فهرست مطالب

Basic Medical Sciences - Volume:22 Issue: 4, 2019
  • Volume:22 Issue: 4, 2019
  • تاریخ انتشار: 1397/12/18
  • تعداد عناوین: 17
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  • Majid Zeinali, Mohammad Reza Zirak, Seyed Abdolrahim Rezaee, Gholamreza Karimi, Hossein Hosseinzadeh* Pages 334-344
    The medicinal uses of saffron, the dried stigmas of Crocus sativus L., have very long history in food coloring agent, and flavoring agent as well as traditional medicine for the treatment of several diseases. Crocus sativus is rich in carotenoids that affect immunity. This review summarizes the putative immunoregulatory effects of saffron and its active its derivatives including crocin, crocetin and safranal. In modern studies, its active constituents including protective effects, anti-inflammatory activities and molecular mechanisms of saffron on the immune system have been demonstrated. Furthermore, the beneficial effects of saffron on inhibition of serum levels nuclear transcription factor κB (NF-κB) p65 unit, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and some interleukin (IL) such as IL-1β, IL-6, IL-12, IL-17A were reported. Furthermore, saffron has been known as the antagonist of NF-κB and the agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ). In addition, saffron down-regulates the key pro-inflammatory enzymes such as myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phospholipase A2, and prostanoids.
    This review summarizes the protective roles of C. sativus and its constituents against the pathogenesis of immune diseases and understanding a better management of these problems. Taken together, the main bioactive constituents of saffron may have health-promoting with important benefits in immune-related disorders. Finally, our study indicates that these bioactive constituents can affect both cellular and humoral immunity functions.
    Keywords: Anti-inflammatory, Crocus sativus, Cytokines, Immunomodulatory, Saffron
  • Showkat Ahmad Bhat_Sabhiya Majid *_Muneeb U Rehman Pages 345-352
    Carcinoma of the stomach is one of the major prevalent and principal causes of cancer-related deaths worldwide. Current advancement in technology has improved the understanding of the pathogenesis and pathology of gastric cancers (GC). But, high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate novel early diagnostic/prognostic markers and therapeutic targets for GC, which are sufficiently sensitive to GC. Current biomedical investigations have explored several budding GC biomarker by utilizing serum proteins, natural oncogenic genes during improvement in molecular technologies as microarray, and RNA/DNA-Seq. Recently, small non-coding microRNAs (miRNAs) are becoming vital regulators in oncogenesis pathways and can act as handy clinical biomarkers. The newly introduced class of biomarkers is rising as new molecules for cancer diagnosis and prognosis. For better understanding of the gastric carcinogenesis, miRNAs may help to elucidate the mechanisms of tumor growth and can help to discover novel untimely potent markers for early detection of GC. Here in this review, we summarize the recent research studies supporting the utility of miRNAs as novel early diagnostic/prognostic tools and therapeutic targets. Thus, here we introduce potential future treatment strategies for gastrointestinal (GI) cancers, which indicate the practicality and clinical applications of miRNAs in GC.
    Keywords: Biomarkers, Clinical applications, Diagnosis, prognosis, Gastric cancer, microRNAs, Noninvasive biomarkers
  • MohamadJavad Bagheripour, Firouz Ebrahimi *, Abbas Hajizade, Shahram Nazarian Pages 353-359
    Objective(s)
    The Botulism syndrome is caused by types A to G of botulinum neurotoxins. The binding domains of these neurotoxins are immunogenic and considered as appropriate candidate vaccines. Due to the low immunogenicity of recombinant vaccines, there have been many studies on the use of biocompatible carriers such as chitosan nanoparticles for the delivery of these vaccines. The aim of this study was evaluating the efficiency of chitosan nanoparticles as carriers for a candidate vaccine, binding domain of BoNT/E, through oral and intranasal routes.
    Materials and Methods
    Chitosan nanoparticles containing rBoNT/E binding domain, were synthesized via ionic gelation. After administration of the nanoparticles to mice through oral and intranasal routes, antibody titers were assessed by ELISA and, finally, all groups were challenged by active botulinum neurotoxin type E.
    Results
    The groups that received nanoparticles containing the antigen, through oral and intranasal routes, and the group that received the bare antigen orally, were able to tolerate 5×102 folds of MLD. The intranasally immunized mice by the bare antigen were able to tolerate 2×103 folds of the toxin’s MLD.
