Iranian Journal of Basic Medical Sciences
Year:2018 | Volume:21 | Issue:12|Papers Count:17

Wound healing is a natural response to restore the injured tissue to normal. Wound healing is also complicated process involving different cellular, molecular and biochemical mechanisms and various types of cytokines and growth factors. Calcium channel blockers belong to cardiovascular medicine and administrated to treatment of hypertension, angina and cardiac arrhythmia because of vasodilatory effect. Calcium channel blockers is divided to dihydropyridine and non-dihydropyrine. The potential of both dihydropyridine and non-dihydropyrine calcium channel blockers in wound healing have been reported in different animal models and in vitro previously. Amlodipine, verapamil, diltiazem, nifedipine, and azelnidipine are calcium channel blockers that indicated wound healing property. The various mechanisms that involve in wound healing effect of calcium channel blockers are discussed in this article.

Objective(s): Black cumin (Nigella sativa) belonging to Ranunculaceae family has a long history of medicinal use in various folk and traditional systems of medicine, including Iranian traditional medicine (ITM). These valuable medicinal seeds have been used traditionally against a variety of diseases such as dyspepsia, diabetes, headache, influenza and asthma. In addition, several scientific investigations have reported the therapeutic properties of N. sativa and thymoquinone (TQ), one of the most important constituent of black cumin, for treatment of a large number of diseases, including ischemia. As there is no comprehensive review study about the anti-ischemic activity of black cumin and its mechanism of action, in the current study, we aimed to review the anti-ischemic activities of N. sativa and TQ in different organ-related disorders. Materials and Methods: We searched the words N. sativa or black cumin and ischemia in the combination of related organs through available databases including Scopus, Web of Science, and Google Scholar. Results: Several studies were found reporting the anti-ischemic activity of black cumin and its active constituent on different organs including brain, kidneys, heart, and liver. Black cumin exert its beneficial effects as an antioxidant, anti-inflammatory, anti-apoptosis, and anti-necrosis agent through inhibition of growth factors, biochemical and oxidative stress markers and regulating gene expression. Conclusion: Thus, N. sativa could be a potential candidate for treatment of ischemia related disorders in key organs such as brain, liver, digestive system, kidney, and heart. To figure out the exact mechanism of action, further investigations are proposed in this regard.

Objective(s): To benefit from reproduction and deal with challenges in the environmental conditions, animals must adapt internal physiology to maximize the reproduction rate. Maladaptive variations in the neurochemical systems and reproductive system can lead to manifestation of several significant mammalian reprocesses, including mammalian ovarian lifespan. RFamide-related peptide (RFRP, Rfrp), mammalian orthologues of gonadotropin-inhibitory hormone (GnIH), which is a regulator to prevent the gonadotropin-releasing hormone (GnRH) neural activity, is known to be related to reproductive traits. This review aimed to summarize recent five-year observations to outline historic insights and novel perspectives into the functions of RFRPs in coding the mammalian reproductive physiology, especially highlight recent advances in the impact on RFRPs in regulating mammalian ovary lifespan. Materials and Methods: We reviewed the recent five-year important findings of RFRP system involved in mammalian ovary development. Data for this review were collected from Google Scholar and PubMed using the RFRP keyword combined with the keywords related to physiological or pathological reproductive functions. Results: Recent discoveries are focused on three major fronts in research on RFRP role in female reproduction including reproductive functions, energy balance, and stress regulation. The roles of RFRPs in various development phases of mammal reproduction including prepuberty, puberty, estrous cycle, pregnancy, milking, menopause, and/or ovarian diseases have been shown. Conclusion: Overall, these recent advances demonstrate that RFRPs serve as critical mediators in mammalian ovarian development.

