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Objective Experimental and clinical studies suggest that oxidative stress plays an important role in the pathogenesis of multiple sclerosis. In this study, we have investigated the effects of the non-psychoactive cannabinoid cannabidiol (CBD), which exerts antioxidant effects and has recently been approved for the treatment of inflammation, pain, and spasticity associated with MS patients and in a MS mouse model, i.e. cuprizone-induced demyelination. Methods Adult male BL/6 mice were fed with 0.2% cuprizone for 5 weeks, which caused severe demyelination of the corpus callosum (CC). Animals were simultaneously treated with 5 mg·kg−1 CBD by daily intra-peritoneal injections. Using immunohistochemistry and transmission electron microscope, we evaluated the effects of CBD on demyelination, malondialdehyde levels and the activity of reduced glutathione, catalase and superoxide dismutase was evaluated by Biochemical analysis. Results CBD ameliorate the cuprizone-induced demyelination and microglia accumulation. Biochemical analysis showed that oxidative stress induced by cuprizone was reduced by CBD. Conclusion Our data implicate that CBD attenuates destructive cuprizone effects in the CC by decreasing oxidative stress and as well microglia repletion. Keywords cannabidiol, demyelination, oxidative stress, microglia, cuprizone

Background: There are numerous investigations on wide range of issues that disrupt regulatory spermatogenesis, individuals who are exposed to drug abuse faced infertility and immature spermatogenesis. Objective: The aim of this study was to evaluate the addiction effects of morphine and its derivatives on rats spermatogenesis. Materials and Methods: 40 male Wistar rats were randomly divided into 5 equal groups, which were exposed either with intravenous morphine, naloxone, naloxone and morphine, sham (with normal saline injection) and a control group without infusion. Spermatogenesis was assessed after three months via histological sections with hematoxylin and eosin staining, using a light microscope based on measurement of spermatogonia, spermatocyte, spermatid, and spermatozoa. Results: Those rats that received opioids had changes in spermatogenesis function. The population of spermatogenesis cycle cells at spermatogonia, spermatocyte, spermatid, and spermatozoa stages was significantly decreased in those rats that received opioid in comparison to the control group (p

Background: Sperm parameters and motion kinetics are affected by cryopreservation. Objective: The main purpose of the current study was to determine the effect of different concentrations of Trolox as an antioxidant to freezing-thawing procedure on human sperm kinematic parameter. Materials and Methods: Semen was collected from 20 normal donors and divided into five aliquots prior to cryopreservation. The first aliquot was analyzed by computer-assisted sperm analysis (CASA). Other aliquots were mixed with cryo-protective agent containing 0, 20, 40, and 80 μmol Trolox and treated samples were cryopreserved in liquid nitrogen. After two weeks samples were thawed and sperm motion kinematics was measured by CASA. Percent motility (Mot), curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), linearity (LIN), and amplitude of lateral head displacement (ALH) were compared before and after freeze. Results: Addition of 40μmol Trolox resulted in significantly higher (p

Oxidative stress plays a major role in the pathogenesis of Alzheimer's disease (AD) of sporadic origin. The expression of DHCR24 (Seladin-1), marker for neuronal oxidative stress and degeneration, has been reported to be altered in the brains of AD patients. In the present study, we investigated the effect of trimetazidine (TMZ) on the hippocampal oxidative parameters and the expression of DHCR24 (Seladin-1) in an animal model of sporadic AD. Male rats were pre-treated with TMZ (25 mg/kg) after which injected with intracerebroventricular-streptozotocin (ICV-STZ)/Saline. Following 2, 7 and 14 days, animals of different groups were sacrificed with their brain excised to detect the hippocampal lipid peroxidation, superoxide dismutase (SOD), catalase activity, DHCR24 (Seladin-1) expression and possible histopathological changes. ICV-STZ administration induced significant oxidative changes in the hippocampus. Meanwhile, TMZ pre-treatment showed to ameliorate the oxidative stress, which was demonstrated by a significant rise in the hippocampal SOD and catalase activity, as well as a significant decrease in the malondialdehyde (MDA) level. TMZ administration also increased the expression of DHCR24 (Seladin-1) gene in the hippocampus. In conclusion, our findings indicated a neuroprotective effect of TMZ possibly related to its antioxidant activity resulting in the up-regulation of DHCR24 (Seladin-1). Such TMZ effects may be beneficial in minimizing oxidative stress in sporadic Alzheimer's disease and possible prevention of disease progression.

