferula gummosa oleo-resin has the potential to prevent or delay the complications of diabetes by inhibiting the progression of hyperglycemia and attenuating oxidative stress-induced damage in the liver and kidneys.
    Keywords: Diabetes, Ferula gummosa, Glucose, Lipid, Sesquiterpene coumarins
  • Farnaz Mohajertehran *, Hossein Ayatollahi, Amir Hossein Jafarian, Kamran Khazaeni, Mohammad Soukhtanloo, Mohammad Taghi Shakeri, Nooshin Mohtasham
    Background
    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy that is associated with high morbidity and mortality. Salivary lactate dehydrogenase (LDH concentration), as an expression of cellular necrosis, may be a special marker of lesions that occur with changes in the integrity of the oral mucosa. This study was performed to determine the accuracy of salivary LDH as a clinical marker for HNSCC detection and to investigate the relationship between salivary LDH levels and tissue tumor detection.
    Methods
    The case group consisted of 44 HNSCC patients and the control group consisted of 44 healthy subjects. The stage and grade of HNSCC were determined, and the LDH levels in collected saliva samples were measured in all subjects. The expression of LDH in tumors and healthy tissue margins was evaluated via immunohistochemistry.
    Results
    The expression of LDH in the saliva of patients with HNSCC is significantly higher than that in the saliva of the healthy control group. The expression of salivary LDH in patients with oral squamous cell carcinoma (OSCC) is significantly higher than that in the other patients and healthy individuals in the control group. The levels of salivary LDH in patients with SCC of the tongue and lower oral cavity were significantly higher than those in other patients affected with SCC in other parts of the head and neck (P<0.01).
    Conclusions
    As this enzyme increases simultaneously in both tumoral tissues and saliva, it can serve as a useful diagnostic marker for the early diagnosis and prediction of HNSCC.
    Keywords: Biomarker, Early diagnosis, Head, neck squamous cell carcinoma (HNSCC), Lactate dehydrogenase (LDH), Saliva
  • Yasamin Roohbakhsh, Kambiz Alizadeh, Lida Jarahi, Mohammad Soukhtanloo, Baratali Mashkani, Farnaz Zahedi Avval
    Introduction
    Galectin-3 is known as a biomarker in patients with heart failure. This protein participates in different mechanisms involved in atherosclerosis including inflammation and plaque formation. This study was conducted to investigate whether this factor could be a predictive biomarker for the severity of atherosclerosis.
    Materials and Methods
    The study group consisted of 80 patients with coronary atherosclerosis referred to the Department of Cardiac Surgery of Ghaem Hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran. The serum level of galectin-3 was measured using a commercial enzyme-linked immunosorbent assay kit. The severity of coronary artery disease (CAD), evaluated by the serum levels of galectin-3, was expressed as the number of involved vessels.
    Results
    Galectin-3 concentration was directly correlated with the number of involved vessels.The serum level of galectin-3 was significantly higher in patients with four involved vessels (20.76±7.20 ng/ml) than those with three-vessel disease (14.31±4.45 ng/ml; P<0.001). Patients with three-vessel disease had higher levels of galectin-3 than patients with one and two involved vessels (7.20±4.09 ng/ml; P<0.001).
    Conclusion
    The relationship between the number of vessels involved and the concentration of Galectin-3 was statistically significant. According to the results, serum galectin-3 level is considered as a noninvasive tool for the diagnosis of preliminary assuming the coronary artery involvement. Although this study needs further detailed investigations with preferably larger sample size, the results of the present study highlighted the importance of this factor in CAD. This protein can help in early evaluations for preliminary determining the prognosis before the complementary aggressive intervention
    Keywords: Atherosclerosis, Coronary Artery Disease, Galectin-3
  • Narges Amel Zabihi, Seyed Mojtaba Mousavi, Maryam Mahmoudabady, Mohammad Soukhtanloo, Farzaneh Sohrabi, Saeed Niazmand *
    Background
    Diabetes mellitus (DM) is a prime risk factor for cardiovascular disease. The convincing experimental and clinical evidence indicated that the onset of DM is closely associated with oxidative stress and that the generation of reactive oxygen species increases in both the types of diabetes. The aim of the present study was to evaluate the effect of Teucrium polium (TP) hydroalcoholic extract on the blood glucose, cholesterol, triglyceride, and oxidative stress markers of the heart and aorta in streptozotocin (STZ)‑induced diabetic rats.
    Methods
    The male Wistar rats assigned into six groups (n = 8 in each group): Control, diabetic, and diabetic rats treated with TP extract (100, 200, and 400 mg/kg) or met and metformin (300 mg/kg) formin (300 mg/kg) group, by daily gavage for 6 weeks. Diabetes was induced by injection of STZ (60 mg/kg, i.p). Serum lipids and glucose, malondialdehyde (MDA) level, total thiol level, and also the activities of Cu, Zn‑superoxide dismutase (SOD) in the cardiac and aortic tissues were assessed.
