فهرست مطالب
Iranian Journal of Basic Medical Sciences
Volume:20 Issue: 11, Nov 2017
- تاریخ انتشار: 1396/08/29
- تعداد عناوین: 15
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Quetiapine reverse paclitaxel-induced neuropathic pain in mice: Role of Alpha2- adrenergic receptorsPages 1182-1188Objective(s)Paclitaxel-induced peripheral neuropathy is a common adverse effect of cancer chemo -therapy. This neuropathy has a profound impact on quality of life and patients survival. Preventing and treating paclitaxel-induced peripheral neuropathy is a major concern. First- and second-generation antipsychotics have shown analgesic effects both in humans and animals. Quetiapine is a novel atypical antipsychotic with low propensity to induce extrapyramidal or hyperprolactinemia side effects. The present study was designed to investigate the effects of quetiapine on the development and expression of neuropathic pain induced by paclitaxel in mice and the role of α2-adrenoceptors on its antinociception.Materials And MethodsPaclitaxel (2 mg/kg IP) was injected for five consecutive days which resulted in thermal hyperalgesia and mechanical and cold allodynia.ResultsEarly administration of quetiapine from the 1st day until the 5th day (5, 10, and 15 mg/kg PO) did not affect thermal, mechanical, and cold stimuli and could not prevent the development of neuropathic pain. In contrast, when quetiapine (10 and 15 mg/kg PO) administration was started on the 6th day after the first paclitaxel injections, once the model had been established, and given daily until the 10th day, heat hyperalgesia and mechanical and cold allodynia were significantly attenuated. Also, the effect of quetiapine on heat hyperalgesia was reversed by pretreatment with yohimbine, as an alpha-2 adrenergic receptor antagonist.ConclusionThese results indicate that quetiapine, when administered after nerve injury can reverse the expression of neuropathic pain. Also, we conclude that α2-adrenoceptors participate in the antinociceptive effects of quetiapine.Keywords: Hyperalgesia, Mice, Neuropathic pain, Paclitaxel, Quetiapine, Yohimbine
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Pages 1189-1193Objective(s)Cardiotoxicity is one of the major consequences in carbon monoxide poisoning. Following our previous work, in this study we aimed to define the myocardium changes induced by carbon monoxide (CO) intoxication and evaluate erythropoietin (EPO) effect on CO cardiotoxicity in rat.Materials And MethodsSevere carbon monoxide toxicity induced by 3000 ppm CO in Wistar rat. EPO was administrated (5000 IU/Kg, intraperitoneal injection) at the end of CO exposure and then the animals were re-oxygenated with the ambient air. Subsequently heart was removed and assessed by histopathology and electron microscopy examinations.Results3000 ppm CO induced significant myocardium injury; multiple foci of necrosis and lymphocyte infiltration compare with the control (P˂0.05). Electron microscopy examination showed myofibril lysis and mitochondrial swelling in myocardium due to 3000 ppm CO poisoning. However EPO administration after CO exposure resulted in significant reduction in cardiomyocytes injury (P˂0.05).ConclusionOur results represented protective effect of EPO on cardiac injury induced by CO intoxication in rat.Keywords: Carbon monoxide Poisoning, Cardiotoxicity, Erythropoietin, Histopathology, Rat
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Pages 1194-1199Objective(s)The aim of this study was to explore the effects of Squid ink polysaccharide (SIP) on prevention of autophagy and oxidative stress induced by cyclophosphamide (CP) in Leydig cells of mice.Materials And MethodsExamination of reproductive organ exponents, abnormal sperm rate, activities of superoxide dismutase (SOD), catalase (CAT), contents of malondialdehyde (MDA), and histological structure were performed to detect the optimal dose of SIP against oxidative stress damage in vivo, and autophagy-associated protein LC3 and Beclin-1 were examined by immunofluorescence, and their expression was detected by Western blot analysis. Leydig cells ultrastructural changes were observed by transmission fluorescent microscope.ResultsSIP significantly inhibited sperm aberration, histological structure and injury of seminiferous tubules caused by CP, as well as the antioxidant activity of SOD and CAT were increased; contents of MDA were