Gilaburu (Viburnum opulus L.) fruit extract has potential therapeutic and prophylactic role in a rat model of acetic acid-induced oxidant colonic damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) which has a global impact on the health care system with its recurrent and incompletely curable characteristics, affects the patients' quality of life. Gilaburu (GB; Viburnum opulus L.) is a fruit with rich polyphenol ingredient which is used ethnobotanically in Türkiye for medicinal purposes (for example, to pass kidney stones, to treat stomach, heart, and liver diseases, hemorrhages, hypertension, ulcers, common cold, tuberculosis, rheumatic and menstrual pain, and diabetes). On the other hand, the effects of GB in the experimental UC model have not been studied. AIM OF THE STUDY: This study aimed to explore the potential antioxidant and anti-inflammatory effects of GB fruit extract in improving acetic acid (AA)-induced UC. MATERIALS AND METHODS: Starting immediately after (AA + GB group) or 1 week before (GB + AA + GB group) the colitis induced by intrarectal AA (5%; v/v) administration, the rats orally received GB (100 mg/kg) once per day for 3 days. The control and AA groups were administered orally saline (1 ml), while the AA + SS group were administered sulfasalazine (SS; 100 mg/kg; orally) as a positive control once per day for 3 days. Distal colonic tissue specimens were obtained for the histological and biochemical [myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), chemiluminescence (CL), caspase-3, 8-hydroxy-2'-deoxyguanosine (8-OHdG), matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-ß1, smad-3 and cytokine (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, interferon (IFN)-γ), measurements] evaluations on the 3rd day. RESULTS: Elevated macroscopic and microscopic damage scores, high tissue wet weight values, increased tissue-associated MPO, MDA, CL, caspase-3, 8-OHdG, cytokines (TNF-α, IL-1ß, IL-6, IL-8), MMP-9, TGF-ß1, smad-3 levels, and decreased GSH values of the AA group were all reversed by GB treatments (AA + GB and GB + AA + GB groups) (p < 0.05-0.001). However, sulfasalazine treatment (AA + SS group) did not change the IL-8, 8-OHdG, MMP-9, and TGF-ß1 measurements significantly. CONCLUSIONS: Gilaburu shows both anti-inflammatory and antioxidant effects against AA-induced colonic damage by suppressing neutrophil infiltration, regulating inflammatory mediators, inhibiting reactive species production, lipid peroxidation, and apoptosis, conserving endogenous antioxidant glutathione, and ameliorating oxidative DNA damage. Since the current ulcerative colitis drugs display limited benefits and adverse side effects, potential therapeutic and/or prophylactic role of gilaburu can be evaluated in ulcerative colitis.

SARS-CoV-2 Causes Brain Damage: Therapeutic Intervention with AZD8797.

Elevated CX3CL1 is associated with severe COVID-19 and neurologic symptoms. We aimed to investigate the potential protective effects of selective CX3CR1 antagonist AZD8797 on SARS-CoV-2-induced neuronal damage, and to identify the underlying mechanisms. K18-hACE2 transgenic mice (n = 37) were randomly divided into control groups and SARS-CoV-2 groups, with and without intraperitoneal administration of vehicle or AZD8797 (2.5 mg/mL/day), following exposure to either a single dose of SARS-CoV-2 inhalation or no exposure. Object recognition and hole board tests were performed to assess memory function. Postinfection 8 days, brain tissues were analyzed for histopathological changes, viral, glial, apoptotic, and other immunohistochemical markers, along with measuring malondialdehyde, glutathione, and myeloperoxidase activities. Serum samples were analyzed for proinflammatory cytokines. The SARS-CoV-2 group showed significant weight loss, neuronal damage, oxidative stress, and impaired object recognition memory, while AZD8797 treatment mitigated some of these effects, especially in weight, apoptosis, glutathione, and MCP-1. Histopathological analyses supported the protective effects of AZD8797 against SARS-CoV-2-induced damage. The CX3CL1-CX3CR1 signaling pathway could offer a promising target for reducing SARS-CoV-2's neurological impact, but additional research is needed to confirm these findings in combination with other therapies and assess the clinical significance.

Effects of sodium fluoride on neural tube development in chick embryos.

