مقالات  رامين سيديان  

  Enzymatic analysis of Hemiscorpius lepturus scorpion venom using zymography and venom-specific antivenin Toxicon Toxicon 56 (2010) 521–525 ISI 2.581 Ramin Seyedian a, Mohammad Hassan Pipelzadeh b,*, Amir Jalali c, Euikyung Kim d,**, Hyunkyoung Lee d, Changkeun Kang d, Mijin Cha d, Eun-tae Sohn d, Eun-Sun Jung d, Ali Hassan Rahmani e, Abbas Zare Mirakabady 1 از 11
Hemiscorpius lepturus envenomation exhibits various pathological changes in the affected tissues, including skin, blood cells, cardiovascular and central nervous systems. The enzymatic activity and protein component of the venom have not been described previously. In the present study, the electrophoretic profile of H lepturus venom was determined by SDS-PAGE (12 and 15%), resulting in major protein bands at 3.5-5, 30-35 and 50-60 kDa. The enzymatic activities of the venom was, for the first time, investigated using various zymography techniques, which showed the gelatinolytic, caseinolytic, and hyaluronidase activities mainly at around 50-60 kDa, 30-40 kDa. and 40-50 kDa, respectively. Among these, the proteolytic activities was almost completely disappeared in the presence of a matrix metalloproteinase inhibitor, 1, 10-phenanthroline. Antigen-antibody interactions between the venom and its Iranian antivenin was observed by Western blotting, and it showed several antigenic proteins in the range of w30-160 kDa. This strong antigen-antibody reaction was also demonstrated through an enzyme-linked immunosorbent assay (ELISA). The gelatinase activity of the venom was suppressed by Razi institute polyvalent antivenin, suggesting the inhibitory effect of the antivenin against H lepturus venom protease activities Prudently, more extensive clinical studies are necessary for validation of its use in envenomed patients. (C) 2010 Elsevier Ltd. All rights reserved.

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  A biodistribution study of Hemiscorpius lepturus scorpion venom and available polyclonal antivenom in rats Journal of Venomous Animals and Toxins including Tropical Diseases ISSN 1678-9199 | 2012 | volume 18 | issue 4 | pages 375-383 ISI 0.43 Seyedian R (1), Jalali A (2), Babaee MH (2), Pipelzadeh MH (3), Rezaee S (4) اول از چهار نفر
Abstract: The purpose of the present study was to investigate the biodistribution profile of the venom of Hemiscorpius lepturus, the most dangerous scorpion in Iran. Blood and tissue samples were taken at various predetermined intervals during a 400-minute period for the venom and a 360-minute period for the antivenom in rats. The radio-iodination was carried out using the chloramine-T method. The results showed that the descending order of venom uptake was skin, kidneys and intestine, respectively. The descending order of polyclonal antivenom uptake was kidneys, intestine, heart and lungs. The calculated pharmacokinetic parameters of the venom were Telimination half-life = 521.5 ± 12.6 minutes; Vd/F (apparent volume of distribution) = 14.9 ± 3.3 mL; clearance (CL/F, apparent total clearance of the drug from plasma) 0.02 ± 0.005 mL/minute and for the antivenom Telimination half-life = 113.7 ± 7.4 minutes; Vd/F = 13 ± 1.2 mL and CL/F 0.08 ± 0.01 mL/minute. The pharmacokinetics profile comparison of the venom with that of the antivenom shows that serotherapy may be more effective if administered within 2-4 hours following envenomation by H. lepturus.


  An in vitro Comparative study upon the Hemolytic, Thrombogenic, Coagulation parameters and Stability properties of the Hemiscorpiuslepturus Venom Archives of Razi Archives of Razi Institute, Vol. 69, No. 1, June (2014) 69-76 Scopus Seyedian1, R., Hoseiny2, S.M., Kamyab 3, M., Mansury4, R., Seyedian 5, N., Gharibi6, S., Zare Mirakabadi7, A. اول از 7 نفر
Hemiscorpius lepturus belonging to Hemiscorpiidae family is the most venomous of all types of scorpion existing in south west of Iran causing hemoglobinuria and dermal lesions by envenomation. We compare the hemolytic pattern upon time in different domestic animals upon time according to their different sphingomyelin contents. In addition other in vitro hematologic parameters, platelet lysis, coagulation changes and finally preservative factors (temperature, pH, protases) are discussed. The hemolytic activity was inhibited significantly by heating at 100 °C for 60 minutes (26%) and reached 38% via incubation with papain (10U/ml) while retained over a pH range of 4-11. Horses and sheep have the lower (61%) and upper (100%) rate of hemolysis. Calcium and magnesium ions could increase rate of hemolysis and EDTA solution had significantly decresing effect. The venom significantly changed in vitro coagulation factors (PT and APTT) from base line levels and had no effect on platelet lysis. It seems that our venom belongs to metalloproteinases due to potentiation effects of bivalent cations (calcium and magnesium) and ghost cell formation in our study indicatiing hemoglobin efflux.

