Protective role of Eugenol against the destructive effects of lead on conditioned fear memory in male rats with post-traumatic stress disorder-related behavioral traits.

Introduction: Post-traumatic stress disorder (PTSD) is a consequence of living in today's stressful society. Patients have difficulty forgetting traumatic events. lead pollution has many effects on the nervous system, one of which is memory and learning disorders. The herbal medicine Eugenol has a beneficial effect on memory. Aim: This study aims to investigate the protective effect of Eugenol on lead-induced memory impairments in stressed rats. Methods: In the first experiment, the animals were divided into three groups: SPS+Saline, SPS+Pb, and naïve. The SPS+Saline, SPS+Pb groups received normal saline and lead through gavage for 21 days, while the sham group remained untreated. Rats were subjected to the modified single prolonged stress model. Memory tests were conducted one week later, evaluating freezing levels in three consecutive tests over three days. In the second experiment, rats were divided into a SPS+Pb+Saline and three treatment groups. The SPS+Pb+Saline group received daily saline injections, while the other groups received different doses of Eugenol (25, 50, and 100 mg/kg). Memory tests similar to the first experiment were conducted. Results: The results showed significantly higher immobility levels in the SPS+Saline and SPS+Pb groups compared to the sham. Additionally, the SPS+Pb group had a significant higher immobility compared to the SPS+Saline group. In the second experiment, the SPS+Pb+EU 25 group showed a significant lower freezing compared to the SPS+Pb+Saline group. Additionally, freezing in the SPS+Pb+EU 50 and SPS+Pb+EU 100 groups was significantly higher than in the SPS+Pb+EU 25 group. The SPS+Pb+EU 50 group showed a significant higher freezing compared to the SPS+Pb+Saline group. Conclusion: lead acetate exacerbated memory impairments in stressed rats and Eugenol, particularly at a dose of 25 mg/kg, improved these impairments. Therefore, Eugenol has the potential to partially reduce the negative effects of lead on memory in individuals with PTSD.

Evaluation of the Expression of Infection-Related Long Noncoding RNAs among COVID-19 Patients: A Case-Control Study.

Background and Aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a worldwide pandemic, activates signaling cascades and leads to innate immune responses and secretion of multiple chemokines and cytokines. Long noncoding RNAs (lncRNAs) have a crucial role in inflammatory pathways. Through our search on the PubMed database, we discovered that existing research has primarily focused on examining the regulatory impacts of five lncRNAs in the context of viral infections. However, their role in regulating other conditions, including SARS-CoV-2, has not been explored. Therefore, this study aimed to investigate the expression pattern of lncRNAs in the peripheral blood mononuclear cells (PBMC) and their potential roles in SARS-CoV-2 infection. Potentially significant competing endogenous RNA (ceRNA) networks of these five lncRNAs were found using online in-silico techniques. Methods: Ethylenediaminetetraacetic acid (EDTA) blood samples of the control group consisted of 45 healthy people, and a total of 53 COVID-19-infected patients in case group, with a written informed consent, was collected. PBMCs were extracted, and then, the RNA extraction and complementary DNA (cDNA) synthesis was performed. The expression of five lncRNAs (lnc ISR, lnc ATV, lnc PAAN, lnc SG20, and lnc HEAL) was assessed by real-time PCR. In order to evaluate the biomarker roles of genes, receiver operating characteristic (ROC) curve was drawn. Results: Twenty-four (53.3%) and 29 (54.7%) of healthy and COVID-19-infected participants were male, respectively. The most prevalent symptoms were as follows: cough, general weakness, contusion, headache, and sore throat. The results showed that three lncRNAs, including lnc ISR, lnc ATV, and lnc HEAL, were expressed dramatically higher in the case group compared to healthy controls. According to ROC curve analysis, lnc ATV has a higher AUC and is a better biomarker to differentiate COVID-19 patients from the healthy controls. Then, using bioinformatics methods, the ceRNA network of these lncRNAs enabled the identification of mRNAs and miRNAs with crucial functions in COVID-19. Conclusion: The considerable higher expression of ISR, ATV, and HEAL lncRNAs and the significant area under curve (AUC) in ROC curve demonstrate that these RNAs probably have a potential role in controlling the host innate immune responses and regulate the viral replication of SARS-CoV-2. However, these assumptions need further in vitro and in vivo investigations to be confirmed.