OBJECTIVE: Various environmental factors encountered in daily life are associated with the development of neural tube defects. This study aims to investigate the effects of fluoride on neural tube development in chick embryos. METHODS: A total of 60 specific pathogen-free, fertile, zero-day Leghorn-type eggs were used in the study. Group 1 was the control group, in which only saline was administered. Group 2 was the low-dose group, in which 0.003 mg of fluoride was administered, and Group 3 was the high-dose group, in which 0.006 mg of fluoride was administered. After 72 h of incubation, the embryonic disc was evaluated microscopically. RESULTS: In the control group, the surface ectoderm of all sections was intact, the neural tube was closed, and the neuroepithelium, the basement membrane surrounding the neuroepithelium, the somites, and the notochord displayed standard structure. Neural tube defects were observed in 3 of the chick embryos, that was given low-dose fluoride. In Group 3, which was administered high doses of fluoride, neural tube defects were observed in 4 embryos. It was observed that the development of neural tube defects was no statistically significantly higher in low and high-dose fluoride group compared to the control group. CONCLUSION: Low and high-dose fluoride exposure was associated with developing neural tube defects, but there was no statisticaly significance.

Anti-Inflammatory, Antioxidant and Neuroprotective Effects of Niacin on Mild Traumatic Brain Injury in Rats.

AIM: To study the effects of niacin, a water-soluble vitamin, on inflammation, oxidative stress and apoptotic processes observed after mild traumatic brain injury (TBI). MATERIAL AND METHODS: A total of 25 Wistar albino male rats were randomly divided into control (n=9), TBI + Placebo group (n=9), TBI + niacin (500 mg/kg; n=7) groups. Mild TBI was performed under anesthesia by dropping a 300 g weight from a height of 1 meter onto the skull. Behavioral tests were applied before and 24 hours after TBI. Luminol and lucigenin levels and tissue cytokine levels were measured. Histopathological damage was scored in brain tissue. RESULTS: After mild TBI, luminol and lucigenin levels were increased (p < 0.001), and their levels were decreased with niacin treatment (p < 0.01-p < 0.001). An increased score was obtained with trauma in the tail suspension test (p < 0.01), showing depressive behavior. The number of entries to arms in Y-maze test were decreased in TBI group compared to pre-traumatic values (p < 0.01), while discrimination (p < 0.05) and recognition indices (p < 0.05) in object recognition test were decreased with trauma, but niacin treatment did not change the outcomes in behavioral tests. Levels of the anti-inflammatory cytokine IL-10 were decreased with trauma, and increased with niacin treatment (p < 0.05). The histological damage score was increased with trauma (p < 0.001), and decreased with niacin treatment in the cortex (p < 0.05), and hippocampal dentate gyrus region (p < 0.01). CONCLUSION: Niacin treatment after mild TBI inhibited trauma-induced production of reactive oxygen derivatives and elevated the anti-inflammatory IL-10 level. Niacin treatment ameliorated the histopathologically evident damage.

Weekend warrior exercise model for protection from chronic mild stress­induced depression and ongoing cognitive impairment.

We aim to investigate the role and biological mechanisms of the weekend warrior (WW) exercise model on depression­induced rats in comparison to the continuous exercise (CE) model. Sedentary, WW, and CE rats were subjected to chronic mild stress (CMS) procedure. CMS and exercise protocols continued for six weeks. Anhedonia was evaluated by sucrose preference, depressive behavior by Porsolt, cognitive functions by object recognition and passive avoidance, and anxiety levels by open field and elevated plus maze. After behavioral assessments, brain tissue myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, superoxide dismutase and catalase activities and GSH content, tumor necrosis factor­α (TNF­α), interleukin­6 (IL­6), IL­1ß, cortisol and brain­derived neurotrophic factor levels and histological damage was assessed. CMS­induced depression­like outcomes with increases in anhedonia and decreases in cognitive measures that are rescued with both exercise models. The increased immobilization time in the Porsolt test was decreased with only WW. Exercise also normalized the suppression of antioxidant capacity and MPO increase induced by CMS in both exercise models. MDA levels also declined with both exercise models. Anxiety­like behavior, cortisol levels, and histological damage scores were exacerbated with depression and improved by both exercise models. TNF­α levels were depleted with both exercise models, and IL­6 only with WW. WW was as protective as CE in CMS­induced depression­like cognitive and behavioral changes via suppressing inflammatory processes and improving antioxidant capacity.