Objective(s): Hemiscorpius lepturus is one of the dangerous scorpions of Iran leading to acute kidney injury (AKI) especially in infants. The purpose of this animal study was to compare the serological, pathological and scintigraphic data to quickly predict the occurrence of this disorder. Materials and Methods: In two groups of animals, each contained five rats, H. lepturus venom (1200 μ g/ Kg) were injected intravenously via the tail vein. At three hours and one week later, 99m Tc-DMSA (3 mCi) was intravenously injected and renal scintigraphy was performed after an hour. Moreover, plasma levels of creatinine, sodium, potassium, and blood urea nitrogen (BUN) were measured. At the end of the study, renal tissues were excised and prepared to perform pathological evaluation after Hematoxylin and Eosin staining. Results: All serological indices were remained unchanged compared to control. A large number of glomerular fibrin thrombi with entrapped red blood cells and simplified tubular epithelium in dilated and ectatic tubules were observed in high power field (×100) four hours after envenomation, which reduced significantly one week later. In our scintigraphic study, there was a statistically significant difference (P<0. 05) in kidney count rate per pixels (CRPP) in both acute and chronic phases compared to the sham group that received normal saline (0. 84± 0. 05 and 1. 36± 0. 07 versus 1. 7± 0. 05). Conclusion: The results of this preliminary animal study suggest renal scintigraphy is a non-invasive method to predict the occurrence of the AKI in H. lepturus envenomation. It leads the way for more investigation to counteract the renal failure induced by this venom.

Objective(s): Regarding the global burden of uropathogenic Escherichia coli (UPEC) infections, prevention and treatment of such infections play a significant role in healthcare management. The inordinate use of fluoroquinolones led to a worldwide spread of quinolone-resistant strains. Therefore, this study aimed to investigate mutations in codons 83 and 106 of gyrA gene in UPEC isolates in the north of Iran. Materials and Methods: This cross-sectional study performed on a total of 223 UPEC isolates which were recovered within 6 months in 2017. Isolates were identified and confirmed by standard microbiologic tests, and antimicrobial susceptibility testing was carried out by disk diffusion and E-test methods. PCR reaction was performed to amplify gyrA gene, and PCR-RFLP was performed using BsiEI and BstU I restriction enzymes to investigate mutations in gyrA gene. Results: The nalidixic acid, ciprofloxacin, ofloxacin, and norfloxacin resistance rates were 61. 9%, 50. 2%, 48. 25, and 45. 3%, respectively. Overall, 55. 2% of E. coli isolates had a mutation in gyrA gene in codon 83, and 20. 2% in codon 106. Also, 15. 2% of isolates had simultaneously mutation. Moreover, a significant association was found between mutations in gyrA gene and quinolone and fluoroquinolones resistance pattern of UPEC isolates. Conclusion: Our results revealed a high level of quinolone resistance associated with the mutations in gyrA among the clinical isolates of UPEC in our region. To the best of our knowledge, this study is the first investigation on the role of gyrA alteration in quinolone resistance among UPEC isolates from the north of Iran.

Objective(s): Long-term exposure to stress leads to memory deficits and certain mood disorders such as depression and anxiety. We aimed to study the effect of gallic acid (GA) on chronic restraint stress (CRS) induced anxiety and memory deficits in male BALB/c mice. Materials and Methods: Ninety male BALB/c mice were assigned to nine groups including caged control (CC): food-water deprived (FWD), under chronic restraint stress (CRS), CRS+ gallic acid (5, 10, and 20 mg/ kg), and gallic acid (5, 10, and 20 mg/kg). Behavioral assays were performed after 21 days of daily treatment with CRS and GA. Serum and brain levels of malondialdehyde (MDA) and total antioxidant capacity (TCA) and serum corticosterone level were also measured. Results: Treatment of CRS mice with GA significantly improved passive avoidance memory in the shuttle box and ameliorated anxiety-like behaviors in the elevated plus maze (EPM) and open filed test (OFT). GA treatment significantly reduced elevated levels of serum and brain MDA and increased brain TCA. CRS and GA did not affect serum corticosterone levels. Treatment of healthy mice with GA had some adverse effects and induced some anxiety and oxidative stress. Conclusion: GA exerted protective effects against stress-induced mood and memory deficit disorders.

