Publications by authors named "Sussan Kaboudanian Ardestani"

16 Publications

  • Page 1 of 1

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

Iran J Allergy Asthma Immunol 2021 Feb 11;20(1):46-66. Epub 2021 Feb 11.

Department of Biostatistics and Social Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.
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http://dx.doi.org/10.18502/ijaai.v20i1.5412DOI Listing
February 2021

Inhibition of protein disulfide isomerase has neuroprotective effects in a mouse model of experimental autoimmune encephalomyelitis.

Int Immunopharmacol 2020 Mar 12;82:106286. Epub 2020 Mar 12.

Iranian Centre of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Endoplasmic reticulum (ER) stress is strictly linked to neuroinflammation and involves in the development of neurodegenerative disorders. Protein disulfide isomerase (PDI) is an enzyme that catalyzes formation and isomerization of disulfide bonds and also acts as a chaperone that survives the cells against cell death by removal of misfolded proteins. Our previous work revealed that PDI is explicitly upregulated in response to myelin oligodendrocyte glycoprotein (MOG)-induced ER stress in the brain of experimental autoimmune encephalomyelitis (EAE) mice. The significance of overexpression of PDI in the apoptosis of neural cells prompted us to study the effect of CCF642, efficient inhibitor of PDI, in the recovery of EAE clinical symptoms. Using this in vivo model, we characterized the ability of CCF642 to decrease the expression of ER stress markers and neuroinflammation in the hippocampus of EAE mice. Our observations suggested that CCF642 administration attenuates EAE clinical symptomsand the expression of ER stress-related proteins. Further, it suppressed the inflammatory infiltration of CD4 + T cells and the activation of hippocampus-resident microglia and Th17 cells. We reported here that the inhibition of PDI protected EAE mice against neuronal apoptosis induced by prolonged ER stress and resulted in neuroprotection.
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http://dx.doi.org/10.1016/j.intimp.2020.106286DOI Listing
March 2020

2-(Bipiperidin-1-yl)-5-(nitroaryl)-1,3,4-thiadiazoles: Synthesis, evaluation of in vitro leishmanicidal activity, and mechanism of action.

Bioorg Med Chem 2019 08 5;27(16):3682-3691. Epub 2019 Jul 5.

Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

The development of novel leishmanicidal agents that are capable of being replaced by the available therapeutic options has become a priority. In the present study, the synthesis and leishmanicidal activity of a series of 5-(nitroheteroaryl-2-yl)-1,3,4-thiadiazole derivatives are described. All compounds appeared to be potent anti-leishmanial agents against both promastigote and amastigote forms of Leishmania major (L. major). Amongst the synthesized compounds, 2-([1,4'-bipiperidin]-1'-yl)-5-(5-nitrofuran-2-yl)-1,3,4-thiadiazole (IIa) and 1-(5-(1-methyl-5-nitro-1H-imidazole-2-yl)-1,3,4-thiadiazol-2-yl)-4-(piperidine-1-yl) piperidine (IIc) are the most effective. Infection index was statistically declined in the presence of all compounds. The analysis of redox-related factors revealed that exposure of L. major cells to IIa and IIc led to an increase in reactive oxygen species (ROS). Furthermore, two compounds were able to increase ROS and NO levels in infected macrophages in a dose-independent manner. In addition, we showed that these compounds induced cell death in promastigotes. Altogether, our results indicated the anti-leishmanial potential of IIa and IIc is mediated by apoptosis through an imbalance in the redox system resulting in the elevation of ROS. This new class of compound seems to hold great promise for the development of new and useful anti-leishmanial agents.
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http://dx.doi.org/10.1016/j.bmc.2019.07.009DOI Listing
August 2019

Circulating mesenchymal stem cells in sulfur mustard-exposed patients with long-term pulmonary complications.

Toxicol Lett 2019 Sep 13;312:188-194. Epub 2019 May 13.

Department of Biostatistics and Social Medicine, Zanjan University of Medical Sciences, Zanjan, Islamic Republic of Iran.

