فهرست مطالب
Iranian Journal of Basic Medical Sciences
Volume:18 Issue: 3, Mar 2015
- تاریخ انتشار: 1394/02/06
- تعداد عناوین: 14
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Pages 212-220In mammals, the intrauterine condition has an important role in the development of fetal physiological systems in later life. Suboptimal maternal environment can alter the regulatory pathways that determine the normal development of the fetus in utero, which in post-natal life may render the individual more susceptible to cardiovascular or metabolic adult-life diseases. Changes in the intrauterine availability of nutrients, oxygen and hormones can change the fetal tissue developmental regulatory planning, which occurs genomically and non-genomically and can cause permanent structural and functional changes in the systems, leading to diseases in early years of life and those that particularly become overt in adulthood. In this review we take a brief look at the main elements which program the fetal system development and consequently induce a crucial impact on the cardiovascular, nervous and hormonal systems in adulthood.Keywords: Adulthood, Cardiovascular, Development, Disorders, fetus, Intrauterine programming
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Pages 221-227Objective(s)Oxytetracycline (OTC) is a broad spectrum antibiotic widely used for treatment of a wide range of infections. However, its improper human and animal use leads to toxic effects, including hepatonephrotoxicity. Our objective was to evaluate protective effects of Nigella sativa oil (NSO) and/or ascorbic acid (AA), against OTC-induced hepatonephrotoxicity in rabbits.Materials And MethodsForty male white New Zealand rabbits were divided into 5 groups of eight each. The 1st group (control) was given saline. The 2nd group was given OTC (200 mg/kg, orally). The 3rd and 4th groups were orally administered NSO and AA (2 ml/kg and 200 mg/kg respectively) 1 hr before OTC administration at the same dose regimen used for the 2nd group. Both NSO and AA were given in combination for the 5th group along with OTC administration. Serum biochemical parameters related to liver and kidney injury were evaluated, and lipid peroxidation as well as antioxidant markers in hepatic and renal tissues were examined.ResultsOTC-treated animals revealed significant alterations in serum biochemical hepato-renal injury markers, and showed a markedly increase in hepato-renal lipid peroxidation and inhibition in tissue antioxidant biomarkers. NSO and AA protect against OTC-induced serum and tissue biochemical alterations when each of them is used alone or in combination along with OTC treatment. Furthermore, both NSO and AA produced synergetic hepatoprotective and antioxidant properties.ConclusionThe present study revealed the preventive role of NSO and/or AA against the toxic effects of OTC through their free radical-scavenging and potent antioxidant activities.Keywords: Antioxidant, Ascorbic acid, Hepato, Renal, Nigella sativa, Oxytetracycline, Rabbit
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Pages 228-233Objective(s)To investigate the effect of topical administration of alpha-lipoic acid into chitosan conduit on peripheral nerve regeneration using a rat sciatic nerve transection model.Materials And MethodsForty five Wistar rats were divided into three experimental groups randomly. A 10-mm gap of sciatic nerve was bridged with a chitosan conduit following surgical preparation and anesthesia. In treatment group, the conduit was filled with 30 µl alpha-lipoic acid (10 mg/kg/bw).It was filled with 30 µl phosphate buffered saline solution in control group. In Sham group sciatic nerve was just exposed.ResultsThe recovery of nerve function was faster in treatment group than in control, at 4 and 8 weeks after surgery (P-value<0.05). Conduction velocity was better in treatment group than in control group at 4 and 12 weeks (P-value<0.05). Recovery index was higher in treatment group than the control group, 8 weeks after surgery (P-value <0.05). Greater nerve fiber diameter, axon diameter, and myelin sheath thickness were observed in treatment group compared to control group at 8 and 12 weeks after surgery (P-value<0.05). The immunoreactivity of regenerated axons and myelin sheath in treatment group were far more similar to sham group.ConclusionAlpha-lipoic acid when loaded in a chitosan conduit could improve transected sciatic nerve regeneration in rat.Keywords: Alpha, lipoic acid, Chitosan conduit, Rat, Sciatic nerve regeneration