Cotinus coggygria Scop. Attenuates Acetic Acid-Induced Colitis in Rats by Regulation of Inflammatory Mediators.

In traditional medicine, many medicinal plants are used in the treatment of various diseases caused by inflammation. The objective of the present study is to elucidate for the first time the effects of Cotinus coggygria (CC) ethanol extract (CCE) on colonic structure and inflammation of acetic acid-induced ulcerative colitis in rats. Colonic damage was assessed using disease activity index score, enzyme-linked immunosorbent assay, and hematoxylin-eosin staining. Also, in vitro antioxidant activity of CCE was investigated by ABTS methods. Total phytochemical content of CCE was measured spectroscopically. Acetic acid caused colonic damage according to disease activity index and macroscopic scoring. CCE significantly reversed these damages. While the levels of proinflammatory cytokines TNF-alpha, IL-1beta, IL-6, and TGF-1beta increased in tissue with UC, IL-10 level decreased. CCE increased inflammatory cytokine levels to values close to the sham group. At the same time, while markers indicating disease severity such as VEGF, COX-2, PGE2, and 8-OHdG indicated the disease in the colitis group, these values returned to normal with CCE. Histological research results support biochemical analysis. CCE exhibited significant antioxidant against ABTS radical. Also, CCE was found to have a high content of total polyphenolic compounds. These findings provide evidence that CCE might be benefit as a promising novel therapy in the treatment of UC in humans due to high polyphenol content and justify the use of CC in folkloric medicine for treatment of inflamed diseases.

Antioxidant and neuroprotective effects of dexpanthenol in rats induced with traumatic brain injury.

Trauma-induced primary damage is followed by secondary damage, exacerbating traumatic brain injury (TBI). Dexpanthenol has been shown to protect tissues against oxidative damage in various inflammation models. This study aimed to investigate possible antioxidant and neuroprotective effects of dexpanthenol in TBI. Wistar albino male rats were randomly assigned to control (n = 16), trauma (n = 16) and dexpanthenol (500 mg/kg; n = 14) groups. TBI was induced under anesthesia by dropping a 300 g weight from 70-cm height onto the skulls of the rats. Twenty-four hours after the trauma, the rats were decapitated and myeloperoxidase (MPO) levels, luminol- and lucigenin-enhanced chemiluminescence (CL), malondialdehyde (MDA) levels, superoxide dismutase (SOD) levels, and catalase (CAT) and caspase-3 activities were measured in brain tissues. Following transcardiac paraformaldehyde perfusion, histopathological damage was graded on hematoxylin-eosin-stained brain tissues. In the trauma group, MPO level, caspase-3 activity and luminol-lucigenin CL levels were elevated (p < 0.05-0.001) when compared to controls; meanwhile in the dexpanthenol group these increases were not seen (p < 0.05-0.001) and MDA levels were decreased (p < 0.05). Decreased SOD and CAT activities (p < 0.01) in the vehicle-treated TBI group were increased above control levels in the dexpanthenol group (p < 0.05-0.001). in the dexpanthenol group there was relatively less neuronal damage observed microscopically in the cortices after TBI. Dexpanthenol reduced oxidative damage, suppressed apoptosis by stimulating antioxidant systems and alleviated brain damage caused by TBI. Further experimental and clinical investigations are needed to confirm that dexpanthenol can be administered in the early stages of TBI.

The effects of long-term prenatal exposure to 900, 1800, and 2100 MHz electromagnetic field radiation on myocardial tissue of rats.