Sulfur mustard (SM) is a toxic agent that causes acute and long-term pulmonary complications. Recent evidence has shown the impact of SM on mesenchymal stem cells (MSCs). These cells have a critical role in repairing the damaged tissues. In this study, we evaluated the mobilization of MSCs in SM-exposed patients with long-term pulmonary complications. Fifty-nine SM-injured patients with prolonged pulmonary complications and 20 healthy individuals were included. Patients were classified based on taking drugs, having comorbidities, and severity of respiratory consequence. MSCs with phenotype of CD45-CD44CD29CD105 were evaluated in peripheral blood using flow cytometry. Circulating MSCs were lower in SM-exposed patients compared to the control group (0.93 vs. 2.72 respectively, P = 0.005). No significant difference was observed in the MSC count between patients taking corticosteroids or antibiotics and those patients not taking them. Comorbidities like liver and kidney diseases had changed the count of MSCs in SM-exposed subjects. In addition, the frequency of MSCs did not show any association with the severity of long-term pulmonary complications. In conclusion, SM-exposure causes a decline in the frequency of circulating MSCs in survivors. The lower number of the peripheral MSC population in SM-exposed patients was not affected by taking corticosteroids or antibiotics, but comorbidities are probably involved in MSC frequency. The decreases observed in the number of circulating MSCs was not associated with the severity of the pulmonary complications; however, further studies in mustard lung models are required to demonstrate the therapeutic or pathologic role of MSCs in SM injuries.
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http://dx.doi.org/10.1016/j.toxlet.2019.05.015DOI Listing
September 2019

Time course study of oxidative stress in sulfur mustard analog 2‑chloroethyl ethyl sulfide-induced toxicity.

Int Immunopharmacol 2019 Aug 10;73:81-93. Epub 2019 May 10.

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address:

Oxidative stress is the major mechanism impairing cell homeostasis, inducing cell death and tissue damage in sulfur mustard (SM)-exposed individuals. The aim of the present study was to evaluate time course changes of oxidative stress in the mice exposed with 2‑chloroethyl ethyl sulfide (CEES) as SM analog. For this purpose, male BALB/c mice were divided into control groups and experimental groups that received CEES (10 mg/kg) through intraperitoneal injection. In both groups, animals were euthanized at three periods: short (12, 24 h and 1 week), medium (1, 2 and 3 months) and long-term (5 and 6 months) after CEES exposure. Oxidative stress indices and the antioxidant defense systems were evaluated in lung and liver tissues. The time course findings in both tissues showed a significant increase in oxidative damage markers such as malondialdehyde (lung P < 0.001, liver P < 0.001), protein carbonyl (lung P < 0.0001), and 8-hydroxy-deoxyguanosine (lung P < 0.0001, Liver P < 0.0001) and also a significant reduction in the antioxidant defense system including reduced glutathione level (lung P < 0.001, Liver P < 0.001,), activities of catalase (lung P < 0.01 and liver P < 0.05), superoxide dismutase (lung P < 0.05), glutathione S‑transferase (lung P < 0.05, liver P < 0.01), glutathione peroxidase (lung, P < 0.05, Liver P < 0.05) and glutathione reductase (lung P < 0.001, liver P < 0.01) in the long-term. However, these changes occur with less intensity in the short-term and return to the normal status in the medium-term. Moreover, there was a positive time course correlation between oxidative damage indices and the percent of histopathological damage in both tissues (P < 0.05). This correlation finding confirms and supports the fact that time course oxidative-antioxidant imbalance plays an important role in the development of SM-induced acute and delayed injuries.
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http://dx.doi.org/10.1016/j.intimp.2019.04.055DOI Listing
August 2019

Altered levels of GST activity, Vit C, TPX and Cu in individuals with long-term sulfur mustard-induced lung complications.

Inhal Toxicol 2018 Nov - Dec;30(13-14):483-491. Epub 2019 Mar 8.

d Immunoregulation Research Center , Shahed University , Tehran , Iran.

Context: Sulfur mustard (SM) as a cytotoxic and blistering agent can alkylate a variety of cellular components, causing the incidence of ongoing oxidative stress.

Objective: The present study was conducted to assess oxidative stress index (OSI) in SM-exposed veterans with long-term pulmonary complications.