Objective(s): Obstructive sleep apnea (OSA) is confirmed to cause lesions in multiple organs, especially in the lung tissue. Tempol is an antioxidant that has been reported to restrain inflammation and oxidative stress, with its role in OSA-induced lung injury being unclear. This study aimed to investigate the beneficial effect of tempol on chronic intermittent hypoxia (IH)-induced lung injury. Materials and Methods: A rat model of OSA was established by IH. There were four groups: normal air (NA), IH, IH+tempol, NA+tempol. Inflammatory response was evaluated by TNF-α , IL-1β , and IL-6 levels. Oxidative stress was detected by MDA and GSH levels, and SOD activity. The protein levels were assessed by Western blot. DNA binding activity of NF-κ B or Nrf2 was determined by electrophoretic mobility shift assay. Results: According to the results, tempol administration alleviated pathological changes of the lung tissue, decreased leukocyte count and protein content (P<0. 001) in bronchoalveolar lavage fluid (BALF). Inflammation response in lung tissue induced by IH was suppressed by tempol as evidenced by decreased levels of TNF-α , IL-1β , and IL-6 (P<0. 001) and protein levels of COX-2 and iNOS (P<0. 001). Moreover, tempol inhibited oxidative stress in lung tissue by down-regulating the MDA level (P<0. 001) and enhancing SOD activity (P<0. 001) and the GSH level (P<0. 05). In addition, tempol repressed inflammation response via inactivation of the NF-κ B pathway. Furthermore, the results suggested that tempol repressed oxidative stress by activating the Nrf2/HO-1 pathway. Conclusion: Our findings suggest that tempol effectively relieves OSA-induced lung injury.

Objective(s): Alzheimer’ s disease (AD) is dysfunction of the central nervous system and as a neurodegenerative disease. The objective of this work is to investigate metabolic profiling in the serum of animal models of AD compared to healthy controls and then to peruse the role of ghrelin as a therapeutic approach for the AD. Materials and Methods: Nuclear magnetic resonance (NMR) technique was used for identification of metabolites that are differentially expressed in the serum of a rat model of the AD with or without ghrelin treatment. Using multivariate statistical analysis, models were built and indicated. Results: There were significant differences and high predictive power between AD and ghrelin-treated groups. The area under curve (AUC) of receiver operating characteristic (ROC) curve and Q2 were 0. 870 and 0. 759, respectively. A biomarker panel consisting of 14 metabolites was identified to discriminate the AD from the control group. Another panel of 12 serum metabolites was used to differentiate AD models from treated models. Conclusion: Both panels had good agreements with clinical diagnosis. Analysis of the results displayed that ghrelin improved memory and cognitive abilities. Affected pathways by ghrelin included oxidative stress, and osteoporosis pathways and vascular risk factors.

Objective(s): Metabolic syndrome is a multiplex risk factor for diabetes and cardiovascular disease. Since some dietary fats such as mono-unsaturated fatty acids (MUFA) modify metabolic syndrome components the aim of the present study was to evaluate the preventive effects of mixture, kernel and hull oils of wild pistachio (WP) (Pistacia atlantica mutica) as good sources of MUFA on different features of this abnormality in rats under induction. Materials and Methods: In this study rats were randomly assigned to six groups with 12 animals per group. Metabolic syndrome was induced by fructose solution in groups 2, 3, 4, 5, and 6. Group 3 received sunflower oil and groups 4, 5, and 6 received mixture, hull and kernel oils of WP (2 ml/kg/day), respectively, for 10 weeks. Then, lipid profiles, glycemic indices, oxidative stress and inflammatory parameters were measured using standard laboratory tests. Results: Different forms of WP oil induced hypotriglyceridemia, but the hypocholesterolemia effect was seen only in the mixed and kernel oil groups. Kernel oil also significantly reduced LDL and HDL cholesterol (P<0. 05). In addition, mixed and kernel oils notably decreased glycemic indices (fasting blood glucose and insulin resistance) compared with the fructose group. Serum insulin levels were significantly increased in the kernel oil group (P<0. 05). All WP oils also significantly decreased inflammation (IL-6). Conclusion: The results showed that the consumption of WP kernel oil may have beneficial effects on preventing hyperglycemia, hypertriglyceridemia, hypercholesterolemia, inflammation and pancreatic secretory disorders.

