Publications by authors named "Reza Khorasani"

20 Publications

  • Page 1 of 1

α-Lipoic acid prevents senescence, cell cycle arrest, and inflammatory cues in fibroblasts by inhibiting oxidative stress.

Pharmacol Res 2019 03 3;141:214-223. Epub 2019 Jan 3.

Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Senescence is a process characterized by an irreversible growth arrest in cells and induced by oxidative stress. In the current study, anti-aging potential of a well-known antioxidant, α-lipoic acid (α-LA), in rat embryonic fibroblast (REF) cells was assessed. In this regard, oxidative stress, inflammation, and apoptosis pathways were investigated on REF cells exposed to HO as a senescence inducer and α-LA as a protective compound. In cells treated with α-LA and HO level of β-galactosidase, as an aging marker, and oxidative stress biomarkers, were significantly lower than those exposed to HO only. Furthermore, flow cytometry assay showed that α-LA caused a significant reduction in the number of apoptotic cells via the caspase-dependent pathway. In addition, it could neutralize the inflammatory effects of HO and attenuated the concentration of inflammatory cytokines. In comparison to HO group, a significant increase in G0/G1 arrest was observed during cell cycle analysis in cells exposed to HO and α-LA. The results of this study show that α-LA has beneficial effects on HO-induced cellular senescence. α-LA works by attenuating the reactive oxygen species, subsiding inflammation, and affecting cell division.
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http://dx.doi.org/10.1016/j.phrs.2019.01.003DOI Listing
March 2019

Molecular and biochemical evidence on the protective role of ellagic acid and silybin against oxidative stress-induced cellular aging.

Mol Cell Biochem 2018 Apr 8;441(1-2):21-33. Epub 2017 Sep 8.

Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Aging is a natural process in living organisms that is defined by some molecular and cellular changes with time. Various causes such as mitochondrial DNA aberrations, aggregation of proteins, telomere shortening, and oxidative stress have an influential role in aging of the cells. Natural antioxidants are compounds that are potent to protect the body from detrimental effects of molecules such as free radicals. The aim of this study was to evaluate the anti-aging properties of ellagic acid (EA) and silybin (SIL), as natural antioxidant compounds on rat embryonic fibroblast (REF) cells. These cells were pre-incubated with EA and SIL, thereafter were exposed to hydrogen peroxide (HO). Then, the cell viability, SA-β-GAL activity, distribution of cell cycle, NF-κB, and mitochondrial complex I, II/IV enzyme activity were measured. The results of this study revealed the protective effects of EA and SIL in HO-treated REF cells, which confirm the previous achieved data on antioxidant and anti-inflammatory characteristics of EA and SIL against HO in the treated REF cells. However, more new in vivo experiments are required to discover the anti-aging effects and mechanism of action of such compounds.
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http://dx.doi.org/10.1007/s11010-017-3172-0DOI Listing
April 2018

Preclinical assessment of β-d-mannuronic acid (M2000) as a non-steroidal anti-inflammatory drug.

Immunopharmacol Immunotoxicol 2015 ;37(6):535-40

a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .

Context: β-d-Mannuronic acid (M2000) has shown its therapeutic effects with the greatest tolerability and efficacy in various experimental models such as experimental autoimmune encephalomyelitis (EAE), adjuvant induced arthritis (AIA), nephrotic syndrome, and acute glomerulonephritis. Despite pharmacological effects of β-D-mannuronic acid, there have been no systematic toxicological studies on its safety so far.

Objective: The study was designed to determine the acute and subchronic toxicity of β-D-mannuronic acid, an anti-inflammatory agent, in healthy male NMRI mice and Wistar rats, respectively.

Materials And Methods: For the acute toxicity study, the animals received orally five different single doses of β-D-mannuronic acid and were kept under observation for 14 d. In the subchronic study, 24 Wistar male rats were divided into four groups and were treated orally (gavage) once daily with test substance preparation at dose levels of 0, 50, 250, and 1250 mg/kg body weight for at least 63 consecutive days (9 weeks). Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histopathological determinations were monitored during the study.

