Unexposed Rats Research Articles

Effects of Tomato and Carrot-Supplemented Diets on Physical and Haemalogical Characteristics of Wistar Rats Exposed to Breast Carcinogen (Dimethylbenz-[A]-Anthracene)

Cancer, particularly of the breast, is one of the most common cases of morbidity and mortality in women globally. This research aimed at exploring the potentials of tomato and/or carrot-supplemented diets in mitigating against breast cancer carcinogen, DMBA in rats. Forty-eight female rats were randomly distributed into 8 groups. Groups 1 and 2 comprised of unexposed rats fed standard diet and DMBA-administered group fed standard diet respectively. Groups 3-5 were DMBA-administered groups fed diets containing 20% tomato, 20% carrot, and 20% of an equally mixed tomato and carrot respectively. For groups 6-8, unexposed rats fed diets containing 20% tomato, carrot, and 20% of an equally mixed tomato and carrot respectively. The feeding was for a period of 10 weeks. Feed intake, changes in weight and hematological changes were determined. The exposed rats fed supplemented diets had significantly (p<0.05) higher feed intake and percentage weight gain compared with the exposed group fed standard diet. Similarly, the unexposed groups fed supplemented diets had significantly (p<0.05) higher feed intake and percentage weight gain in comparison with the unexposed group fed standard diet. DMBA- Exposed group and unexposed group fed 20% tomato-supplemented diet had significantly higher WBC and hemoglobin compared with the control. In conclusion, supplementation of diets with either carrot or tomato improves feed intake in normal rats and antagonizes appetite-suppressing effects of cancer, and ameliorate weight loss in rats exposed to breast carcinogen.

The effect of 6GHz radiofrequency electromagnetic radiation on rat pain perception

ABSTRACT This paper presents data on pain perception in rats exposed to 6 GHz radiofrequency electromagnetic radiation (RF-EMR). Rats were divided into two groups: control (n = 10, 4 replicates per test) and RF-EMR exposed group (n = 10, 4 replicates per test). Nociceptive responses of the groups were measured using rodent analgesiometry. Rats were divided into control and RF-EMR exposed groups. Nociceptive responses were measured using rodent analgesiometry. RF-EMR exposed rats had a 15% delay in responding to hot plate thermal stimulation compared to unexposed rats. The delay in responding to radiant heat thermal stimulation was 21%. We determined that RF-EMR promoted the occurrence of pressure pain as statistical significance by + 42% (p < 0.001). We observed that RF-EMR exposure increased nociceptive pain by + 35% by promoting cold plate stimulation (p < 0.05). RF-EMR exposure did not affect thermal preference as statistical significance but did support the formation of pressure pain perception.

Does acute exposure to thimerosal, an organic mercury compound, affect the mitochondrial function of an infant model?

BackgroundThimerosal (TM) is a toxic, organometallic mercury compound (which releases ethyl-mercury-containing compounds in aqueous solutions) used as a preservative in vaccines. Mitochondria are organelle which are highly vulnerable to many chemical compounds, including mercury (Hg) and its derivatives. MethodWistar rats (at 21 days of age) were used to model a child’s TM exposure following childhood vaccination, divided in two groups: TM exposed (20 μg/kg/day) and unexposed controls (saline solution), both for 24 h. Atomic Fluorescence Spectrometry was used to quantify the amounts of mercury in tissues. The electron transport chain (ETC) from isolated mitochondria was evaluated using an oxygen electrode. The mitochondrial membrane potential and H2O2 production were analyzed using selective fluorescence probes. The activity of some enzymes (SOD, CAT, GPx, and AChE) and secondary markers of oxidative stress (GSH, GSSG, total free thiol) were also examined in tissues. ResultsHg accumulation in the brain and liver was higher in exposed animals when compared to the control. Liver-isolated mitochondria showed that TM improved respiratory control by 23%; however, states 3 and 4 of the ETC presented a decrease of 16% and 37%, respectively. Furthermore, brain-isolated mitochondria presented an improvement of 61% in respiratory control. Brain enzyme activities were significantly impacted in TM-exposed rats compared to unexposed rats as follows: decreases in SOD (32%) and AChE (42%) and increases in GPx (79%) and CAT (100%). GPx enzyme activity in the liver was significantly increased (37%). Among secondary oxidative stress markers, the brain’s total reduced thiol (SH) concentration was significantly increased (41%). ConclusionAcute TM treatment exposure in a Wistar rat model mimicking TM exposure in an infant following childhood vaccination significantly damaged brain bioenergetic pathways. This study supports the ability of TM exposure to preferentially damage the nervous system.