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Pages 234-239Objective(s)There is controversial evidence about the effect of methamphetamine (METH) on spatial memory. We tested the time- dependent effects of METH on spatial short-term (working) and long-term (reference) memory in METH –sensitized and withdrawn rats in the Morris water maze.Materials And MethodsRats were sensitized to METH (2 mg/kg, daily/5 days, SC). Rats were trained in water maze (4 trials/day/ for 5 days). Probe test was performed 24 hr after training. Two days after probe test, working memory training (2 trials/day/ for 5 days) was conducted. Acquisition–retention interval was 75 min. The treatment was continued per day 30 and 120 min before the test. Two groups of METH –sensitized rats were trained in reference memory after a longer period of withdrawal (30 days).ResultsSensitized rats exhibited significantly longer escape latencies on the training, spent significantly less time in the target zone (all, P<0.05), and their working memory impaired 30 min after injection. While, METH has no effect on the spatial learning process 120 min after injection, and rats spent significantly less time in the target zone (P<0.05), as well it has no effect on working memory. Also, impairment of reference memory persisted after prolonged abstinence.ConclusionOur findings indicated that METH impaired spatial learning and memory 30 min after injection, but spared spatial learning, either acquisition or retention of spatial working, but partially impaired retention of spatial reference memory following 120 min after injection in sensitized rats, which persisted even after prolonged abstinence.Keywords: Long, term memory, METH, sensitized rats, Short, term memory, Spatial memory
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Pages 240-245Objective(s)Theneuroprotective effect of lithium has been attributed to its therapeutic action. However, the role of glial cells particularly astrocytes, and the possible interactions between neurons and astrocytes in neuroprotective effects of lithium have been disregarded. Thus, the aim of this study was to evaluate the direct effects of lithium on brain derived neurotrophic factor (BDNF) and glial cell line derived neurotrophic factor (GDNF) in rat primary neuronal, astrocytes, and mixed neuro-astroglial cultures to assess the possible effects of lithium on astrocytes and neuro-astroglia interactions.Materials And MethodsRat primary astrocyte, neuronal and mixed neuro-astrocyte cultures were prepared from cortices of 18-day embryos. Cell cultures were exposed to lithium (1 mM) or vehicle for 1 day (acute) or 7 days (chronic). BDNF and GDNF mRNA and protein levels were determined by RT-PCR and ELISA, respectively.ResultsChronic but not acute lithium treatment increased intracellular BDNF and GDNF protein levels in rat primary neuronal and astrocyte cultures, respectively (P<0.05). However, chronic lithium treatment had no significant effect on intracellular BDNF protein level in astrocyte and mixed neuron-astrocyte cultures or GDNF protein levels in mixed neuron-astrocyte culture. Furthermore, acute and chronic lithium treatment had no significant effect on mRNA and extracellular BDNF and GDNF protein levels in three studied cultures.ConclusionPresent study showed that chronic lithium treatment affected neurotrophins both in neurons and astrocytes in a cell-type specific manner with no effect on neuron-astrocyte interactions. The findings of this study also highlighted the importance of astrocytes as drug targets involved in the neuroprotective action of lithium.Keywords: Astrocytes, BDNF, Culture, GDNF, Lithium, Neuro, astroglial, Neurons
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Pages 247-251Objective(s)Pentoxifylline is an immunomodulatory and anti-inflammatory agent and is used in vascular disorders. It has been shown that pentoxifylline inhibits proinflammatory [d1] cytokines production. The purpose of this study was to investigate the therapeutic effects of pentoxifylline on the treatment of autoimmune diabetes in mice.Materials And MethodsDiabetes was induced by multiple low dose of streptozotocin (MLDS) injection (40 mg/kg/day for 5 consecutive days) in male C57BL/6 mice. After induction of diabetes, mice were treated with pentoxifylline (100 mg/kg/day IP) for 21 days. Blood glucose levels and plasma levels of insulin were measured. Splenocytes were tested for proliferation by MTT test and cytokine production by ELISA.ResultsPentoxifylline treatment prevented hyperglycemia and increased plasma insulin levels in the diabetic mice. Aside from reducing lymphocyte proliferation, pentoxifylline significantly inhibited the production of proinflammatory interleukin 17 (IL-17) as well as interferon gamma (IFN-γ), while increased anti-inflammatory cytokine IL-10 as compared with those in MLDS group (diabetic control group).ConclusionThese findings indicate that pentoxifylline may have therapeutic effect against the autoimmune destruction of the pancreatic beta-cells during the development of MLDS-induced type 1 diabetes in mice.Keywords: Cytokine_Pentoxifylline_Type 1 diabetes mellitus