decreased. The optimal dose of SIP for prevention of oxidative stress injury by CP was 80 mg/kg. In addition, LC3 and Beclin-1 fluorescent granules were much less in the Leydig cell layer after treatment via SIP compared with the CP-treated group, and the expression levels of LC3 and Beclin-1 were also decreased. Furthermore, characteristics of cell autophagy such as mitochondrial swelling, autophagic vacuoles, and chromatin pyknosis were observed in CP-treated Leydig cells, but SIP could effectively weaken injury of Leydig cell ultrastructure by CP.ConclusionSIP, as an antioxidant, prevents the cytoskeleton damage through up-regulation antioxidant capacity and inhibition autophagy caused by CP.Keywords: Autophagy, Cyclophosphamide, Leydig cells, Oxidative stress, Squid ink polysaccharide
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Pages 1200-1206Objective(s)In some previous studies, the extract of embryonic carcinoma cells (ECCs) and embryonic stem cells (ESCs) have been used to reprogram somatic cells to more dedifferentiated state. The aim of this study was to investigate the effect of mouse ESCs extract on the expression of some pluripotency markers in human adipose tissue-derived stem cells (ADSCs).Materials And MethodsHuman ADSCs were isolated from subcutaneous abdominal adipose tissue and characterized by flow cytometric analysis for the expression of some mesenchymal stem cell markers and adipogenic and osteogenic differentiation. Frequent freeze-thaw technique was used to prepare cytoplasmic extract of ESCs. Plasma membranes of the ADSCs were reversibly permeabilized by streptolysin-O (SLO). Then the permeabilized ADSCs were incubated with the ESC extract and cultured in resealing medium.After reprogramming, the expression of some pluripotency genes was evaluated by RT-PCR and quantitative real-time PCR (qPCR) analyses.ResultsThird-passaged ADSCs showed a fibroblast-like morphology and expressed mesenchymal stem cell markers. They also showed adipogenic and osteogenic differentiation potential. QPCR analysis revealed a significant upregulation in the expression of some pluripotency genes including OCT4, SOX2, NANOG, REX1 and ESG1 in the reprogrammed ADSCs compared to the control group.ConclusionThese findings showed that mouse ESC extract can be used to induce reprogramming of human ADSCs. In fact, this method is applicable for reprogramming of human adult stem cells to a more pluripotent sate and may have a potential in regenerative medicine.Keywords: Adipose tissue-derived stem cells, Dedifferentiation, Embryonic stem cells extract, Reprogramming
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Pages 1207-1212Objective(s)Arachidonic Acid/5-lipoxygenase (AA/5-LOX) pathway connects lipid metabolism and proinflammatory cytokine, which are both related to the development and progression of nonalcoholic fatty liver disease (NAFLD). Therefore, the present study was designed to investigate the role of AA/5-LOX pathway in progression of NAFLD, and the effect of zileuton, an inhibitor of 5-LOX, in this model.Materials And MethodsAnimal model for progression of NAFLD was established via feeding high saturated fat diet (HFD). Liver function, HE staining, NAFLD activity score (NAS) were used to evaluate NAFLD progression. We detected the lipid metabolism substrates: free fatty acids (FFA) and AA, products: cysteinyl-leukotrienes (CysLTs), and changes in gene and protein level of key enzyme in AA/5-LOX pathway including PLA2 and 5-LOX. Furthermore, we determined whether NAFLD progression pathway was delayed or reversed when zileuton (1-[1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea) was administrated.ResultsRat model for progression of NAFLD was well established as analyzed by liver transaminase activities, hematoxylin-eosin (HE) staining and NAS. The concentrations of substrates and products in AA/5-LOX pathway were increased with the progression of NAFLD. mRNA and protein expression of PLA2 and 5-LOX were all enhanced. Moreover, administration of zileuton inhibited AA/5-LOX pathway and reversed the increased transamine activities and NAS.ConclusionAA/5-LOX pathway promotes the progression of NAFLD, which can be reversed by zileuton.Keywords: Arachidonic acid, Lipid metabolism, 5-Lipoxygenase, Nonalcoholic fatty liver-disease, Proinflammatory mediators, Zileuton
