scholarly journals The Effect of Quercetin on Pro- and Anti-Inflammatory Cytokines in a Prenatally Stressed Rat Model of Febrile Seizures

2017 ◽  
Vol 11 ◽  
pp. 117906951770466 ◽  
Author(s):  
Nombuso Valencia Pearl Mkhize ◽  
Lihle Qulu ◽  
Musa Vuyisile Mabandla

Febrile seizures are childhood convulsions resulting from an infection that leads to an inflammatory response and subsequent convulsions. Prenatal stress has been shown to heighten the progression and intensity of febrile seizures. Current medications are costly and have adverse effects associated with prolonged use. Quercetin flavonoid exhibits anti-inflammatory, anti-convulsant, and anti-stress effects. This study was aimed to investigate the therapeutic effect of quercetin in a prenatally stressed rat model of febrile seizures. We hypothesized that quercetin will alleviate the effects of prenatal stress in a febrile seizure rat model. On gestational day 13, Sprague-Dawley rat dams were subjected to restraint stress for 1 hour/d for 7 days. Febrile seizures were induced on postnatal day 14 on rat pups by intraperitoneally injecting lipopolysaccharide followed by kainic acid and quercetin on seizure onset. Hippocampal tissue was harvested to profile cytokine concentrations. Our results show that quercetin suppresses prenatal stress–induced pro-inflammatory marker (interleukin 1 beta) levels, subsequently attenuating febrile seizures. This shows that quercetin can be therapeutic for febrile seizures in prenatally stressed individuals.

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Sen Zhang ◽  
Hongqi Xin ◽  
Yan Li ◽  
Dongming Zhang ◽  
Jing Shi ◽  
...  

Skimmin is one of the major pharmacologically active molecules present inHydrangea paniculata, a medical herb used in the traditional Chinese medicine as an anti-inflammatory agent. In the current study, we attempted to investigate its renoprotective activity and underlying mechanisms in a rat model of membranous glomerulonephritis induced by cationic bovine serum albumin (c-BSA). Sprague-Dawley (SD) rats were divided into five groups, including normal control, model control, Mycophenolate Mofetil-treated group, and two skimming-treated groups (15 mg/kg and 30 mg/kg). Our research showed that treatment with skimmin significantly reduced the levels of blood urea nitrogen (BUN), urinary albumin excretion (UAE), and serum creatinine (Scr) as compared with model control after experimental induction of membranous glomerulonephritis (P<0.01). Moreover, glomerular hypercellularity, tubulointerstitial injury, and glomerular deposition of IgG were less intense after skimmin treatment. By immunochemistry analysis, we demonstrated that skimmin could significantly inhibit interleukin-1β(IL1β) and IL-6 expression (P<0.05), reduce the loss of nephrin and podocin, and suppress the infiltration of renal interstitium by CD3-positive T cell and CD20-positive B cell. These results suggest that treatment with skimmin can significantly improve renal function and suppress the IgG deposition as well as the development of glomerular lesions in a rat model of membranous glomerulonephritis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gary P. Brennan ◽  
Megan M. Garcia-Curran ◽  
Katelin P. Patterson ◽  
Renhao Luo ◽  
Tallie Z. Baram

Background and Rationale: Bi-directional neuronal-glial communication is a critical mediator of normal brain function and is disrupted in the epileptic brain. The potential role of aberrant microglia and astrocyte function during epileptogenesis is important because the mediators involved provide tangible targets for intervention and prevention of epilepsy. Glial activation is intrinsically involved in the generation of childhood febrile seizures (FS), and prolonged FS (febrile status epilepticus, FSE) antecede a proportion of adult temporal lobe epilepsy (TLE). Because TLE is often refractory to treatment and accompanied by significant memory and emotional difficulties, we probed the role of disruptions of glial-neuronal networks in the epileptogenesis that follows experimental FSE (eFSE).Methods: We performed a multi-pronged examination of neuronal-glia communication and the resulting activation of molecular signaling cascades in these cell types following eFSE in immature mice and rats. Specifically, we examined pathways involving cytokines, microRNAs, high mobility group B-1 (HMGB1) and the prostaglandin E2 signaling. We aimed to block epileptogenesis using network-specific interventions as well as via a global anti-inflammatory approach using dexamethasone.Results: (A) eFSE elicited a strong inflammatory response with rapid and sustained upregulation of pro-inflammatory cytokines. (B) Within minutes of the end of the eFSE, HMGB1 translocated from neuronal nuclei to dendrites, en route to the extracellular space and glial Toll-like receptors. Administration of an HMGB1 blocker to eFSE rat pups did not decrease expression of downstream inflammatory cascades and led to unacceptable side effects. (C) Prolonged seizure-like activity caused overall microRNA-124 (miR-124) levels to plunge in hippocampus and release of this microRNA from neurons via extra-cellular vesicles. (D) Within hours of eFSE, structural astrocyte and microglia activation was associated not only with cytokine production, but also with activation of the PGE2 cascade. However, administration of TG6-10-1, a blocker of the PGE2 receptor EP2 had little effect on spike-series provoked by eFSE. (E) In contrast to the failure of selective interventions, a 3-day treatment of eFSE–experiencing rat pups with the broad anti-inflammatory drug dexamethasone attenuated eFSE-provoked pro-epileptogenic EEG changes.Conclusions: eFSE, a provoker of TLE-like epilepsy in rodents leads to multiple and rapid disruptions of interconnected glial-neuronal networks, with a likely important role in epileptogenesis. The intricate, cell-specific and homeostatic interplays among these networks constitute a serious challenge to effective selective interventions that aim to prevent epilepsy. In contrast, a broad suppression of glial-neuronal dysfunction holds promise for mitigating FSE-induced hyperexcitability and epileptogenesis in experimental models and in humans.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Dan-Dan Mao ◽  
Wen-Yu Yang ◽  
Yan Li ◽  
Jian-Wei Lin ◽  
Shi-Yu Gao ◽  
...  

