Publications by authors named "Mohammad Sheibani"

22 Publications

  • Page 1 of 1

Involvement of nNOS, and α1, α2, β1, and β2 Subunits of Soluble Guanylyl Cyclase Genes Expression in Anticonvulsant Effect of Sumatriptan on Pentylenetetrazole-Induced Seizure in Mice.

Iran J Pharm Res 2020 ;19(4):181-192

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Epileptic seizure is phenomenon of abnormal synchronous neuronal discharge of a set of neurons in brain as a result of neuronal excitation. Evidence shows the nitric oxide (NO) involvement in neuronal excitability. Moreover, the role of cyclic guanosine monophosphate (cGMP) activation in seizure pathogenesis is well-established. Sumatriptan is a selective agonist of 5-Hydroxytryptamine1B/D auto-receptor, has been reassessed for its neuroprotection. This study was aimed to explore the anticonvulsant effect of sumatriptan through possible involvement of NO-cGMP pathway in mice. For this purpose, the protective effect of sumatriptan on PTZ-induced clonic seizure threshold (CST) was measured using NO-cGMP pathway inhibitors including N(G)-nitro-L-arginine (L-NNA, 1, 5, and 10 mg/kg), 7-nitroindazole (7-NI, 30, 45, and 60 mg/kg), aminoguanidine (AG, 30, 50, and 100 mg/kg), methylene blue (MB, 0.1, 0.5, and 1 mg/kg) and sildenafil (5, 10, and 20 mg/kg). The involvement of nitrergic system was further confirmed by measurement of nitrite levels by Griess reaction. The gene expression of neuronal nitric oxide synthase (nNOS) and subunits of soluble guanylyl cyclase (sGC) was studied using qRT-PCR analysis. Acute administration of sumatriptan (1.2 and 0.3 mg/kg) in combination with subeffective doses of NOS, sGC, and phosphodiesterase 5 inhibitors significantly reversed the PTZ-induced CST ( 0.001). The nitrite level in prefrontal cortex was significantly attenuated by sumatriptan ( ≤ 0.01). Furthermore, sumatriptan downregulated the PTZ-induced mRNA expression of nNOS ( ≤ 0.01), α1 ( ≤ 0.001), α2 ( ≤ 0.05), and β1 ( ≤ 0.05) genes in cerebral cortex of mice. In conclusion, the anticonvulsant activity of sumatriptan at least, in part, is mediated through inhibiting NO-cGMP pathway.
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http://dx.doi.org/10.22037/ijpr.2020.112594.13844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019868PMC
January 2020

Glatiramer acetate treatment inhibits inflammatory responses and improves survival in a mice model of cecal ligation and puncture-induced sepsis.

J Basic Clin Physiol Pharmacol 2021 Feb 9. Epub 2021 Feb 9.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Sepsis is a clinical crisis which has been considered as one of the important causes of mortality across the world. We hypothesized that modulation of hyper-inflammatory phase of sepsis pathophysiology can lead to protective effects on survival outcome. Glatiramer acetate (GA) is a neuroprotective drug commonly used in multiple sclerosis (MS). GA is characterized by immunom activity via regulation of innate and adaptive immunity. This study was designed to evaluate the acute treatment with GA on initial inflammatory response-induced mortality in septic mice.

Methods: Cecal ligation and puncture (CLP) model was operated on male mice as a model of Polymicrobial sepsis. GA was administrated intraperitoneally after the sepsis induction at doses of 0.5, 1, and 2 mg/kg in three treatment groups. To investigate the effect of GA on short-term survival, septic mice were observed during 72 h after CLP. Serum levels of TNF-α, IL-1β, and IL-6 as pro-inflammatory cytokines and also IL-10 as a critical anti-inflammatory cytokine were analysed. To consider sepsis-induced acute kidney injury, renal functional biomarkers and histopathological changes was assessed.

Results: GA treatment significantly improved survival rate at doses of 1, and 2 mg/kg. Survival improvement was accompanied by remarkable reduction in the pro-inflammatory cytokines and enhanced production of IL-10. GA showed to have protective effects on renal function as well.

Conclusions: Immunomodulatory and anti-inflammatory properties of GA resulted in increase in survival rate and decrease in inflammatory markers in mice model of cecal ligation and puncture-induced sepsis.
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http://dx.doi.org/10.1515/jbcpp-2020-0303DOI Listing
February 2021

Insight into the mechanism of aspartame-induced toxicity in male reproductive system following long-term consumption in mice model.

Environ Toxicol 2021 Feb 20;36(2):223-237. Epub 2020 Sep 20.

Department of Comparative Biomedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.