    Results
    TP extract reduced serum glucose, triglyceride and cholesterol. The MDA levels were reduced signifcantly in all TP‑treated groups and metformin. Total thiol levels were improved in the heart and aorta of TP extract‑treated groups and metformin compared to the diabetic rats. The activity of SOD in the cardiac and aortic tissues of TP extract‑ and metformin‑treated groups was higher than diabetic group.
    Conclusions
    The results showed that chronic administration of TP in STZ‑induced diabetic rats could decrease blood glucose, cholesterol, and triglyceride and also attenuate the oxidative stress in the aortic and cardiac tissues.
    Keywords: Aorta, diabetes mellitus, heart, oxidative stress, Teucrium polium
  • Nazanin Entezari Heravi, Reza Mohebbati, Zohreh Naji Ebrahimi, Abolfazl Khajavi Rad *, Mohammad Naser Shafei, Mohammad Soukhtanloo, Farimah Beheshti, Sara Hosseinian
    Introduction
    Nephropathy is defined as rational loss of renal function related with glomerulosclerosis and declining glomerular filtration rate. Inflammation and oxidative stress play a critical role in nephropathy. Plantago major has antioxidant effects. The aim of present study is the investigation of the effect of Plantago major hydro-alcoholic extract on the oxidative stress and renal function in kidney of rat.
    Methods
    Rats were divided into five groups: control (Co), doxorubicin (DOX), doxorubicin+vitamin E (DOX+Vit E), 600mg/kg Plantago major (PM)+doxorubicin (PM600+DOX), 1200mg/kg Plantago major (PM)+doxorubicin (PM1200+DOX). DOX (5mg/kg, IV), Vit E and PM extract (600 and 1200mg/kg, PO) were administrated for 35 days. Finally, urine, blood samples and renal tissue were collected to measurement of redox markers, functional parameters and renal index percentage.
    Results
    The renal superoxide dismutase (SOD) activity, total thiol and functional parameters significantly reduced and malondialdehyde (MDA) concentration increased in DOX group in comparison with control group. The renal SOD, catalase activities and total thiol content were significantly increased and MDA level decreased in PM treated groups along with DOX group in comparison with DOX group. The functional parameters significantly enhanced in treated groups with PM in comparison with the DOX group. The extract did not relive enhanced % renal index induced by DOX.
    Conclusion
    Hydro-alcoholic extracts of PM, specially at its high dose led to an improvement in DOX-induced renal function and oxidative stress.
    Keywords: Doxorubicin, Plantago major, Oxidative stress, Renal function
  • Mahdi Jalali, Mohammad Soukhtanloo, Mahmoud Moghaddam Dorafshani *, Mohammad Reza Nikravesh **
    Background
    Liver cells or hepatocytes facilitate different hepatic functions. The liver reportedly accounts for up to 500 separate functions, alongside other systems and organs. The high consumption of the food containing high levels of nitrate in the community and the presence of this harmful substance in water endanger the health of many people. N-nitroso compounds, as potential free radicals, can damage the tissues through oxidative stress.
    Objectives
    The current study was targeted toward examining the impact of drinking water nitrate and vitamin C on hepatic enzymes and oxidative markers in rats.
    Methods
    The present experimental study was performed on 49 rats in Mashhad, Iran, during 2017 - 2018. The subjects were assigned into seven groups. Group one received water without nitrates (control) while groups two, three, and four received different concentration of nitrates (10, 45, 200 mg/L). Groups five, six, and seven received the same concentration of nitrates and vitamin C (20 mg/100g body weight). After 91 days, blood samples were obtained to determine hepatic enzymes (namely, ALT/SGPT: alanine aminotransferase, AST/SGOT: aspartate aminotransferase, and ALP: alkaline phosphatase). Furthermore, an autopsy was carried out to examine the liver tissue regarding the markers of oxidation (namely, MDA: Malondialdehyde, SOD: Superoxide-dismutase, CAT: Catalase enzyme, and GSH: Glutathione), according to the protocol.
    Results
    The results revealed a significant elevation in ALP (P = 0.034), AST (P = 0.018), and ALT (155.14 ± 25.67, 92 ± 17.72, P = 0.000), compared to those in the control group. In addition, the fourth group demonstrated a significant enhancement in MDA level, collated to the group one (P = 0.44), while there was a significant drop in CAT (P = 0.025), SOD (P = 0.002), and GSH levels (P = 0.000). Furthermore, use of vitamin C led to a significant drop in the levels of ALP, AST, ALT, and MDA, as well as a significant elevation in GSH, SOD, and CAT in the seventh group in comparison to the fourth group (P < 0.05).
    Conclusions
    As the findings indicated, drinking water nitrate and Vitamin C exerted a non-significant effect on the doses of nitrate (10 and 45 mg/L). Nonetheless, a nitrate dose of 200 mg/L had a significant impact on ALT, ALP, AST, and oxidative stress indicators leading to hepatic diseases.
    Keywords: Ascorbic Acid, Drinking Water, Free Radicals, Liver Diseases, Nitrates, Oxidative Stress, Rats
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