It is well-known that wireless communication technologies facilitate human life. However, the harmful effects of electromagnetic field (EMF) radiation on the human body should not be ignored. In the present study, we evaluated the effects of long-term, prenatal exposure to EMF radiation on the myocardium of rats at varying durations. Overall, 18 pregnant Sprague-Dawley rats were assigned into six groups (n = 3 in each group). In all groups other than the control group, three pregnant rats were exposed to EMF radiation (900, 1800 and 2100 MHz) for 6, 12 and 24 h over 20 days. After delivery, the newborn male pups were identified and six newborn male pups from each group were randomly selected. Then, histopathological and biochemical analysis of myocardial samples were performed. When 24-h/day prenatal exposures to 900, 1800, 2100 MHz EMF radiation were evaluated, myocardial damage was greater in the 2100 MHz EMF-24h group than the other groups. In addition, when malondialdehyde (MDA) and glutathione (GSH) levels associated with reactive oxidative species (ROS) were evaluated, the MDA level was higher in the 2100 MHz EMF-24h group compared with the other groups. The GSH level was also lower in the 2100 MHz EMF-24h group. When the 6, 12 and 24 h/day prenatal exposures to 1800 MHz EMF radiation were evaluated, myocardial damage was greater in 1800 MHz EMF-24h group than the remaining groups (p < 0.0001). Also, MDA level was greater in the 1800 MHz EMF-24h group compared with the other groups while the GSH level was lower in this group. It was shown that myocardial tissue was affected more by long-term exposure to EMF radiation at high frequencies. The data raise concerns that the harmful effects of non-ionizing radiation exposure on cardiac tissue will increase with 5G technology.

Possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of mild traumatic brain injury: an investigation.

OBJECTIVE: Apigenin is a plant flavone proven with biological properties such as anti-inflammatory, antioxidant, and antimicrobial effects. This study, it was aimed to examine the possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of the mild traumatic brain injury (TBI) model. METHODS: Wistar albino male rats were randomly assigned to groups: control (n = 9), TBI (n = 9), TBI + vehicle (n = 8), and TBI + apigenin (20 and 40 mg/kg, immediately after trauma; n = 6 and n = 7). TBI was performed by dropping a 300 g weight from a height of 1 m onto the skull under anesthesia. Neurological examination and tail suspension tests were applied before and 24 h after trauma, as well as Y-maze and object recognition tests, after that rats were decapitated. In brain tissue, luminol- and lucigenin-enhanced chemiluminescence levels and cytokine ELISA levels were measured. Histological damage was scored. Data were analyzed with one-way ANOVA. RESULTS: After TBI, luminol (p < .001) and lucigenin (p < .001) levels increased, and luminol and lucigenin levels decreased with apigenin treatments (p < .01-.001). The tail suspension test score increased with trauma (p < .01). According to the pre-traumatic values, the number of entrances to the arms (p < .01) in the Y-maze decreased after trauma (p < .01). In the object recognition test, discrimination (p < .05) and recognition indexes (p < .05) decreased with trauma. There was no significant difference among trauma apigenin groups in behavioral tests. Interleukin (IL)-10 levels, one of the anti-inflammatory cytokines, decreased with trauma (p < .05), and increased with 20 and 40 mg apigenin treatment (p < .001 and p < .01, respectively). The histological damage score in the cortex was decreased in the apigenin 20 mg treatment group significantly (p < .05), but the decrease observed in the apigenin 40 mg group was not significant. CONCLUSION: The results of this study revealed that apigenin 20 and 40 mg treatment may have neuroprotective effects in mild TBI via decreasing the level of luminol and lucigenin and increasing the IL-10 levels. Additionally, apigenin 20 mg treatment ameliorated the trauma-induced cortical tissue damage.

The α2C-adrenoceptor antagonist JP-1302 controls behavioral parameters, tyrosine hydroxylase activity and receptor expression in a rat model of ketamine-induced schizophrenia-like deficits.