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  Neutralization effects of Iranian vipera lebetina biological properties by Razi Institute Antivenom ISMJ ISMJ 2013; 16(3): 215-24 . سامانه‌ی مقالات گوگل (scholar.google.com) R. Seyedian 1*, SM. Hosseini 1, N.Seyyedian 2, S. Gharibi 1, N. Sepahy 1, اول از ده نفر
Background: The hemotoxic and neurotoxic factors of snakevenoms is the main responsible for necrosis and tissue sloughing. Envenomations are common in rural areas in all provinces of Iran caused by snake species which causes local swelling, ecchymosis and alterations in blood profile in case of hemotoxic venom. In this study some in vivo and in vitro properties (Hemorrhagic, edematogenic and coagualant) of Iranian Vipera lebetina venom in addition to neutralizing capacity of pepsin derived Razi Institute polyvalent antivenin were assayed. Material and Methods: Escalating doses of Vipera lebetina venom dissolved in Normal saline (2.5-50 μg/ml) were injected (100μl) subcutaneously to dorsal area of rats (n=3) to investigate mean hemorrhagic amount after 24 hours.Groups of three mice were injected subcutaneously in the right foodpad with various amounts of venom (10-150μg).The left foodpad received the same amount (100μl) ofnormal saline alone (negative control) to evaluate the edematogenic property of this venom. To determine the coagulant activity, various amounts of venom dissolved in normal saline (50μl) were added to human plasma (200μl) and coagulation time was measured. Razi Institute antivenom was used for neutralization of all three measured biological parameters. Results: Mean hemorrhagic, procoagulant and edematous amounts (increasing 30% in hind paw edema) were 8.5, 1.1 and 70 microgram, respectively. Preincubation with polyvalent antibody (30 and 200 microliter) decreased hemorrhagic and procoagulant activity. Edematogenic property of this venom decreased significantly by incubation with antivenom (78% to 38% by incubation with 1000 microliter of polyvalent antivenom). Intra peritoneal injection of this remedy following envenomation had no effect in relieving symptoms. Myonecrotic effects were seen by intramuscular injection of Vipera lebetina venom in rats. Conclusion: Our study shows that Iranian antivenom could neutralize some in vivo and in vitro hazardous effects of envenomation by this snake like hemorrhagic, edematogenic and procoagulant properties that paves the way for separation and purification of multiple enzymes present in this venom to investigate the neutralizing capacity from Razi Institute polyvalent antivenom.

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  n vivo pharmacological study on the effectiveness of available polyclonal antivenom against Hemiscorpius lepturus venom Journal of Venomous Animals and Toxins including Tropical Diseases ISSN 1678-9199 | 2011 | volume 17 | issue 2 | pages 142-149 ISI 0.43 Jalali A (1, 2), Pipelzadeh M H (3, 2), Seyedian R (4), Rahmani A H (5), Omidian N (6 سوم از پنج نفر
The available Razi Institute antivenom is still, empirically, used by intramuscular (IM) administration for the treatment of scorpion stings in humans by six medically dangerous species including Hemiscorpius lepturus (H. lepturus). The aim of this study was to assess the neutralizing ability and effectiveness of the antivenom in inhibiting hemoglobinuria, biochemical changes, increased microalbuminuria and urinary lactate dehydrogenase (LDH) following H. lepturus sting. Simultaneous intramuscular administration of 10 mu L and 100 mu L of antivenom, after 24 hours, had no significant preventive effect on the extent and degree of hemoglobinuria or proteinuria produced in venom-treated rats. After IM administration of antivenom, no significant changes in decreased red blood cell (RBC) count and hemoglobin were observed. Immediate intramuscular administration of 10 mu L of antivenom had no significant effects on both LDH and microalbuminuria. The present findings did not present correlation with clinical signs. Therefore, to fully assess the efficacy of the available antivenom and make appropriate recommendations, more in vivo or in vitro investigations including antigen-antibody interaction, enzymatic analysis and route-dependent administration are required.