Objective. Depression during pregnancy is a relatively common problem. Since little is known about the teratogenic effects of concomitant administration of fluoxetine and olanzapine during the organogenesis period, the aim of the present study was to evaluate the teratogenic effects of coadministration of fluoxetine and olanzapine on rat fetuses. Method. Forty-two pregnant rats were divided into seven groups, randomly. The first group received 0.5 mL of normal saline as the control. The second and third groups received fluoxetine at doses of 9 mg/kg and 18 mg/kg, respectively. Olanzapine was injected at 3 mg/kg and 6 mg/kg to the fourth and fifth groups, respectively. The sixth group received 9 mg/kg fluoxetine and 3 mg/kg olanzapine. Finally, the seventh group was administrated with fluoxetine and olanzapine at 18 mg/kg and 6 mg/kg, respectively. Drugs were injected intraperitoneally between day eight and day 15 of the pregnancy. On the 17th day of pregnancy, the fetuses were removed and micro-/macroscopically studied. Results. Fetuses of rats receiving high doses of these drugs showed a significant rate of cleft palate development, premature eyelid opening and torsion anomalies, compared to the control group (P≤0.01). It is concluded that these drugs can lead to teratogenicity, so their concomitant use during pregnancy should be avoided, or if necessary their doses must be decreased.

Since little is known about the teratogenic effects of clomipramine used concurrently with caffeine during the organogenesis period, the aim of this study was to test the teratogenic effects of a coadministration of caffeine and clomipramine on rat fetuses. We divided 42 pregnant rats into seven groups, randomly. The first group (control) received 0.5 mL of normal saline. Clomipramine was injected at 40 mg/kg and 80 mg/kg to the second and third groups, respectively. The fourth and fifth groups received caffeine in doses of 60 mg/kg and 120 mg/kg, respectively. The sixth group received a combination of 40 mg/kg clomipramine and 60 mg/kg caffeine, and the seventh group was given clomipramine and caffeine at 80 mg/kg and 120 mg/kg, respectively. The fetuses were removed on the 17th day of pregnancy and studied in terms of microscopic and macroscopic morphological features. Fetuses of rats receiving high doses of caffeine or combinations of caffeine and clomipramine showed a significant rate of cleft palate development, open eyelids, mortality, torsion anomalies, shrinkage of skin, and subcutaneous haemorrhage (P≤0.001). This study concludes that caffeine in high doses or the simultaneous administration of caffeine and clomipramine leads to teratogenicity.

Background: One of the most important issues in medical science is the healing of burn wounds. The use of medicinal plants has been common for many years and today cell therapy offers new approaches to the management of skin wound healing. The present study aimed to evaluate the the combination treatment of lotion containing honey, Aloe, and propolis with BM-MSCs in the healing of second-degree burns in animal models. Methods: this experimental study from October 2020 to November 2020, was performed in the animal house of Tehran University of Medical Sciences. 72 rats with an age range of 3-4 months and a weight of about 200-250 gr, after burns were randomly divided into 6 groups of 12 with study periods of 7, 14 and 21 days. The groups were as following: control (no treatment), Positive control (SSD1%), First experimental (Stem cells), Second experimental(lotion), Third experimental(Stem cells and lotion), and Fourth experimental (DMEM). To measure the percentage of healing from the wound surface on days 0, 4, 7, 10, 14, 17, and 21 photos were taken and the wound surface area was calculated by Image J software. After sacrificing rats, tissue samples were taken on days 7, 14 and 21 after burning induction. Samples were prepared for staining H&E and Trichrome Masson’s, as well as RT-PCR examination. The results were analyzed using Graph Pad Prism8 software and Tukey and one-way variance tests. Results: Treatment preference was with the combination therapy group and then with the lotion group. According to macroscopic and microscopic images of H&E and Trichrome Mason, the highest amount of wound coverage and the presence of mature collagen fibers were also observed in the combination therapy group. The results of statistical analysis and scoring also showed increased epithelization, granulation tissue formation, collagen deposition, angiogenesis and fibroblast cell proliferation, and decreased inflammation in the combination therapy group. The combination therapy group also had the highest expression of the TGF-β gene. (P