Aspartame is one of the most common consumed artificial sweeteners utilized in many food products and beverages. It has been indicated that long-term consumption of aspartame leads to reproductive toxicity but its mechanism is not well-clear. In this study we investigated mechanism of aspartame-induced reproductive toxicity in male mice. For this purpose, 36 NMRI mature male mice received three doses of 40, 80, and 160 mg/kg body weight of aspartame, respectively per day by gavage for 90 days and also a control group was considered which received 0.5 mL of normal saline as the same route. The results revealed that long-term administration of aspartame at high doses significantly (P < .05) reduced gonadosomatic index, serum concentration of pituitary-testicular axis hormones (FSH, LH, and testosterone). It also decreased sperm parameters and total antioxidant capacity, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), while it caused increase in nitric oxide and malondialdehyde levels in testis tissue and sperm samples. Also, it decreased attenuated testicular histomorphometric indices (tubular differentiation index, spermiogenesis index, and repopulation index), and steroidogenic foci, while increased mRNA damages and apoptosis rate, downregulated antiapoptotic (Bcl-2) and upregulated proapoptotic (P53, BAX, and caspase-3) mediators respectively in testis. These findings indicated that consumption of aspartame for a long period results in male reproductive toxicity by decrease in serum concentration of pituitary-testis axis hormones and induction of oxidative stress and apoptosis in testis.
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http://dx.doi.org/10.1002/tox.23028DOI Listing
February 2021

Protective Effects of Spermidine Against Cirrhotic Cardiomyopathy in Bile Duct-Ligated Rats.

J Cardiovasc Pharmacol 2020 09;76(3):286-295

*Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; and †Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Cirrhotic cardiomyopathy is a critical factor that causes morbidity and mortality in crucial conditions such as liver transplantation. In animal model, the common pathophysiologic mechanisms of cirrhotic cardiomyopathy are similar to those associated with bile duct ligation (BDL). Overproduction of inflammatory and oxidant markers plays a crucial role in cirrhotic cardiomyopathy. Spermidine, a multifunctional polyamine, is known for its antioxidant and anti-inflammatory effects. In this study, we investigated the effects of spermidine on development of cirrhotic cardiomyopathy in BDL rats. Rats were randomly housed in 6 groups. Except the normal and sham groups, BDL was performed for all the control and spermidine groups. Seven days after operation, 3 different doses of spermidine (5, 10 and 50 mg/kg) were administrated until day 28, in spermidine groups. At the end of the fourth week, the electrocardiography (ECG) and papillary muscle isolation were performed. The serum level of tumor necrosis factor-a (TNF-α), interleukin-1β (IL-1β), and IL-10 and cardiac level of superoxide dismutase, glutathione (GSH). and malondialdehyde (MDA) were assessed. Furthermore, the nuclear factor-κB (NF-κB) expression was assessed by western blot. Cardiac histopathological changes were monitored. The serum levels of magnesium (Mg) and potassium (K) were investigated. Control group, exhibited exaggerated signs of cirrhotic cardiomyopathy in comparison with the sham group. Co-administration of spermidine at the dose of 10 mg/kg in BDL rats significantly improved the cardiac condition, reduced the inflammatory mediators, and increased antioxidant enzymes. In addition, the histopathologic findings were in accordance with the other results of the study. Besides, there was no significant alteration in serum levels of Mg and K. This study demonstrates that spermidine at the dose of 10 mg/kg significantly improved the cirrhotic cardiomyopathy in BDL model in rats.
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http://dx.doi.org/10.1097/FJC.0000000000000872DOI Listing
September 2020

Lithium reverses the effect of opioids on eNOS/nitric oxide pathway in human umbilical vein endothelial cells.

Mol Biol Rep 2020 Sep 4;47(9):6829-6840. Epub 2020 Sep 4.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.

The main challenge of pain management with opioids is development of acute and chronic analgesic tolerance. Several studies on neuronal cells have focused on the molecular mechanisms involved in tolerance such as cyclic AMP (cAMP) activation, and nitric oxide (NO) pathway. However, the effects of opioids on non-neuronal cells and tolerance development have been poorly investigated. Lithium chloride is a glycogen synthase kinase 3β (GSK-3β) inhibitor and exert its effects through modulation of nitric oxide pathway. In this study we examined the effect of lithium on acute/chronic morphine and methadone administration in endothelial cells which express mu opioid receptors. Human umbilical vein endothelial cells (HUVECs) were treated with different doses of morphine, methadone, and lithium for six and 48 h. Then we evaluated cell viability, nitrite and cyclic AMP levels, as well as the expression of endothelial nitric oxide synthase (eNOS) protein using Immunocytochemistry (ICC) assay and phosphorylated GSK-3β enzyme by western blot analysis in cells. Both chronic morphine and methadone treatment increased NO level and eNOS expression in HUVECs. Morphine induced cAMP overproduction after 48 h exposure with cells. Lithium pretreatment (10 mM) in both morphine and methadone received groups significantly reduced nitrite and cAMP levels as well as eNOS expression as compared to the control. The decreased amount of phospho GSK-3β due to the opioid exposure was increased following lithium treatment. Tolerance like pattern may occur in non-neuronal cells with opioid receptors and this study clearly revealed the attenuation of morphine and methadone tolerance like behavior by lithium treatment in HUVECs.
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http://dx.doi.org/10.1007/s11033-020-05740-9DOI Listing
September 2020

Long-Term Effect of Aspartame on Male Reproductive System: Evidence for Testicular Histomorphometrics, Hsp70-2 Protein Expression and Biochemical Status.