Ameliorative Potentials of Quercetin in Some Histo-Physiological and Biochemical Parameters Against Alterations Induced Benzene Inhalation in Albino Rats

Present study investigates the protective role of quercetin in reducing benzene-induced toxicity in rats. Sixteen adult rats, weighing 200-250 g, were selected. They were divided into four groups: 1. Control group, 2. Benzene inhaled group, 3. Quercetin group and 4. Group of benzene and quercetin in combination. Biochemical, spermatological parameters, and histopathological changes in lungs were recorded. Results of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea and creatinine levels in the serum of rats were higher in benzene exposed rats than in unexposed rats. Conversely, exposure to benzene led to a decrease in sperm quality compared to the unexposed rats. Histopathological examinations of the lung tissues revealed structural changes in exposed rats, including emphysema, thinning of the wall of the alveolar sac, congestion between the alveolar sacs and more elasticity in the wall of smooth muscles. The present study showed that quercetin treatment can reverse the negative effects of benzene in approximately all studied parameters and showed amelioration in the histological anomalies induced by benzene toxicity.

Selected Vegetables and Spices Improve DNA Quality and Histopathological Abnormalities in Roof Rats (Rattus rattus) Exposed to Cement Dust

Highlights: 1. This study identified feasible and affordable alternatives to ineffective conventional cement production pollution control strategies.2.M. oleifera, H. sabdariffa, T. occidentalis, and Z. officinale are effective as personal interventions to ameliorate the effects of cement pollution. Abstract Conventional pollution control strategies in the cement industry have proven ineffective. As a result, effective and targeted complementary interventions are necessary. This study used roof rats (Rattus rattus) inhabiting the premises of a cement plant in Sagamu, Ogun State, Nigeria, to evaluate the ameliorative effects of moringa (Moringa oleifera), roselle (Hibiscus sabdariffa), fluted pumpkin (Telfairia occidentalis), and ginger (Zingiber officinale) on cement dust exposure. A total of 42 rats were divided into seven groups, with each group consisting of six rats. Group 1 served as the negative control group and was not exposed to any substances, while group 2 served as the positive control group and received standard feed throughout the experiment. Meanwhile, groups 3, 4, 5, 6, and 7 served as the experimental group. Rats in these groups were fed with 400 mg/kg of ethanolic extracts of Z. officinale, M. oleifera, T. occidentalis, H. sabdariffa, and a mixture of the four extracts with a composition of 1:1:1:1, respectively, for 90 days. The plasma DNA concentrations, DNA purity, and lungs of the rats were examined before and after the experiment. Prior to the experiment, the exposed rats had higher plasma DNA concentrations and lower DNA purity, as well as severe fibrosis and congested alveoli in their lungs, compared to the unexposed rats. At the end of the experiment, the experimental groups showed a significant increase in DNA purity (p≤0.05) and a decline in plasma DNA concentrations compared to the positive control group. In addition, the experimental groups showed fewer histopathological abnormalities than the positive control group. The mixture of the extracts yielded the most favorable results, followed by the extracts of Z. officinale, M. oleifera, T. occidentalis, and H. sabdariffa, respectively. These findings suggested that the selected vegetables and spices have the properties to ameliorate the effects of cement dust exposure. Therefore, individuals residing in close proximity to cement plants are encouraged to consume these vegetables and spices.

The Ketogenic Diet Improves Gut-Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems.

Altered gut–brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT3B and 5-HT4, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT3B, and 5-HT4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.