Results: The results of acute toxicity indicated that the LD50 of β-D-mannuronic acid is 4.6 g/kg. We found no mortality and no abnormality in clinical signs, body weight, relative organ weights, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.

Conclusions: Our results suggest that β-D-mannuronic acid is relatively safe when administered orally in animals.
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http://dx.doi.org/10.3109/08923973.2015.1113296DOI Listing
September 2016

In situ stabilization of As and Sb with naturally occurring Mn, Al and Fe oxides in a calcareous soil: bioaccessibility, bioavailability and speciation studies.

J Hazard Mater 2014 May 2;273:247-52. Epub 2014 Apr 2.

Department of Ecosystem Science and Management, Materials Research Institute, Materials Research Laboratory, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address:

This study investigated the effectiveness of 6 different types of naturally occurring manganese, aluminum and iron oxides for stabilization of As and Sb in a calcareous soil spiked with 50mgkg(-1) of As or Sb and two dosages of treatments (2% and 5%). The resulting contaminated soils were subjected to a series of chemical extraction studies including sequential extraction, single step extraction with DTPA and Simplified Bioaccessibility Extraction Test (SBET) for estimation of bioaccessible fraction of As and Sb in soil and a greenhouse experiment using barley as the test crop. The results showed that Fe-associated and carbonate-bound fraction of As and Sb were predominant fractions. However, the amounts of labile fractions were higher in As contaminated soils, whereas the percentage of Sb associated with crystalline Fe-oxide and residual fractions were higher. The results revealed that application of natural metal oxides reduced DTPA and SBET extractable amounts and plant uptake of As and Sb. After application of amendments, the exchangeable fraction of As decreased dramatically by up to 82% while Sb exchangeable fraction decreased by up to 60% depending upon the additive. The results of chemical extractions and plant uptake confirmed that Sb had lower bioavailability, compared with As.
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http://dx.doi.org/10.1016/j.jhazmat.2014.03.054DOI Listing
May 2014

Imidazolylchromanone oxime ethers as potential anticonvulsant agents: Anticonvulsive evaluation in PTZ-kindling model of epilepsy and SAR study.

Bioorg Med Chem Lett 2011 Jan 10;21(2):655-9. Epub 2010 Dec 10.

Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

As a continuation of our efforts to develop the azolylchromanone derivatives as potential anticonvulsant agents, we explored (Z)- and (E)-oxime ether derivatives of imidazolylchromanones bearing different lipophilic O-benzyl groups and tested their anticonvulsant activities in PTZ-kindling model of epilepsy. O-(2,4-Dichlorobenzyl) oximes 8a, 16a and 20a were significantly effective in delaying the onset of the PTZ-evoked seizures at the dose of 30mg/kg in kindled animals. The most effective compounds in delaying seizures were 7-chlorochromanone-O-(2,4-dichlorobenzyl) oximes 8a and 20a. SAR studies showed that introduction of a chlorine atom to the 7-position and/or a methyl group to the 2-position of the chroman ring resulted in an improvement of anti-seizure efficacy in O-(2,4-dichlorobenzyl) oxime series.
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http://dx.doi.org/10.1016/j.bmcl.2010.12.021DOI Listing
January 2011

Non-normal Lanczos methods for quantum scattering.

J Chem Phys 2008 Jul;129(3):034110

Department of Chemistry, McMaster University, 1280 Main St. W. Hamilton, Ontario L8S 4M1, Canada.