Methods: Participants consisted of 289 SM-exposed individuals with pulmonary complications (classified into three groups: mild, moderate and severe) and 66 healthy individuals as the control group. Enzymatic and non-enzymatic antioxidant and also trace elements were measured in the study groups. Moreover, some of oxidative stress indicators consist of malondialdehyde (MDA), protein carbonyl (CO), total antioxidant (TA) and total peroxide (TPX) were measured and then OSI was calculated.

Results: Glutathione-S-transferase (GST) activity and vitamin C (Vit C) were significantly decreased in SM-exposed patients as compared with controls. Besides, Cu level and Cu/Zn ratio in SM-exposed veterans showed a significant correlation with the severity of the diseases. Serum TPX was significantly increased in SM-exposed individuals, as a result of which the OSI was slightly higher in them than controls. This can be considered as an indicative for oxidative stress in SM-exposed patients.

Conclusion: This study suggests a particular role for TPX, Cu, Vit C and GST in SM-induced pulmonary complications. Therefore, a special attention should be paid to these factors in designing therapeutic protocols, which can reduce the progression risk of the disease.
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http://dx.doi.org/10.1080/08958378.2018.1545809DOI Listing
September 2019

The protective effect of rifampicin on behavioral deficits, biochemical, and neuropathological changes in a cuprizone model of demyelination.

Cytokine 2019 01 24;113:417-426. Epub 2018 Oct 24.

Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) in which both neuroinflammation and neurodegeneration play critical roles in the pathogenesis of the disease. A growing body of evidence indicates that some antibiotics have anti-inflammatory and neuroprotective properties. Rifampicin, commonly used for the treatment of mycobacteria, has been shown to exert neuroprotective activities in neurodegenerative diseases. In this study, we examined the efficacy of rifampicin on demyelination, gliosis, apoptosis, inflammation, behavioral dysfunction, and biochemical alterations in the cuprizone model of demyelination. For this aim, male C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 6 weeks to induce reversible demyelination in the corpus callosum. Mice intraperitoneally received serial doses of rifampicin (10, 20, or 40 mg/kg body weight) in the last 7 days of a 6-week period of cuprizone treatment. The results showed that the administration of rifampicin led to the improvement in motor behavioral deficits. In line with this, rifampicin decreased the number of apoptotic cells in the corpus callosum thereby diminishing the expression of cleaved caspase-3 and Bax, as well as increasing Bcl-2. Moreover, rifampicin significantly lowered the levels of interleukin-6, interleukin-1β, caspase-12 activity, heme oxygenase-1(HO-1), nitric oxide (NO), and malondialdehyde (MDA) in mice treated with cuprizone. Conversely, the activity of glutathione peroxidase (GPx) and the level of ferric reducing ability of plasma (FRAP) were increased in response to the treatment with rifampicin. Histopathological findings demonstrated that rifampicin statistically promoted remyelination and mitigated microgliosis and astrogliosis. It seems that rifampicin is able to be added to the armamentarium of therapies for multiple sclerosis.
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http://dx.doi.org/10.1016/j.cyto.2018.10.016DOI Listing
January 2019

Association of glutathione S-transferase polymorphisms with the severity of mustard lung.

Bioimpacts 2017 30;7(4):255-261. Epub 2017 Aug 30.

Immunoregulation Research Center, Shahed University, Tehran, Iran.

Glutathione S-transferase (GST) is one of the major detoxifiers in alveoli. Polymorphism in GST genes can influence the ability of individuals to suppress oxidative stress and inflammation. The present study was aimed to explore the hypothesis that the genetic polymorphisms of GST , and are associated with the severity of the mustard lung in the sulfur mustard-exposed individuals. Blood samples were taken from 185 sulfur mustard-exposed and 57 unexposed subjects. According to the stage of the mustard lung, sulfur mustard-exposed patients were categorized in the mild/moderate and severe/very severe groups. A multiplex PCR method was conducted to identify and null genotypes. To determine the polymorphisms of GSTP1 in exon 5 (Ile105Val) and exon 6 (Ala114Val), RFLP-PCR method was performed. The frequency of homozygous deletion was significantly higher in the severe/very severe patients compared with the mild/moderate subjects (66.3% vs. 48%, = 0.013). The null genotype was associated with the severity of mustard lung (adjusted odds ratio [OR], 2.257; 95% CI, 1.219-4.180). There was no significant association between and polymorphisms with the severity of the mustard lung. The different distribution of null genotype in severe/very severe and mild/moderate groups indicated that the severity of the mustard lung might be associated with the genetic polymorphism(s).
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http://dx.doi.org/10.15171/bi.2017.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801537PMC
August 2017