Int J Fertil Steril 2020 Jul 15;14(2):91-101. Epub 2020 Jul 15.

Department of Comparative Histology and Embryology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Background: Aspartame is one of the most commonly consumed artificial sweeteners that is widely used in foodstuffs. There are many debatable reports about aspartame toxicity in different tissues; however, on the subject of its effects on the reproductive system, few literatures are available. The present study was carried out for evaluating effects of aspartame on the reproductive system in male mice.

Materials And Methods: In this experimental study, a total of 36 adult male mice were randomly divided into four groups of nine animals each. Three groups received aspartame at doses of 40, 80 and 160 mg/kg (gavage) for 90 days; also, a control group was considered. Twenty-four hours after the last treatment, animals were sacrificed. Then, body and testis weights, sperm parameters, serum testosterone concentration, total antioxidant capacity, and malondialdehyde (MDA) levels, antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)] activities in blood, histomorphometrical indices and histochemical changes in testis were evaluated; also, mRNA and immunohistochemical expression of Hsp70-2 was measured in testis tissue.

Results: The results revealed remarkable differences in sperm parameters, testosterone and oxidative stress biomarkers levels, and histomorphometrical indices, between the control and treatment groups. Also, in 80 and 160 mg/kg aspartametreated groups, expression of Hsp70-2 was decreased. Besides, in the aspartame receiving groups, some histochemical changes in testicular tissue were observed.

Conclusion: The findings of the present study elucidated that long-term consumption of aspartame resulted in reproductive damages in male mice through induction of oxidative stress.
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http://dx.doi.org/10.22074/ijfs.2020.6065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382684PMC
July 2020

Phytochemical screening of Alstonia venenata leaf and bark extracts and their antimicrobial activities.

Cell Mol Biol (Noisy-le-grand) 2020 Jun 25;66(4):224-231. Epub 2020 Jun 25.

Department of Chemical and Physical Properties of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Tuwima Street 10, 10-748 Olsztyn, Poland.

Alstonia venenata is a plant commonly found in South India and used in traditional medicine. The aim of this study was to characterize the phytochemicals present in A. venenata leaf and bark extracts and study their antimicrobial activities. Solvent extractions with Soxhlet apparatus of leaves and bark were obtained using hexane, benzene, isopropanol, methanol, and water. The crude extracts were concentrated and screened for qualitative phytochemical content and analyzed by thin layer chromatography. The antibacterial, antifungal and antiviral activities of crude extracts were measured by in vitro methods. Alkaloids, carbohydrates, tannins, phenolic compounds, terpenoids, cardiac glycosides and amino acids were found in the different crude extracts analyzed. Isopropanol extracts showed antifungal activity and it was more pronounced in the bark extract than the leaf extract. Moreover, the isopropanol extract exhibited antibacterial and antiviral activity. In conclusion, the leaves and bark of A. venenata have antimicrobial components which are more present in the isopropanol fraction.
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June 2020

Protective effect of dapsone against renal ischemia-reperfusion injury in rat.

Immunopharmacol Immunotoxicol 2020 Jun 23;42(3):272-279. Epub 2020 Apr 23.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Ischemia/reperfusion can cause injury to tissues and compromise functionality of organs due to inflammatory processes. Significantly, development of these effects in kidney tissue has been a challenging issue that leads to acute renal injury. In this study, anti-inflammatory, anti-oxidative, and protective features of dapsone on kidney ischemia/reperfusion injury were investigated. Renal ischemia was induced in rats by bilateral renal arteries clamping for 45 min followed by 24 h reperfusion phase. The effects of different doses of dapsone (1, 3, 10 mg/kg) on ischemia/reperfusion injury in kidney tissue were investigated by targeting BUN, Creatinine, LDH, MDA, MPO, IL-1β, TNF-α, and NFκB. In addition histopathological examination was performed by H&E staining method. Comparing the findings of this study showed significant reduction in BUN and LDH in 10 mg/kg dapsone received groups, and Cr, MDA, and MPO in 3 mg/kg dapsone received groups. The serum level of TNF-α was significantly decreased with both doses of 3 and 10 mg/kg dapsone. The same results were observed in the serum level of IL-1β and NFκB. Besides, remarkable improvement in histological damages was also observed with dapsone treatment. These results support the hypothesis that the positive effects of dapsone on the renal ischemia/reperfusion injury are mediated by modulating inflammatory cascades.
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http://dx.doi.org/10.1080/08923973.2020.1755308DOI Listing
June 2020

Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats.

Cancer Chemother Pharmacol 2020 03 8;85(3):563-571. Epub 2020 Jan 8.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.

Purpose: It has been supposed that cardiac toxicity of doxorubicin is due to its production of free radicals and inflammatory cytokines. Dapsone, an antibiotic drug which is the principal in a multidrug regimen for the treatment of leprosy, is a sulfone with anti-inflammatory and antioxidant immunosuppressive properties. Therefore, we designed this study to investigate the possible effects of dapsone on doxorubicin-induced cardiotoxicity.