This article presents a new complex absorbing potential (CAP) block Lanczos method for computing scattering eigenfunctions and reaction probabilities. The method reduces the problem of computing energy eigenfunctions to solving two energy dependent systems of equations. An energy independent block Lanczos factorization casts the system into a block tridiagonal form, which can be solved very efficiently for all energies. We show that CAP-Lanczos methods exhibit instability due to the non-normality of CAP Hamiltonians and may break down for some systems. The instability is not due to loss of orthogonality but to non-normality of the Hamiltonian matrix. While use of a Woods-Saxon exponential CAP-as opposed to a polynomial CAP-reduced non-normality, it did not always ensure convergence. Our results indicate that the Arnoldi algorithm is more robust for non-normal systems and less prone to break down. An Arnoldi version of our method is applied to a nonadiabatic tunneling Hamiltonian with excellent results, while the Lanczos algorithm breaks down for this system.
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http://dx.doi.org/10.1063/1.2940733DOI Listing
July 2008

Anticonvulsant and antiepileptogenic effects of azolylchromanones on lithium-pilocarpine induced seizures and pentylenetetrazole-kindling model of epilepsy.

Biomed Pharmacother 2008 Apr-May;62(4):208-11. Epub 2007 Dec 28.

Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Recently, we described the design and synthesis of azolylchroman derivatives as conformationally constrained analogs of (arylalkyl)azole anticonvulsants. In the present study, two distinct pharmacological models, lithium-pilocarpine induced seizure and PTZ-induced kindling were used to investigate both anticonvulsive and antiepileptogenic properties of the selected azolylchromanones including 7-chloro-3-(1H-imidazol-1-yl)chroman-4-one (I), 3-(1H-1,2,4-triazol-1-yl)chroman-4-one (II), trans-3-(1H-imidazol-1-yl)-2-methylchroman-4-one (III) and trans-7-chloro-3-(1H-imidazol-1-yl)-2-methylchroman-4-one (IV). Although compounds I and II were highly effective at the dose of 5 mg/kg against acute PTZ-induced convulsions as previously reported by us, these compounds exhibited limited effects in PTZ-induced kindling model. However, compound I was found to exert respectable action in delaying seizures and reducing seizure index at the dose of 10 mg/kg. In contrast, all tested compounds showed an anticonvulsant effect due to the considerably delayed onset of seizures in lithium-pilocarpine model. Compound I exhibited more effective action in delaying seizures as well as decreasing seizure duration in this model of epilepsy. In conclusion, the azolylchromanones I-IV, especially 7-chloro-3-(1H-imidazol-1-yl)chroman-4-one (I), were effective against lithium-pilocarpine induced status epilepticus, suggesting the potential application of the test compounds in the treatment of status epilepticus.
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http://dx.doi.org/10.1016/j.biopha.2007.12.003DOI Listing
August 2008

Rat Plasma Oxidation Status After Nigella Sativa L. Botanical Treatment in CCL(4)-Treated Rats.

Toxicol Mech Methods 2008 Jan;18(9):725-31

Laboratory of Toxicology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

ABSTRACT Nigella sativa Linn. (family Ranunculaceae), commonly known as black cumin, is native to the Mediterranean area and has been used for thousands of years as a health and beauty aid. The present study investigated the protective effects of Nigella sativa (NS) extract (NSE) and oil (NSO) on CCl(4)-induced nitrosative stress and protein oxidation in rat. CCl(4) (0.8 mg/kg) was used as an aid for induction of nitrosative stress. In vitro antioxidant potential was tested in the presence of 2,4-dinitrophenylhyrdazine (DPPH) as an organic nitrogen radical. Doses of 0.2, 0.3, and 1 mg/kg of the NS extract and oil were administered to CCL(4)-treated rats for 10 days. At the end of treatment, blood was taken from rats under anesthesia and plasma was separated. The concentration of nitric oxide (NO), total antioxidant power (TAP), carbonyl molecules (CM) as measure of protein oxidation (PO), tumor necrosis factor-alpha (TNF-alpha), and total thiol molecules (TTM) were measured in plasma. In vitro evaluation of antioxidant effects of NSE and NSO showed that the highest antioxidant activity (80%) was observed with the concentration of 10 and 20 mg/ml, respectively, that were equal to vitamin E (200 mg/ml). Administration of CCL(4) increased plasma PO, NO, TNF-alpha and decreased TAP and TTM. Both NSE and NSO showed significant protection against CCl(4)-induced changes in biochemical parameters, but not dose-dependently. Doses of 0.3 and 1 mg/kg were more effective than doses of 0.2 mg/kg for both NSE and NSO, but dose of 1 mg/kg was the most effective one. The results indicate the potential of NS in preventing CCL(4)-induced toxic nitrosative stress. It is concluded that NS has marked antioxidant potentials that may be beneficial in alleviating complications of many illnesses related to oxidative/nitrosative stress in humans, but preclinical safety measures should be completed before clinical trials.
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http://dx.doi.org/10.1080/15376510802232233DOI Listing
January 2008