Context Airway remodelling is one of the most refractory problems in asthma. According to the critical roles of oxidative stress and inflammation in airway remodelling, it is supposed that ascorbic acid and calcitriol have beneficial effects. However, a combination of antioxidants may be more effective for asthma therapy. Objective This study investigated the protective effects of ascorbic acid in combination with calcitriol on airway remodelling in ovalbumin (OVA)-induced chronic asthma. Materials and methods BALB/c mice were assigned into seven groups: (1) Control; (2) Asthma; (3) Ineffective C (orally 39 mg/kg ascorbic acid); (4) Ineffective D (intraperitoneally 1.5 μg/kg calcitriol); (5) Effective C (orally 130 mg/kg ascorbic acid); (6) Effective D (intraperitoneally 5 μg/kg calcitriol); (7) Combination (orally 39 mg/kg ascorbic acid + intraperitoneally 1.5 μg/kg calcitriol). All animals were sensitized and challenged with OVA except in the control group (normal saline). In all treatment groups, mice were administrated vitamins 30 min before each challenge (three times per week for 8 consecutive weeks). Results In comparison with the asthma group, co-administration of ineffective doses of ascorbic acid and calcitriol led to the decreased levels of IL-13 (50.5 ± 1.85 vs. 42.13 ± 0.37 pg/mL, p = 0.02) and IgE (58.74 ± 0.43 vs. 45.78 ± 2.05 ng/mL, p = 0.003) as well as the reduction of goblet hyperplasia and subepithelial fibrosis (5 vs. 1 score, p = 0.001 and 5 vs. 2 score, p = 0.001, respectively). Discussion and conclusions Combination of ascorbic acid with calcitriol in ineffective doses improves airway remodelling due to additive effects possibly through reduction of oxidative stress and inflammation. This study provides a scientific basis for further research and clinical applications of ascorbic acid and calcitriol and can be generalized to the broader pharmacological studies.

Background: Open skin lesions cause many problems for the health and the economy of societies in recent years, importance and effectiveness of traditional and complementary medicine have been increased. Objective: So this study was performed to investigate the synergistic effect of topical use of Mentha pulegium essential oil and honey in healing of cutaneous ulcers in rats. Method: This experimental study was performed on 75 healthy wistar male rats. Under anesthesia, a 1.5 * 1.5 mm full thickness square wound was created. In the experimental groups, the surface of the wounds was covered once daily with peppermint, honey, a combination of them and phenytoin ointment. No treatments were performed on the wounds of the control group. For histological studies, using staining (H & E) wound surface and wound healing were evaluated. Data were analyzed by using one-way ANOVA with post hoc Tukey test and P < 0.05 was significant. Results: The results of microscopic study showed histological parameters in wounds bed in the experimental group were significantly different from the control group. Generally, rats treated with honey or mint, or the combination of them, had higher percentage of wound healing and less wound surface, than negative and positive controls groups (P

Background and Aims: Most children get a lot of anxiety while they visit a dentist. The most important factor in the child's fear at the beginning of treatment is the syringe and needle. Ways to cope with this anxiety include behavioural control techniques such as mental regeneration, distraction, and induction. The purpose of this study was to compare the pain and anxiety in children when using a syringe and toy- shape syringe needle. This study was the first study that used a toy-shape needle cover. Materials and Methods: This clinical trial study was conducted on 20 children age from 5 to 8 years. More than half of them were anxious with Cfss-Ds (Dental Subscale of the Children's Fear Survey Schedule) and FIS (Facial Image Scale) anxiety diagnostic tests, and the rest of them were not anxious. Patients were randomly divided into two groups. The first group received local anesthesia with conventional syringe and the second group, by syringe with toy shape needle cover. Following, the first group received local anesthesia by syringe with toy shape needle cover, and the second group, by a conventional syringe. Heart rate measuring and pain evaluating test was performed. Analysis of heart rate and anxiety data was performed by non-parametric wilcoxonsianed Ranks T-test (P-value was considered significant at 0.001). Results: The mean amount of pain measured after using a syringe with a toy shape needle cover and using conventional syringe had a significant difference of 5.20% between the two groups. The pain was reduced in children who received local anesthesia by syringe with toy shape needle cover (P

Testicular torsion-detorsion results in enhanced formation of free radicals which contribute to the pathophysiology of testicular tissue damage. Recent reports have identified protective role of pentoxifylline (PTX) against free radicals. Thus, we determined the protective effect of pentoxifylline against testicular damage in mouse model of testicular torsion-detorsion.Twenty (6 weeks old) male mice were divided into 4 groups of 5 animals each namely: Control (sham operated group), T1 (Torsion-detosion + single dose 100 mg/kg PTX, T2 (torsion-detorsion + 20 mg/kg PTX for 2 weeks and T/D (torsion-detorsion only). Animals in T1, T2 and T/D groups underwent 2 h of testicular torsion with the left testes rotated 720° (clockwisely) followed by 30 min of detorsion. After detorsion, drug administration was done intraperitoneally. The left testes of all the animals were excised on the 35th day after torsion-detortion for histopathological and biochemical assay. Histomorphological analysis of the seminiferous tubules showed that there were significant increase (P < 0.01 or 0.05) in the mean seminiferous tubule diameter, Johnson score and germ cells of animals in Control and T1 compared to T2 and T/D with no significant difference (P > 0.05) in testes weight, sertoli, leydig and myoid cells in all groups. IHC results showed significant increase (P < 0.01 or 0.05) in id4 and scp3 protein markers in Control, T1 and T2 compared to T/D. Oxidative stress analysis revealed that Pentoxifylline significantly increased (P < 0.01 or 0.05) the level of SOD, catalase, mRNA expression of akt and pi3k genes but significantly suppress (P < 0.01 or 0.05) MDA and Caspase-3 level in Control, T1 and T2 compared to T/D. Pentoxifylline could be used as an adjunct therapy to surgery in the treatment of torsion-detorsion related testicular injury, However, Further studies are needed to evaluate the effects of pentoxifylline on testicular torsion.

