The Role of Cannabinoid-1 Receptor Ligands in the Ovalbumin-Induced Mouse Model of Allergic Asthma: Is It Related to Transient Receptor Potential Vanilloid-1 Channels?

Objectives: The aim of this study was to investigate the role of cannabinoid (CB1) receptors on airway inflammation and hypersensitivity in allergic asthma and the potential interactions with TRPV1 channels. Materials and Methods: BALB/c mice were sensitized and provoked with ovalbumin to create a model of allergic asthma. CB1 selective agonist arachidonoyl 2'-chloroethylamide (ACEA) was administered intraperitoneally at doses of 0.5, 3, and 5 mg/kg. Receptor antagonism studies were performed utilizing selective CB1 antagonists AM251 at a dose of 3 mg/kg. TRPV1 channel was selectively blocked by capsazepine at a dose of 2.5 mg/kg. Penh values were recorded in vivo by a whole-body plethysmograph under methacholine challenge. Inflammatory cell count was performed in bronchoalveolar lavage fluid (BALF). Serum levels of proinflammatory cytokines were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). Inflammation in the lung tissue was scored histopathologically. Statistical significance was determined using one-way analysis of variance or Kruskal-Wallis test and expressed as p<0.05. Results: In sensitized animals, provocation with inhaled ovalbumin increased Penh values, serum interleukin (IL)-4, IL-5, IL-13 levels, eosinophil, neutrophil, lymphocyte, macrophage counts in BALF, and inflammation in the lung tissue. ACEA applications did not significantly alter Penh values, BALF inflammatory cell levels, and histological changes related to inflammation in the lung tissue according to the disease group; however, only at a dose of 5 mg/kg, it reduced the levels of the inflammatory cytokine IL-4. AM251 decreased Penh values, eosinophil and neutrophil migration in BALF, and inflammation score of lung tissue compared with the disease group. Although BALF inflammatory cell levels and Penh values were higher in the AM251+ACEA group than in the AM251 group, the differences were insignificant. In the CPZ+ACEA group, Penh values were significantly higher, and serum IL-4 and IL-13 levels and BALF eosinophil counts were lower than that in the CPZ group. Conclusions: This study demonstrated an important role of the CB1 receptors in allergic asthma. CB1 antagonism reduced airway hyperresponsiveness and inflammation and showed immunomodulatory effects. The effect of the CB1 agonist ACEA on asthma does not appear to be related to TRPV1 channels.

Ganoderma lucidum and Hypericum perforatum Exhibit Anti-Inflammatory, Antioxidant, and Anti-Androgen Effect in Rat Model of Experimental Polycystic Ovarian Syndrome.

OBJECTIVE: Chronic inflammation is considered to be of key importance in the pathogenesis of polycystic ovarian syndrome (PCOS). Ganoderma lucidum polysaccharide (GLP) and Hypericum perforatum (HP) have been reported to have anti-inflammatory and antioxidant activities. We studied the effects of these agents on ovarian tissue in a rat model of experimental PCOS. MATERIALS AND METHODS: Forty-two Sprague-Dawley female rats were divided into 6 groups with 7 animals in each group as listed below: Group 1: Control, Group 2: PCOS, Group 3: PCOS + HP, Group 4: HP only, Group 5: PCOS+ GLP, Group 6: GLP only. At the end of the experimental procedures, all the animals underwent bilateral oophorectomy and blood samples were collected. Ovarian tissue and blood samples were used for biochemical and histopathological analysis. RESULTS: Follicle degeneration in the PCOS group showed a statistically significant increase compared to the other groups (p < 0.05). Cystic follicles were significantly reduced in the PCOS+GLP and PCOS+HP groups as compared to the PCOS group. Levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were elevated in PCOS rats (p < 0.01). Levels of sex hormone binding globulin (SHBG) levels were diminished (p < 0.01). Levels of malondialdehyde (MDA) and insulin-like growth factor 1 (IGF-1) were increased in PCOS rats as compared to the other groups (p < 0.02, p < 0.02, respectively). GLP supplementation diminished the levels of IGF-1 and MDA. GLP or HP supplementation increased reduced glutathione (GSH). CONCLUSION: GLP and HP treatment normalizes SHBG levels while correcting PCOS-induced hyperandrogenemia. Both herbs regulate the redox balance by decreasing the levels of MDA and increasing the level of GSH.