Sub-chronic oral toxicity study of “Kien Nao Dan” tablets in experimental animal

“Kien nao dan” (KND) tablet is composed of 13 traditional medicines that may has preventive and effective treatment of cerebral ischemia. However, there are no scientific reports of its toxicological properties which guarantee of the safety its usage treatment. Therefore, the aim of this study was to investigate the sub-chronic toxicity of KND tablet on rats through oral administration. The sub-chronic toxicity was evaluated by the recommendation of WHO in Wistar rats at doses of 0.72 g/kg/day (equal to recommended human dose) and 2.16 g/kg/day (3 times as high as recommended human dose) for 8 consecutive weeks. In the evaluation of sub-chronic toxicity, there were no behavioral and physiological changes or signs of toxicity. The result of the hematological and biological parameters after administration of KND tablets showed no change. The histopathologic analysis of livers and kidneys indicated that no significant differences were observed between the exposed and unexposed rat groups. In conclusion, “Kien nao dan” tablets did not produce sub-chronic toxicity in Wistar rats.

Sub-chronic oral toxicity study of “Phong Thap Dan” tablets in experimental animal

The present study aimed to investigate the sub-chronic toxicity of “Phong thap dan” (PTD) tablets through oral administration in experimental animal. The sub-chronic toxicity was evaluated by the WHO recommendation in Wistar rats at doses of 0.72 g/kg/day (equal to recommended human dose) and 2.16 g/kg/day (3 times as high as recommended human dose). In the sub-chronic experimental group, the PTD was administered orally daily for 8 consecutive weeks. In the evaluation of sub-chronic toxicity, there were no behavioral and physiological change or sign of toxicity. The result of the hematological and biological parameters after administration of PTD tablets showed no change. The histopathology analysis of livers and kidneys indicated that no significant difference was observed between the exposed and unexposed rat groups. In conclusion, “Phong thap dan” tablets did not produce sub-chronic toxicity in Wistar rats.

Peucedanum japonicum Thunberg and Its Active Components Mitigate Oxidative Stress, Inflammation and Apoptosis after Urban Particulate Matter-Induced Ocular Surface Damage.

We previously demonstrated that urban particulate matter (UPM) exposure decreases the migration activity and survival of human corneal epithelial cells (HCECs). Herein, we investigated the potential to improve the corneal wound-healing ability of Peucedanum japonicum Thunb. leaf extract (PJE) and its active components on UPM-induced ocular surface damage in vitro and in vivo. PJE effectively assisted wound healing without altering HCEC survival and enhanced catalase (CAT), heme oxygenase 1 (HO1) and glutathione peroxidase 1 (GPX1) antioxidant gene expression. A corneal wound was uniformly induced on the right eye in all experimental animals and divided into eight groups such as two control groups (wounded right eye group—NR and non-wounded left eye group—NL), UPM treated group and PJEs (25, 50, 100, 200, 400 mg/kg) treated groups. Corneal abrasion model rats exposed to UPM showed delayed wound healing compared to unexposed rats, but wound healing was dose-dependently enhanced by PJE oral administration. Seventy-two hours after wound generation, inflammatory cells, apoptotic cells and interleukin-6 (IL-6) expression were increased substantially after UPM exposure, but PJE treatment significantly reduced the wound to an almost normal level while enhancing re-epithelialization without changing corneal thickness. Next, we tried to identify the key molecules for enhancing wound healing through fractionation. The major compounds in the fraction, confirmed by high-performance liquid chromatography (HPLC), were chlorogenic acid (CA), neochlorogenic acid (NCA) and cryptochlorogenic acid (CCA). Each type of CA isomers showed slightly different half maximal effective (EC50) and maximal effective (ECmax) concentrations, and their mixtures synergistically enhanced HCEC migration. Thus, corneal abrasion wound recovery after UPM exposure improved after PJE treatment, and the active PJE components were identified, providing an important basis to develop therapeutics for ocular surface damage using PJE.