Background: Identifying the best species of medicinal plants and extracting effective substances can be effective in preventing oral and dental illness. The Malva sylvestris L. is among these plants. Malva sylvestris L. belongs to Malvaceae family from which A great deal of (Malvone A: 2-methyl-3-methoxy-5,6-di- hydroxy-1,4-naphthoquinone) anthocyanin and important natural pigments have been extracted. Anthocyanins and other substances of Malva sylvestris own antibacterial properties. Antibacterial properties of Malva sylvestris were investigated on the bacterial species. The purpose of this study was to investigate the antibacterial effects of the Malva sylvestris L. extract on the Streptococcus mutans and compare it with the effect of chlorohexidine (0.12%). Methods: This experimental study was carried out at the Shahed University of Medical Sciences, Tehran, Iran in the field of microbiology in January 2016 to September 2016. Methanolic aqueous extract of Malva sylvestris L. was prepared by decoction extraction method. The presence of polyphenol trepnoid, saponine, anthocyanins compounds in the extract was approved by high performance thin layer chromatography. Chromatographic and spectral fingerprint analysis plays an important role in the quality control of complex herbal medicines. The antimicrobial effect of the Malva sylvestris L. on the growth of Streptococcus mutans was evaluated. Results: Extract at different concentrations (16.8-4.2 mg/ml) had an antibacterial effect and compared with commonly used chlorohexidine in dentistry. The non-growth halo against Streptococcus mutans showed an average of 1.66 mm. The minimum inhibitory concentration against Streptococcus was 2 mg/ml. The presence of polyphenols, troponides of saponin, was characterized by high performance thin-layer chromatography (HPTLC). Conclusion: However, antibiotics play an important role in human health, with the increasing occurrence of bacterial resistance against available antibiotics. The results of this study showed that the aqueous-methanolic extract of the Malva sylvestris L. plant has antimicrobial activity affecting Streptococcus mutans. The flowers extract also showed high antibacterial effects against some human pathogen bacteria strains. This property of polyphenolic compounds of the plant, identified by fingerprint analysis, was less susceptible to chlorohexidine than gold standard.

Objective Gonadotropins are generally used in animals and humans to stimulate ovulation and increase the number of available oocytes for techniques such as in vitro fertilization. Ovulation-inducing drugs are used to achieve multiple oocytes in one cycle, thereby increasing the chances of pregnancy in patients with infertility. The aim of this study was to evaluate the effect of gonadotropins on stimulation of ovulation and their inductive role on the growth and development of follicles in the ovary. Methods To determine the effect of human chronic gonadotrophin (HCG) and pregnant mare serum gonadotrophin (PMSG) on ovary, this study used 20 rats that were randomly divided to experimental and control groups. Rats were subsequently euthanized 48 h after injection and the ovaries were fixed and stained with H&E. Data were analyzed with Tukey’s multiple comparisons with one-way ANOVA test in GraphPad Prism software. Result Our analysis demonstrated that HCG and PMSG hormones will significantly increase the number of stimulated oocyte in the ovary but it does not have any significant role on the ovary weight and volume (P < 0.05). Conclusion This study’s results confirmed the inductive role of PMSG and HCG hormones on folliculogenesis.