A study on the possible neurotoxic effects of CUMYL-4CN-BINACA in Sprague Dawley rats.

Substances such as Δ9-tetrahydrocannabinol (THC) and cannabidiol cross the blood-brain barrier. Detecting the damage of these substances in the brain provides important data in drug abuse studies. The aim of the study is to define the neurotoxicity of a novel synthetic cannabinoid (CUMYL-4CN-BINACA) in the Sprague-Dawley rats. Histopathological, immunohistochemical, behavioral, and biochemical examinations were performed to determine the acute and subacute toxicity of the cannabinoid. Three cannabinoid doses were administered for 2 days in the acute exposure groups and 14 days in the subacute exposure groups. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. No mortality was determined. Serious pathological changes such as neurodegeneration, focal plague formation, vacuolation, edema, congestion, and fibrosis were observed in the cerebral cortex and hippocampus of the brain in a dose-dependent manner. Brain tissue caspase-3 activity showed that the cannabinoid triggered apoptosis in the rat brain. The detected cellular oxidative stress (higher lipid peroxidation and lower antioxidant enzyme activity) also supported neurotoxicity. Significant behavioral abnormalities were also observed in the acute groups, while no behavioral changes were detected in the subacute groups. This study showed for the first time that CUMYL-4CN-BINACA adversely affects the rat brain. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.

Effect of caffeine on hippocampal memory and levels of gene expression in social isolation stress.

BACKGROUND: Caffeine (Cf) antagonizes the adenosine receptors and has neuroprotective properties. The effect of Cf has been seen on stress-induced deficits of cognitive. In this study, we have investigated the effect of Cf on learning and memory functions induced by social isolation (SI) stress. MATERIALS AND METHODS: In the present study, 21-day-old Wistar albino male rats (n = 28) were divided into four groups: the control (C), the SI, the Cf, and the social isolation + caffeine (SICf). Cf (0.3 g/L) was added to the drinking water of the experimental animals for 4 weeks. The learning and memory functions were assessed using the Morris Water Maze Test (MWMT). Following, was performed histopathological evaluation and determined hippocampal gene expression levels by RT-qPCR. RESULTS: According to MWMT findings, the time spent in the quadrant where the platform removed was decreased in the SI group compared with the C (p < 0.05). Histological evaluation showed morphological changes in SI by irregular appearance, cellular edema, and dark pycnotic appearance of nuclei in some neurons. However, it was observed that the histological structure of most of the neurons in the SICf group was similar to the C and Cf groups. Hippocampal SNAP25 expression was decreased in the Cf and SICf groups than in the C group (p < 0.05). The GFAP expression was increased in the SICf group than in the C group (p < 0.05). NR2A increased in the SI and SICf groups compared with C and Cf groups (p < 0.05). NR2B expression decreased in the Cf group compared with C and SI groups (p < 0.05). CONCLUSIONS: SI impaired spatial memory and causes morphological changes in adolescent rats, but this effect of isolation was not seen in Cf-treated animals. The effects of SI on NR2A, Cf on NR2B, and SNAP25 are remarkable. Here, we propose that the impaired effect of SI on spatial memory may be mediated by NR2A, but further studies are needed to explain this effect.

Identification of royal jelly as a potential new drug to protect the ovarian reserve and uterus against cyclophosphamide in rats.