Methods: Male rats were administrated doxorubicin (2.5 mg/kg) and dapsone (1, 3, 10 mg/kg) intraperitoneally six times in 2 weeks. Then electrocardiographic (ECG) parameters (QRS complexes, RR and QT intervals) alternation, papillary muscle contraction and excitation, and histopathological changes were assessed. Also, the heart tissue levels of malondialdehyde (MDA) as oxidant factor and superoxide dismutase (SOD) as antioxidant enzyme, tumor necrosis factor-alpha (TNF-α) and serum level of CK-MB were analyzed.

Results: Administration of dapsone with doxorubicin significantly reversed alterations induced by doxorubicin in serum levels of CK-MB, ECG parameters, papillary muscle contractility and excitation. Furthermore, the measurement of MDA, SOD and TNF-α tissue level indicated that dapsone significantly reduced oxidative stress and inflammation. These findings were consistent with histopathological analysis.

Conclusion: Dapsone exerts cardioprotective effects on doxorubicin-induced cardiotoxicity through its anti-inflammatory and antioxidant mechanism.
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http://dx.doi.org/10.1007/s00280-019-04019-6DOI Listing
March 2020

Glatiramer acetate attenuates renal ischemia reperfusion injury in rat model.

Exp Mol Pathol 2020 02 4;112:104329. Epub 2019 Nov 4.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, P.O. Box 13145-784, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, P.O. Box 13145-784, Iran. Electronic address:

Chronic renal failure can ultimately lead to kidney transplantation. Renal transplantation is associated with ischemia-reperfusion injury (I/R). The subsequent processes of kidney I/R can lead to irreversible damages to the kidney tissue. Glatiramer acetate is an immunomodulatory drug for the treatment of multiple sclerosis (MS) and the anti-inflammatory effects of this drug have already been proven in some inflammatory models. The purpose of this study was to evaluate the protective effects of Glatiramer on reducing the damages arising from kidney ischemia-reperfusion. In this study, 35 Wistar rats were used which divided into 5 groups: sham, control (I/R), I/R + Glatiramer 0.5 mg/kg, I/R + Glatiramer 1 mg/kg, I/R + Glatiramer 2 mg/kg. Renal arteries were clamped bilaterally for 45 min, then the clamps were removed and the reperfusion process continued to 24 h. In the following, serum and kidneys were separated for analysis. In the control group, serum levels of LDH, inflammatory factor TNF-α and renal functional markers such as BUN and Creatinine were remarkably increased, but in the treatment groups, especially in Glatiramer 2 mg/kg received group, a significant decrease in these factors was observed. Tissue concentration of MDA was reduced following Glatiramer treatment. Besides, Glatiramer attenuated the increased kidney level of NF-κB protein using immunohistochemical assay. NFkB migration to the nucleolus increases inflammatory cytokines production. The anti-inflammatory factor, IL-10, in serum was significantly increased in the treatment group of Glatiramer 2 mg/kg. Furthermore, Glatiramer decreased renal tissue injury score according to the histopathological study. These results demonstrate that Glatiramer may play protective effects in kidney ischemia-reperfusion injury by reducing inflammatory and oxidative damages.
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http://dx.doi.org/10.1016/j.yexmp.2019.104329DOI Listing
February 2020

Sumatriptan protects against myocardial ischaemia-reperfusion injury by inhibition of inflammation in rat model.

Inflammopharmacology 2019 Oct 30;27(5):1071-1080. Epub 2019 Mar 30.

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.

Ischemic heart disease is a leading cause of death on a global scale, placing major socio-economic burdens on health systems worldwide. Myocardial ischaemia and reperfusion (I/R)-induced tissue injury is associated with alteration in activity of inflammatory system and nitric oxide pathway. Sumatriptan, which is mainly used to relieve migraine headache, has recently been shown to exert anti-inflammatory properties. In this study, we aimed to assess the possible cardioprotective effect of sumatriptan in a rat model of I/R injury. Male Wistar rats were subjected to 30-min ligation of left anterior descending coronary artery and 120-min reperfusion. Animals were randomly divided into five groups: (1) Sham (2) I/R (3) I/R treated with sumatriptan (0.3 mg/kg i.p.) 20 min after induction of I/R rats, (4) GR127935 (a selective antagonist of 5-HT1B/D serotonin receptors; 0.3 mg/kg) 20 min after induction of I/R, and (5) GR127935 (0.3 mg/kg) 15 min before administration of sumatriptan. Post-infarct treatment with sumatriptan increased left ventricular function, which was damaged in I/R animal's heart. Sumatriptan (0.3 mg/kg) decreased lipid peroxidation, CK-MB and lactate dehydrogenase levels; tumor necrosis factor concentration; and Nf-ҡB' protein production. Treatment with sumatriptan significantly increased the endothelial nitric oxide synthase (eNOS) expression consequences nitric oxide metabolites' level in I/R rats. Also, injection of sumatriptan remarkably decreased myocardial tissue injury assessed by histopathological study. These findings suggest that sumatriptan may attenuate I/R injury via modulating the inflammatory responses and endothelial NOS activity. But therapeutic index of sumatriptan is narrow according to the result of this study.
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http://dx.doi.org/10.1007/s10787-019-00586-5DOI Listing
October 2019

Actinomycotic Osteomyelitis of Mandible.