Objective(s): The aim of this study is to determine the therapeutic effects of pomegranate seed oil, which is a powerful antioxidant and anti-inflammatory agent, on ovarian-ischemia and reperfusion injury in rats. Materials and Methods: Fifty-six female albino Wistar rats were divided into 7 equal groups. Group 1; Sham Operation, Group 2; Ischemia, Group 3; Ischemia + Reperfusion, Group 4; Ischemia + Pomegranate 0, 32 ml / kg (IP), Group 5; Ischemia + Pomegranate 0. 64 ml / kg, Group 6; Ischemia + Pomegranate 0, 32 ml / kg + reperfusion, Group 7; Ischemia + Pomegranate 0, 64 ml / kg + reperfusion. Three hours after ischemia and 3 hours after reperfusion, the study was terminated. Results: While NADPH oxidase activity, MDA and TNF-α levels were significantly increased, SOD activity and GSH levels were reduced in ischemia and I/R groups. Low dose pomegranate seed oil application reduced significantly oxidative stress and NADPH oxidase activity in both ischemic and ischemic/reperfusion groups. At the same time, low-dose pomegranate seed oil extract reduced TNF-α levels and significantly increased antioxidant activity. Conclusion: PSO demonstrated an important therapeutic effect in the treatment of ovarian ischemia and reperfusion injury.

Objective(s): Nowadays, the electromagnetic field-emitting devices are used routinely in our lives. Controversial reports exist concerning the effects of mobile radiofrequency (RF) on different parts of the body, especially stress hormones. The main goal of the present work was to study the long-term effects of mobile RF900 MHz exposure with special focus on the adrenal gland pathophysiology and function. Materials and Methods: Adult male Wistar rats were exposed to mobile RF 6 hr daily for 4– 8 weeks. Intact and switched-off exposed animals were considered as controls. Plasma ACTH and cortisol levels were measured by the ELISA method. At the end of the experiment, a histological study was done on adrenal gland and brain tissues by hematoxylin and eosin staining. The thickness of the fasciculate layer of the adrenal gland, and its cell count and perimeter were measured using the Fiji software. Results: Enhanced plasma ACTH and cortisol levels were found after prolonged exposure to mobile RF. The fasciculata layer of adrenal cortex eventually thickened following mobile RF radiation. While the number of cells in zona fasciculata remained constant, the cell size and perimeter increased during RF exposure. Finally, we found that vacuolization in brain tissue and the number and size of vacuoles considerably increased during two months of RF exposure. Conclusion: Cell phone RF exposure induced significant hormonal and structural changes in adrenal gland and brain tissues. Therefore, the public should be aware and limit their exposure as much as possible.

Objective(s): Oxytocin is involved in modulation of many brain-mediated functions. In the present study, we investigated the central effects of oxytocin and its receptor antagonist, atosiban on inflammatory pain. The contribution of opiate receptors was explored using non-selective and selective antagonists. Materials and Methods: The fourth ventricle of the brain of anesthetized rats was implanted with a guide cannula. Inflammatory pain in the orofacial region was induced by subcutaneous (SC) injection of formalin into the vibrissa pad, and time duration of face rubbing behavior was measured for 45 min. Results: A typical biphasic pain was observed after formalin injection. This biphasic pain behavior was attenuated by intra-fourth ventricle administration of oxytocin (12. 5, 50, and 200 ng/rat). Central prior administration of 400 ng/rat atosiban (an oxytocin receptor antagonist), naloxone (a nonselective opiate receptor antagonist), naloxonazine (a selective μ-opiate receptor antagonist), and norbinaltorphimine (a selective κ-opiate receptor antagonist), but not naltrindole (a δ-opiate receptor antagonist), prevented oxytocin-induced (200 ng/rat) antinociception. Except for naltrindole, other antagonists increased pain intensity when used alone. Above-mentioned drugs did not alter locomotor activity. Conclusion: Oxytocin, as a neuropeptide neurotransmitter, may be involved in the supraspinal modulation of inflammatory pain through μ-and κ-, but not δ-opiate receptors.