OBJECTIVE: The aim of this study was to investigate the effect of royal jelly (RJ), a powerful natural antioxidant, on cyclophosphamide-induced ovarian damage. METHODS: Thirty-two Wistar albino rats were divided into four groups. Oral treatment was administered to all rats for 16 days after a single intraperitoneal injection. The control group received intraperitoneal and oral saline; the RJ group received intraperitoneal saline and 100 mg/kg/day oral RJ; the cyclophosphamide group received intraperitoneal 100 mg/kg cyclophosphamide and oral saline; and the treatment group received intraperitoneal 100 mg/kg cyclophosphamide and 100 mg/kg/day oral RJ. The groups were compared in terms of ovarian reserve tests and histopathological changes in the ovary and uterus. RESULTS: All follicle counts were higher in the treatment group than in the cyclophosphamide group. The increase in the number of preantral follicles (p=0.001) and the decrease in the number of atretic follicles (p=0.004) were statistically significant. RJ treatment significantly improved follicular degeneration and cortical fibrosis in the ovary and epithelial and gland degeneration in the uterus due to cyclophosphamide toxicity. CONCLUSION: According to these results, RJ reduces cyclophosphamide-related ovarian and endometrial damage in rats. For this reason, it should be further investigated to determine its effects on reproductive function.

The protective effects of pomegranate juice on lead acetate-induced neurotoxicity in the male rat: A histomorphometric and biochemical study.

The purpose of this study was to investigate the potential side-effects of lead acetate (LA), which is toxic to the nerves, blood and muscles, in the rat brain. The neuroprotective effects of pomegranate juice (PJ) against LA exposure were also observed. The experiment involved 28 male Wistar albino rats aged 12 weeks. These were divided into four groups: Control, PJ, LA and LA+PJ. Stereological techniques were employed to determine hippocampal volume in each rat brain. Biochemical investigations and histopathological examinations were also performed. Analysis demonstrated a significant decrease in hippocampal volume in the LA group compared to the control group (p < .05). The stereology results also indicated that PJ has protective effects when compared with the LA and LA+PJ groups. A significant increase was also determined in malondialdehyde (MDA) levels and glutathione S-transferase (GST) activity in the LA group compared to the control group, in contrast to glutathione (GSH) levels and carboxylesterase (CaE) and acetylcholinesterase (AchE) activities. MDA and GST activity decreased significantly in the LA+PJ group compared to the LA group in contrast to GSH levels and CaE and AchE activities. Histopathological examination revealed a number of degenerative changes in the LA group. Exposure to LA adversely affects the hippocampus on the male rat brain. It might also be suggested that PJ may ameliorate these deleterious effects.

The effect of mesenchymal stem cell lyophilizate on the recovery of the zone of stasis following thermal burns.

INTRODUCTION AND AIM: Mesenchymal Stem Cells (MSCs) are known to contribute to wound healing by increasing tissue regeneration. This study examined the effect of MSC-Lyophilizate (MSC-L) on the recovery of the zone of stasis in thermal burns. METHODS: A comb was used to induce second-degree thermal burns (1 × 2 cm) on the dorsum of the rats. Within 30 min after the burn, MSC-L derived from the umbilical cord was administered to the experimental group and 1.5 ml of 0.9% isotonic sodium chloride to the sham group. The control group did not receive any intervention. Tissue samples were collected on postoperative day 7. Histopathological assessments were made using a microscope with digital camera attachment. SPSS for IBM 25 was used for data analysis. RESULTS: Epithelial loss and subepidermal bullae were observed in the control and sham groups on day 7. In the experimental group, the MSC-L administration was found to increase epithelial tissue formation and neovascularization in the dermis. We found no significant pathological findings in the epidermis and dermis in the experimental group. CONCLUSION: Administration of umbilical cord-derived MSC-L is of potential importance in wound healing. In our study, we observed that MSC-L that contained 1.5 million cells contributed significantly to the recovery of the stasis zone of burn.

The effect of mesenchymal stem cells lyophilisate femoral artery of rat anastomosis: A histopathological and histomorphometric study.