  IN VITRO PHARMACOLOGICAL STUDY UPON THE EFFECTIVENESS OF AVAILABLE ANTIVENOM AGAINST HEMISCORPIUS LEPTURUS VENOM Jundishapur J Nat Pharm Prod Jundishapur Journal of Natural Pharmaceutical Products 2011; 6(1): 1-8 Scopus Jalali A1,6*, Pipelzadeh M H2,6, Seyedian R3, Rahmani A H4, Omidian N5, سوم از شش نفر
The available Razi Institute antivenom is still, empirically, used by intramuscular (IM) or intravenous (IV) administration for the treatment of human scorpion envenoming by 6 medically dangerous scorpion species including Hemiscorpius lepturus (H.lepturus). The aim of this study was to assess the neutralizing ability of the antivenom upon the hemolysis effects of the venom from H. lepturus under in vitro conditions in rat. In vitro studies were including evaluation of hemolysis potency of the venom on rat washed RBC, assessment of antihemolytic potency of antivenom on rat washed RBC suspension and time profile of antihemolytic effectiveness of antivenom on treated rat washed RBC with venom, respectively. The in vitro results showed that the antivenom (at 10μl/ml of rat washed RBC suspension) reduced the concentration-dependent hemolysis of 1% rat washed RBC produced by venom from 71 to 43 % after 24 hours of incubation. Time profile of in vitro antihemolytic effectiveness of 10 μl available antivenom against hemolysis produced by 10μg of venom was dependent on the duration of incubation. In conclusion the findings of this study on animal model demonstrate that in vitro results were not correlated well with clinical findings in human

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  Saffron (Crocus sativus L.) increases glucose uptake and in muscle cells via multipathway mechanisms Food Chemistry 15 December 2012, Pages 2350–2358 ISI (4.05) Changkeun Kang a, Hyunkyoung Lee a, Eun-Sun Jung a, Ramin Seyedian a,1, MiNa Jo a, Jehein Kim a, چهارم از هشت نفر
Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C2C12 skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients. (C) 2012 Elsevier Ltd. All rights reserved.

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  Acute renal failure: A prospective four months study at Shariati Hospital Acta Medica Iranica 39,2,2001 Pubmed Najafi I, Ganji MR, Kayedi M, Haghighatkhah HR, Seyedian R " نفر پنجم از پنج نفر
o delineate the incidence , epidemiology, etiology, and prognosis of acute renal failure (ARF) and to compaed the findings with international data, we prospectively studied 2360 patients, admitted at shariati hospital during a four months period ending on Jan, 6, 1996. One hundred and twenty-four (5.1%) patients meeting ARF crieteria were encountered. The most common cause of ARF was prerenal azotemia, nephrotoxins were the second common cause, and primary renal disease were the third.In-hospital mortality was 5.5% and 31% of this mortality was related to ARF. Poor prognostic factors were oliguria, maximum serum ceratinine (Cr) level, rise of Cr during admission, multiorgan failure,and sepsis.

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  Cardiotoxic and Arrhythmogenic Effects of Hemiscorpius lepturus Scorpion Venom in Rats Journal of Arthropod-Borne Diseases Vol. 9, No. 2, 2015 ISI Khalil Pourkhalili, Euikyung Kim, NavidReza Mashayekhy, Mostafa Kamyab, SeyedMehdi Hoseiny, Reihane Evazy, Abbas Zare-Mirakabadi, Ramin Seyedian نویسنده مسئول از هشت نفر
Background: Envenomation by Hemiscorpius lepturus is not painful and the clinical manifestations include bloody urine due to hemoglobinuria or hematuria, dermonecrotic reactions,cardiac arrhythmia and in minority of cases acute renal failure which may lead to death following disseminated intravascular coagulation in infants. Cardiac effects of envenomation by H. lepturus venom including inotropic, chronotropic and arrhythmogenic properties are not studied as now in rat hearts with Langendorff apparatus. Methods: Rat hearts were allowed to equilibrate in its buffer and cardiotropic plus arrhythmogenic effects induced by injection of different doses of H. lepturus venom were detected and recorded by computer acquisition based data in Langendorff apparatus. The neutralizing effects of Razi Institute antivenom and autonomic drugs were assayed in parallel studies. Results: Hemiscorpius lepturus venom (25 μg/100 l) treatment caused a negative inotropic (65.4 ± 3.2 versus 110.2 ± 3.4) and chronotropic effects (186.3 ± 4.2 versus 302 ± 6.3) in comparison to normal saline. Arrhythmogenic aspects including bradycardia, QRS widening and ST depression were induced by venom injection. Pre venom treatment (20 min) of Razi Institute antivenom (10 μl) neutralized cardiotropic effects but post venom injection (15 min later) had no therapeutic role. Pre (10 min before) and post (15 min after) injection of adrenaline (10 μl) neneutralized cardiotropic effects while pre venom injection (20 min) of propanolol (10 μl) had aggravating effects. Conclusion: Our study paves the way for further in vivo investigation of cardiovascular effects of this venom for finding suitable treatments instead of its ordinary antivenom medication in cardiogenic shock induced by the venom.