J Craniofac Surg 2016 Jul;27(5):e452-4

Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Babol University of Medical Sciences, Babol, Iran.

Actinomycosis is an infection of filamentous, gram-positive anaerobic bacteria. Actinomycosis of jaw bone is rare and the diagnosis is often difficult. The aim of this patient report is to present an actinomycotic osteomyelitis of mandible in a 30-year-old male patient. The patient presented with a chief complaint of pain and unhealed dental socket after mandibular teeth extractions. Radiographs showed ill-defined radiolucencies and perforation of buccal and lingual cortical plate; several biopsies and different therapy could not improve the lesion because of fault diagnosis and improper treatment. Finally, the authors' histopathological examination revealed granulation tissue surrounded bacterial colonies compatible with actinomycotic colonies. Follow-up examinations showed that the patient was well 6 months after prolonged treatment without any pain and discharge from dental socket.
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http://dx.doi.org/10.1097/SCS.0000000000002793DOI Listing
July 2016

The effects of Melissa officinalis (lemon balm) pretreatment on the resistance of the heart to myocardial injury.

Pharm Biol 2016 12;54(6):1005-13. Epub 2015 Oct 12.

e Department of Pathology , School of Medicine, Kerman University of Medical Sciences , Kerman , Iran.

Context: The antihyperlipidemic, antiarrhythmic, neuroprotective and hepatoprotective effects of Melissa officinalis L. (Lamiaceae) have been reported. However, no study has examined its effects on the resistance of the heart to stressful conditions.

Objective: The objective of this study is to evaluate the effects of aqueous extract of M. officinalis aerial parts on Wistar rat heart with/without cardiac injury.

Materials And Methods: Animals were grouped as control, isoproterenol (ISO), M. officinalis without (M50, M100, and M200) and with isoproterenol (M50 + ISO, M100 + ISO, and M200 + ISO). The aqueous extract of M. officinalis was orally administered at dosages of 50, 100, and 200 mg/kg/d, respectively, for 7 consecutive days. On the 6th and 7th day, ISO, M50 + ISO, M100 + ISO, and M200 + ISO groups received 85 mg/kg of isoproterenol for myocardial injury induction. On day 8, hemodynamic parameters were recorded and samplings were done.

Results: The extract (50, 100, and 200 mg/kg) significantly reduced the heart rate (264 ± 5, 259 ± 5 and 281 ± 3 versus 377 ± 13 in control group, p < 0.01). Blood pressure was significantly decreased in M50 + ISO (75 ± 5) versus M50 (110 ± 6) and M100 + ISO (72 ± 6) versus M100 (105 ± 5 mmHg, p < 0.01). The malondialdehyde levels of the injured hearts were lower in M50 + ISO and M100 + ISO groups than in the ISO group (p < 0.05). Serum cardiac troponin I was higher in the M200 + ISO group (5.1 ± 1.7) than in the ISO group (2.7 ± 0.7 ng/ml, p < 0.05).

Conclusion: The lower dose of extract, by improving the balance of the redox system and by reducing the heart rate, may increase the heart resistance to injury. However, the higher doses of extract may intensify the injury of ischemic heart.
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http://dx.doi.org/10.3109/13880209.2015.1091845DOI Listing
January 2017

Evaluation of histopathologic and histomorphometric changes of testicular tissue and gonadotropin levels following consumption of methylphenidate in male mice.

Turk J Med Sci 2014 ;44(4):554-9

Department of Anatomy, Tehran Medical Branch, Islamic Azad University, Iran.

Background/aim: One of the most common psychiatric disorders in children is attention-deficit/hyperactivity disorder, which is treated extensively by methylphenidate. This study investigates the assessment of the effects of methylphenidate on histopathologic and histomorphometric changes of the testes and serum levels of gonadotropin in mice.

Materials And Methods: In this study, 36 adult male mice were used. After determining their body weights, the animals were divided randomly into 2 experimental groups and 1 control group. The experimental groups received methylphenidate (2 and 10 mg kg(-1) day(-1)) via gavage for a period of 40 days. After evaluation of body weight, general anesthesia was used for taking blood samples from the heart in order to measure testosterone and levels of gonadotropin in serum. For the purpose of weighing the bodies and measuring the thickness of the germinal epithelium, the testes were removed and the possibility of any pathological changes was considered.

Results: The results showed that methylphenidate could decrease the thickness of the germinal epithelium and body weight significantly, and could increase the levels of spermatogonia and serum gonadotropins and testosterone. Histopathological changes were also seen for vascular dilatation and congestion in interstitial tissue.

Conclusion: Our findings demonstrated that administration of methylphenidate in adulthood may have an effect on spermatogenesis due to the influence of gonadotropin hormones on testis function.
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http://dx.doi.org/10.3906/sag-1301-109DOI Listing
January 2015

The onset of stress response in rainbow trout Oncorhynchus mykiss embryos subjected to density and handling.