Long time wave packet dynamics from energy eigenfunctions: nonuniform energy resolution via adaptive bisection fast Fourier transformation.

J Chem Phys 2007 Nov;127(18):184107

Department of Chemistry, McMaster University, 1280 Main Street W., Hamilton, Ontario L8S 4M1, Canada.

This article presents a new approach to long time wave packet propagation. The methodology relies on energy domain calculations and an on-the-surface straightforward energy to time transformation to provide wave packet time evolution. The adaptive bisection fast Fourier transform method employs selective bisection to create a multiresolution energy grid, dense near resonances. To implement fast Fourier transforms on the nonuniform grid, the uniform grid corresponding to the finest resolution is reconstructed using an iterative interpolation process. By proper choice of the energy grid points, we are able to produce results equivalent to grids of the finest resolution, with far fewer grid points. We have seen savings 20-fold in the number of eigenfunction calculations. Since the method requires computation of energy eigenfunctions, it is best suited for situations where many wave packet propagations are of interest at a fixed small set of points--as in time dependent flux computations. The fast Fourier transform (FFT) algorithm used is an adaptation of the Danielson-Lanczos FFT algorithm to sparse input data. A specific advantage of the adaptive bisection FFT is the possibility of long time wave packet propagations showing slow resonant decay. A method is discussed for obtaining resonance parameters by least squares fitting of energy domain data. The key innovation presented is the means of separating out the smooth background from the sharp resonance structure.
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http://dx.doi.org/10.1063/1.2780155DOI Listing
November 2007

Benefits of Zataria multiflora Boiss in Experimental Model of Mouse Inflammatory Bowel Disease.

Evid Based Complement Alternat Med 2007 Mar 14;4(1):43-50. Epub 2006 Sep 14.

Laboratory of Toxicology, Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Laboratory of Pharmacognosy, Faculty of Pharmacy and Medicinal Plants Research Center and Laboratory of Histopathology, School of Medicine, Tehran University of Medical Sciences Tehran, Iran.

Inflammatory bowel disease (IBD) is a chronic condition of the intestine with unknown etiology involving multiple immune, genetic and environmental factors. We were interested to examine the effect of total extract from Zataria multiflora Boiss, a folk medicinal plant on prevention and treatment of experimental IBD. Z. multiflora was administered (400, 600, 900 p.p.m.) through drinking water to IBD mice induced by intrarectal administration of acetic acid. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic and microscopic examinations of colon were performed. Biochemical evaluation of inflamed colon was done using assay of myeloperoxidase (MPO) activity and thiobarbituric acid reactive substances (TBARS) concentration as indicators of free radical activity and cell lipid peroxidation. The activity of MPO and lipid peroxidation products (TBARS) increased in acetic acid-treated groups while recovered by pretreatment of animals with Z. multiflora (400-900 p.p.m.) and prednisolone. Z. multiflora (600 and 900 p.p.m.) and prednisolone-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared with the acetic acid-treated group. The beneficial effect of Z. multiflora (900 p.p.m.) was comparable with that of prednisolone. The antioxidant, antimicrobial and anti-inflammatory potentials of Z. multiflora might be the mechanisms by which this herbal extract protects animals against experimentally induced IBD. Proper clinical investigation should be carried out to confirm the activity in human.
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http://dx.doi.org/10.1093/ecam/nel051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1810372PMC
March 2007

Protective Effects of alpha-Tocopherol and N-Acetyl-Cysteine on Diazinon-Induced Oxidative Stress and Acetylcholinesterase Inhibition in Rats.