Objective(s): The present study was conducted to examine the effect of sleep deprivation (SD) on the anti-apoptotic pathways in Parkinsonian rats. Materials and Methods: Male Wistar rats (n = 40) were assigned to four groups (10 animals each): sham surgery (Sham), 6-hydroxydopamine (6-OHDA)-lesioned (OH), 6-OHDA-lesioned plus grid control (OH+GC), 6-OHDA-lesioned plus SD (OH+SD). Parkinson’ s disease (PD) model was induced by the unilateral intra-striatal infusion of 6-OHDA (10 μ g/rat). SD (4 hr/day, for 14 days) was induced using a multiple platforms water tank. On the last day of interventions, animals were subjected to open field test for horizontal motor performance assessment. Also, brain-derived neurotrophic factor (BDNF), Bcl-2 and Bax were assessed in the striatum of study groups. Results: SD obscured the motor deficits of PD animals observed in open field test. BDNF level and Bcl2/Bax ratio significantly increased in the OH group, and SD reduced their levels in the PD animals. Conclusion: SD suppressed the anti-apoptotic compensatory responses in the striatum; therefore, it may accelerate continual neuronal cell death in PD.

Objective(s): To analyze the potential influences of propofol on the oxidative stress of H2O2-induced human esophageal squamous cell carcinoma (ESCC) Eca109 cell through mediating the Wnt/β-catenin signaling pathway. Materials and Methods: Eca109 cells were classified into 5 groups: Control group, H2O2 group, Propofol + H2O2 group, Dkk1 (Dickkopf-1, Wnt/β-catenin pathway antagonist) + H2O2 group, and Propofol + LiCl (Lithium chloride, Wnt/β-catenin pathway agonist) + H2O2 group. Western blotting was performed to determine the protein expressions, flow cytometry to measure the content of ROS, immunofluorescence staining to detect the oxidative DNA damage, as well as MTT, AnnexinV-FITC/PI, Wound-healing, and Transwell assays to test the biological characteristics of Eca109 cells. Results: H2O2 resulted in the increased nuclear and cytoplasmatic expression of β-catenin, reduced p-GSK3β expression, up-regulated ROS content, and induced oxidative DNA damage in Eca109 cells. Moreover, Eca109 cells treated with H2O2 alone had enhanced cell proliferation and metastasis but decreased cell apoptosis, as compared with those without any treatment; meanwhile, the declined Cyt C, Bax, and cleaved caspase-3, as well as the elevated Bcl-2 were also observed in Eca109 cells in the H2O2 group, which were reversed by Propofol or Dkk1. Moreover, Propofol could inhibit the effect of LiCl on activating the Wnt/β-catenin signaling pathway in H2O2-induced Eca109 cells. Conclusion: Propofol elicits protective effects to inhibit H2O2-induced proliferation and metastasis and promote apoptosis of Eca109 cells via blocking the Wnt/β-catenin pathway, offering a possible therapeutic modality for ESCC.

Objective(s): Apelin/APJ system plays an important role in the regulation of myocardial contractility (MC) and blood pressure. Opioid receptors (OPRs) are also important cardiovascular regulators and exert many of their effects through modulating the function of other systems. This study analyzed the interaction between APJ and kappa OPRs (KOR) in cardiac responsiveness to apelin in acute renovascular hypertension (2K1C). Materials and Methods: MC studies were carried out on 2K1C rats. F13A (APJ blocker), Naloxone (OPR inhibitor), nor-Binaltorphiminedihydrochloride (nor-BNI; kappa OPR inhibitor), PTX (Gi path inhibitor) and chelerytrine (protein kinase C; PKC inhibitor) were administered prior to apelin 20 and 40 μ g/kg. The phosphorylation of extracellular signal– regulated kinases (ERK1/2) (PERK) was also assessed. Dimerization of APJ and KOR was evaluated by immunoprecipitation. Results: Both doses of apelin reduced blood pressure. Apelin 40 exerted a negative inotropic effect, which was inhibited by nor-BNI, but apelin 20 showed a positive inotropic effect, which was resistant to this inhibition. Hypertension increased heterodimerization of the APJ and KOR and this was reduced by apelin 20. F13A, naloxone and PTX significantly reduced PERK in apelin 40 group, but F13A, naloxone, and chelerytrine significantly increased PERK in the apelin 20 group. Conclusion: The lowering effect of apelin 40 on MC and its non-effectiveness on APJ/KOR dimerization, while augmenting the contractility and reducing the dimerization by apelin 20 implies the APJ/KORrelated effects of apelin on the MC under acute reno-vascular hypertension. This may have potential clinical applications as apelin has been introduced as a potential therapeutic agent in heart failure and opioids are being currently used in the treatment of myocardial infarction.