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  Evaluation of oxidative quality parameters in imported edible oils in Iran British Food Journal Vol115 No 6,2013 ISI Mehdi Mohammadi,Parvaneh Hajeb,Ramin Seyedian,Gholam Hosein Mohebbi ,Alireza Barmak سوم از پنج نفر
Purpose – The purpose of this paper is to determine the peroxide value (PV), p-anisidine and total oxidation value (TOTOX) values of imported edible oils in Iran. Design/methodology/approach – A total 196 oil samples of different origin and types (corn, olive, canola and grape-seed oil) were collected randomly from Boushehr port of Iran and a total 27 oil samples were also collected from frying pans used to deep-fry local food items at different restaurants in Boushehr city. Findings – The PVs ranged from 1.38-13.74, 3.90-20.00, 0.83-2.99, 0.67-11.95 and 0.00-9.96 mequiv/kg found in refined olive oil, virgin olive oil, canola oil, grape-seed oil and corn oil, respectively. The results showed that PVs of 18.37 percent of imported oil and 62.96 percent of frying oils from restaurant exceeded the maximum acceptable limits set by Institute of Standards and Industrial Research of Iran (ISIRI) (2-20 mequiv/kg for different types of oils). P-anisidine value ranged from 0.89-27.56 mequiv/kg in imported oils and 2.21-30.76 mequiv/kg found in frying oil from restaurants. The TOTOX value increased linearly with peroxide values and p-anisidine values. It ranged from 0.89-76.62. Originality/value – Fried foods are very common in Iranians' diet. A major portion of the edible oils in Iran are imported from other countries through Boushehr port. ISIRI has set maximum acceptable limit for PVs in different oils imported to the country. The possible effects of storage on oil oxidation are the original criteria of this research. The results of the study indicate that inappropriate storage of edible oils and their use in frying applications at restaurants facilitate oil oxidation and deterioration.


  Characterization and Pharmacological Activities of Jellyfish, Chrysaora hysoscella Captured in Bushehr Port, Iran Iranian Journal of Toxicology Vol 10, No 5, September-October 2016 Chemical abstract Somayyeh Gharibi 1, Iraj Nabipour 1, Euikyung Kim 2, Seyede Maryam Ghafari 3, Seyed Mehdi Hoseiny 1, Mostafa Kamyab 4, Ramin Seyedian*1 نویسنده مسئول از هفت نفر
ABSTRACT Background: Cutaneous reactions like pruritus and erythema are common in warm months of the year in Bushehr Port, Persian Gulf, Iran due to jellyfish envenomation. This study reports isolation of the Chrysaora hysoscella nematocysts and evaluating its pharmacological activities during a bloom in 2013. Methods: The venom of C. hysoscella captured in Jofre area in Bushehr port was analyzed. The electrophoretic profile was assessed by SDS-PAGE (12.5%) and the crude sample was analyzed using reverse phase HPLC. Caseinase activity was also determined. Results: After separation of tentacles and isolation of their nematocysts, three different major protein components were revealed at 72-250 kDa with SDS-PAGE, signifying the presence of peptides in its venom. Two major peaks at 8.62 and 11.23 min were observed in reverse phase HPLC of the crude venom denoting protease peptide structural identities. Caseinase activity of C. hysoscella's venom was extremely low as compared with other jellyfish venoms. Conclusion: This was the first report on the structural examination of jellyfish in Persian Gulf and may pave the way for determination and separation of destructive enzymes inducing cutaneous reactions in fishermen and swimmers.

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  The toxinology of sea snakes: A systematic review دوماهنامه طب جنوب سال نوزدهم-شماره چهار-صفحه 703- 662 Google scholar غلام حسین محبی-رامین سیدیان-ایرج نبی پور دوم از سه نفر
Background: Sea snakes belong to Hydrophiidae family mainly are found in tropical and subtropical waters of the world including the Persian Gulf. Their highly lethal venoms are more potent than snakes with terrestrial origin and contain complex mixtures of organic and inorganic bioactive substances, such as enzyme, and non-enzymatic proteins. There were limited studies on the venoms and toxins of sea snake; hence, the aim of this systematic review was to investigate the toxinological dimensions of sea snakes. Materials and Methods: In order to investigate of the toxins of sea snakes, the “Hydrophis schistosus toxin", "Hydrophis cyanocinctus toxin", " Hydrophis lapemoides toxin", "Hydrophis spiralis toxin", and "Lapemis curtus toxin " terms were searched separately, in "PubMed database", in 10/08/2016 which obtained 32, 9, 2, 2 and 4 papers, respectively. The "Hydrophis gracilis toxin" term had no any results. For the “Hydrophis gracilis" term, two studies were obtained. The first one related to the sea snakes phylogenetic characteristics and the second one shared with other search results and well-connected with the issue. Some papers were similar in different searches. Of these, those studies were selected that had direct relevance to the subject . Results: The main isolated toxins from different sea snakes venoms included three-finger toxin (3FTx (short chain neurotoxins isoforms: AAL54893, AAL54892, ABN54806; long chain neurotoxins isoforms: AAL54894, AAL54895, P68416 , ABN54805), pelamitoxin (P62388), phospholipase A2 (both the basic and acidic PLA2), two phospholipases A2 (PLA2-H1 and H2), cysteine-rich secretory protein (CRISP), snake venom Zn2+-metalloproteinase (SVMP), L-amino acid oxidase (LAAO), 5′-nucleotidase, Hydrophitoxins a, b and c, Hydrophis ornatus a, Hydrophis lapemoides a, PDGF and α- neurotoxins of rSN311, rSN316 and rSN285. Each toxin and protein family presents a wide range of pharmacological activities. Some of these neurotoxins were linked to acetylcholine receptors in the neuromuscular junctions. These toxins showed protease (gelatinase and caseinase) activities, and/or they produce the myonecrosis and biochemical and histopathological changes. Conclusion: There is scant variability in the venom composition in the same and different species of sea snakes. Our study revealed that there is a rather simple venom profile with an affinity towards a lethal mixture of high abundance of neurotoxins and PLA2s, and lower amounts of toxins such as CRISP, SVMP and LAAO.