BACKGROUND AND OBJECTIVE: Mesenchymal Stem Cells (MSCs) are well known for their tissue regeneration enhancing effect and their contribution to immune regulation. However, their contribution to the healing process of femoral artery anastomosis, especially to endothelialization, has not been studied sufficiently in the clinic. This study was carried out to evaluate the effects of MSC-lyophilisate from the human umbilical cord on anastomosis experimental study in rats histopathologically. METHOD: After intraperitoneal anesthesia was applied to the rats, the femoral artery was exposed with a 2 cm incision in the right femoral region. After the artery was cut in the experiment and sham groups, femoral artery end-to-end anastomosis was performed using the primary suture technique. MSC-lyophilisate was poured in powder form onto the anastomosed outer surface of the vessel in the treatment group and saline solution was poured to the sham group. No intervention was made to the control group. The data analysis was performed with IBM SPSS Statistics 25. RESULTS: In the experiment group, flattening of the inner elastic lamina, morphological changes and vacuolization in the muscle fibers, inflammation in the adventitia and significant vascular wall thickening were observed in the femoral arteries of the rats after the intervention. According to the histopathological scoring results, tissue samples belonging to sham and experimental groups showed marked pathological findings such as endothelial damage, flattened areas where the folded structure in the inner elastic lamina disappeared, muscle fiber degeneration and inflammation in the adventitia. CONCLUSION: Human umbilical cord-origin MSC-lyophilisate application holds an important place in femoral artery surgery. We evaluate that it will be meaningful to determine the MSC-lyophilisate dose for hemostasis without creating thrombus after anastomosis. MSC-lyophilisate will be used to provide hemostasis in areas with local bleeding in the future. In addition, it is recommended to make plans for an in-depth examination of possible problems and cases in future studies.

Histopathological Examination of the Mucosal Effects of Obstetric Gel on Vaginal Wound Healing in an Incision-Inflicted Rat Model.

Background and objective The present study intended to investigate the histopathological efficacy of obstetric gels on the healing of vaginal lacerations in rats. To the best of our knowledge, this is the first such study. Materials and methods Twenty-one female Wistar albino rats were divided into three groups, comprising seven animals per group. The first group (group 1) was the control group, the second (group 2) was the polyvinyl iodine (PI) group, and the third group (group 3) was the obstetric gel (OG) group. In all three groups, a vaginal incision was made with a No. 10 scalpel, and the incision site was sutured with a 3-0 Vicryl suture. In the control group, the incision site was left for routine healing. The incision site was washed with PI in the PI group and with OG in the OG group. After 15 days, vaginal tissues were obtained from all three groups for histopathological examination. In addition, immunohistochemistry staining was performed using caspase 3 and fibrillin 1 antibodies. Results There was no significant difference between the groups in terms of congestion, vascular proliferation, and inflammation stages in the examinations performed on the vaginal wall. However, the amount of collagen and elastic fibers increased during the remodeling and fibrosis phase, and the fibrillin 1 score increased in immunohistochemistry staining (p < 0.001). Conclusion It has been shown in rat vaginal tissue that obstetric gels do not have negative effects on wound healing; however, they contribute to wound healing by positively affecting the fibrosis stage.

Fabrication, characterization, and in vivo biocompatibility evaluation of titanium-niobium implants.

In this study, biocompatible titanium-niobium (Ti-Nb) alloys were fabricated by using powder metallurgy methods. Physical, morphological, thermal, and mechanical analyses were performed and their in vivo compatibility was evaluated. Besides α, ß, and α″ martensitic phases, α+ß Widmanstätten phase due to increasing sintering temperature was seen in the microstructure of the alloys. Phase transformation temperatures of the samples decreased as Nb content increased. The ratio of Nb in the samples affected their mechanical properties. No toxic effect was observed on implanted sites. This study shows that Ti-Nb alloys can be potentially used for orthopedic applications without any toxic effects.