Improving behavioral deficits induced by perinatal ethanol and stress exposure in adolescent male rat progeny via maternal melatonin treatment.

BACKGROUND AND AIM: Early-life stressful situations and binge drinking have been thus far acknowledged as two burdensome conditions that potentially give rise to negative outcomes and then synergistically affect brain development. In this context, the hippocampus, with the greatest number of glucocorticoid receptors (GCRs) in the brain, is responsible for regulating negative responses to stress. Prolonged glucocorticoid (GC) exposure can accordingly cause oxidative stress (OS), leading to cognitive and emotional dysfunction. Against this background, melatonin, as a powerful antioxidant and hypothalamus-pituitary-adrenal (HPA) axis regulator, was administered in this study to ameliorate cognitive impairments induced by perinatal ethanol and stress exposure in adolescent male rat progeny. METHODS: Wistar rat dams were exposed to ethanol (4 g/kg) and melatonin (10 mg/kg) from gestational day (GD) 6 to postnatal day (PND) 14 and then limited nesting material (LNS) from PND0 to PND14 individually or in combination. Maternal behavior was then investigated in mothers. Afterward, the plasma corticosterone (CORT) concentration, the OS marker, the corticotropin-releasing hormone receptor type 1 (CRHR1) expression, and the GCR and brain-derived neurotrophic factor (BDNF) levels were measured in the male pups. Moreover, behavioral tasks, including the elevated plus maze (EPM), the Morris water maze (MWM), the novel object recognition (NORT), and the object-location memory (OLM) tests were completed and assessed. RESULTS: The quantity and quality of maternal care significantly decreased in the mothers with dual exposure to ethanol and stress. The plasma CORT concentration in the progeny also dropped in the Ethanol + LNS group, but the risk-taking behavior elevated significantly. The ethanol and stress exposure further revealed a significant fall in the GCR and CRHR1 expression levels, compared with stress alone. The results of learning and memory tasks also indicated a significant reduction in spatial learning and memory among animals exposed to ethanol and stress. The BDNF mRNA levels correspondingly increased in the Ethanol + LNS group, compared with LNS alone. In the presence of ethanol and stress, the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities correspondingly declined. On the other hand, the malondialdehyde (MDA) levels augmented in the hippocampus of the animals with ethanol and LNS dual exposure, as compared with the control group. Melatonin treatment (MT) thus improved nursing behaviors in dams, prevented OS, enhanced the CRHR1 and GCR expression, and reduced the BDNF levels to the similar ones in the control group. The animals in the Ethanol + LNS + MT group ultimately showed an ameliorated performance at behavioral tasks, including the memory and risk-taking behavior. CONCLUSION: It was concluded that MT could prevent stress response and memory impairments arising from dual exposure to ethanol and stress by inhibiting OS.

Postnatal melatonin administration to stressed dams for ameliorating risk-taking behaviour in rat pups through maternal care improvement.

BACKGROUND AND AIM: Anxiety often occurs both concurrently and sequentially in childhood and adolescence in association with prenatal stress, which may reduce the quality of maternal care and then cause mood disorders among children in later life. Against this background, melatonin, as a powerful antioxidant, was used in the present study to ameliorate risk-taking behaviour induced by pure maternal care in rat pups. MATERIALS AND METHODS: The Wistar rat dams recruited in this study were exposed to restraint stress from gestational day (GD) 11 until delivery. They further received melatonin (10 mg/kg) during the postnatal days (PNDs) 0-7 by intraperitoneal (IP) injections at 4:00 PM. The pregnant rats were then divided into four groups, namely, control, stress, stress + melatonin and melatonin, and their maternal behaviour and corticosterone levels were measured. In the offspring, the outcomes of some behavioural tasks, including the elevated plus-maze (EPM) and open-field (OF) tests were ultimately assessed. RESULTS: The study results revealed that the quantity and quality of maternal care significantly declined and the plasma corticosterone levels compounded in the stressed dams. Melatonin treatment, however, improved their nursing behaviour and reduced their plasma corticosterone levels. The offspring performance in two tasks also showed an upward trend in risk-taking behaviour in the stress group, and melatonin administration ameliorated the effects of stress and lessened their anxiety-like behaviour. CONCLUSION: It was concluded that prenatal restraint stress could impair stress responses and quality of maternal care, whereas postnatal melatonin administration potentially contributed to the normalization of stress reaction and anxiolysis.