Comparison of Biological and Immunological Characterization of Lipopolysaccharides From Brucella abortus RB51 and S19.

Jundishapur J Microbiol 2015 Nov 7;8(11):e24853. Epub 2015 Nov 7.

Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, IR Iran.

Background: Brucella abortus RB51 is a rough stable mutant strain, which has been widely used as a live vaccine for prevention of brucellosis in cattle instead of B. abortus strain S19. B. abortus lipopolysaccharide (LPS) has unique properties in comparison to other bacterial LPS.

Objectives: In the current study, two types of LPS, smooth (S-LPS) and rough (R-LPS) were purified from B. abortus S19 and RB51, respectively. The aim of this study was to evaluate biological and immunological properties of purified LPS as an immunogenical determinant.

Materials And Methods: Primarily, S19 and RB51 LPS were extracted and purified by two different modifications of the phenol water method. The final purity of LPS was determined by chemical analysis (2-keto-3-deoxyoctonate (KDO), glycan, phosphate and protein content) and different staining methods, following sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). C57BL/6 mice were immunized subcutaneously three times at biweekly intervals with the same amount of purified LPSs. The humoral immunity was evaluated by measuring specific IgG levels and also different cytokine levels, such as IFN-γ, TNF-α, IL-4 and IL-10, were determined for assessing T-cell immune response.

Results: Biochemical analysis data and SDS-PAGE profile showed that the chemical nature of S19 LPS is different from RB51 LPS. Both S and R-LPS induce an immune response. T-cell immune response induced by both S and R-LPS had almost the same pattern whereas S19 LPS elicited humoral immunity, which was higher than RB51 LPS.

Conclusions: Purified LPS can be considered as a safe adjuvant and can be used as a component in prophylactic and therapeutic vaccines targeting infectious disease, cancer and allergies.
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http://dx.doi.org/10.5812/jjm.24853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741057PMC
November 2015

Role of the salt bridge between glutamate 546 and arginine 907 in preservation of autoinhibited form of Apaf-1.

Int J Biol Macromol 2015 Nov 13;81:370-4. Epub 2015 Aug 13.

Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran. Electronic address:

Apaf-1, the key element of apoptotic mitochondrial pathway, normally exists in an auto-inhibited form inside the cytosol. WRD-domain of Apaf-1 has a critical role in the preservation of auto-inhibited form; however the underlying mechanism is unclear. It seems the salt bridges between WRD and NOD domains are involved in maintaining the inactive conformation of Apaf-1. At the present study, we have investigated the effect of E546-R907 salt bridge on the maintenance of auto-inhibited form of human Apaf-1. E546 is mutated to glutamine (Q) and arginine (R). Over-expression of wild type Apaf-1 and its E546Q and E546R variants in HEK293T cells does not induce apoptosis unlike - HL-60 cancer cell line. In vitro apoptosome formation assay showed that all variants are cytochrome c and dATP dependent to form apoptosome and activate endogenous procaspase-9 in Apaf-1-knockout MEF cell line. These results suggest that E546 is not a critical residue for preservation of auto-inhibited Apaf-1. Furthermore, the behavior of Apaf-1 variants for in vitro apoptosome formation in HEK293T cell is similar to exogenous wild type Apaf-1. Wild type and its variants can form apoptosome in HEK293T cell with different procaspase-3 processing pattern in the presence and absence of exogenous cytochrome c and dATP.
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http://dx.doi.org/10.1016/j.ijbiomac.2015.08.027DOI Listing
November 2015

Improved immunogenicity of tetanus toxoid by Brucella abortus S19 LPS adjuvant.