Toxicol Mech Methods 2007 ;17(2):109-15

Loghman-Hakim Hospital Poison Center, Faculty of Medicine, and Toxicological Research Center, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.

ABSTRACT Diazinon, an organophosphate (OP) insecticide, is widely used in agriculture and domestically. Reactive oxygen species (ROS) caused by OPs are involved in the toxicity of various pesticides. The aim of the present study was to analyze the role of diazinon in inducing oxidative stress in adult male Wistar rats and to evaluate the possible protective effects of alpha-tocopherol (TPH) and the glutathione prodrug N-acetyl-cysteine (NAC) after 4 weeks of exposure to a sublethal dose of diazinon. TPH (10 mg/kg/day), NAC (160 mg/kg/day), diazinon (25 mg/kg/day), a combination of NAC (160 mg/kg/day) and diazinon (25 mg/kg/day), and a combination of TPH (10 mg/kg/day) and diazinon (25 mg/kg/day) were given to rats orally via gavage for 4 weeks. The thiobarbituric acid reactive substances (TBARS) marker of lipid peroxides levels, total thiol molecules, and total antioxidant capacity of plasma were all analyzed as biomarkers of oxidative stress. In addition, the acetylcholinesterase (AChE) activity was measured as a biomarker of toxicity. The results from this study well indicate diazinon-induced oxidative stress demonstrated by enhanced TBARS, decreased total thiol molecules, and total antioxidant capacity. In addition, AChE activity was inhibited as a marker of OP toxicity. Data show the protective roles of TPH and NAC in reducing the diazinon-induced oxidative stress. Interestingly, both TPH and NAC recovered diazinon-induced AChE inhibition. It is concluded that supplementation with TPH and NAC can reduce toxicity of OP in human exposure.
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http://dx.doi.org/10.1080/15376510600860318DOI Listing
October 2012

Effect of Satureja khuzestanica essential oil on male rat fertility.

Fitoterapia 2006 Dec 6;77(7-8):495-9. Epub 2006 Jul 6.

Laboratory of Toxicology, Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Centre, Tehran University of Medical Sciences, Iran.

This study was undertaken to study the effect of Satureja khuzestanica essential oil (SKEO) in male rat fertility. SKEO was administered orally at doses of 75, 150, and 225 mg/kg/day for 45 days through drinking water. Treated and control rats were mated with female on day 45 of treatment. SKEO significantly improved all the parameters evaluated such as potency, fecundity, fertility index, and litter size. Moreover, concentrations of FSH and testosterone were significantly increased in SKEO-treated groups. Also the weights of testes, seminal vesicles, and ventral prostate weights were increased by SKEO (225 mg/kg). Histopathological analysis showed that in male rats treated with SKEO (150, 225 mg/kg) the number of spermatogonium, spermatid cords, Leydig cells, and spermatozoids was increased. Also in these groups, the Sertoli cells were hypertrophic.
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http://dx.doi.org/10.1016/j.fitote.2006.05.025DOI Listing
December 2006

Antioxidant potentials of Iranian Carica papaya juice in vitro and in vivo are comparable to alpha-tocopherol.

Phytother Res 2006 Jul;20(7):591-4

Laboratory of Toxicology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Carica papaya is widely cultivated throughout the world and is used as a food and also as a traditional medicine, particularly as an antiseptic and contraceptive. The present study was designed to explore the toxicological and antioxidant potential of dried C. papaya juice in vitro and in vivo. The oral LD(50) of the juice of C. papaya was determined, and the antioxidant potentials determined by DPPH and FRAP tests. In vivo examination was performed after oral administration of dried papaya juice to rats for 2 weeks at doses of 100, 200 and 400 mg/kg. Blood TBARS and FRAP assays were used to determine the potential of the juice to act against oxidative stress. The acute toxicity test (LD(50)) demonstrated that papaya juice is not lethal up to a dose of 1500 mg/kg after oral administration and thus is considered nontoxic. In treated groups, no sign of toxicity was observed. In vitro evaluation of the antioxidant effects of papaya showed that the highest antioxidant activity (80%) was observed with a concentration of 17.6 mg/mL. Blood lipid peroxidation levels decreased significantly after administration of all doses of papaya juice (100, 200, 400 mg/kg/day) to 35.5%, 39.5% and 40.86% of the control, respectively, compared with a value of 28.8% for vitamin E. The blood total antioxidant power was increased significantly by all doses of papaya juice (100, 200, 400 mg/kg/day) to 11.11%, 23.58% and 23.14% of the control, respectively. The value for vitamin E was 18.44%. This preliminary study indicates the safety and antioxidative stress potential of the juice of C. papaya, which was found to be comparable to the standard antioxidant compound alpha-tocopherol.
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http://dx.doi.org/10.1002/ptr.1932DOI Listing
July 2006