Fish Physiol Biochem 2015 Apr 22;41(2):485-93. Epub 2014 Oct 22.

Fisheries Department, Faculty of Natural Resources, Khorramshahr University of Marine Science and Technology, Khorramshahr, Khouzestan, Iran.

The present study made an attempt to measure the cortisol content, as an indicator of stress response, in rainbow trout embryos which were exposed to different densities and handling stress (air exposure) during incubation. The three densities of experimental embryos at early development stages were considered as 2.55 embryos/cm(2) (low density), 5.10 embryos/cm(2) (normal density) and 7.65 embryos/cm(2) (high density). The cortisol content of eggs (5.09 ± 0.12 ng/g) decreased to 3.68 ± 0.14 ng/g in newly fertilized eggs. Resting level of cortisol dropped at three densities by day 18 of post fertilization. Then, cortisol increased at hatching stage to 1.16 ± 0.11, 1.20 ± 0.12 and 1.21 ± 0.14 ng/g at low, normal and high densities, respectively. There were no statistically significant differences between cortisol concentrations in three densities. The acute handling stress test (5-min out-of-water), conducted on embryos (48 h post fertilization, organogenesis and eyed stage) in three densities, revealed no differences in whole-body cortisol levels between stressed and unstressed experimental groups. At hatching stage in low-density group, level of cortisol increased but the difference with the pre-stress levels was not statistically significant. Furthermore, significant differences in cortisol levels of stressed and unstressed embryos were detected on hatching in normal and high density groups [1.20 ± 0.12 at time 0-1.49 ± 0.11 ng/g at 1 hps (hours post stress) and from 1.21 ± 0.14 at time 0 to 1.53 ± 0.10 ng/g at 3 hps, respectively]. The results showed no difference in profile of cortisol in different densities, but acute stress conducted on embryos, incubated in different densities, revealed differences in cortisol stress response at hatching between normal and high density, which lead to cortisol increase at hatching time. It indicates that the lag time in the cortisol response to stressors immediately after hatching does not occur when the siblings were stressed during the embryo stage. Results, finally, indicated that hypothalamus-pituitary-interrenal axis was active and responded to an acute stressor under normal and high density, but it is unresponsive to a stressor around hatching under low density.
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http://dx.doi.org/10.1007/s10695-014-9999-3DOI Listing
April 2015

Histological and histometrical evidences for phenol immunotoxicity in mice.

Comp Clin Path 2014 17;23:529-534. Epub 2012 Nov 17.

Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

Phenol is a common industrial and ubiquitous environmental chemical which is used to synthesize resins and plastics. Due to its anesthetic and disinfectant properties, phenol is also widely used in pharmaceutical products. Since there were no adequate data about phenol immunotoxicity, the purpose of the present study is to investigate its toxic effects on the histological structures of the lymphoid organs in the mice. A total of 80 mice were randomly distributed into one control group and three experimental groups. The control group received only distilled water, whereas experimental groups were orally administered phenol at the concentrations of 80, 180, and 320 mg/kg/day, respectively. After 28 consecutive days, tissue samples were taken and histological changes of the spleens, thymuses, adrenal glands, and lymph nodes were examined using optical microscopy. The results showed that in the phenol treated animals; splenic megakaryocyte counts increased, the diameter of the splenic follicles decreased, the thymocyte population in both cortex and medulla reduced, the thickness of the reticular layers of adrenal gland increased and lymphatic cells populations in the lymph node were reduced, significantly ( < 0.01). Also, remarkable histological changes were noted in the various lymphatic organs of the treated mice. Overall, present findings give some histological evidences that selected qualitative and quantitative parameters of the lymphatic organs were significantly altered by phenol administration. In conclusion, the significant decreases of the immune cell populations together with histological alterations in the immunocompetent organs of the mice exposed to phenol indicate the immunosuppressive and immunotoxic properties of this chemical material.
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http://dx.doi.org/10.1007/s00580-012-1645-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016808PMC
November 2012

Cardioprotective effect of mumie (shilajit) on experimentally induced myocardial injury.

Cardiovasc Toxicol 2014 Sep;14(3):214-21

Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran,

This study assessed the effects of mumie (shilajit) pre-treatment, a traditional drug which is well known in the ancient medicine of both east and west, on cardiac performance of rats subjected to myocardial injury. Animals were divided into control, M250, and M500 (received mumie at dosages of 250 and 500 mg/kg/day, orally for 7 days, respectively) main groups each consisting of two subgroups-with and without heart injury. On the 6th and 7th days, isoproterenol (ISO) (85 mg/kg i.p.) was injected (s.c.) to half of the animal subgroups to induce myocardial damage. On the 8th day, after hemodynamic parameter recordings, hearts were removed for further evaluation. Mumie pre-treatment had no significant effects on hemodynamic and cardiac indices of normal animals. When the cardiac injury was induced, mumie maintained the ±dp/dt maximum, attenuated the serum cardiac troponin I, and reduced the severity of cardiac lesions. Despite the mild positive effects of mumie on total antioxidant capacity and lipid proxidation index, no significant difference was observed among animal groups. The findings suggest the prominent cardioprotective effect of mumie against destructive effects of ISO. It seems that other mechanisms than reinforcements of antioxidant system are involved in this beneficial effect.
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http://dx.doi.org/10.1007/s12012-014-9245-3DOI Listing
September 2014

Whole egg and alevin changes of cortisol and interrenal tissue differences in rainbow trout Oncorhynchus mykiss exposed to different stocking densities during early development.