The influence of developmental noise exposure on the temporal processing of acoustical signals in the auditory cortex of rats

Previous experiments have acknowledged that inappropriate or missing auditory inputs during the critical period of development cause permanent changes of the structure and function of the auditory system (Bures et al., 2017). We explore in this study how developmental noise exposure influences the coding of temporally structured stimuli in the neurons of the primary auditory cortex (AC) in Long Evans rats. The animals were exposed on postnatal day 14 (P14) for 12 minutes to a loud (125 dB SPL) broad-band noise. The responses to an amplitude-modulated (AM) noise, frequency-modulated (FM) tones, and click trains, were recorded from the right AC of rats of two age groups: young-adult (ca. 6 months old) and adult (ca. 2 years old), both in the exposed animals and in control unexposed rats. The neonatal exposure resulted in a higher synchronization ability (phase-locking) of the AC neurons for all three stimuli; furthermore, the similarity of neuronal response patterns to repetitive stimulation was higher in the exposed rats. On the other hand, the exposed animals showed a steeper decline of modulation-transfer functions towards higher modulation frequencies/repetition rates. Differences between the two age groups were also apparent; in general, aging had qualitatively the same effect as the developmental exposure. The current results demonstrate that brief noise exposure during the maturation of the auditory system influences both the temporal and the rate coding of periodically modulated sounds in the AC of rats; the changes are permanent and observable up to late adulthood.

Neuroprotectin D1 Attenuates Blast Overpressure Induced Reactive Microglial Cells in the Cochlea.

We examined a neuroinflammatory response associated with glial activation in the cochlea exposed to blast overpressure and evaluated the potential therapeutic efficacy of specialized pro-resolving mediators such as neuroprotectin D1, NPD1; (10R, 17S-dihydroxy-4Z, 7Z, 11E, 13E, 15Z, 19Z-docosahexaenoic acid) in a rodent blast-induced auditory injury model. Animal Research. A compressed-air driven shock tube was used to expose anesthetized adult male Long-Evan rats to shock waves simulating an open-field blast exposure. Approximately 30 minutes after blast exposure, rats were treated with NPD1 (100 ng/kg body wt.) or vehicle delivered intravenously via tail vein injection. Rats were then euthanized 48 hours after blast exposure. Unexposed rats were included as controls. Tissue sections containing both middle and inner ear were prepared with hematoxylin-eosin staining to elucidate histopathological changes associated with blast exposure. Cochlear tissues were evaluated for relative expression of ionized calcium-binding adaptor 1 (Iba1), as an indicator of microglial activation by immunohistochemistry and western blot analyses. Our animal model resulted in an acute injury mechanism manifested by damage to the tympanic membrane, hemorrhage, infiltration of inflammatory cells, and increased expression of Iba1 protein. Moreover, therapeutic intervention with NPD1 significantly reduced Iba1 expression in the cochlea, suggesting a reduction of a neuroinflammatory response caused by blast overpressure. Blast overpressure resulted in an increased expression of proteins involved in gliosis within the auditory system, which were reduced by NPD1. Treatment of NPD1 suggests an effective strategy to reduce or halt auditory microglial cell activation due to primary blast exposure. NA Laryngoscope, 131:E2018-E2025, 2021.

Effects of an Orexin‐2 Receptor Antagonist on Sleep and Event‐Related Oscillations in Female Rats Exposed to Chronic Intermittent Ethanol During Adolescence

Alcohol use is on the rise among women in the United States which is especially concerning since women who drink have a higher risk of alcohol-related problems. Orexin (hypocretin) receptor antagonists may have some therapeutic value for alcohol-induced insomnia; however, the use of this class of drugs following female adolescent binge drinking is limited. The current study will address whether adolescent intermittent ethanol (AIE) in female rats can result in lasting changes in sleep pathology and whether orexin-targeted treatment can alleviate these deficits. Following a 5-week AIE vapor model, young adult rats were evaluated on waking event-related oscillations (EROs) and EEG sleep. Subsequently, AIE rats were treated with orexin receptor 2 (OX2 R) antagonist (MK-1064; 10, 20mg/kg) to test for modifications in sleep pathology and waking ERO. Female AIE rats exhibited lasting changes in sleep compared to controls. This was demonstrated by increased fragmentation of slow wave sleep (SWS) and rapid eye movement sleep, as well as reductions in delta and theta power during SWS. There was no impact of AIE on waking EROs. Acute MK-1064 hastened SWS onset and increased the number of SWS episodes, without increasing sleep fragmentation in AIE and controls. While treatment with MK-1064 did not impact sleep EEG spectra, waking ERO energy was increased in delta, theta, and beta frequency bands. These results demonstrate that AIE can produce lasting changes in sleep in female rats, highly similar to what we previously found in males. Additionally, while the OX2 R antagonist promoted sleep in both alcohol-exposed and unexposed rats, it did not reverse most of the alcohol-induced disruptions in sleep. Thus, OX2 R antagonism may serve as a potential therapeutic strategy for the treatment of insomnia, but not the specific signs of alcohol-induced insomnia.