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Pages 1213-1219Objective(s)Regulation of pro-inflammatory factors such as TNF-𝛼, which are secreted by the immune cells through induction of their several receptors including dopamine receptors (especially DRD2 and DRD3) is one of the noticeable problems in diabetic severe foot ulcer healing. This study was conducted to evaluate the alteration of TNF-𝛼 in plasma as well as DRD2 and DRD3 changes in PBMCs of diabetics with severe foot ulcers.Materials And MethodsPeripheral blood samples were collected from 31 subjects with ulcers, 29 without ulcers, and 25 healthy individuals. Total mRNA was extracted from PBMCs for the study of DRD2, DRD3, and TNF-𝛼 gene expression variations. Expression patterns of these genes were evaluated by real-time PCR. Consequently, concentration of TNF-𝛼 was investigated in plasma.ResultsSignificant decrease in gene expression and plasma concentration of TNF-𝛼 in PBMCs was observed in both patient groups at PConclusionWe concluded that DRD2 and DRD3 expression alteration and presence of new DRD3 transcripts can be effective in reduction of TNF-α expression as a pro-inflammatory factor. Performing complementary studies, may explain that variations in DRD2 and DRD3 are prognostic and effective markers attributed to the development of diabetes severe foot ulcers.Keywords: Diabetic severe foot ulcers, Dopamine receptor, Medical genetics, Regenerative medicine, Tumor necrosis factor-?
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Pages 1220-1226Objective(s)Increasing evidence suggests that regular physical exercise improves type 2 diabetes mellitus (T2DM). However, the potential beneficial effects of swimming on insulin resistance and lipid disorder in T2DM, and its underlying mechanisms remain unclear.Materials And MethodsRats were fed with high fat diet and given a low dosage of Streptozotocin (STZ) to induce T2DM model, and subsequently treated with or without swimming exercise. An 8-week swimming program (30, 60 or 120 min per day, 5 days per week) decreased body weight, fasting blood glucose and fasting insulin.ResultsSwimming ameliorated lipid disorder, improved muscular atrophy and revealed a reduced glycogen deposit in skeletal muscles of diabetic rats. Furthermore, swimming also inhibited the activation of Wnt3a/β-catenin signaling pathway, decreased Wnt3a mRNA and protein level, upregulated GSK3β phosphorylation activity and reduced the expression of β-catenin phosphorylation in diabetic rats.ConclusionThe trend of the result suggests that swimming exercise proved to be a potent ameliorator of insulin resistancein T2DM through the modulation of Wnt3a/β-catenin pathway and therefore, could present a promising therapeutic measure towards the treatment of diabetes and its relatives.Keywords: GSK3? Insulin resistance_Swimming training_Type 2 diabetes mellitus_Wnt3a-?-catenin signaling
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Pages 1227-1231Objective(s)In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue.Materials And MethodsForty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies.ResultsThe results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats.ConclusionFrom the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.Keywords: Antioxidants, Lead acetate, Nephrotoxicity, Piperine, Protective
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Pages 1232-1241Objective(s)Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress.Materials And MethodsThe CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC: received Bicuculline; MLP: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD: underwent ASD in an aquarium with multiple small platforms; and BICĠ︡: received bicuculline prior to ASD.ResultsBicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BICĠ︡ as compared to the ASD group.ConclusionBlockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production.Keywords: Acute sleep deprivation, Bicuculline, GABA-A receptor, Infarct size, Myocardial ischemia-Reperfusion, Nitric oxide