The Combined Effects of Perinatal Ethanol and Early-Life Stress on Cognition and Risk-Taking Behavior through Oxidative Stress in Rats.

Both prenatal ethanol and early-life stress have been shown to induce reduced risk-taking and explorative behavior as well as cognitive dysfunction in the offspring. In this study, we examined the effect of combined exposure to ethanol and early stress on maternal care, exploratory behavior, memory performances, and oxidative stress in male offspring. Pregnant rats were exposed to ethanol (4 g/kg) from gestational day (GD) 6-to postnatal day (PND) 14 and limited nesting material (LNS) from PND0-PND14 individually or in combination. Maternal behavior was evaluated during diurnal cycle. The level of corticosterone hormone and markers of oxidative stress were evaluated in the pups. Risk-taking and explorative behavior were assessed with the elevated-plus maze (EPM) test and cognitive behavior with the Morris water maze (MWM), novel object recognition (NORT), and object location memory (OLM) tests. In the mothers, perinatal alcohol or LNS either alone or in combination decreased maternal behavior. In the offspring, the combination of the two factors significantly increased the pup's plasma corticosterone concentration in comparison with ethanol and LNS alone. Reduced risk-taking behavior was observed in the ethanol, LNS and ethanol + LNS groups compared with the control group, and this was amplified in the co-exposure of ethanol and LNS groups. The MWM, NORT, and OLM tests revealed spatial and recognition memory impairment in the ethanol and LNS groups. This impairment was more profound in the co-exposure of ethanol and LNS. Also, we observed a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and an increase in malondialdehyde (MDA) level in the hippocampus of ethanol and LNS co-exposed animals as compared with individual exposure of ethanol and LNS. While each factor independently produced similar outcomes, the results indicate that the dual exposure paradigm could significantly strengthen the outcomes.

Maternal stress programs accelerated aging of the basal ganglia motor system in offspring.

Early-life stress involved in the programming of stress-related illnesses can have a toxic influence on the functioning of the nigrostriatal motor system during aging. We examined the effects of perinatal stress (PRS) on the neurochemical, electrophysiological, histological, neuroimaging, and behavioral correlates of striatal motor function in adult (4 months of age) and old (21 months of age) male rats. Adult PRS offspring rats showed reduced dopamine (DA) release in the striatum associated with reductions in tyrosine hydroxylase-positive (TH+) cells and DA transporter (DAT) levels, with no loss of striatal dopaminergic terminals as assessed by positron emission tomography analysis with fluorine-18-l-dihydroxyphenylalanine. Striatal levels of DA and its metabolites were increased in PRS rats. In contrast, D2 DA receptor signaling was reduced and A2A adenosine receptor signaling was increased in the striatum of adult PRS rats. This indicated enhanced activity of the indirect pathway of the basal ganglia motor circuit. Adult PRS rats also showed poorer performance in the grip strength test and motor learning tasks. The aged PRS rats also showed a persistent reduction in striatal DA release and defective motor skills in the pasta matrix and ladder rung walking tests. In addition, the old rats showed large increases in the levels of SNAP-25 and synaptophysin, which are synaptic vesicle-related proteins in the striatum, and in the PRS group only, reductions in Syntaxin-1 and Rab3a protein levels were observed. Our findings indicated that the age-dependent threshold for motor dysfunction was lowered in PRS rats. This area of research is underdeveloped, and our study suggests that early-life stress can contribute to an increased understanding of how aging diseases are programmed in early-life.