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Pages 253-258Objective(s)This study was undertaken to investigate the protective effects of vitamin B6, cofactor for cystathionine-γ lyase and cystathionine-β synthase (producers of H2S), alone and in combination with L-cysteine, H2S precursor, on indomethacin-, and ethanol-induced gastric lesions in male NMRI mice.Materials And MethodsFasted male NMRI mice were randomly assigned into 12 groups (7 in each). The gastroprotective activity of vitamin B6 alone and in combination with L-cysteine and sodium hydrosulfate (NaHS) was evaluated against ethanol-, and indomethacin-induced gastric lesions. The animals were received vehicle, vitamin B6, L-cysteine, L-cysteine+vitamin B6, NaHS or NaHS+B6 before the induction of gastric lesions by ethanol (50%, 0.5 ml/25 g of body weight, orally) or indomethacin (40 mg/kg, orally). One and five hours after the administration of ethanol and indomethacin, respectively, the animals were sacrificed using anesthetics. The stomachs were removed, rinsed with normal saline and assessed for gastric wall mucus changes.ResultsPretreatment with L-cysteine, sodium hydrosulfate, and vitamin B6 significantly decreased the total area of gastric lesions (P<0.01). The mucus production in L-cysteine-, sodium hydrosulfate-, and vitamin B6-treated animals were significantly higher than in control rats (P<0.05). The gastroprotective activity of L-cysteine and sodium hydrosulfate in combination with vitamin B6 were higher than when administered alone (P<0.05).ConclusionThe result of this survey showed that the protective activity of L-cysteine and sodium hydrosulfate enhances in the presence of vitamin B6.Keywords: Ethanol, Indomethacin, L, cysteine, Mice, NaHS, Vitamin B6
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Differentiation of adipocytes and osteocytes from human adipose and placental mesenchymal stem cellsPages 259-266Objective(s)Mesenchymal stem cells (MSC) can be isolated from adult tissues such as adipose tissue and other sources. Among these sources, adipose tissue (because of easy access) and placenta (due to its immunomodulatory properties, in addition to other useful properties), have attracted more attention in terms of research. The isolation and comparison of MSC from these two sources provides a proper source for clinical experimentation. The aim of this study was to compare the characteristics of MSC isolated from human adipose tissue and placenta.Materials And MethodsAdipose and placental MSC were isolated from the subcutaneous adipose tissues of 10 healthy women (25 to 40 years) and from a fresh term placenta (n= 1), respectively. Stem cells were characterized and compared by flow cytometry using CD29, CD31, CD34, CD44, CD45, CD105, CD166 and HLA-DR markers. Osteocytes and adipocytes were differentiated from isolated human mesenchymal stem cells (HMSC).ResultsAdipose and placenta-derived MSC exhibited the same morphological features. ADSC differentiated faster than placenta; however, both were differentiated, taking up to 21 days for osteocyte and 14 days for adipocyte differentiation. About 90% of PLC-MSC and ADSC were positive for CD29, CD44, CD105, and CD166; and negative for CD31, CD34, CD45, and HLA-DR.ConclusionThe two sources of stem cells showed similar surface markers, morphology and differentiation potential and because of their multipotency for differentiating to adipocytes and osteocytes, they can be applied as attractive sources of MSC for regenerative medicine.Keywords: Adult stem cells, Differentiation, Fetal stem cells, Mesenchymal stem cells