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  A review of epidemiological, clinical and in vitro physiological studies of envenomation by the scorpion Hemiscorpius lepturus (Hemiscorpiidae) in Iran Toxicon Volume 55, Issue 2-3, February 2010, Pages 173-179 ISI Amir Jalali a,*, Mohammad H. Pipelzadeh b, Ramin Sayedian a, E.G. Rowan c سوم از چهار نفر
Many of the published accounts of envenomation by Hemiscorpius lepturus (H. lepturus) are in a form that makes it difficult for non Farsi readers to access. The purpose of this review is to summarise the Iranian literature on the toxinological effects of the venom of H. lepturus using both in vivo and in vitro data and where appropriate, details of methods and ethics statements will be reported

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  The protective role of oral consumption of N-acetyl cysteine during a single session of exhaustive exercise in untrained subjects African Journal of Biotechnology Research Vol.8(1), pp. 7-13 , January 2014 Google scholar Iranpour D Movahed ALI Goudarzi A Tarverdizadeh Bahman Akbarzadeh Samad Motamed Niloufar Pakdel Farhad Hagian Ali Akbar Seyedian Ramin Vahdi Saeid Tahmasebi Rahim نهم از یازدهم
The aim of the current study was to verify the effect of N-acetyl cysteine (NAC) supplementation on markers of oxidative stress and inflammatory response during a single session of exhaustive exercise. In a randomized placebo-controlled double-blind clinical trial, thirty healthy, untrained young males and females with a mean age of 21.33±2.39 years, weight of 59.63± 9.24 kg and height of 166.20±10.15 cm were selected and divided into 2 groups. Before starting the supplementation, blood samples were collected from all the participants. The next blood samples were collected just before the exercise started, immediately after the exhaustive exercise and after one hour of rest. Malondialdehyde (MDA), total antioxidative capacity (TAC), CRP, BMI and Vo2 max were determined. A significant increase was observed in MDA and CRP levels during the experiment in the placebo group. But in the treated group, the concentrations remained the same throughout the experiment. The TAC levels were significantly raised in the samples collected after NAC supplementation as compared to the placebo group. No changes were observed in the time to fatigue. Results of the current study suggest that oral consumption of n-acetyl cysteine for 24 h before a single bout of an exhaustive physical exercise could significantly reduce the harmful effects of oxidative stress.


  Persian gulf jellyfish (Cassiopea andromeda) venom fractions induce selective injury and cytochrome c release in mitochondria obtained from breast adenocarcinoma patients Asian Pacific Journal of Cancer Prevention DOI:10.22034/APJCP.2017.18.1.277 Scopus Mohammad Reza Mirshamsi1, Ramesh Omranipour2, Amir Vazirizadeh3, Amir Fakhri1, Fatemeh Zangeneh1, Gholam Hussain Mohebbi4, Ramin Seyedian5, Jalal Pourahmad1 هفت از هشت
Objective: This study was conducted to investigate whether fractions of jellyfish Cassiope andromeda venom, could selectively induce toxicity on mitochondria isolated from cancer tissue of patients with breast adenocarcinomas. Methods: Firstly, we extracted two fractions, (f1 and f2) from crude jellyfish venom by gel filtration on Sephadex G-200.Then different dilutions of these extracted fractions were applied to mitochondria isolated from human breast tumoral- and extra-tumoral tissues. Parameters of mitochondrial toxicity including generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, swelling, cytochrome c release, activation of caspase3 and apoptosis were then assayed. Result: Our results demonstrate that fraction 2 of Cassiopea andromeda crude venom significantly (P<0.05) decreased mitochondrial succinate dehydrogenase activity, increased mitochondrial ROS production, induced mitochondrial swelling, MMP collapse and cytochrome c release, activated caspase3 and induced apoptosis only in tumoral mitochondria, and not in mitochondria obtained from extra-tumoral tissue (P<0.05). Conclusion: In conclusion this study suggested that fraction 2 of Cassiopea andromeda crude venom selectively induces ROS mediated cytotoxicity by directly targeting mitochondria isolated from human breast tumor tissue.