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Pages 1242-1249Objective(s)We investigated the relationship between the expression of tumor necrosis factor-inducible gene 6 (TSG-6) with inflammation and integrity of the bladder epithelium in the bladder tissues of patients with bladder pain syndrome/interstitial cystitis (BPS/IC) and the mechanism of action using a rat model of BPS/IC.Materials And MethodsExpression of TSG-6 and uroplakin III was determined by immuno- histochemistry of bladder biopsy samples from control human subjects and patients with verified BPS/IC. Our rat model of BPS/IC was employed to measure the perfusion of bladders with hyaluronidase, and assessment of the effect of TSG-6 administration on disease progression. Treatment effects were assessed by measurement of metabolic characteristics, RT-PCR of TGR-6 and interleukin-6, bladder histomorphology, and immunohistochemistry of TGR-6 and uroplakin III.ResultsThe bladders of patients with BPS/IC had lower expression of uroplakin III and higher expression of TSG-6 than controls. Rats treated with hyaluronidase for 1 week developed the typical signs and symptoms of BPS/IC, and rats treated with hyaluronidase for 4 weeks had more serious disease. Administration of TSG-6 reversed the effects of hyaluronidase and protected against disease progression.ConclusionOur results indicate that TSG-6 plays an important role in maintaining the integrity of the bladder epithelial barrier.Keywords: Bladder pain syndrome-interstitial cystitis, Immunofluorescence staining, Interleukin-6, TSG-6, Uroplakin III
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Pages 1250-1259Objective(s)The neurodegeneration and loss of memory function are common consequences of aging. Medicinal plants have potent protective effects against chronic neurodegenerative diseases. The aim of this study was to investigate the beneficial effects and molecular mechanisms of crocin on brain function in D-galactose (D-gal)-induced aging model in rats.Materials And MethodsMale Wistar rats weighing 220 ± 20 g were randomly divided into six groups: control, D-gal (400 mg/kg, SC), D-gal (400 mg/kg) plus crocin (7.5, 15, 30 mg/kg, IP) and crocin alone at dose of 30 mg/kg for 8 weeks. The neuroprotective effects of crocin were evaluated by Morris water maze, determination of malondialdehyde (MDA) levels and Western blot analysis.ResultsCrocin significantly inhibited the neurotoxic effects of D-gal through improvement of spatial learning and memory functions as well as the reduction of MDA levels. It was also found that administration of crocin up-regulated pAkt/Akt and pErk/Erk ratio which were decreased by chronic D-gal treatment. In addition, the elevated level of carboxymethyl lysine (CML), as an advance glycation product (AGE), NF-κB p65, TNFα and IL1β significantly decreased in crocin treated rats compared to D-gal group.ConclusionThese findings suggest that crocin is able to enhance memory function in D-gal aging model through anti-glycative and anti-oxidative properties which finally can suppress brain inflammatory mediators (IL-1, TNF and NF-κB) formations and increase PI3K/Akt and Erk/MAPK pathways activity. Therefore, crocin can be considered as healthcare product to prevent age-related brain diseases such as Alzheimer.Keywords: Advance glycation product, Brain aging, Crocin, D-galactose, Inflammation
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Pages 1260-1267Objective(s)To investigate the role of the microRNA-125a (miR-125a) and BAK1 in intervertebral disc degeneration (IDD).Materials And MethodsDegenerative lumbar nucleus pulposus (NP) tissues were obtained from 193 patients who underwent resection, and normal controls consisted of normal NP tissues from 32 patients with traumatic lumbar fracture in our hospital. All patients were graded according to the Pfirrmann criteria. QRT-PCR was used to detect the expression of miR-125a and BAK1, and apoptosis of NP tissues detected by TUNEL staining. After isolation of non- degenerative and degenerative nucleus pulposus cells (NPCs), the targeting relationship between miR-125a and BAK1 was verified by dual luciferase reporter gene assay. Flow cytometry was determined the NPCs apoptosis, and Western blot to measure the expressions of BAK1, Caspase-3, Bax and Bcl-2.ResultsMiR-125a was reduced while BAK1 was elevated in IDD patients with the increase of Pfirrmann grade. Besides, miRNA-125a was negatively correlated to the NPCs apoptosis, while BAK1 mRNA was positively correlated to cell apoptosis. Additionally, BAK1 is the target gene of miRNA-125a. When transfection of miR-125a mimics in vitro, the apoptosis of NPCs were inhibited, with the down-regulation of BAK1, Caspase-3, and Bax, and the upregulation of Bcl-2. In addition, siBAK1 can reverse the pro-apoptosis function of miR-125a inhibitors in NPCs.ConclusionmiRNA-125a may regulate the apoptosis status of the NPCs by inhibiting the expression of its target gene BAK1, which provided a potential strategy for further development of IDD therapies.Keywords: Apoptosis, BAK1 protein, Intervertebral disc degeneration, MIRN125 microRNA, Nucleus pulposus