Objective(s): Methamphetamine is a stimulant compound that penetrates readily into the central nervous system. Repeated exposure to methamphetamine leads to damage in the dopaminergic and serotonergic axons of selected brain regions. Previous studies showed that cinnamaldehyde improved memory impairment in animals. In the present study, we aimed to elucidate the effects of cinnamaldehyde on methamphetamine-induced memory impairment in rats. Materials and Methods: Male Wistar rats received methamphetamine (10 mg/kg, intraperitoneally) for 7 days. Thirty minutes before each injection, animals were given cinnamaldehyde (20, 40, or 80 mg/kg) or rivastigmine (1 mg/kg). The spatial learning and memory were examined using the Morris water maze test. The expression of extracellular signal-regulated kinase (ERK) phosphorylation in the frontal cortex and hippocampus was also detected by immunohistochemical method. Results: Administration of methamphetamine increased the latency to find the platform in the learning phase, while administration of cinnamaldehyde (40 mg/kg) or rivastigmine before methamphetamine reversed the increased latency. Administration of cinnamaldehyde, at the dose of 40 mg/kg with methamphetamine, increased the time and distance traveled in the target quadrant in comparison with the amphetamine group. Moreover, the methamphetamine and cinnamaldehyde-treated group had higher expression of phosphorylated ERK1/2 in the prefrontal cortex in comparison with the methamphetamine-treated animals. Conclusion: The present data demonstrated that repeated METH administration impaired cognitive performance through the ERK pathway and decreased the phosphorylation of ERK1/2 in the prefrontal cortex while administration of cinnamaldehyde restored both effects. Accordingly, cinnamaldehyde may be a valuable therapeutic tool for the treatment of cognitive deficits associated with methamphetamine consumption.

Objective(s): Broad range of metabolic changes associated with highly active antiretroviral therapy (HAART) has been reported over decades including reproductive perturbations. The current study aimed at investigating the role of Hypoxis hemerocallidea (Hyp) in the seminal and morphometric alterations in the testes of streptozotocin-nicotinamide-induced diabetic rats under HAART. Materials and Methods: Sixty-two adult male Sprague-Dawley rats were divided into A-H groups, containing 6 rats in the control group A and 8 rats in the treatment groups B-H. Diabetes was induced by intraperitoneal injection of nicotinamide (110 mg/kg BW) followed by streptozotocin (45 mg/kg BW). The animals were then subjected to various treatments with HAART, Hyp, and melatonin. Results: weights (body and testicular), histological, histochemical, seminal fluid, and morphometric analyses were carried out. Sperm count and motility were reduced in HAART (P<0. 05/0. 003) and Hyp200 (P<. 003) groups compared with normal and diabetic controls, respectively. Sperm count was higher (P<. 003) in HAART+ Mel and HAART+Hyp100 groups. Morphometry showed the reduction in germinal epithelium height and basement membrane thickness (P<. 003) in the Hyp100 group compared with diabetic controls. Adjuvant use of Hyp and melatonin with HAART did not significantly raise these indices (P>. 05). Histological slides showed gross distortions in HAART, diabetic and HAART +Hyp groups with marked atrophy in tubules, germ cell loss and areas of focal depletion of the cell. PAS staining revealed detached basement membrane in diabetic groups with strong PAS-stain. Conclusion: The use of Hyp or melatonin does not ameliorate the testicular damages in diabetic animals under antiretroviral therapy.