    Conclusion
    It seems that the use of chitosan nanoparticles has no significant effect on the protective immunization of the mice against botulinum BoNT/E in either route (P>0.05), even intranasal administration of the bare antigen gives better mice immunization against the toxin.
    Keywords: Botulinum toxin type E, Chitosan, Mucosal administration, Nanoparticles, Recombinant protein
  • Soheil Yousefi, Tooba Abbassi, Daloii, Mojtaba Tahmoorespour, Mohammad Hadi Sekhavati * Pages 360-366
    Objective(s)
    Brucellosis is a common infectious disease among animals and humans. While subunit vaccines could be used as an efficient strategy against pathogens, they usually seem to be less immunogenic than live or killed vaccines. However, the use of a suitable adjuvant accompanied by subunit vaccines can be a good alternative to enhance the immune response.
    Materials and Methods
    To find a proper adjuvant against Brucellosis, the immune response of induced mice by Aluminum Hydroxide (AH), Incomplete Freund (IFA), and Chitosan Nanoparticle (CS) adjuvants in individuals and in combination with CS were assessed.
    Results
    Immunization with CS stimulated higher interferon gamma (IFN-γ) immunity, while there were no significant differences between rOMP25 (IFA), rOMP25 (AH), rOMP25 (AH-CS) and rOMP25 (IFA-CS) recombinant proteins. Tumor necrosis factor alpha (TNF-α) analysis revealed there were no significant differences between immunized groups and the positive control group, except for the treatment formulated in single IFA. Furthermore, unlike IFN-γ, there was a reverse interleukin-4 (IL-4) immune response trend for treatments, as rOMP25 (CS) displayed the lowest response. rOMP25 (CS) induced higher titer of total antibody than the other ones. Although the recombinant proteins emulsified in different adjuvants induced similar titer of IgG1 antibody, the ones that were formulated in CS, IFA and IFA-CS showed a higher titer of IgG2a. The cell proliferation assay demonstrating the antigen-specific cell proliferative response could be promoted after immunization with CS.
    Conclusion
    CS whether single or in combination with IF adjuvants has potential to improve Th1-Th2 responses.
    Keywords: Aluminum hydroxide, Brucellosis, Chitosan, Freund, Omp25
  • Irma Edith Carranza, Torres, Ezequiel Viveros, Valdez, Nancy Elena Guzm?n, Delgado, Sara Garc?a, Davis, Javier Mor?n, Mart?nez, Nadia Denys Betancourt, Mart?nez, Isa?as Balderas, Renter?a, Pilar Carranza, Rosales* Pages 367-375
    Objective(s)
    Precision-cut tissue slices are considered an organotypic 3D model widely used in biomedical research. The comet assay is an important screening test for early genotoxicity risk assessment that is mainly applied on in vitro models. The aim of the present study was to provide a 3D organ system for determination of genotoxicity using a modified method of the comet assay since the stromal components from the original tissue make this technique complicated.
    Materials and Methods
    A modified comet assay technique was validated using precision-cut hamster kidney slices to analyze the antigenotoxic effect of the phenolic compounds caffeic acid, chlorogenic acid, and rosmarinic acid in tissue slices incubated with 15 µM HgCl2. Cytotoxicity of the phenolic compounds was studied in Vero cells, and by morphologic analysis in tissue slices co-incubated with HgCl2 and phenolic compounds.
    Results
    A modification of the comet assay allows obtaining better and clear comet profiles for analysis. Non-cytotoxic concentrations of phenolic acids protected kidney tissue slices against mercury-induced DNA damage, and at the same time, were not nephrotoxic. The highest protection was provided by 3 µg/ml caffeic acid, although 6 µg/ml rosmarinic and 9 µg/ml chlorogenic acids also exhibited protective effects.
    Conclusion
    This is the first time that a modification of the comet assay technique is reported as a tool to visualize the comets from kidney tissue slices in a clear and simple way. The phenolic compounds tested in this study provided protection against mercury-induced genotoxic damage in precision-cut kidney slices.