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Volume 18, Issue 1, January 2017, Page 277-286

  Enzymatic Analysis of Iranian Echis carinatus Venom Using Zymography Iranian Journal of Pharmaceutical Research (2017), 16 (3): 1155-1160 ISI(IF=1.352) مصطفی کامیاب-اوی کیونگ کیم-سیدمهدی حسینی-رامین سیدیان نویسنده مسئول
Snakebite is a common problem especially in tropical areas all over the world including Iran. Echis carinatus as one of the most dangerous Iranian snakes is spreading in this country excluding central and northwest provinces. In this study gelatinase and fibrinogenolytic properties as two disintegrating matrix metalloproteinase enzymes were evaluated by a strong clear halo between 56-72 kDa in addition to another band located 76-102 kDa for gelatinase and one major band around 38 kDa for fibrinogenolytic enzyme respectively. The electrophorectc profile of our venom demonstrated at least one protein band between 24-31 kDa like previous reports and another two bands between 52-76 kDa and below 17 kDa stemmed probably due to the effect of natural selection in one species. According to our results Razi institute antivenin could neutralize in-vitro effects of gelatinase enzyme comprehensively. The electrophoretic profile of Iranian commercial antivenom as the main intravenous treatment of envenomed patients showed impurities in addition to F (abʹ) 2 weighing 96 kDa in SDS-PAGE analysis. It proposes more efforts for refinement to avoid short and long unwanted effects in envenomed patients.

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  Hemodynamic Changes in Experimentally Envenomed Anaesthetized Rats by Intravenous Injection of Hemiscorpius lepturus Venom Journal of Arthropod-Borne Diseases 13 Feb 2018) ISI IF=1.1 Khalil Pourkhalili 1, Hossein Fatemikia 2, Euikyung Kim 3, Navid Reza Mashayekhy 4, Naser Mohammadpour Dounighi 5, Abdollah Hajivandi 6, Yaghoob Hassan 7, *Ramin Seyedian 8 نویسنده پاسخ گو
Background: We investigated the hemodynamic changes (Inotropic, chronotropic and arrhythmogenic) in intrave-nously envenomed anesthetized rats with Hemiscorpius lepturus venom. The neutralizing potencies of different drugs and commercial antivenom were assessed simultaneously. Methods: Different doses of the crude venom (100, 200 and 400μg/rat) were injected during five minutes via the femoral vein and cardiovascular changes were recorded in rats in Razi Institute Corporation, Karaj, Iran in 2017. The drugs (Atropine, lidocaine, propranolol and prazosin) were injected before the venom for determination of the coun-teracting effects. Different volumes (100, 500 and 1000μl) of the antivenom were pre envenomed to neutralize cardi-ovascular changes. Results: Temporary hypertension and bradycardia with no arrhythmogenic effects were depicted within twenty minutes. There was a difference in arterial pressure between the venom (400μg/rat) and the vehicle at 8 minutes (114.68±5.1mmHg versus 70.2±4.3mmHg). Elevation of the mean arterial pressure was inhibited by propranolol (2 mg/kg) and neutralized by prazosin (1mg/kg) while lidocaine (4mg/kg) and atropine (1mg/kg) had no effects. Pre-medication with Iranian commercial antivenom (1000μl) produced surprisingly temporary hypertension compared to the vehicle (140.84±4.5 versus 84.3±3.2). It had no neutralizing properties on blood pressure variation before the venom injection. Volume-expanded hypertension phenomenon was ruled out in a parallel study. Conclusion: This venom has vasoconstrictive effects in rats probably due to the presence of norepinephrine like ma-terials in its content or liberated from adrenal gland inhibited by prazosin premedication. The neutralizing effects of antivenom on venom-induced hypertension are questionable.