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The correlation of anandamide with gonadotrophin and sex steroid hormones during the menstrual cyclePages 1268-1274Objective(s)The purpose of this study was to investigate the change in plasma anandamide (AEA) levels throughout the normal menstrual cycle, and to analyze the relationship among AEA, sex steroids and gonadotrophins.Materials And MethodsThe patients were fertile women with normal menstrual cycle, proposed to get in vitro fertilization (IVF) treatment due to oviduct obstruction or male infertility. Patients were divided into two groups, cross-sectional (n=79) and longitudinal (n=10). The plasma AEA levels were examined by the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) system. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) were measured by chemiluminescence.ResultsThe AEA levels in the late follicular phase were slightly higher than those in the early follicular phase. Subsequently, the AEA levels peaked at the time of ovulation in both two cohorts. Finally, the lowest AEA levels were measured in the luteal phase. Moreover, there were highly significant positive correlations between the plasma AEA concentration and the serum levels of FSH, LH and E2, whereas the AEA level was not correlated with P during the normal menstrual cycle.ConclusionOur observations reveal a dynamic change in the plasma AEA level, which is closely associated with the levels of gonadotrophin and sex steroid hormones, suggesting that the hormones may be involved in the regulation of AEA levels during the menstrual cycle. Our studies help to design new strategies to improve implantation and treatments for reproductive diseases.Keywords: Anandamide, Endocannabinoid, Gonadotrophin, Menstrual cycle, Sex steroid hormones
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Pages 1275-1281Objective(s)Oxidative stress has a pivotal role in the pathogenesis of diabetic retinopathy (DR). Juglans regia L. (JRL) leaf extract has hypoglycemic and antioxidative properties. This study aimed to determine the ameliorative effects of JRL against diabetic retinopathy.Materials And MethodsThe DR rat model was generated by injection of streptozotocin (STZ). A subset of the diabetic rats received JRL or metformin after the onset of hyperglycemia. Histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with biochemical assessments of lipid peroxidation and antioxidant status.ResultsLipid peroxidation level and catalase activity significantly improved after JRL consumption (PPPConclusionJRL leaf extract exert protective effects against diabetic retinopathy.Keywords: Antioxidant, Apoptosis, Diabetic retinopathy, Hyperglycemia, Inflammation, Juglans regia L. leaf
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Pages 1282-1286Objective(s)Antibiotic resistance in Acinetobacter baumannii and outbreaks caused by this organism have been reported from several areas of the world. The present study aimed at determining the antibiotic susceptibility profiles and the distribution of OXA-type beta-lactamases among Iranian Acinetobacter baumannii isolates from Qom of Iran.Materials And MethodsFor this study, 108 non-duplicate A. baumannii isolates were obtained from clinical specimens in four teaching hospitals in Qom in the central of Iran. The antimicrobial susceptibility of isolates was tested by standard disk diffusion and prevalence of bla OXA genes was investigated by PCR method.ResultsAmong 97 carbapenem non-susceptible isolates of A. baumannii, 90.72% (88 isolates) isolates showed extensive drug resistance to multiple antibiotics. Among carbapenem resistant isolates, 100% carried blaOXA-51-like, 82.47% carried blaOXA-23-like, 55.67% carried blaOXA-58-like, 22.68% carried blaOXA-40-like and 14.43% had blaOXA-143-like resistance genes.ConclusionThis study demonstrated high genetic diversity of OXA genes among isolates of A. baumannii in Qom, Iran.Keywords: Acinetobacter baumannii, blaOXA-143, Carbapenem resistance, Iran, Polymerase chain reaction