    Keywords: Comet assay, Genotoxicity, Mercuric chloride, Phenolic compounds, Precision-cut tissue slices
  • Hassan Ghasemi, Behzad Einollahi *, Nejat khiripour, Seyed, Reza Hosseini, Zijoud, Masumeh Farhadiannezhad Pages 376-383
    Objective(s)
    One of the serious complications of Type1 diabetes (T1D) is diabetic nephropathy, which is accompanied with overexpression of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) and enhanced oxidative stress. The present study was conducted to examine the protective effect of curcumin on the expression of KIM-1, NGAL genes and oxidative damage in the kidney of T1D rats.
    Materials and Methods
    Thirty-six adult male rats were divided into 6 groups (n=6). The control and T1D groups received treatment with curcumin or without it (80 and 130 mg/kg, respectively). After 60 days of treatment, using spectrophotometric methods, biochemical factors and oxidative stress markers were measured. Gene expression of KIM-1 and NGAL was evaluated using quantitative PCR. Also, plasma and urine levels of these two proteins were assayed by the ELISA kit.
    Results
    Diabetes caused a significant increase in the levels of creatinine, FBS, uric acid, urea, and creatinine in the serum, which were attenuated after the administration of curcumin. There was a significant reduction in the values of creatinine, uric acid, and urea in urine in the diabetic group whereas in the rats treated with curcumin, these values were normalized to the normal level (especially in 130 mg/kg). Curcumin administration had a significant role in modulation of serum lipid profile, and it was shown to decrease the kidney and urinary expression levels of KIM-1 and NGAL genes and improve oxidative toxic stress in the kidney tissues.
    Conclusion
    Curcumin can play a protective role in reducing the unpleasant consequences of diabetic nephropathy.
    Keywords: Curcumin_Kidney injury molecule 1_Neutrophil gelatinase associated lipocalin protein_Oxidative stress_Type 1 Diabetes Mellitus
  • Zahra Ashrafi Jigheh, Amir Ghorbani Haghjo *, Hassan Argani, Leila Roshangar, Nadereh Rashtchizadeh, Davoud Sanajou, Saeed Nazari Soltan Ahmad, Jalil Rashedi, Siavoush Dastmalchi, Mehran Mesgari Abbasi Pages 384-390
    Objective(s)
    Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, possesses verified anti-inflammatory and anti-oxidative stress effects against diabetic nephropathy. The present investigation aims to examine empagliflozin effects on the renal levels of high mobility group box-1 (HMGB1), a potent inflammatory cytokine, and its respective receptor toll-like receptor-4 (TLR-4) in STZ-induced diabetic rats.
    Materials and Methods
    Empagliflozin at 10 mg/kg per os (p.o.) was administered for 4 weeks, starting 8 weeks after the induction of diabetes. Renal function, kidney inflammation, oxidative stress, and apoptosis markers as well as renal HMGB1, receptor for advanced glycation end products (RAGE), and TLR-4 levels were assessed.
    Results
    In addition to down-regulating NF-κB activity in renal cortices, empagliflozin reduced renal levels of HMGB1, RAGE, and TLR-4. It alleviated renal inflammation as indicated by diminished renal expressions of inflammatory cytokines and chemokines like tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) and also decreased urinary levels of interleukin-6 (IL-6) and alpha-1 acid glycoprotein (AGP). Moreover, empagliflozin ameliorated renal oxidative stress as demonstrated by decreased renal malondialdehyde (MDA) and elevated renal activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX). It also suppressed renal caspase-3, the marker of apoptosis; and furthermore, enhanced renal function noticed by the declined levels of serum urea and creatinine.
    Conclusion
    These findings underline that empagliflozin is able to attenuate diabetes-related elevations in renal HMGB1 levels, an influential inflammatory cytokine released from the necrotic and activated cells, and its correspondent receptors, i.e., RAGE and TLR-4.
    Keywords: Diabetic nephropathy, Empagliflozin, HMGB1, Inflammation, TLR-4
  • Rui Yan, Huiling Tian, Zhongxiu Du * Pages 391-398
    Objective(s)
    Impairment of nerve cells of brain induced by hypoxia results in energy-deprivation and dysfunction, which accompanies with neurons apoptosis. Improving function of nerve cells is important for treating cerebral anoxia. This study aimed to investigate the role of Quercetin (Quer) in hypoxia-induced injury of pheochromocytoma (PC-12) cells.