Schizophrenia is a chronic disabling disease affecting 1 % of the population. Current antipsychotics have limited efficacy in mitigating the severity of the symptoms of the disease. Therefore, searching for new therapeutic targets is essential. Previous studies have shown that α2C-adrenoceptor antagonists may have antipsychotic and pro-cognitive effects. Therefore, the current study evaluates the behavioral and neurochemical effects of JP-1302, a selective α2C-adrenoceptor antagonist, in a model of schizophrenia-like deficits induced by sub-chronic ketamine (KET) administration. Here, we administered ketamine (25 mg/kg, i.p.) to male and female Wistar rats for eight consecutive days. On the last two days of ketamine administration, rats were pretreated with either JP-1302 (1-3-10 µmol/kg, i.p.), chlorpromazine (0.1 mg/kg, i.p.), or saline, and the behavioral tests were performed. Behaviors related to positive (locomotor activity), negative (social interaction), and cognitive (novel object recognition) symptoms of schizophrenia were assessed. Glutamate, glutamine, GABA levels, and α2C-adrenoceptor expression were measured in the frontal cortex and the hippocampus. Tyrosine hydroxylase immunocytochemical reactivity was also shown in the midbrain regions. Sub-chronic ketamine administration increased locomotor activity and produced robust social interaction and object recognition deficits, and JP-1302 significantly ameliorated ketamine-induced cognitive deficits. Ketamine induced a hyperdopaminergic activity in the striatum, which was reversed by the treatment with JP-1302. Also, the α2C-adrenoceptor expression was higher in the frontal cortex and hippocampus in the ketamine-treated rats. Our findings confirm that α2C-adrenoceptor antagonism may be a potential drug target for treating cognitive disorders related to schizophrenia.

Phoenixin 14 ameloriates pancreatic injury in streptozotocin-induced diabetic rats by alleviating oxidative burden.

Phoenixin-14 (PNX) is a neuropeptide that has been shown to prevent oxidative damage and stimulates insulin secretion. We investigated the effects of PNX on pancreatic injury induced by streptozotocin (STZ), and nicotinamide (NAD). Male Sprague-Dawley rats, in control (C) and diabetic (STZ) groups, were treated with either saline, or PNX (0.45 nmol/kg, or 45 nmol/kg) daily for 3 days 1 week after STZ injection. Fasting blood glucose (FBG) and gastric emptying rate (GER) were measured. Tissue and blood samples were collected. PNX treatments prevented pancreatic damage and ß cell loss. Increased luminol and lucigenin levels in the pancreas, ileum and liver tissues of STZ groups were alleviated by PNX treatment in pancreatic and ileal tissues. PNX0.45 decreased FBG without any change in insulin blood level and pancreatic mRNA. GER increased in all diabetic rats while PNX0.45 delayed GER only in the C group. PNX diminishes pancreatic damage and lowers FBG by reducing oxidative load.

Duration of Ciprofloxacin Use Is Important in the Development of Abdominal Aortic Aneurysm in a Rat Model.

BACKGROUND: Recent findings suggest that fluoroquinolones, most prescribed antibiotic to treat various infections, have increased abdominal aortic aneurysm formation. We aimed to investigate the relation of the development of abdominal aortic aneurysm and the duration of ciprofloxacin use. METHODS: Male Sprague-Dawley rats were divided into 2 groups to administer saline to the control groups and CaCl2 to the aneurysm groups. These groups were then divided into 3 subgroups: intraperitoneal saline, ciprofloxacin for 2 weeks, and ciprofloxacin for 4 weeks. At the end of 4 weeks, the diameter of abdominal aorta was determined by ultrasonography and animals were sacrificed to obtain abdominal aorta specimens. Elastic fiber fracture, tunica media layer thickness, and aortic tissue damage were evaluated histologically. RESULTS: Aortic diameter of control-saline (2.15 mm ± 0.06), control-2 weeks (2.25 mm ± 0.06), and control-4 weeks (3.31 mm ± 0.09) ciprofloxacin groups was significantly different (P < .0001). Also, aortic diameter of aneurysm-saline (2.07mm ± 0.02), aneurysm-2 weeks ciprofloxacin (3.33 mm ± 0.64), and aneurysm-4 weeks ciprofloxacin (8.55 mm ± 1.70) groups showed significant increase in aortic diameter with increasing duration of ciprofloxacin use (P < .01). A significant difference was found between the control-saline (0.00 ± 0.00), control-2 weeks (1.50 ± 0.33), and control-4 weeks ciprofloxacin groups (1.57 ± 0.20) in the histological aneurysm scores (P < .001). Aortic tunica media thickness did not change between control-saline and control-ciprofloxaci n groups (P > .05). CONCLUSION: The study showed that ciprofloxacin caused injury in the aortic wall but not a significant change in the thickness of the aortic tunica media layer. The duration of ciprofloxacin use was important in the development of aneurysm and aneurysm severity.