Background: One of the most important issues in medical sciences is wound healing and repair. Application of natural ingredients and herbs for treating ulcers has been in the history of human life. Nowadays, due to the lack of side effects of medicinal plants and a variety of effective compounds in plants, as well as numerous disadvantages of synthetic drugs there has been tendency to use medicinal plants in clinic. Aloe vera is an herbal drug used for treatment of dermal diseases. In this study we evaluated, effects of aloe vera on the wound healing through the microscopic techniques and cell counting. Methods: In this experimental study, sixty Wistar rats weighing 200-250 g were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5´1.5 mm dimension was made on the back of the neck. Rats were randomly divided to control and experimental group’s. Each group was divided to three subgroups with 4, 7, and 14 study days. In 1st experimental group aloe vera was used twice on the wound surface and in 2nd experimental group was used once daily and the positive control group were applied phenytoin cream 1% from the zero days of surgery. The control group did not get any treatment on the wound surface. For histological studies, during the fourth, seventh and fourteenth day’s rats were sacrificed and samples were taken from the wound area and adjacent skin. After histological staining with hematoxylin and eosin (H&E) and Masson's trichrome stains, the cells were counted, wound surface and wound healing were investigated. Results: The macroscopic and microscopic evaluation showed that wound healing increased because the fibroblast numbers in two experimental groups improved compared with control group. The percentage of wound healing on different days in the experimental and control groups were significant. Data were analyzed by using one-way ANOVA test and P< 0.05 was significant. Conclusion: Present study showed that the twice application of topical aloe vera mucilage can result in rapid wound healing in rats.

Background: Clinicians have been searching for ways to obtain "super normal" wound healing. Honey is a traditional remedy for the treatment of infected wounds. We aimed to evaluate the wound contraction and antibacterial properties of locally produced Thyme honey on managing full-thickness wounds in vivo. Methods: This experimental study was conducted in 2015, in Department of Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran on 54 adult male Wistar rats weighing 200-250 gr, and ages of 3-4 months. A square 1.5*1.5 wound was made on the back of the neck. The rats were divided into control and two experimental groups. Additionally, the control and experimental groups were separated into three subgroups corresponding to 4, 7, and 14 d of study. The control group did not receive any treatment. For histological studies, samples were taken from the wound and adjacent skin. This tissue was examined using histological staining (H&E). Wound surface and wound healing were evaluated. Data were analyzed by using one-way ANOVA with post hoc Tukey test and (P

Background: Considering nitric oxide (NO) has an important role in many biologic processes of cells and tissues such as in the digestive system and in this system act as a second messenger in pathological and physiological events in gastrointestinal region, in this study we investigated the effects of L-NG-Nitro arginine Methyl Ester (L-NAME) as the NO formation inhibitor on parietal cells of stomach in pregnant rats. Methods: Twenty four female rats were prepared and with eight weeks old and 200-250 g weight were used in this study. After matting of the female rats with the male rats, time of observing vaginal plaque considered as the zero day of pregnancy. Then the animals were divided into three groups of studying. Each group was containing eight rats. In this study, except the control group, the saline group received 2 ml/kg normal saline and experimental group received 20 ml/kg L-NAME interaperitoneally (IP), respectively on third, fourth, and fifth days of pregnancy for evaluation of its effects. On the 18th day of pregnancy, after anesthesia with ether, the animals were killed and dissected and the laparotomy was performed to separate the mother’s stomach. Then, the stomach was fixed in 10% formalin and after tissue passage, the sections were stained with Hematoxylin-Eosin (H&E). Then the changes of count and diameter in parietal cells were observed via light microscopy and Image Tools III. Results: Results of this study after analysis showed the significant changes in parietal cells count (mean 61.3±4.32) and its diameters (mean 16.12±1.18 µm) in L-NAME group in comparison to control and the sham groups in pregnant rats (P≤0.05). Conclusion: Results of this study showed L-NAME with effects on NO synthesis can reduce the count of parietal cells and increase its diameter in pregnant rats and has destructive effects on structure of stomach parietal cells in pregnancy rats.

Accelerating wound healing is now considered as a principle clinical treatment and increasing the quality and speed of healing which has always been emphasized by the scientists. Propolis and honey are natural bee products with wide range of biological and medicinal properties. This study was aimed to determine the synergistic effect of honey and propolis in wound healing of rat skin. A total of 75 Wistar rats weighing 200-250 gr were placed under general anesthesia and sterile conditions. Then a square shape wound with 1.5*1.5 mm dimension was made on the back of the neck. Animals were randomly divided into control, honey, propolis, combined honey propolis and phenytoin 1% groups, respectively. Rats were randomly divided into the following groups: 4th, 7th and, 14th days of treatment in each period of study. Wound area in the experimental group was covered once daily with a fixed amount of thyme honey, propolis, propolis and honey and phenytoin cream (1%), the control group did not receive any treatment. For histological studies, during the fourth, seventh and fourteenth day’s rats were sacrificed and samples were taken from the wound and adjacent skin. After histological staining fibroblast, neutrophils, macrophages and vascular sections were counted in the wound bed. The macroscopic and microscopic evaluations showed that the percentage of wound healing on different days in the experimental and control groups were significant (P