    Materials and Methods
    PC-12 cells were cultured under anoxic condition for induction of hypoxia injury and/or treatment with Quer, transfection with pre-miR-122, anti-miR-122 or their negative controls. After Quer treatment, viability, migration, and cell apoptosis of PC-12 cells were analyzed by CCK-8 assay, transwell assay and flowcytometry analysis, respectively. Cell proliferation-associated proteins and cell apoptosis-associated proteins were analyzed by Western blot. Relative miR-122 expression in Quer-treated cells or transfection efficacy of miR-122 was analyzed by qRT-PCR. Finally, main components in AMP-activated protein kinase (AMPK) and Wnt/β-catenin signaling pathways were analyzed by Western blot.
    Results
    Quer alleviated hypoxia-induced injury in PC-12 cells by increasing viability, promoting cell proliferation, enhancing migration and repressing apoptosis. Also, miR-122 was down-regulated in Quer-treated cells. miR-122 overexpression decreased cell viability and migration, and increased cell apoptosis in hypoxia- treated PC-12 cells, but miR-122 silencing led to the opposite results. We also found that AMPK and Wnt/β-catenin signaling pathways were activated by Quer in hypoxia-induced injury, but were inactivated in hypoxia-induced cells by overexpression of miR-122.
    Conclusion
    Quer could repress hypoxia-induced injury in PC-12 cells by activating AMPK and Wnt/β-catenin signaling pathways via down-regulation of miR-122.
    Keywords: AMPK pathway, Hypoxia injury, miR-122, Quercetin, Wnt-?-catenin pathway
  • Zahra Sarlak, Mahtab Moazzami *, Seyyed Reza Attarzadeh Hosseini, Reza Gharakhanlou Pages 399-406
    Objective(s)
    The purpose of this study was to investigate the effects of aerobic training before and after the induction of Alzheimer’s disease on ABCA1 and APOE mRNA expression and the level of soluble Aβ1-42 in the hippocampus of male Wistar rats.
    Materials and Methods
    Ninety six eight-week-old male Wistar rats were randomly divided into two groups: Training (n=48) and Rest (n=48). After four weeks, each group was randomly divided into two subgroups: intra-hippocampal injection of Aβ1-42 (n=24) and DMSO (n=24). Then, each group was again randomly divided into two groups: Training (n=12) and Rest (n=12). After four weeks, each group was again randomly divided into two groups: Behavioral test (n=7) and sacrificed (n=5).
    Results
    The one-way ANOVA showed a significant increase in the mRNA expression of ABCA1 (P<0.05), a significant decrease in the level of soluble Aβ1-42, and no significant difference in the expression of APOE mRNA (P>0.05) in the hippocampus as a result of training. The analysis of the Morris water maze data showed that intra-hippocampal injection of Aβ1-42 impaired spatial learning and memory and exercise improved spatial learning (P<0.05) and memory (P<0.05).
    Conclusion
    Therefore, aerobic training by a significant increase in the mRNA expression of ABCA1, which is the main factors of lipid metabolism in the brain and which is involved in the pathology of Alzheimer’s disease, can be consistent with improving cognitive function as an effective way of preventing and improving the symptoms of Alzheimer’s disease.
    Keywords: ABCA1, Aerobic training, Alzheimer’s disease, APOE, Soluble A?1-42
  • Evren Kose *, Fatih Oguz, Nigar Vardi, Mehmet Sarihan, Ali Beytur, Aytac yucel, Alaadin Polat, Nihat Ekinci Pages 407-411
    Objective(s)
    The current study was designed to investigate the therapeutic and protective effects of montelukast (ML) against doxorubicin (DOX)-induced acute kidney damage in rats.
    Materials and Methods
    Thirty-five Wistar albino female rats were randomly divided into 5 groups as follows: Group I: Control; Group II: Control+ML; Group III: DOX; Group IV: DOX+ML; Group V: ML+DOX. At the end of the experiment, the kidney tissues of rats were collected. Thiobarbituric acid reactive substance (TBARS), reduced glutathione, superoxide dismutase (SOD), and catalase levels were determined from the kidney tissues. In addition, the kidney tissues were examined histologically.