Bilayered laponite/alginate-poly(acrylamide) composite hydrogel for osteochondral injuries enhances macrophage polarization: An in vivo study.

Addressing osteochondral defects, the objective of current study was to synthesize bilayered hydrogel, where the cartilage layer was formed by alginate (Alg)-polyacrylamide (PAAm) with and without the addition of TGF-ß3 and bone layer by laponite XLS/Alg-PAAm and characterize by in vitro and in vivo experiments. Exceeding the mechanical strength of Alg-PAAm (32.95 ± 1.23 kPa) and XLS based (317.5 ± 21.72 kPa) hydrogels, XLS/Alg-PAAm hydrogel (469.7 ± 6.1 kPa) activated macrophages towards M2 phenotype and stimulated the expression of anti-inflammatory factors. The addition of TGF-ß3 accelerated transition of macrophage polarization, especially between day 4 and 7. The expression levels of M1-related genes such as CD80, iNOS and TNF-α decreased gradually after day 4, reaching lowest values at day 13, whereas the expression levels of M2-related genes, CD206, Arg1 and STAT6 significantly increased promoting M2 macrophage polarization, which might be associated with accelerated bone repair. Moreover, bilayer structure exhibited a better cell viability as well as repairment thorough the XLS contents. In vivo histological examinations verified the significant surface regularity and hyaline like tissue formation employment, along with synchronized degradation profile of the hydrogel with tissue healing at the end of 12 weeks. A mechanically durable, biocompatible and immunocompatible hydrogel was formulated to be utilized in bone-cartilage engineering applications.

Nesfatin-1 ameliorates oxidative brain damage and memory impairment in rats induced with a single acute epileptic seizure.

AIMS: We aimed to investigate putative neuroprotective effects of nesfatin-1 on oxidative brain injury and memory dysfunction induced by a single epileptic seizure and to compare these effects with those of antiepileptic phenytoin. MAIN METHODS: Wistar albino rats were randomly divided into a control group and pentylenetetrazole (PTZ)-seizure groups pretreated intraperitoneally (ip) with saline or nesfatin-1 (NES-1; 0.3, 1 or 3 µg/kg/day) or phenytoin (PHE; 40 mg/kg/day) or PHE + NES-1 (0.3 µg/kg/day) at 30 min before the single-dose PTZ injection (45 mg/kg; ip). All treatments were repeated at the 24th and 48th h of the provoked epileptic seizure. Passive-avoidance test was performed to assess memory function. The rats were decapitated at the 72nd hour of seizures and brain tissues were analyzed for histopathological changes and for measuring levels of malondialdehyde, glutathione, myeloperoxidase activity and reactive oxygen/nitrogen species. KEY FINDINGS: In parallel to the effects of phenytoin, NES-1 reduced seizure score, elevated antioxidant glutathione content, depressed generation of nitric oxide and protected against seizure-induced neuronal damage. Additionally, increased malondialdehyde levels and elevated glial fibrillary acidic protein immunoreactivity in the cortex and hippocampus were decreased and memory dysfunction was improved by NES-1. However, NES-1 had no impact on myeloperoxidase activity or production of reactive oxygen species in the brain. SIGNIFICANCE: The findings of the present study demonstrate that nesfatin-1 treatment provides neuroprotection against seizure-induced oxidative damage and memory dysfunction by inhibiting reactive nitrogen species and upregulating antioxidant capacity, indicating its potential in alleviating memory deficits and increasing the effectiveness of conventional anti-convulsant therapies.

Neuroprotective Effect of Plasminogen Activator Inhibitor-1 Antagonist in the Rat Model of Mild Traumatic Brain Injury.