Synthesis and analgesic activity of N-Arylhydrazone derivatives of mefenamic acid.

J Pharm Pharm Sci 2005 Sep 1;8(3):419-25. Epub 2005 Sep 1.

Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: A series of N-Arylhydrazone derivatives of mefenamic acid (a known non-steroidal anti-inflammatory drug) were synthesized in order to obtain new compounds with potential analgesic and anti-inflammatory activity.

Methods: The structures of all synthesized compounds were confirmed by means of infrared, proton magnetic resonance and mass spectroscopy. All compounds were evaluated for their analgesic and anti-inflammatory activities by abdominal constriction test (writhing test) and carrageenan-induced rat paw edema test respectively.

Results: Most of the synthesized compounds induced significant reduction in the writhing response when compared to control. Among them, compounds 11, 12, 15, 16, 19, 20, and 21 were significantly more potent than mefenamic acid in the writhing test. The anti-inflammatory activity of these 7 compounds were evaluated and compounds 11, 12, 16, 19 and 20 showed significant anti-inflammatory activity in comparison to control but their effect was weaker than mefenamic acid.

Conclusions: The antinociceptive relative activity of some of these newly synthesized compounds is greater than mefenamic acid but they are not potent anti-inflammatory agents.
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September 2005

Biochemical and histopathological evidences for beneficial effects of satureja khuzestanica jamzad essential oil on the mouse model of inflammatory bowel diseases.

Toxicol Mech Methods 2006 ;16(7):365-72

Laboratory of Toxicology, Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

The essential oil from Satureja Khuzestanica Jamzad (SKEO), an endemic plant from Iran, was evaluated for its activity against inflammatory bowel disease (IBD). SKEO was examined on the experimental mouse model of inflammatory bowel disease, which is acetic acid-induced colitis. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic, and microscopic examinations of colon were performed. Lipid peroxidation significantly increased in acetic acid-treated mice in comparison to the normal group (4.88 vs. 3.02 mumol/g) and was significantly restored by SKEO (500, 1000, 1500 ppm) and prednisolone treatment. The mean percentage of decreases of lipid peroxidation in SKEO (500, 1000, 1500 ppm)- and prednisolone-treated groups were 10.5, 28.5, 42.85, and 33.33 of control, respectively. The myeloperoxidase activity significantly increased in acetic acid-treated mice in comparison to the normal group (4.1 vs. 0.8 U/g) and significantly restored in SKEO (1000 and 1500 ppm)- and prednisolone-treated groups. The mean percentage of decreases of myeloperoxidase activity in SKEO (1000 and 1500 ppm)- and prednisolone-treated groups were 24.56, 50, and 52.63 of control, respectively. SKEO (1000 and 1500 ppm)- and prednisolone-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared to the acetic acid-treated group. The beneficial effect of SKEO (1500 ppm) was comparable to that of prednisolone. Known antioxidant, antimicrobial, antiinflammatory, and antispasmodic potentials of Satureja Khuzestanica may be the mechanisms by which this plant protects animals against experimentally induced IBD. Proper clinical investigation should be carried out to confirm the activity in human disease.
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http://dx.doi.org/10.1080/15376520600620125DOI Listing
October 2012

Alteration of cyclic nucleotides levels and oxidative stress in saliva of human subjects with periodontitis.