    Results
    DOX induced a significant increase in the kidney TBARS levels, whereas SOD contents significantly decreased when compared with the control group. On the other hand, ML administration before and after DOX injection caused significant decreases in TBARS production and also increases in SOD levels. Histologically, the most remarkable damage was glomerulosclerosis and tubular changes in the DOX group. Moreover, marked tubular necrosis and swelling in tubular epithelial cells were observed in this group. Contrarily, although glomerulosclerosis was recognized as alleviated also in both DOX+ML and ML+DOX groups, the lesions did not completely ameliorate. However, treatment with ML after DOX injection was more effective than treatment with ML before DOX injection with respect to the protection of tubular structures.
    Conclusion
    It was determined that ML treatment after DOX injection caused therapeutic effects against DOX-induced kidney damage. Thence, ML treatment is of some clinical properties for oxidative stress damage in kidney tissues.
    Keywords: Doxorubicin, Histology, Kidney, Leukotrienes, Oxidative stress, TBARS
  • Masumeh Mohammadpour, Gholam Hossein Farjah *, Mojtaba Karimipour, Bagher Pourheidar, Mohammad Hassan Khadem Ansari Pages 412-417
    Objective(s)
    Paraplegia is deterioration in motor or sensory function of the lower limbs that can occur after modification of a thoracoabdominal aortic aneurysm. The purpose of this survey was to determine the protective action of lutein on spinal cord ischemia-reperfusion (I-R) damage.
    Materials and Methods
    Thirty-five male rats were distributed into five groups: intact, sham, dimethyl sulfoxide (I-R+DMSO), low dose lutein (I-R+0.2 mg/kg lutein), and high dose lutein (I-R + 0.4 mg/kg lutein). Thirty minutes before surgery, a single dose lutein or DMSO was administered to rats of experimental groups. Next, the abdominal aorta was clamped exactly under the left renal artery and proximal to the abdominal aortic bifurcation for 60 min. All animals were evaluated by neurological function and histological and biochemical examinations at 72 hr after I-R.
    Results
    The mean motor deficit index (MDI) scores in lutein groups were lower compared with the DMSO group (P<0.001). Plasma level of malondialdehyde in lutein groups decreased compared with the DMSO group (P<0.05). Plasma level of total antioxidative capacity was increased in the high lutein group compared with low dose lutein and sham groups (P<0.05). Mean number of normal motor neurons in lutein groups was greater compared with the DMSO group (P<0.001). There was a significant negative correlation between MDI scores and the number of normal neurons (r= -0.764, P<0.001).
    Conclusion
    Findings of the present study demonstrate that lutein may support spinal cord neurons from I-R damage.
    Keywords: Ischemia, Lutein, Rat, Reperfusion, Spinal Cord
  • Seher Yilmaz *, Harun Ulger, Tolga Ertekin, Arzu Yay, Mehtap Nisari, ?erife Alpa, Niyazi Acer Pages 418-425
    Objective(s)
    In this study, the effects of different doses of curcumin application on Ehrlich ascites tumor (EAT) created in the mice of BALB/c type were investigated.
    Materials and Methods
    Curcumin extracts can have hindering effect on tumor volume, vascular density, EAT cells around the tissues, and can support apoptosis. EAT cells (1x106) received from stock animals were injected intraperitoneally (IP) and subcutaneously (SC) to the animals. Then, curcumin was administered IP. Doses of 25 mg/kg IP and 50 mg/kg were administered over 10 days to the animals in the treatment groups in which ascites tumor was induced. The same doses were administered over 15 days in the treatment groups in which solid tumor was induced.
    Results
    Histopathological examination in ascites tumor groups revealed that number of EAT cells at surrounding tissues was smaller in the group received 50 mg/kg curcumin when compared to tumor control group (P<0.05). The lowest increase in tumor volume was observed in the group received 25 mg/kg curcumin when compared to tumor control group (P<0.05).
    Conclusion
    It was demonstrated once again in our study that curcumin had an anti-tumoral effect on both the development of ascites tumor created through EAT cells and the development of solid tumor.
    Keywords: Animal, Apoptosis, Cell, Curcumin, Factor VIII, injection, Mice
  • Fatemeh sadat Amjadi, Ensieh Salehi, Zahra Zandieh, Mandana Rashidi, Sara Taleahmad, Mojgan Javedani masrour, Reza Aflatoonian, Mehdi Mehdizadeh* Pages 426-431
    Objective(s)
    NOTCH signaling pathway is well known for its role in cell fate, cell survival, cell differentiation, and apoptosis. Some of the NOTCH signaling genes are critical for endometrial function and implantation in animals and appear to play a similar role in humans. The purpose of the current study was to investigate the potential roles of some main components of the NOTCH family in human endometrium during implantation period in common gynecological diseases.