Iran J Immunol 2014 Sep;11(3):189-99

Immunology Lab, Institute of Biochemistry and Biophysics, University of Tehran, Iran,

Background: Adjuvants are used to increase the immunogenicity of new generation vaccines, especially those based on recombinant proteins. Despite immunostimulatory properties, the use of bacterial lipopolysaccharide (LPS) as an adjuvant has been hampered due to its toxicity and pyrogenicity. Brucella abortus LPS is less toxic and has no pyrogenic properties compared to LPS from other gram negative bacteria.

Objectives: To evaluate the adjuvant effect of B. abortus (vaccine strain, S19) LPS for tetanus toxoid antigen (TT) and to investigate the protective effect of different tetanus vaccine preparations.

Methods: LPS was extracted and purified from B. abortus S19 and KDO, glycan, phosphate content, and protein contamination were measured. Adipic acid dihydrazide (ADH) was used as a linker for conjugation of TT to LPS. Different amounts of B. abortus LPS, TT, TT conjugated with LPS, and TT mixed with LPS or complete Freund's adjuvant (CFA) were injected into mice and antibody production against TT was measured. The protective effect of induced antibodies was determined by LD50.

Results: Immunization of mice with TT+LPS produced the highest anti-TT antibody titer in comparison to the group immunized with TT without any adjuvant or the groups immunized with TT-LPS or TT+CFA. Tetanus toxid-S19 LPS also produced a 100% protective effect against TT in immunized mice.

Conclusion: These data indicate that B. abortus LPS enhances the immune responses to TT and suggest the possible use of B. abortus LPS as an adjuvant in vaccine preparations.
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http://dx.doi.org/IJIv11i3A5DOI Listing
September 2014

In solution cation-induced secondary and tertiary structure alterations of human calprotectin.

Protein J 2014 Oct;33(5):465-73

Department of Basic Science, Faculty of Veterinary Medicine, Urmia University, Nazloo, Urmia, Iran,

Calprotectin (CP) is widely considered to have diverse roles including growth inhibitory and apoptosis induction in a number of tumor cell lines and antimicrobial activities. As CP has been proposed to bind metal ions with high affinity, we have studied its functional and primarily its structural behavior upon Zn(2+) and Mn(2+) chelation solely and along with Ca(2+). We employed fluorescence spectroscopy and circular dichroism to determine the resulting modifications. Based upon our findings it is clear that treating CP with ions effectively weakened its natural growth inhibitory activity. Moreover, structural analysis of Zn(2+) and Mn(2+)-treated CPs indicated remarkable alterations in the regular secondary structures in favor of irregular structures while Zn(2+) and Mn(2+) treatment of CP after incubation with Ca(2+) displayed no remarkable shifts. Tertiary structure investigation using fluorescence spectroscopy showed that CP undergoes conformational changes upon Zn(2+) and Mn(2+) treatment whereby Trp residues of protein is slightly exposed to the hydrophilic environment, compactness of CP is compromised, whereas in Ca(2+)-treated CP, the tertiary structure integrity is intact upon Zn(2+) and Mn(2+) chelation. Interestingly, CP structural modifications upon Zn(2+) and Mn(2+) treatment was significantly comparable, probably due to similar radii and charges of ions. Taken all together, we have concluded that CP maintains its normal nature in Ca(2+)-loaded state when treated with Zn(2+) and Mn(2+) ions. It can be suggested that Ca(2+) not only stabilize CP structure but also helps CP to keep its structure upon metal ions chelation which is involved in host organism defense system.
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http://dx.doi.org/10.1007/s10930-014-9578-6DOI Listing
October 2014

In vitro immunobiological studies of novel 5-(5-nitrofuran-2-yl)-1, 3, 4-thiadiazoles with piperazinyl-linked benzamidine substituents against Leishmania major.

Iran J Allergy Asthma Immunol 2013 Aug 28;12(4):368-76. Epub 2013 Aug 28.

Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran.