J Contemp Dent Pract 2005 Nov 15;6(4):46-53. Epub 2005 Nov 15.

Tehran University of Medical Sciences.

Experimental findings suggest a protective role for cyclic nucleotides against induction of oxidative stress in saliva. Oxidative stress is a major contributor to the pathogenesis of inflammatory diseases. This study was conducted to evaluate salivary oxidative stress along with cGMP and cAMP levels in periodontitis subjects. cAMP and cGMP are second messengers that have important roles in salivary gland functions. Unstimulated whole saliva samples were obtained from periodontitis patients and age- and sex-matched healthy individuals. Saliva samples were analyzed for thiobarbituric reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total antioxidant power, TAP), and levels of cAMP and cGMP. Concentrations of cAMP and cGMP were reduced in the saliva of patients with moderate and severe periodontitis. Saliva of patients with severe periodontitis had higher TBARS and lower TAP than control subjects. The presence of oxidative stress and lower levels of salivary cGMP and cAMP in periodontitis are in association with disease severity.
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November 2005

Reduction of diabetes-induced oxidative stress by phosphodiesterase inhibitors in rats.

Comp Biochem Physiol C Toxicol Pharmacol 2005 Feb 17;140(2):251-5. Epub 2005 Mar 17.

Laboratory of Toxicology, Department of Pharmacology and Toxicology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. The aim of this study was to investigate the effect of different phosphodiesterase inhibitors on lipid peroxidation and total antioxidant capacity (TAC) of plasma in streptozotocin-induced diabetic rats (Rattus norvegicus). Rats became diabetic by a single administration of streptozotocin (STZ, 45 mg/kg). The effects of 15-days treatment by milrinone, sildenafil, and theophylline as cyclic-AMP and -GMP phosphodiesterase inhibitors (PDEIs) on diabetes-induced oxidative stress were studied. The levels of glucose, malonedialdehyde (MDA) the by product of lipid peroxides, and TAC (FRAP test) were estimated in plasma of control and experimental groups of rats. A significant increase in the levels of plasma glucose, and MDA and a concomitant decrease in the levels of TAC were observed in diabetic rats. These alterations were reverted back to near normal level after the treatment with PDEIs. Treatment of diabetic rats by PDEIs reduced MDA levels and increased TAC in the order of milrinone>sildenafil>theophylline. In conclusion, the present investigation show that PDIS possesses antioxidant activities, which may be attributed to their enhancing effect on cellular cyclic nucleotides contributing to the protection against oxidative stress in streptozotocin-induced diabetes. Exact mechanism of protective actions of cAMP- and cGMP-phosphodiesterase remains to be elucidated by further studies. This finding may suggest a place for PDEIs in maintaining health in diabetes.
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http://dx.doi.org/10.1016/j.cca.2005.02.010DOI Listing
February 2005

On the relation of nitric oxide to nifedipine-induced gingival hyperplasia and impaired submandibular glands function in rats in vivo.

Fundam Clin Pharmacol 2005 Feb;19(1):65-71

Laboratory of Toxicology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Calcium-channel blockers such as nifedipine could be associated with gingival overgrowth. The aim of this study was to examine the role of nitric oxide (NO) on nifedipine-induced gingival hyperplasia along with submandibular secretory function in rats. Animals in divided groups received nifedipine (250 mg/kg diet) alone and in combination with L-arginine (2.25% w/v) or N(omega)-nitro-L-arginine methyl ester (L-NAME) (0.7% w/v) in drinking water for 20 days. Controls received only tap water. Pure submandibular saliva was collected intraorally by micropolyethylene cannula and the mandibular gingiva was examined by means of dissecting microscope for signs of redness, thickness, inflammation and exuda. Twenty-day nifedipine treatment induced gingival hyperplasia accompanied with reduced salivary flow rate and concentrations of total protein, epidermal growth factor (EGF) and calcium in comparison with controls. Co-treatment of animals with nifedipine and L-arginine protected from gingival hyperplasia and retained flow rate, and concentrations of total protein, EGF and calcium in normal levels. Co-treatment of animals with nifedipine and L-NAME potentiated nifedipine-induced gingival hyperplasia and reductions in flow rate and concentrations of total protein, EGF, and calcium. It is concluded that nifedipine-induced gingival hyperplasia is associated with salivary dysfunction. Activation of cGMP-dependent positive signal-transduction mechanisms in salivary glands might be the mechanism for protective effects of NO against nifedipine-induced gingival hyperplasia.
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http://dx.doi.org/10.1111/j.1472-8206.2004.00313.xDOI Listing
February 2005