    Materials and Methods
    Endometrial NOTCH receptors NOTCH1, 3, 4 and ligand JAG1, 2 and survivin mRNA expression were investigated using the Q-PCR technique and the amount of the JAG1, 2 proteins was also determined by Western blot. Samples were obtained from 12 patients with endometriosis, 12 patients with repeated implantation failure (RIF), 12 patients with Polycystic Ovary Syndrome (PCOS) and 10 healthy fertile women as a control group. Data were analyzed using SPSS version 18. Group comparisons were performed by one-way ANOVA or Kruskal-Wallis.
    Results
    All patient groups failed to show the expected mid-luteal increase in NOTCH1, JAG 1, 2, and survivin expression as documented in the control group. Moreover, a significant rise in NOTCH3 expression levels was found only in PCOS women. There was a direct correlation between gene expression and protein level for JAG 1, 2.
    Conclusion
    Aberrant NOTCH signaling molecules expression suggests that altered development of the endometrium at the molecular level may be associated with the impaired decidualization and implantation failure in gynecological disorders such as endometriosis, PCOS, and RIF.
    Keywords: Endometriosis, NOTCH signaling, PCOS, Repeated implantation-failure (RIF), Window of implantation
  • Gelareh Shokri, Fatemeh Kouhkan, shahrzad nojehdehi, Masoud Soleimani, Ali Akbar Pourfathlah, Mahin Nikoguftar Zarif, Mona Tamadon, Narges Obeidi* Pages 432-438
    Objective(s)
    Various microRNAs (miRNAs) are expressed during development of mammalian cells, when they aid in modulating gene expression by mediating mRNA transcript cleavage and/or regulation of translation rate. miR-191 and miR-451 have been shown to be critical regulators of hematopoiesis and have important roles in the induction of erythroid fate decision. So, the aim of this study is investigation of the miR-191 and miR-451 roles in the controlling mouse embryonic stem cell (mESC) differentiation toward the erythroid lineage.
    Materials and Methods
    mESCs were infected with either pCDH-miR-Off-191 viruses in pCDH-miR-Off-191 group or simultaneously with pCDH-miR-Off-191 and pCDH-miR-451 lentiviruses in simultaneous group. Then, the expression profiles of erythroid specific transcription factors and globin genes were analyzed using QRT-PCR on day 14 and 21 of differentiation. Flow cytometry analysis was used to evaluate of TER119 and CD235a erythroid specific surface markers.
    Results
    Gata-1, Klf-1, Epor and globin chains were found to be expressed in pCDH-miR-Off-191 and in simultaneous groups. The majority of globin chains showed changes in their expression levels with progression of differentiation from day 14 to day 21. Flow cytometry results showed that miR-451 up- regulation and miR-191 down-regulation is associated with the expression of TER119 and CD235a. Of these two groups analyzed, simultaneous group was most significantly potent in stimulation of erythroid fate decision of mESCs.
    Conclusion
    Together, present data demonstrate that down-regulation of miR-191 alone can enhance the differentiation of mESCs. However, the simultaneous effect of miR-451up-regulation and miR-191 down-regulation is much stronger and can have more practical use in artificial blood production.
    Keywords: Differentiation, Erythropoiesis, miR-451, miR-191, Mouse embryonic stem cell
  • Ghaidafeh Akbari, Feryal Savari, Seyyed Ali Mard *, Annahita Rezaie, Mojtaba Moradi Pages 439-444
    Objective(s)
    Gallic acid (GA) is a highly effective antioxidant, which its beneficial effects are well known, but its impact on expression of microRNAs (miRs) following hepatic ischemia-reperfusion (I/R) is not well recognized. Therefore, the current research was designed to specify the beneficial effect of GA on miRs (122 and 34a), liver functional tests, and histopathological alterations beyond I/R-induced hepatic injury.