It was recently demonstrated that 5-(5-nitrofuran-2-yl)-1, 3, 4-thiadiazoles with piperazinyl-linked benzamidine substituents are effective in vitro against Leishmania major.Following on this evidence, we used colorimetric assay of acid phosphatase activity in the promastigotes as an indicator for cell viability. Also we studied the effect of these compounds on induction of nitric oxide (NO) in macrophage and production of reactive oxygen species (ROS) in lymphocyte that have important role in activation of immune response against Leishmania and elimination of parasite.Results showed that these compounds decrease the viability of the parasite and increase ROS and NO production in lymphocyte and macrophage respectively.These compounds can induce parasite killing, directly by decreasing the parasite viability and indirectly by exhibiting a significant increase on immune system.
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August 2013

The effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 in hepatic fibrosis in bile duct ligated rats.

Hepatol Res 2008 Dec 18;38(12):1252-63. Epub 2008 Aug 18.

Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran.

Aim: N-acetylcysteine can inhibit the formation of intracellular reactive oxygen intermediates. Cellular redox state plays a role in regulating the secretion of matrix metalloproteinase-2. We investigated the effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2.

Methods: Bile duct ligated rats were used as a model of hepatic fibrosis. We compared the level of gene expression (using real-time reverse transcription polymerase chain reaction [RT-PCR]), liver function parameters, hepatic reactive oxygen production, lipid peroxidation and glutathione state in experimental groups.

Results: N-acetylcysteine treatment significantly improved liver function parameters including the plasma levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and bilirubin. In addition, significant improvement of glutathione state and reactive oxygen production were observed. Hepatic lipid peroxidation was reversed by N-acetylcysteine treatment. Although N-acetylcysteine treatment did not completely normalize the increased matrix metalloproteinase-2 expression, it significantly decreased its level by 65%. N-acetylcysteine treatment also significantly decreased matrix metalloproteinase-2 activity and normalized tissue inhibitor of matrix metalloproteinase-2 expression.

Conclusion: Collectively, N-acetylcysteine showed inhibition of matrix metalloproteinase-2 expression and activity. In addition, administration of N-acetylcysteine was associated with downregulation of the expression of tissue inhibitor of matrix metalloproteinase-2 and amelioration of oxidative stress in the liver of bile duct ligated rats.
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http://dx.doi.org/10.1111/j.1872-034X.2008.00393.xDOI Listing
December 2008

Synthesis and in vitro anti-leishmanial activity of 1-[5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-yl]- and 1-[5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-yl]-4-aroylpiperazines.

Bioorg Med Chem 2008 Apr 20;16(8):4509-15. Epub 2008 Feb 20.

Department of Medicinal Chemistry, Faculty of Pharmacy & Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14174, Iran.

The synthesis and anti-leishmanial activity of nitroheteroaryl-1,3,4-thiadiazole-based compounds including 1-[5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-yl]-4-aroylpiperazines and 1-[5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-yl]-4-aroylpiperazines were described. Most of the synthesized compounds exhibited potent anti-leishmanial activity against both promastigote and amastigote forms of Leishmania major at non-cytotoxic concentrations. In general, 5-nitrofuran derivatives were more active than the corresponding 5-nitrothiophene analogues.
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http://dx.doi.org/10.1016/j.bmc.2008.02.052DOI Listing
April 2008

The effect of vitamin e on splenocytes apoptosis of gamma- irradiated BALB/c mice.

Iran J Allergy Asthma Immunol 2005 Jun;4(2):77-82

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

Apoptosis, a physiologic mechanism to eliminate unwanted cells, is also induced by ionizing irradiation, through production of free radicals. It has been demonstrated that antioxidants such as vitamin E are able to protect cells from damage caused by free radicals. Taken together we found it reasonable to make an attempt to evaluate the protective effect of vitamin E against apoptosis. The irradiated mice received 1 Gy/day gamma radiation for one day (low dose) or for three successive days (high dose, 3Gy). The splenocytes were then isolated at 6, 14 and 24 h after exposure. DNA gel electrophoresis and DNA fragmentation assay were done in addition to the evaluation of splenocytes cytology.Our results showed that Vitamin E can reduce apoptosis against low dose irradiation. However it is not able to completely block programmed cell death in high dose irradiation.
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http://dx.doi.org/04.02/ijaai.7782DOI Listing
June 2005