Plasminogen activator inhibitor-1 (PAI-1) antagonists are known for their neuroprotective effects. In this study, it was aimed to investigate the possible protective effects of PAI-1 antagonists in a rat mild traumatic brain injury (TBI) model. Sprague-Dawley male rats were grouped as sham (n = 7), TBI (n = 9), and TBI + PAI-1 antagonist (5 and 10 mg/kg TM5441 and TM5484; n = 6-7). Under anesthesia, TBI was induced by dropping a metal 300-g weight from a height of 1 m on the skull. Before and 24-h after trauma neurological examination, tail suspension, Y-maze, and novel object recognition tests were performed. Twenty-four hours after TBI, the rats were decapitated and activities of myeloperoxidase, nitric oxide release, luminol-, and lucigenin-enhanced chemiluminescence were measured. Also, interleukin-1ß, interleukin-6, tumor necrosis factor, interleukin-10, tumor growth factor-ß, caspase-3, cleaved caspase-3, and PAI levels were measured with the ELISA method in the brain tissue. Brain injury was graded histopathologically following hematoxylin-eosin staining. Western blot and immunohistochemical investigation for low-density lipoprotein receptor, matrix metalloproteinase-3, and nuclear factor-κB were also performed. Data were analyzed using GraphPad Prism 8.0 (GraphPad Software, San Diego, CA, USA) and expressed as means ± SEM. Values of p < 0.05 were considered to be statistically significant. Higher levels of myeloperoxidase activity in the TBI group (p < 0.05) were found to be suppressed in 5 and 10 mg/kg TM5441 treatment groups (p < 0.05-p < 0.01). The tail suspension test score was increased in the TBI group (p < 0.001) and decreased in all treatment groups (p < 0.05-0.001). The histologic damage score was increased statistically significantly in the cortex, dentate gyrus, and CA3 regions in the TBI group (p < 0.01-0.001), decreased in the treatment groups in the cortex and dentate gyrus (p < 0.05-0.001). PAI antagonists, especially TM5441, have antioxidant and anti-inflammatory properties against mild TBI in the acute period. Behavioral test results were also improved after PAI antagonist treatment after mild TBI.

Neuroprotective Effect of Cinnamaldehyde on Secondary Brain Injury After Traumatic Brain Injury in a Rat Model.

OBJECTIVE: The aim of this study was to investigate the possible neuroprotective effects of cinnamaldehyde (CA) on secondary brain injury after traumatic brain injury (TBI) in a rat model. METHODS: Rats were randomly divided into 4 groups: control (n = 9), TBI (n = 9), vehicle (0.1% Tween 80; n = 8), and CA (100 mg/kg) (n = 9). TBI was induced by the weight-drop model. In brain tissues, myeloperoxidase activity and the levels of luminol-enhanced and lucigenin-enhanced chemiluminescence were measured. Interleukin 1ß, interleukin 6, tumor necrosis factor α, tumor growth factor ß, caspase-3, and cleaved caspase-3 were evaluated with an enzyme-linked immunosorbent assay method. Brain injury was histopathologically graded after hematoxylin-eosin staining. Y-maze and novel object recognition tests were performed before TBI and within 24 hours of TBI. RESULTS: Higher myeloperoxidase activity levels in the TBI group (P < 0.001) were suppressed in the CA group (P < 0.05). Luminol-enhanced and lucigenin-enhanced chemiluminescence, which were increased in the TBI group (P < 0.001, for both), were decreased in the group that received CA treatment (P < 0.001 for both). Compared with the increased histologic damage scores in the cerebral cortex and dentate gyrus of the TBI group (P < 0.001), scores of the CA group were lower (P < 0.001). Decreased number of entries and spontaneous alternation percentage in the Y-maze test of the TBI group (P < 0.05 and P < 0.01, respectively) were not evident in the CA group. CONCLUSIONS: CA has shown neuroprotective effects by limiting neutrophil recruitment, suppressing reactive oxygen species and reducing histologic damage and acute hippocampal dysfunction.

Electromagnetic Waves from Mobile Phones may Affect Rat Brain During Development.