    Materials and Methods
    Thirty-two rats were randomly divided into four groups (8 per group) including: sham-operated (S), I/R, and GA+I/R pretreated groups. Rats in sham-operated group received physiologic saline (N/S, 2 ml/kg), on a weekly basis, once a day via intraperitoneally route), then a midline abdominal surgery was performed. IR, and GA+IR pretreated groups received physiologic saline (2 ml/kg), and GA (50, and 100 mg per kg) for same time, IP, respectively, before induction of transient ischemia. One hour after reperfusion, biochemical, and histopathological evaluations were performed and expression of miRs were evaluated.
    Results
    The results showed that GA reduced the concentrations of liver enzymes, miR-122, and miR-34a in serum, and preserved liver cells changes induced by I/R injury.
    Conclusion
    These findings showed that GA has beneficial effect on liver damage induced by I/R. Therefore, it is suggested that GA can be administered as an anti-miR before elective hepatic surgeries for prevention of this complication.
    Keywords: Gallic acid, Hepatic IR injury, miR-122, MiR-34a, Rat
  • Perham Mohammadi, Mahban Rahimifard, Maryam Baeeri, Mohammad Abdollahi, Sara Mostafalou* Pages 445-451
    Objective(s)
    Diabetes is a metabolic disease with an increasing prevalence for which finding new and efficient therapeutic approaches has always been a challenge. Preserving integrity and functionality of pancreatic β-cells as the only source of insulin in the body is such a case. To achieve this goal different cellular targets have been proposed among which pancreatic estrogen receptors have gotten much attention. In this work, we evaluated the integrity and function of islets of Langerhans under the influence of factors known to intervene with estrogen receptors. Cadmium, a toxic heavy metal, has been recently shown to interact with estrogen receptors but its toxicity in the pancreatic islets regarding this mechanism remains unclear.
    Materials and Methods
    Isolated islets of Langerhans from the pancreas of rats were grouped and treated with cadmium chloride and also cadmium chloride plus β-estradiol. After 24 hr incubation, parameters of cellular viability, oxidative stress, apoptosis, and insulin secretion were measured.
    Results
    The results indicated that cadmium reduced viability of the islets along with an increase in the formation of reactive oxygen species and apoptosis markers, and β-estradiol, in turn, was able to alleviate these disturbances to some extent, implicating the protective role of β-estradiol against pancreatic toxicity of cadmium.
    Conclusion
    It can be concluded that modification of estrogen receptors in the endocrine pancreas and especially β-cells may be a promising target to find a new therapeutic strategy for diabetes and even uncovering mechanisms of environmental toxicants that have been known as risk factors of diabetes.
    Keywords: Cadmium, Diabetes Mellitus, Estradiol, Estrogen receptors, Insulin, Islets of langerhans Pancreas
  • Sridevi Vaadala, Naveen Ponneri, Venkat Shashank Karanam, Ramachandra Reddy Pamuru * Pages 452-459
    Objective(s)
    Baicalein (BC), a phytoestrogen of the flavonoid family shows beneficiary and adverse effects. Effect of BC on reproduction is still not understood. Reproductive toxic effects on female mice were tested in this study.
    Materials and Methods
    Inseminated Wistar mice were divided into four groups and administered IP with 30, 60, and 90 mg/Kg body weight of BC on gestation daydays 11, 13, 15, and 17, and controls treated with DMSO. They were allowed to deliver pups and offspring were separated gender-wise on day 21. The stages of the estrus cycle and its lengthlengths of three successive cycles were measured from day 38 of young females. The mature female offspring of at 60 days age havewere cohabited with control males and the female reproductive endpoints and body weights of dams were measured.
    Results
    The BC exposure increased the length of the estrus cycle, especially the metestrus and diestrus phases were prolonged among other phases of the estrus cycle. Recorded significant reduction in the body weights (P<0.05) of prenatally BC exposed dams on 8 and 18 days of gestation. A significant increase in the conception time (P<0.0001), pre (53.42%) and post (8.82%) implantation loss, and resorptions (P=0.055), whereas a significant decrease in the number of implantations and live fetuses (P<0.0001) were found in BC exposed dams in a dose-dependent manner.
    Conclusion
    Prenatal BC exposure prolonged the estrus cycle due to the augmented length of metestrus and diestrus phase, and is reportingreported for the first time. Female fertility output in mice is affected severely by prenatal BC exposure.
    Keywords: Baicalein, Estrus cycle, Infertility, Mice, Prenatal