Zoolog Sci 2013 Dec;30(12):1102-9

1 Fisheries Department, Faculty of Marine Natural Resources, Khorramshahr University of Marine Science and Technology, Khorramshahr, Khouzestan, 4317564199, Iran.

Cortisol level changes in response to stocking density in the early stages of rainbow trout were measured. Eggs were exposed to low, normal, and high (2.55, 5.10 and 7.65 eggs cm(-2)) densities during the incubation period. Cortisol of maternal origin was found in pre-fertilized eggs (5.09 ± 0.12 ng g(-1)) of rainbow trout. In newly fertilized eggs, resting Cortisol levels (3.68 ± 0.14 ng g(-1)) decreased to 0.58 ± 0.08, 0.60 ± 0.12, and 0.57 ± 0.16 ng g(-1) at low, normal and high densities by day 10 (organo-genesis), respectively. Resting Cortisol levels remained constant until the eyed stage (day 18). Then, Cortisol showed an increase at hatching to 1.16 ± 0.11, 1.20 ± 0.12, and 1.21 ± 0.14 ng g(-1) at low, normal, and high densities, respectively. The pattern of change in Cortisol level was similar in all three densities. Interrenal cells were observed in 1-day old alevins at all three densities. Hematopoietic tissue, renal tubules and nucleated red blood cells were clarified through the head part of kidney. Higher numbers and larger interrenal cells were observed at high-density groups. Chronic density stress test conducted on embryonic stages of rainbow trout revealed no differences in Cortisol levels, but had an effect on the abundance and size of the interrenal cells. Densities were equaled after hatching (200 alevins per replicate) to investigate the different densities of eggs on stress indices in rainbow trout alevins. An acute stress (air exposure of eggs for five minutes) was applied in three treatments two weeks after hatching, and samples were taken at 0, 1, 3, 6, and 24 hps (hours post stress). Cortisol content increased under low density in 1 hps and reached from 5.21 ± 0.13 ng g(-1) to 6.01 ± 0.18 ng g(-1) (P < 0.05). Cortisol levels increased under normal density in 1 hps from 6.03 ± 0.28 ng g(-1) to 10.84 ± 0.18 ng g(-1) (P < 0.05). In high density also Cortisol increased from 6.83 ± 0.23 ng g(-1) to 8.86 ± 0.26 ng g(-1) (P < 0.05). At 3 hps;, Cortisol level was returned to basal level under low (P > 0.05) and normal (P > 0.05) densities, but significantly decreased (P < 0.05) under high density. Results revealed that the Cortisol biosynthesis was observed in rainbow trout between eyeing to the hatching stage. An increase in the density of eggs until 7.65 egg cm(-2) impaired Cortisol secretion and feedback system in alevins. However, more studies are needed to identify the exact time for Cortisol synthesis ability from eyeing to hatching in this species.
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http://dx.doi.org/10.2108/zsj.30.1102DOI Listing
December 2013

The effect of chronic administration of methylphenidate on morphometric parameters of testes and fertility in male mice.

J Reprod Infertil 2012 Oct;13(4):232-6

Department of Anatomy, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.

Background: Due to common use of methylphenidate (MPH) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) and the role of the reproductive system in the production of gametes, studying the effects of this medication on the morphometry of testes, serum testosterone concentration, leydig cells function, and fertility rate was the aim of this study.

Methods: Twenty seven male mice (Balb/C), eight weeks old, were randomly divided into one control and two treated groups. After weighing the mice, the treated groups received MPH (produced in Novartis company) at the doses of 2 mg/kg and 10 mg/kg for 40 days. The control group received only normal saline. Subsequently, after weighing the animals, the weights of testes, dimensions of the testis, and the serum testosterone concentration were measured in six mice belonging to each group. After tissue processing, the samples were stained with hematoxylin and eosin, then the leydig cells were counted. In order to assess male fertility in each group, 3 male mice were chosen and each of them was kept with three female mice in a separate cage. After 10 days, the fertility rates of the male mice were determined by counting the number of embryos in uterus and the corpora lutea in their ovaries.

Results: The results of this study revealed that prescription of different doses of MPH can cause a significant decrease of the body weight. It reduces the number of leydig cells, too (p<0.01). Moreover, serum testosterone concentration (67.72±8.24 ng/ml in control group and 0.302±0.416 ng/ml after treatment with 2 mg/kg/day MPH) and fertility rate (95.42%±4.68% in control group and 64.96%±18.51% after treatment with 2 mg/kg/day MPH) of the male mice declined significantly in the treated groups compared with the control group (p<0.01), but it did not cause any changes in the weight or morphometric parameters of testes.