  Saffron Protection against Bleomycin-Induced Pulmonary Fibrosis in Rats Iranian Journal of Toxicology Volume 11, No 6, November-December2017 Bi monthly Chemical abstract Mehrzad Bahtouee 1 , Hossein Fatemikia 2 , Khalil Pourkhalili 3 , Euikyung Kim 4 , Hamid Reza Rahimi 5 , Zahra Tavosi 1 , Abdol hamid.Esmaili 5 , Abdollah Hajivandi 6 , Yaghoob Hassan 7 , Ramin Seyedian*8 نویسنده پاسخ گو
Background: Bleomycin-induced lung fibrosis has been accepted as an animal model for fibrosis in rats. The aim of this study was to evaluate the effects of saffron aqueous extract on this disorder paving the way for more investigation in treating idiopathic pulmonary fibrosis in human. Methods: Male Wistar rats (250–300 gr) were instilled a single dose of bleomycin (5 mg/kg) via intratracheal tube (n=6) in 2015. Sham group received normal saline. Saffron aqueous extract (50 mg/kg and 100 mg/kg) were given orally in two different treated groups with bleomycin for 28 days. Lung Indices was calculated at the end of this experiment. Lung segments fixed in 10% formaldehyde were used for pathological preparation with Hematoxylin & Eosin and trichrome staining. Results: The body weight was decreased and lung Indices increased in bleomycin group (P<0.5). Bleomycin administration increased myeloperoxidase, malondialdehyde and finally TNF-α in lung tissue homogenates (P<0.05) compared with sham group. The fibrotic process and thickening of alveolar septa in treated rats with bleomycin were increased by H&E and Masson Trichrome staining. Saffron treatment (50 and 100 mg/kg) attenuated the increase in MDA (264.43±10.4 nmol/g by the higher dose versus 378.4±18.1nmol/g), MPO (0.19±0.03 and 0.13± 0.04 IU/ml versus 0.39.2±0.05 IU/ml) and TNF-α level (18.42±3.7 ng/ml and14.31±3.6 ng /ml versus 35.32±4.2) in lung homogenates compared to bleomycin group (P<0.05). It decreased collagen accumulation and alveolar destructive patterns in pulmonary fibrosis. Conclusion: This study introduces saffron as novel anti-fibrotic agent against bleomycin-induced fibrosis due to histological examinations and preventive effects on destructive enzyme release in rats. Keywords: Bleomycin, Fibrosis, Rat, Saffron.

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  A Comparative Analysis of Saffron and Methylprednisolone on Bleomycin-Induced Pulmonary Fibrosis in Rats Iranian Journal of Toxicology Volume 12, Issue 3 (May-June 2018) ISC Mehrzad Bahtouee , Hossein Fatemikia , Ali Movahed , Abdolhamid Esmaili , Yaghoob Hassan , Mohammad Zarei , Ramin Seyedian Corresponding author
Background: The purpose of this study was to compare the effects of saffron and methylprednisolone on bleomycin-induced pulmonary fibrosis in rats. Methods: This study was conducted in Bushehr, southern Iran in 2017.The animals were divided into four groups of five rats each. Three groups were injected with a single intratracheal dose of bleomycin (5 mg/kg). The fourth group was administered with normal saline at the same volume (200 µl). Saffron extract dissolved in water was given to one group (100 mg /body weight) orally while intraperitoneal injection of methylprednisolone (2.5 mg/kg) injected to another one for 16 days. The rats were sacrificed 28 days following surgery and their right and left lungs were removed and washed for measuring lung indices, myeloperoxidase activities and finally histopathological examination. Results: Injection of bleomycin caused decrement of body weight aggravated by intraperitoneal methylprednisolone treatment. Lung indices were increased in the bleomycin-treated group compared with the control, while methylprednisolone, unlike saffron, had no preventive effects on it. Both saffron and methylprednisolone treatment prevented the increase in lung myeloperoxidase as a destructive enzyme. In addition, excessive collagen deposition and thickening of alveolar septa were significantly prevented with saffron treatment as compared to methylprednisolone injection following hematoxylin and eosin staining. Conclusion: Saffron with established antioxidant properties could prevent some detrimental effects in bleomycin-induced pulmonary fibrosis even more than methylprednisolone injection known as a standard therapy in this murine model. More investigations must be carried out to examine the beneficial or harmful effects of this remedy.

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  Serological, pathological and scintigraphic assessment of Hemiscorpius lepturus effects on renal dysfunction in rats IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES Volume: 21 Issue: 12 Pages: 1221-1225 Published: DEC 2018 ISI Ali Movahed 1, Hossein Fatemikia 2, Kaveh Tanha 3, Abdolhamid Esmaili 4, Euikyung Kim 5, Nasser Mohammadpour Dounighi 6, Soodabeh Zendeboodi 7, Ramin Seyedian Corresponding author
Objective(s): Hemiscorpius lepturus is one of the dangerous scorpions of Iran leading to acute kidney injury (AKI) especially in infants. The purpose of this animal study was to compare the serological, pathological and scintigraphic data to quickly predict the occurrence of this disorder. Materials and Methods: In two groups of animals, each contained five rats, H. lepturus venom (1200 μg/ Kg) were injected intravenously via the tail vein. At three hours and one week later, 99m Tc-DMSA (3 mCi) was intravenously injected and renal scintigraphy was performed after an hour. Moreover, plasma levels of creatinine, sodium, potassium, and blood urea nitrogen (BUN) were measured. At the end of the study, renal tissues were excised and prepared to perform pathological evaluation after Hematoxylin and Eosin staining. Results: All serological indices were remained unchanged compared to control. A large number of glomerular fibrin thrombi with entrapped red blood cells and simplified tubular epithelium in dilated and ectatic tubules were observed in high power field (×100) four hours after envenomation, which reduced significantly one week later. In our scintigraphic study, there was a statistically significant difference (P<0.05) in kidney count rate per pixels (CRPP) in both acute and chronic phases compared to the sham group that received normal saline (0.84±0.05 and 1.36±0.07 versus 1.7±0.05). Conclusion: The results of this preliminary animal study suggest renal scintigraphy is a non-invasive method to predict the occurrence of the AKI in H. lepturus envenomation. It leads the way for more investigation to counteract the renal failure induced by this venom.