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Pages 267-176Objective(s)Many cancer cells show significant resistance to drugs that kill drug sensitive cancer cells and non-tumor cells and such resistance might be a consequence of the difference in metabolism. Therefore, studying the metabolism of drug resistant cancer cells and comparison with drug sensitive and normal cell lines is the objective of this research.Material And MethodsMetabolism of cisplatin resistant and sensitive A2780 epithelial ovarian cancer cells and normal ovarian epithelium has been studied using a generic human genome-scale metabolic model and transcription data.ResultThe results demonstrate that the most different metabolisms belong to resistant and normal models, and the different reactions are involved in various metabolic pathways. However, large portion of distinct reactions are related to extracellular transport for three cell lines. Capability of metabolic models to secrete lactate was investigated to find the origin of Warburg effect. Computational results introduced SLC25A10 gene, which encodes mitochondrial dicarboxylate transporter involved in exchanging of small metabolites across the mitochondrial membrane that may play key role in high growing capacity of sensitive and resistant cancer cells. The metabolic models were also used to find single and combinatorial targets that reduce the cancer cells growth. Effect of proposed target genes on growth and oxidative phosphorylation of normal cells were determined to estimate drug side-effects.ConclusionThe deletion results showed that although the cisplatin did not cause resistant cancer cells death, but it shifts the cancer cells to a more vulnerable metabolismKeywords: Cisplatin resistance, Drug target, Lactate, Metabolism, Microarray
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Pages 277-283Objective(s)To evaluate the effect of trinitroglycerin (TNG) as nitric oxide donor agent on serum copper (Cu) and zinc (Zn) levels and liver enzymes in BALB/c mice infected with Leishmania major (L. major) MRHO/IR/75/ER.Materials And MethodsInbred female mice were divided into three groups: healthy group (uninfected naive mice), control group (infected with L. major), and test group (L. major infected mice treated with TNG). TNG (200 µg/µl) was inoculated subcutaneously into the mice of the test group. Serum Cu and Zn levels and liver enzymes activities were then evaluated by atomic absorption spectrophometer and colorimetric methods, respectively.ResultsSerum Cu levels were significantly higher in the test group than in the control and naive groups (P-value <0.05), while Zn levels were higher in the test group than in the control group with no significant difference. Serum glutamicoxaloacetic transaminase concentrations in the test group were significantly lower than those in other groups (P-value <0.05), while serum glutamate pyruvic transaminase concentrations were significantly higher in test compared with those in other groups (P-value <0.05). Moreover, alkaline phosphatase in the control and test groups were significantly lower than that in the naive group (P-value <0.05).ConclusionTNG treatment increased Zn and Cu levels and thus increased resistance to Leishmania because of the role of Zn and Cu; therefore, TNG therapy will be useful for treating cutaneous leishmania. In addition, the decrease of serum glutamicoxaloacetic transaminase activity can be an index of therapeutic process of TNG.Keywords: Copper, Cutaneous leishmania, Liver enzymes, Transaminase, Trinitroglycerin, Zinc
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Pages 284-292Objective(s)Chlorpyrifos (CP) is a broad-spectrum organophosphorus pesticide used extensively in agricultural and domestic pest control, accounting for 50% of the global insecticidal use. In the present study, protective effects of two selenium-enriched strong antioxidative medicines IMOD and Angipars were examined in human lymphocytes treated with CP in vitro.Materials And MethodsIsolated lymphocytes were exposed to 12 µg/ml CP either alone or in combination with effective doses (ED50) of IMOD (0.2 µg/ml) and Angipars (1 µg/ml). After 3 days incubation, the viability and oxidative stress markers including cellular lipid peroxidation (LPO), myeloperoxidase (MPO), total thiol molecules (TTM), and total antioxidant power (TAP) were evaluated. Also, the levels of tumor necrosis factor-α (TNF-α), as inflammatory index along with acetylcholinesterase (AChE) activity and cell apoptosis were assessed by flow cytometry.ResultsResults indicated that effective doses of IMOD and Angipars reduced CP-exposed lymphocyte mortality rate along with oxidative stress. Both agents restored CP-induced elevation of TNF-α and protected the lymphocytes from CP-induced apoptosis and necrosis.ConclusionOverall, results confirm that IMOD and Angipars reduce the toxic effects associated with CP through free radical scavenging and protection from apoptosis and necrosis.Keywords: Angipars, Chlorpyrifos, Human lymphocytes, IMOD, Organophosphorus Oxidative stress