Prenatal Effects of a 1,800-MHz Electromagnetic Field on Rat Livers

The use of devices, including mobile phones, generating electromagnetic fields (EMF) is widespread and is progressively increasing. It has also been shown that EMF may have detrimental effects. This is the first study to investigate the postnatal biochemical and histological effects of prenatal exposure of rat livers to 1,800-MHz EMF at different time intervals in uteroplacental life. The 3 EMF groups of rats were exposed to 1,800-MHz EMF for 6, 12, or 24 h daily for 20 days. Unexposed rats served as control group. All rats were subjected to anesthesia, and on postnatal day 60, the livers were excised, and blood was collected for histological and biochemical analyses. Malondialdehyde levels were significantly higher in the exposed groups than the unexposed controls (p < 0.05). In contrast, EMF-exposed groups had lower liver tissue glutathione levels than controls (p < 0.05). Serum Ca²⁺, alanine transaminase, and aspartate aminotransferase levels were higher in EMF-exposed groups than controls (p < 0.05). In addition, liver tissue total oxidant status levels were increased (p < 0.05), and liver tissue total antioxidant status levels were decreased (p < 0.05) compared to the control group. Furthermore, in the EMF groups, extensive vacuolation and degeneration of the hepatocytes in the portal area, as well as those surrounding the sinusoids, were evident. Affected hepatocytes had polygonally shaped nuclei and vacuolic cytoplasm imparting eosinophilic staining. Loss of cellular membrane integrity and invaginations, as well as picnotic nuclei, was prominent. This study has shown that intrauterine liver damage caused by 1,800-MHz EMF exposure persists into puberty in rats.

Comparative Efficacy of Syzygium Cumini Seed Extracts in Alleviating Arsenic-Induced Hepatotoxicity and Blood Cell Genotoxicity in Wistar Albino Rats

Syzygium cumini is well known for its medicinal values in the indigenous Indian system of medicine. This study was designed to evaluate the protective effect of methanolic (SCM), ethanolic (SCE) and aqueous (SCA) extracts of Syzygium cumini seeds on arsenic-induced blood cell genotoxicity and hepatotoxicity in Wistar albino rats. Rats were divided into five groups: (1) control, (2) arsenic, (3) SCM, (4) SCE and (5) SCA. After completion of 60 days treatment period, comet assays were performed on isolated blood lymphocytes and serum marker assays indicative of hepatic toxicity were carried out. Arsenic exposed rats expressed significantly higher DNA damage in their lymphocytes than the unexposed rats. Increased activities of serum alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and decreased levels of total proteins were observed in arsenic exposed rats. Simultaneous administration of Syzygium cumini seed extracts significantly decreased the arsenic-induced DNA damage and hepatotoxicity. The amelioration of arsenic toxicity was more pronounced with methanolic extract compared to ethanolic and aqueous extracts of Syzygium cumini seeds.

Tobacco-product usage as a risk factor for dental implants.

The oral cavities of tobacco smokers and users of smokeless tobacco products are exposed to high concentrations of nicotine. A limited number of animal studies have assessed the effect of nicotine on osseointegration. Results from experimental studies have reported a statistically significant decrease, at 4weeks of follow-up, in bone-to-implant contact among rats exposed to nicotine compared with unexposed rats. Nicotine increases the production of inflammatory cytokines (such as interleukin-6 and tumor necrosis factor-alpha) by osteoblasts. Waterpipe, pipe, and cigarette smokers are at increased risk of developing oral cancer, periodontal disease, and alveolar bone loss. One explanation for this is that smokers (regardless of the type of tobacco product) are exposed to similar chemicals, such as nicotine, tar, oxidants, polyaromatic hydrocarbons, and carbon monoxide. Moreover, raised levels of proinflammatory cytokines have been identified in the gingival crevicular fluid of cigarette smokers with peri-implant diseases. Therefore, it is hypothesized that nicotine and chemicals in tobacco smoke induce a state of oxidative stress in peri-implant tissues (gingiva and alveolar bone), thereby increasing the likelihood of peri-implant disease development via an inflammatory response, which if left uncontrolled, will result in implant failure/loss. In this regard, tobacco smoking (including cigarettes, waterpipe, and pipe) is a significant risk factor for peri-implant diseases. The impact of vaping electronic cigarettes using nicotine-containing e-juices remains unknown. Habitual use of smokeless tobacco products is associated with oral inflammatory conditions, such as oral precancer, cancer, and periodontal disease. However, the effect of habitual use of smokeless tobacco products on the success and survival of dental implants remains undocumented.