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  The attenuative effects of oral resveratrol on renal changes induced by vanadium injection in rats Journal of Renal Injury Prevention 2019; 8(2): 127-132. ISI Soodabeh Zendeboodi1ID, Abdolhamid Esmaili2, Ali Movahed3, Hossein Fatemikia4, Ali Jamshidi5, Matin Nazari5, Hosein Heydari5, Ramin Seyedian6* Corresponding author
Introduction: Resveratrol (trans-3,5,4’-trihydroxystilbene) as a polyphenol with potential antioxidant and anti-inflammatory properties is known as an effective herbal medicine in different disorders in rats. Objectives: The present study was carried out to investigate the protective effects of oral consumption of resveratrol on vanadium induced renal injury in male Wistar rats. Materials and Methods: Animals received either ammonium metavanadate (AMV, 5 mg/kg/d, (intraperitoneally; 14 consecutive days) or resveratrol solution (10 mg/kg and 50 mg/kg, gastric gavage) along with AMV treatment. The last group received resveratrol alone (50 mg/kg, gastric gavage) for 4 weeks. Results: AMV injection caused progressive tubular damages resembling acute tubular necrosis. Microscopic views revealed tubular attenuation and blebbing. In addition, progressive peritubular congestion of the capillaries observed while no evidence of renal fibrosis was present in trichrome staining. Further, levels of the renal transforming growth factor β1 (TGF-β1) as an index of fibrosis had no difference in treated animals as compared with the control (13.4±1.2 versus 11.24±0.93 pg/mg protein) at the P < 0.05. However, in AMV-treated animals receiving the higher dose of resveratrol (50 mg/kg), the renal superoxide dismutase (SOD) activity, showed no difference as compared with the saline-treated rats (42±1.3 versus 51±1.4). Conclusions It is evident that AMV injection had no ability to induce renal fibrosis in rats while it evokes renal destructive lesions based on pathological results and enzyme levels. Moreover, our preliminary results suggest that resveratrol in high dose (50 mg/kg) could confer a minor role against AMV induced renal tubular necrosis in rats due to pathological results.

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  A comparative study on the equine and camelid antivenoms upon cardiovascular changes induced with Hemiscorpius lepturus venom in rats Iranian Journal of Basic Medical Sciences ISI 1.859 Hossein Fatemikia 1, Mostafa Kamyab 2, Ali Movahed 3, Mehdi Sadeghi 4 , Euikyung Kim 5, Mahdi Behdani 6, Naser Mohammadpour Dounighi 7, Mehrnaz Shahrivar 8 , Ramin Seyedian نویسنده پاسخ گو از نه نفر (نفرآخر)
Objective(s): In this study, the neutralizing abilities of the equine and the recently introduced camelid antivenoms on the hemodynamic parameters (inotropism, chronotropism, and arrhythmogenicity) were assessed following envenomation by Hemiscorpius lepturus venom in rats. Materials and Methods: At first, the electrophoretic profiles of both products were obtained by using the SDS-PAGE method (12.5%) and stained with Coomassie blue and silver nitrate. Secondly, different doses of the camelid antivenom (10, 50, and 100 μl) were given intravenously in 10 min before venom injection (400 μg/rat). The neutralizing potencies of camelid and equine antivenoms were measured by preincubation (100 μl) with H. lepturus venom for 30 min at room temperature. Finally, equal amounts of the antivenoms were injected intravenously to observe the hemodynamic changes. Results: Based on the electrophoretic profile, it was evident that undesired proteins significantly decreased in equine antivenom, owing to impurities. Pretreatment with the camelid antivenom (100 μl), neutralized the elevation of the mean arterial pressure evoked with scorpion venom injection (88.15±4.56 versus 10.2±1.23 percent at the 8th min). The Incubation of the venom and the camelid antivenom counteracted the hemodynamic changes, but the equine product had no effect. The intravascular injection of the equine antivenom transiently increased the mean arterial pressure as compared to the control (108.67±8.63 mmHg versus 52.67±1.93 mmHg at the 10th min). Conclusion: The most obvious finding emerging from this study was that the camelid antivenom neutralized the hemodynamic changes in rats significantly, but in comparison, the equine antivenom had just a minor ability.

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