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Pages 293-300Objective(s)Althoughroutinely applied in assisted reproductive technology, human sperm cryopreservation is not a completely successful procedure. Adverse effects of cryopreservation on the fertilization capacity, motility, morphology, and viability of spermatozoa have been proven; cryopreservation has also shown a role in sperm DNA fragmentation and infertility. The post-thaw survival of spermatozoa improved after addition of supplementation of antioxidant molecules to freezing media. Nerve growth factor (NGF) as one of the prosurvival substances has gained great attention in recent years. The aim of this study was the usage of NGF as prosurvival factor after cryopreservation process of human semen samples to assess the motility and viability of sperm, nitric oxide (NO) concentration, and DNA fragmentation in normozoospermic men.Materials And MethodsSemen samples were collected from 25 normozoospermic men and were divided into fresh semen samples as control group, frozen–thawed semen samples without addition of exogenous NGF, and three groups of semen samples cryopreserved with addition of exogenous NGF (0.5, 1, and 5 ng/ml) in freezing medium. Viability was assessed by eosin-negrosin staining technique. Motility was evaluated with inverted microscope. NO concentration and apoptosis content were measured with flow cytometry.ResultsResults showed that exogenous NGF at 0.5 ng/ml could significantly (P-value <0.05) influence viability, motility, nitric oxide, and DNA fragmentation content.ConclusionExogenous NGF as cryoprotectant improved sperm viability and motility, increased intracellular NO concentration, and decreased apoptosis content in normal human spermatozoa.Keywords: Apoptosis, Cryopreservation, Human sperm, Nerve growth factor, Nitric oxide
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Pages 301-306Objective(s)The neuroprotective effect offruit aqueous extract of Ziziphus jujuba Lam on glucose-induced neurotoxicity in PC12 cells as an appropriate in vitro model of diabetic neuropathy was investigated.Materials And MethodsCell viability was determined by the MTT assay. Cellular reactive oxygen species (ROS) generation was measured by DCFH-DA analysis. Cleaved caspase-3, a biochemical parameter of cellular apoptosis, was measured by western blot analysis.ResultsOur data showed that a 4-fold elevation in glucose levels within the medium significantly reduced cell viability, increased intracellular ROS and caspase-3 activation in PC12 cells after 24 hr. Incubation of the high glucose medium cells with 300-μg/ml Z. jujuba fruit (ZJF) extract decreased the high glucose-induced cell toxicity and prevented caspase-3 activation and excited ROS generation.ConclusionThus, we concluded that the aqueous extract of Z. jujuba protects against hyperglycaemia-induced cellular toxicity. This could be associated with the prevention of ROS generation and neural apoptosis. Moreover, the results suggest that the ZJF has a therapeutic potential to attenuate diabetes complications such as neuropathy.Keywords: Apoptosis, Diabetes, Neuropathy, Ziziphus jujube
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Pages 307-311Objective(s)Predegeneration is a standard technique to obtain mitotically activated and enriched cultures of Schwann cells (SCs). This study, for the first time, evaluated the impact of various duration of predegeneration on cell yield and enrichment of SCs from dog peripheral nerve.Materials And MethodsDog sural nerves were subjected to 5, 10, 15 day-long in vitro predegeneration. The total cell yield and the purity of SCs were evaluated in each group on the first and seventh day after plating.ResultsThe maximum and minimum numbers of cells were counted in 15 day-long predegene-ration and control groups which underwent no predegeneration. The 10 day-long in vitro predegeneration group with 80±0.5% SCs enrichment had the best purity after plating day and could maintain its purity with elapsing on cultures.Conclusion10 day-long predegeneration results in the higher cell number and the better and prolonged purity of SCs in culture.Keywords: Dog, Duration, Sural nerve, Wallerian degeneration, Schwann cell