The impact of exposure of diabetic rats to 900 MHz electromagnetic radiation emitted from mobile phone antenna on hepatic oxidative stress

ABSTRACTThe excessive exposure of patients with type 2 diabetes mellitus (T2DM) to electromagnetic radiation (EMR) from mobile phones or their base stations antenna may influence oxidative stress and development of diabetic complications. Here, we investigated the effects of exposing type 2 diabetic rats to EMR of 900 MHz emitted from GSM mobile phone antenna for 24 hours/day over a period of 28 days on hyperglycemia and hepatic oxidative stress. Male Sprague-Dawley rats were divided into 4 groups (12 rats/group): control rats, normal rats exposed to EMR, T2DM rats generated by nicotinamide/streptozotocin administration, and T2DM rats exposed to EMR. Our results showed that the exposure of T2DM rats to EMR nonsignificantly reduced the hyperglycemia and hyperinsulinemia compared to unexposed T2DM rats. The exposure of T2DM rats to EMR for 28 days increased the hepatic levels of MDA and Nrf-2 as well as the activities of superoxide dismutase (SOD) and catalase but decreased phosphorylated Akt-2 (pAkt-2) as compared to unexposed T2DM rats. Therefore, the decrease in the hepatic pAkt-2 in T2DM rats after the exposure to EMR may result in elevated level of hepatic MDA, even though the level of Nrf-2 and the activities of SOD and catalase were increased.Abbreviations: BGL: blood glucose level; EMR: electromagnetic radiation; GSM: global system for mobile communication; H2O2: hydrogen peroxide; LSD: least significance difference; MDA:malondialdehyde; Nrf-2: nuclear factor erythroid 2- related factor 2; PI3K: phosphoinositide-3-kinase; pAkt-2: phosphorylated Akt-2; Akt-2: protein kinase; ROS: reactive oxygen species; SEM: standard error of the mean; STZ: streptozotocin; SOD: superoxide dismutase ; O2−: superoxide radical; CT: threshold cycle; T2DM: type 2 diabetes mellitus

Role of DNA Methylation in Hypobaric Hypoxia-Induced Neurodegeneration and Spatial Memory Impairment

Hypobaric hypoxia (HH) is a major stress factor that is associated with physiological, biochemical, molecular and genomic alterations. Brain is the organ that reacts sensitively to oxygen deprivation, which leads to oxidative stress and cognitive function impairment. Our previous studies have reported that downregulation of brain derived neurotrophic factor (BDNF) leads to neurodegeneration and memory impairment. The aim of the present study was to investigate the effect of HH exposure on DNA methylation and its regulation in BDNF expression, neurodegeneration and spatial memory impairment. For this purpose, Sprague Dawley rats were exposed to HH at a simulated altitude of 25,000 feet for 14 days. Real-time polymerase chain reaction was used for transcriptional expression of DNA Methyltransferases (DNMTs) including DNMT1, DNMT3a and ­DNMT3b, and immunoblotting was used for the translational expression of DNMT1, DNMT3a, DNMT3b, Methyl CpG binding protein 2 (MeCP2), pMeCP2 and BDNF in rat hippocampus. Additionally, neuronal morphology alteration and neurodegeneration in CA1 region of hippocampus were investigated though Cresyl violet (CV) staining and Fluoro-Jade C staining respectively. Results obtained suggested that HH exposure increased the expression of DNMT1 DNMT3b at the mRNA as well as protein level, whereas no significant change was observed in the level of DNMT3a. Furthermore, the level of pMeCP2 and BDNF were significantly decreased; however, the expression level of MeCP2 was significantly increased. The CV and Fluoro-Jade C-positive cells were significantly enhanced in the CA1 region of hippocampus in the HH exposed group as compared to unexposed rats. Thus, the present study concluded that HH decreases neuronal activation by the upregulation of DNA methylation and MeCP2 and decreased the expression of pMeCP2, which result in the downregulation of BDNF. The decreased BDNF expression is associated with neuronal loss and spatial memory impairment. This study highlights that DNMT inhibition could be an important therapeutic target for neurodegenerative diseases.