Conclusion: The results of this study confirmed that MPH can negatively affect serum testosterone concentration and fertility rate of the male mice by decreasing the number of leydig cells and reducing the body weight.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719348PMC
October 2012

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: a potential anti-arrhythmic agent.

Pharm Biol 2013 Jul 29;51(7):836-43. Epub 2013 Apr 29.

Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran.

Context: Saffron (Crocus sativus L.) has been used as a cuisine spice in eastern and western societies for thousands of years. In traditional medicine, saffron is recommended for the treatment of various kinds of disorders including heart palpitations.

Objective: We investigated the hypothesis of the protective effect of saffron on lethal cardiac arrhythmias induced by heart ischemia-reperfusion in rat.

Materials And Methods: Animals were divided into a control (CTL) group that received tap water, Saf50, Saf100 and Saf200 groups that were orally treated with aqueous extracts of saffron, at dosages of 50, 100 and 200 mg/kg/day, respectively, and amiodarone (Amio) group that orally received 30 mg/kg/day for seven days. On day 8, heart ischemia-reperfusion was induced by ligation and releasing of the left anterior descending coronary artery.

Results: During reperfusion, the numbers and durations of ventricular fibrillation (VF) decreased in all groups compared to the CTL group (p < 0.05). Ventricular tachycardia (VT)/VF numbers (3.2 ± 1.2), durations (4.9 ± 2.6) and also arrhythmia severity (1.9 ± 0.35) were decreased significantly in the Saf100 group versus CTL group values (18.4 ± 11.6, 52 ± 31 and 3.3 ± 0.3, respectively). The PR and QTcn intervals of ECG were significantly longer in the Saf200 group (p < 0.001 versus CTL). The other doses of saffron only significantly prolonged the QTcn interval.

Conclusion: The results suggest that pretreatment with saffron, especially at the dosage of 100 mg/kg/day, attenuates the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat. This protective effect is apparently mediated through reduction of electrical conductivity and prolonging the action potential duration.
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http://dx.doi.org/10.3109/13880209.2013.767362DOI Listing
July 2013

Histological and mucin histochemical study of the small intestine of the Persian squirrel (Sciurus anomalus).

Anat Sci Int 2013 Jan 25;88(1):38-45. Epub 2012 Oct 25.

Department of Basic Sciences, University of Tehran, Tehran, Iran.

This article describes the histological and mucin histochemical properties of the small intestine of the Persian squirrel (Sciurus anomalus). This species is widely distributed in the Middle East and can be found as a companion animal. The histological studies revealed that the plicae circulares were not visible in the tunica mucosa. The maximum height and width of the villi were observed in the duodenum, which then decreased toward the ileum. The muscularis mucosa was scattered, whereas the tunica submucosa was composed of dense connective tissue. The lymphatic nodules were seen in the submucosa of the distal part of the jejunum and ileum, and Brunner's glands were embedded in the initial portion of the duodenum. The tunica muscularis was significantly thicker in the ileum, and the circular muscle layer was thicker than the longitudinal muscle layer throughout the entire length of the small intestine. The mucin histochemistry, which was examined using the periodic acid-Schiff (PAS) and alcian blue (AB) (pH 1.0 and 2.5) and also PAS-AB (pH 2.5) and aldehyde fuchsin-AB (pH 2.5) techniques coupled with methylation and saponification reaction for some sections, showed that the small intestine mucous content included both carboxylated and sulfated acidic mucins with few neutral mucins. The results of this study contribute to the knowledge of the histological and histochemical characteristics of the gastrointestinal tracts of exotic mammals and provide data for comparison with other mammals.
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http://dx.doi.org/10.1007/s12565-012-0159-5DOI Listing
January 2013

Cardiovascular effect of nifedipine in morphine dependent rats: hemodynamic, histopathological, and biochemical evidence.

Croat Med J 2012 Aug;53(4):343-9

Neuroscience Research Center, Physiology Research Center and Department of Physiology and Pharmacology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Aim: To investigate whether administration of nifedipine has considerable therapeutic effect in morphine-dependent rats.

Methods: Sixty animals were randomized into control, morphine, morphine plus nifedipine, and morphine plus dimethyl sulfoxide (DMSO, as nifedipine soluble) groups. Each group consisted of two subgroups, with and without heart injury. The groups were treated with incremental doses of morphine or morphine plus nifedipine daily for 7 days. Myocardial injury was induced by isoproterenol (50 mg/kg i.p.) on the day 7. On the day 8, the heart rate (HR), blood pressure (BP), rate-pressure product (RPP), and the plasma level of cardiac troponin I were measured and the hearts were histopathologically examined.

Results: In morphine-dependent rats, nifedipine administration was associated with a significantly higher decrease in the plasma level of cardiac troponin I than the administration of morphine alone. This finding was also significant in dependent animals that received only DMSO. HR, BP, RPP, and histopathological indices did not show significant changes in the presence of nifedipine.

Conclusion: Administration of nifedipine failed to show a significant therapeutic effect in morphine-dependent rats, especially in the group with myocardial injury.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428822PMC
http://dx.doi.org/10.3325/cmj.2012.53.343DOI Listing
August 2012