Hydrogen Sulfide Attenuates the Neurotoxicity in the Animal Model of Fetal Alcohol Spectrum Disorders.

Fetal alcohol spectrum disorder (FASD), which is caused by prenatal alcohol exposure, can result in cell death in specific brain regions. Alcohol-induced neurocognitive defects offspring's are included with activation of oxidative-inflammatory cascade followed with wide apoptotic neurodegeneration in many brain's regions such as hippocampus. According to the latest studies, H2S (hydrogen sulfide) can protect neuronal cells via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms in different animal models. Therefore, we aimed to evaluate the protective effects of H2S on ethanol-induced neuroinflammation and neuronal apoptosis in pup hippocampus with postnatal alcohol exposure. Administration of ethanol (5.27 g/kg) in milk solution (27.8 mL/kg) for each rat pups was performed through intragastric intubation on 2 to 10 postnatal days and NaHS as H2S donor (1 mg/kg) was injected on similar time, subcutaneously. For examining the antioxidant and anti-inflammatory effects, ELISA assay was performed to determine the levels of TNF-α, IL1ß, and antioxidant enzymes. Immunohistochemical staining was performed to evaluate the expression levels of GFAP and caspase-3 also Nissl staining was done for necrotic cell death evaluation. H2S treatment could significantly increase the activity of total superoxide dismutase, catalase, and glutathione (P < 0.05). It also decreased the levels of TNF-α, IL1ß, and malondialdehyde, compared with the ethanol group (P < 0.05). Moreover, the number of hippocampal caspase-3, GFAP-positive cells, and necrotic cells death reduced in the H2S group (P < 0.01). Based on the findings, H2S can inhibit apoptotic signaling that is mediated by the oxidative-inflammatory cascade following ethanol exposure of rat pups on postnatal period.

Hydrogen sulfide improves spatial memory impairment via increases of BDNF expression and hippocampal neurogenesis following early postnatal alcohol exposure.

According to experimental and clinical findings, fetal brain development may be interrupted by maternal alcohol consumption during pregnancy. Adult hippocampal neurogenesis is thought to play a role in cognition function (i.e. learning and memory). Recent evidence suggests that ethanol administration causes major apoptotic neurodegeneration in many regions of the rats' developing brain during the synaptogenesis period. Based on the recent studies, H2S improve learning and memory via increased neurogenesis and antiapoptotic mechanisms in different animal models. In this study, we aimed to evaluate the protective effects of hydrogen sulfide on alcohol-induced memory impairment, hippocampus neurogenesis and neuronal apoptosis in rat pups with postnatal ethanol exposure. Administration of ethanol to male rat pups was performed through intragastric intubation on postnatal days 2-10. The pups were administered 1 mg/kg of NaHS (H2S donor) on postnatal days 2-10. For examining the spatial memory, Morris water maze test was carried out 36 days after birth. Following the behavioral test, immunohistochemical staining was performed to evaluate the expression levels of BrdU, BDNF and Apoptotic cell death was detected by TUNEL staining. Hydrogen sulfide (H2S) treatment could significantly improve spatial memory impairment (P < 0.05) and significantly increase the expression of BrdU and BDNF in dentate gyrus area (P < 0.05). It also decreased positive TUNEL cells, compared with the ethanol group (P < 0.01). Based on the findings, H2S makes significant neuroprotective effects on Ethanol neurotoxicity due to its neurogenesis and anti-apoptotic activity.

Melatonin prevents oxidative damage induced by maternal ethanol administration and reduces homocysteine in the cerebellum of rat pups.

Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by animal experiments. This study was designed to evaluate the alterations in offspring rat cerebellum following increase of plasma Hcy level induced by maternal exposure to ethanol and to investigate the possible protective role of melatonin administration upon cerebellar ethanol-induced neurotoxicity. The adult female rats were divided randomly into 4 groups, including one control and three experimental groups, after vaginal plagues. Group I received normal saline, group II received ethanol (4 g/kg), group III received ethanol+melatonin (10mg/kg) and group IV received melatonin on day 6 of gestation until weaning. 21 days after birth, plasma Hcy level, level of lipid peroxidation, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and levels of bcl-2 and bax mRNA expression in cerebellum were determined. Our results demonstrated that ethanol could induce lipid peroxidation, and decrease antioxidants activities and increase plasma total Hcy level. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidant activities and significantly reduced plasma total Hcy levels. Moreover, melatonin reduced bax/bcl-2 ratio in the presence of ethanol. We conclude that these results provide evidence that ethanol neurotoxicity in part is related to increase of plasma Hcy levels and melatonin with reducing of plasma Hcy level has neuroprotective effects against ethanol toxicity in cerebellum.

The effect of adipose derived stromal cells on oxidative stress level, lung emphysema and white blood cells of guinea pigs model of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic disease and a major cause of death and disability. The present study aimed to elucidate pharmacological effects of adipose derived stromal cells (ASCs) on pathological and biochemical factors in a guinea pig model of COPD. Guinea pigs were randomized into 5 groups including: Control, COPD, COPD + intratracheal delivery of PBS as a vehicle (COPD-PBS), COPD + intratracheal delivery of ASCs (COPD-ITASC) and COPD + intravenous injection of ASCs (COPD-IVASC). COPD was induced by exposing animals to cigarette smoke for 3 months. Cell therapy was performed immediately after the end of animal exposure to cigarette smoke and 14 days after that, white blood cells, oxidative stress indices and pathological changes of the lung were measured. RESULTS: Compared with control group, emphysema was clearly observed in the COPD and COPD-PBS groups (p < 0.001). Lung histopathologic changes of COPD-ITASC and COPD-IVASC groups showed non-significant improvement compared to COPD-PBS group. The COPD-ITASC group showed a significant increase in total WBC compared to COPD-PBS group but there was not a significant increase in this regard in COPD-IVASC group. The differential WBC showed no significant change in number of different types of leukocytes. The serum level of malondialdehyde (MDA) significantly decreased but thiol groups of broncho-alveolar lavage fluid (BALF) increased in both cell treated groups (p < 0.05 for all cases). Weight of animals decreased during smoke exposure and improved after PBS or cell therapy. However, no significant change was observed between the groups receiving PBS and the ones receiving ASCs. CONCLUSION: Cell therapy with ASCs can help in reducing oxidative damage during smoking which may collectively hold promise in attenuation of the severity of COPD although the lung structural changes couldn't be ameliorated with these pharmacological therapeutic methods.

Chronic administration of a combination of six herbs inhibits the progression of hyperglycemia and decreases serum lipids and aspartate amino transferase activity in diabetic rats.

The effects of a polyherbal compound, containing six plants (Allium sativum, Cinnamomum zeylanicum, Nigella sativa, Punica granatum, Salvia officinalis and Teucrium polium) were tested on biochemical parameters in streptozotocin-induced diabetic rats. Streptozotocin caused an approximately 3-fold increase in fasting blood sugar level after 2 days. The diabetic control rats showed further increase in blood glucose after 30 days (384 ± 25 mg/dl in day 30 versus 280 ± 12 mg/dl in day 2, P < 0.001). Administration of the compound blocked the increase of blood glucose (272 ± 7 and 269 ± 48 mg/dl at day 2 and day 30, respectively). Also, there was significant difference in the level of triglyceride (60 ± 9 versus 158 ± 37 mg/dl, P < 0.01), total cholesterol (55 ± 2 versus 97 ± 11 mg/dl, P < 0.01) and aspartate amino transferase activity (75 ± 12 versus 129 ± 18 U/L, P < 0.05) between treated rats and diabetic control group. In conclusion, the MSEC inhibited the progression of hyperglycemia and decreased serum lipids and hepatic enzyme activity in diabetic rats. Therefore, it has the potential to be used as a natural product for the management of diabetes.