Role of epigenetic mechanisms in transmitting the effects of neonatal sevoflurane exposure to the next generation of male, but not female, rats

BackgroundClinical studies report learning disabilities and attention-deficit/hyperactivity disorders in those exposed to general anaesthesia early in life. Rats, primarily males, exposed to GABAergic anaesthetics as neonates exhibit behavioural abnormalities, exacerbated responses to stress, and reduced expression of hypothalamic K+-2Cl− Cl− exporter (Kcc2). The latter is implicated in development of psychiatric disorders, including male predominant autism spectrum disorders. We tested whether parental early life exposure to sevoflurane, the most frequently used anaesthetic in paediatrics, affects the next generation of unexposed rats. MethodsOffspring (F1) of unexposed or exposed to sevoflurane on postnatal day 5 Sprague-Dawley rats (F0) were subjected to behavioural and brain gene expression evaluations. ResultsMale, but not female, progeny of sevoflurane-exposed parents exhibited abnormalities in behavioural testing and Kcc2 expression. Male F1 rats of both exposed parents exhibited impaired spatial memory and expression of hippocampal and hypothalamic Kcc2. Offspring of only exposed sires had abnormalities in elevated plus maze and prepulse inhibition of startle, but normal spatial memory and impaired expression of hypothalamic, but not hippocampal, Kcc2. In contrast to exposed F0, their progeny exhibited normal corticosterone responses to stress. Bisulphite sequencing revealed increased CpG site methylation in the Kcc2 promoter in F0 sperm and F1 male hippocampus and hypothalamus that was in concordance with the changes in Kcc2 expression in specific F1 groups. ConclusionsNeonatal exposure to sevoflurane can affect the next generation of males through epigenetic modification of Kcc2 expression, while F1 females are at diminished risk.

Effects of Lianhua Qingwen on Pulmonary Oxidative Lesions Induced by Fine Particulates (PM2.5) in Rats

Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats. Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5 (7.5 mg/kg) as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment (crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 days before dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively. The other dust-exposed model rats without treatment were assigned as PM2.5 control group. The un-exposed rats were set as saline control group (1.5 ml/kg saline) and blank control group. All rats were killed after 24 hours of the exposure. Lung tissue, serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of malonaldehyde (MDA), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) in blood serum and BALF, and superoxide dismutase (SOD) in blood surum were measured using fluorescent quantitation PCR; Expression of NF-E2-related factor 2(NRF-2), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO1) in lung tissues were measured using Western blot. Pathological changes of lung tissues in each group were also examined. Results Pathology revealed thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole in the PM2.5 control group, which were significantly relieved in the Lianhua Qingwen treatment groups. Compared to the blank and saline control groups, the PM2.5 control group had significantly higher levels of LDH and MDA (p<0.01) and lower level of GSH-PS (p<0.01) in BALF, significantly higher levels of LDH and MDA (p<0.05) and lower level of GSH-PS (p<0.05) in rat serum. The levels of MDA in blood serum and BALF were significantly lower in each treatment group than that in PM2.5 control group (all P<0.05). In both middle-dose and high-dose treatment group the measurements of LDH in serum and BALF as well as GSH-PX in serum were significant difference from those of PM2.5 control group (all P<0.05). Expressions of NRF-2, HO-1 and NQO1 in lung tissues were significantly different among middle-dose and high-dose treatment group compared with those in PM2.5 control group (all P<0.05). Conclusion Fine particulates PM2.5 in environment may induce pulmonary oxidative lesions in rats. Middle-dose and high-dose Lianhua Qingwen has antagonist effece on the injuries induced by fine particulates.

Hypertension Editors' Picks: Hypertension and Sleep.

Hypertension Editors' Picks: Hypertension and Sleep.