Effects of Prostaglandin Analogue Iloprost Treatment on Distant Organ Damage Following Ovarian Ischemia/Reperfusion Injury in Rats: An Experimental Study.

Background Ischemia/reperfusion (I/R) injury causes oxidative stress, which, in turn, may impair the oxidant/antioxidant balance in tissues and cause damage to the tissues. The local effects of I/R injury can be typically observed in the related organ while systemic effects can be observed predominantly in the heart, brain, lung, and kidney. In this study, we aimed to evaluate the effects of iloprost on heart tissues after an ovarian I/R injury in an experimental rat model. Materials and methods A total of 32 female Sprague Dawley rats were used for the experiment. The rats were divided into four groups with eight rats each: Group I, control group; Group II, ischemia group; Group III, I/R group; Group IV, I/R + iloprost group. Surgical intervention was performed in each group and after the procedures, heart tissues were obtained and examined histopathologically. Results No significant pathological finding was found in Group I and II while degeneration of muscle fibers and interstitial edema was observed in group III and dilation of the vessels was detected in Group IV. No fibrosis or inflammation was observed in any group. Conclusion Iloprost provided protection against I/R injury and thus may be an alternative treatment for I/R injury.

A study on the toxic effect of different doses of diclofenac sodium on the development of the kidney in the postnatal period / Estudio sobre el efecto tóxico de diferentes dosis de diclofenaco sódico en el desarrollo del riñón en el período postnatal

The toxic effects of different doses of diclofenac sodium (DS) on the kidney on the postnatal period (0-7 days) by morphometrical and immunohistochemical methods were investigated. For this purpose, 15 female adult wistar albino rats were used and divided into 5 main groups. Group Ia served as normal control, physiologic group Ib received normal saline, group II received low dose (3.9 mg/kg), group III received medium dose (9 mg/kg) and group IV received high dose (18 mg/kg). Male offspring's from 0-7 days after birth were used in this study. On the 8th day of postnatal life, all animals were anesthetized. Then, the kidney samples were analyzed. Haematoxylin and eosin staining showed degeneration and necrosis, apparent atrophy of the glomeruli, mononuclear cell infiltration, congested vessels, increased fibrous tissue and distortion of the proximal convoluted tubules with interruption of the brush margin of the DS treated group. Increased level of Caspase-3 and upregulation of TNF-α with different doses of DS. In light of our findings, DS may lead to adverse effects that are dose-dependent in the prenatal subjected kidney to this drug.

Se investigaron los efectos tóxicos de diferentes dosis de diclofenaco sódico (DS) en el riñón de ratas, durante su período postnatal (0-7 días), por métodos morfométricos e inmunohistoquímicos. Para este propósito, se utilizaron 20 crías macho, de ratas Wistar albinas, y se dividieron en 5 grupos principales. El grupo Ia sirvió como control normal, el grupo fisiológico Ib recibió solución salina normal, el grupo II recibió una dosis baja de DS (3,9 mg/kg), el grupo III recibió una dosis media de DS (9 mg/kg) y el grupo IV recibió una dosis alta de DS (18 mg/kg). Se administraron los medicamentos de 0 a 7 días después del nacimiento de las ratas. En el octavo día de vida postnatal, todos los animales fueron sacrificados. Luego, se analizaron las muestras de riñón. Mediante hematoxilina-eosina se evidenció degeneración y necrosis, aparente atrofia de los glomérulos, infiltración de células mononucleares, vasos congestionados, aumento del tejido fibroso y distorsión de los túbulos contorneados proximales, con interrupción del margen en cepillo del grupo tratado con DS. Se detectó un aumento del nivel de caspasa-3 y regulación al alza de TNF-α con diferentes dosis de DS. A la luz de nuestros hallazgos, la DS puede provocar efectos adversos en el riñón, que dependen de la dosis de este medicamento administrada en el período posnatal.