AIM: To investigate the effects of electromagnetic waves (EMWs) from mobile phones (MPs) on rat brains of rats by morphological and biochemical analysis. MATERIAL AND METHODS: EMW was applied for two hours/day until birth in stand-by fetal and EMW fetal groups and postnatal 60 < sup > th < /sup > day in stand-by and EMW groups. The control group was not exposed to MP. On postnatal 60 < sup > th < /sup > day, brain malondialdehyde (MDA) and glutathione (GSH) levels were measured, and western blot analysis was performed to determine glial fibrillary acidic protein (GFAP) content. Hematoxylin and eosin staining and GFAP immunohistochemistry were applied. Trigeminal nerves were examined using the transmission electron microscope. RESULTS: In comparison to controls, rats exposed to MP in stand-by or talk modes had significantly increased neuronal damage in the cortex and hippocampus. Increased MDA levels in the EMW group and decreased GSH levels in the stand-by, EMW fetal and EMW groups were found compared with controls. Increased GFAP content in the EMW group and increased GFAP staining in the EMW fetal and EMW groups compared to controls were observed. EMW group had a significantly decreased number of myelinated axons than control animals. CONCLUSION: The results of this study suggests that 1800 MHz EMWs (SAR=1.79 W/kg) exposure in the prenatal and early postnatal life may lead to trigeminal nerve damage in addition to oxidative stress-induced neuronal degeneration and astroglial activation in the rat brain. Effects seem to be mode related, being more detrimental in groups exposed to MP during talk mode.

An alginate-poly(acrylamide) hydrogel with TGF-ß3 loaded nanoparticles for cartilage repair: Biodegradability, biocompatibility and protein adsorption.

Current implantable materials are limited in terms of function as native tissue, and there is still no effective clinical treatment to restore articular impairments. Hereby, a functionalized polyacrylamide (PAAm)-alginate (Alg) Double Network (DN) hydrogel acting as an articular-like tissue is developed. These hydrogels sustain their mechanical stability under different temperature (+4 °C, 25 °C, 40 °C) and humidity conditions (60% and 75%) over 3 months. As for the functionalization, transforming growth factor beta-3 (TGF-ß3) encapsulated (NPTGF-ß3) and empty poly(lactide-co-glycolide) (PLGA) nanoparticles (PLGA NPs) are synthesized by using microfluidic platform, wherein the mean particle sizes are determined as 81.44 ± 9.2 nm and 126 ± 4.52 nm with very low polydispersity indexes (PDI) of 0.194 and 0.137, respectively. Functionalization process of PAAm-Alg hydrogels with ester-end PLGA NPs is confirmed by FTIR analysis, and higher viscoelasticity is obtained for functionalized hydrogels. Moreover, cartilage regeneration capability of these hydrogels is evaluated with in vitro and in vivo experiments. Compared with the PAAm-Alg hydrogels, functionalized formulations exhibit a better cell viability. Histological staining, and score distribution confirmed that proposed hydrogels significantly enhance regeneration of cartilage in rats due to stable hydrogel matrix and controlled release of TGF-ß3. These findings demonstrated that PAAm-Alg hydrogels showed potential for cartilage repair and clinical application.

Investigation of Astaxanthin Effect on Cisplatin Ototoxicity in Rats by Using Otoacoustic Emission, Total Antioxidant Capacity, and Histopathological Methods.

BACKGROUND: Cisplatin-induced ototoxicity is related to oxidative stress. Astaxanthin is one of the most powerful antioxidants in nature. AIMS/OBJECTIVES: To investigate the protective effect of astaxanthin on cisplatin-induced ototoxicity. MATERIALS AND METHODS: Thirty-five Sprague Dawley female rats were divided into 5 groups: control, cisplatin, and cisplatin with 10, 20, and 40 mg/kg astaxanthin groups. Cisplatin group received a single intraperitoneal injection of 14 mg/kg cisplatin. While saline was administered in the control group, in the other 3 groups, 10, 20, and 40 mg/kg daily doses of astaxanthin were administered through orogastric cannula before administration of cisplatin. Baseline and 10th day otoacoustic emission tests were administered. An intracardiac blood sample was taken to measure total antioxidant capacity (TAC), and the cochleas of the animals were investigated histopathologically. RESULTS: Hearing level of astaxanthin 40 mg/kg + cisplatin group was higher at 24 kHz and 32 kHz frequencies compared to the cisplatin group. The TAC value of the cisplatin group was lower than both the control and astaxanthin + cisplatin groups (P < .05). On histopathological examination, the other groups were deformed compared to the control group, but no statistically significant difference was observed between the astaxanthin + cisplatin and cisplatin groups. CONCLUSIONS AND SIGNIFICANCE: Astaxanthin showed protective effect at high frequencies when it was administered at high dose. Thus, astaxanthin may have protective effect against cisplatin-induced ototoxicity.