Alteration of rat hepatic glycogen phosphorylase and phosphoenolpyruvate carboxykinase activities by Satureja khuzestanica Jamzad essential oil.

J Pharm Pharm Sci 2004 Sep 24;7(3):310-4. Epub 2004 Sep 24.

Laboratory of Toxicology, Pharmaceutical Sciences Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran.

Purpose: Regarding reported antidiabetic effect of Satureja khuzestanica essential oil (SKEO) and important role of liver on body glucose metabolism by glycogenolysis and gluconeogenesis, we were interested to examine effect of SKEO treatment on rat hepatic key enzymes of glycogenolysis and gluconeogenesis in vivo.

Methods: Effective antidiabetic dose of SKEO (1000 ppm) was administered to rats through drinking water for 2 weeks. After 18 hours fasting post treatment under general anesthesia, the liver was removed by transverse abdominal incision and perfused with cold 0.9% saline and kept frozen at -70 degrees C until homogenized. The activities of the key enzymes glycogen phosphorylase (GP) and phosphoenolpyruvate carboxykinase (PEPKC) were analyzed in the homogenate. Blood sample was taken by cardiac puncture for glucose assay.

Results: SKEO treatment did not affect blood glucose concentrations but decreased hepatic PEPCK activity by 26% (P<0.01) of control and increased hepatic GP by 24% (P<0.01) of control.

Conclusion: Disturbance of hepatic glucose metabolism is proposed as a mechanism of antidiabetic action of SKEO which could be in relation with antioxidant property of this plant.
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September 2004

Antioxidant, antidiabetic, antihyperlipidemic,reproduction stimulatory properties and safety of essential oil of Satureja Khuzestanica in rat in vivo: a oxicopharmacological study.

Med Sci Monit 2003 Sep;9(9):BR331-5

Department of Toxicology, Pharmaceutical Sciences Research Center and Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Background: Satureja Khuzestanica is an endemic plant of Iran that is widely distributed in the southern part of the country. It is famous for its medical uses as an analgesic and antiseptic in folk medicine. The present study was designed to explore the toxicological and pharmacological effects of essential oil of Satureja Khuzestanica (SKEO) in vivo.

Material/methods: The intraperitoneal LD50 of SKEO was determined. Teratogenicity was determined by administration of SKEO at doses of 500, 1000 and 1500 ppm to pregnant rats during days 6 to 015 of gestation. FRAP and TBARS assays were used to determine total antioxidant power and lipid peroxidation respectively. Diabetes and hyperlipidemia were induced by administration of streptozocin and lipid regimen in rats. SKEO (1000 ppm) was administered in drinking water for 10 days.

Results: SKEO is not lethal up to a dose of 2 g kg-1 in rats. In the teratogenicity test, dams of the treated group were active and did not show any signs of toxicity. A significant increase in the number of implantation and live fetuses were observed with SKEO (500 and 1000 ppm) in comparison to the control group. SKEO treatment decreased the normal blood lipid peroxidation level and increased total antioxidant power. Significant decreases in fasting blood glucose and triglyceride levels were observed with SKEO in diabetic and antihyperlipidemic rats respectively.

Conclusions: This preliminary study indicates the safety and interesting stimulatory effect of SKEO on reproduction. The antioxidant properties of SKEO may explain its antidiabetic and triglyceride-lowering effects.
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September 2003