Objective. To investigate the effects of QKF on expression of amyloid-beta (Aβ), interleukin-1 beta (IL-1β), and glial fibrillary acidic protein (GFAP) using a rat model of AD.Materials and Methods. Fifty-six male Sprague-Dawley rats were randomly divided into seven groups (eight rats each): control group, sham-operated group, AD model group, groups of AD rats administered with low, medium, and high doses of QKF, and the donepezil group. AD was established by bilateral injection ofβ-amyloid (Aβ) 1–40 into the hippocampus. Two days after AD was established, drugs were administered by gavage. After 14 days of treatment, we used RT-PCR, Western blotting, and immunohistochemistry to measure the transcript expression and protein abundance of Aβ, IL-1β, and GFAP, and methenamine silver staining was used to detect amyloid protein particle deposition.Results. Compared to the control group, the rats from the AD model group showed significantly greater expression levels of Aβ, IL-1β, and GFAP. However, these differences in expression were abolished by treatment with QKF or donepezil.Conclusion. QKF possesses therapeutic potential against AD because it downregulated Aβ, IL-1β, and GFAP in the hippocampus of AD rats. Future studies should further examine the mechanisms through which QKF produces its effects and the consequences of long-term QKF administration.


2014 ◽  
Vol 5 (1) ◽  
pp. 90-96
Author(s):  
Irina Pavlovna Butkevich ◽  
Tatyana Nikolayevna Shimarayeva ◽  
Viktor Anatolyevich Mikhaylenko

Previously we revealed for the first time pain response exacerbation caused by inflammation in rats born to dams exposed to stress during pregnancy (prenatal stress). The present study is devoted to tinvestigation of prenatal stress effects on psychoemotional and tonic pain reactions in rat pups during the individual development period that is characterized with a dramatic reduction of the brain serotonin level. Effects of maternal buspirone before stress during pregnancy on functional indices of psychoemotional and tonic pain systems in the offspring were also investigated. Prenatal stress increased the number of pain patterns (flexing + shaking) during different phases of the time-course of formalin-induced pain in females and males to a greater extent in males. Prenatlly stressed rat pups of both sexes failed to show reliable changes in the index of psychoemotional behavior in the forced swim test. With the aim to decrease pain response exacerbation found in prenatally stressed offspring, pregnant dams were exposed to chronic injections of serotoninergic anxiolytic and antidepressant buspirone which is an agonist of 5-HT1A receptors; prenatal effect of buspirone on psychoemotional behavior in prenatally stressed rat pups was also evaluated. Maternal buspirone normalized pain behavior and decreased considerably the time of immobility, the index of depressive behavior in the forced swim test. The present results indicate analgesic and antidepressive effects of maternal buspirone in prenatally stressed 10-day old rat pups and demonstrate sexual dimorphism in effects of prenatal stress on the time-course of formalin-induced pain. Differences in effects of prenatal influences on pain respone during the interphase in males and females indicate earlier maturation of the descending serotonergic inhibitory system of afferent pain signals modulation in males than in females and demonstrate that 5-HT1A receptors are involved in this process.


2001 ◽  
Vol 73 (2) ◽  
pp. 279-287 ◽  
Author(s):  
W. Often ◽  
E. Kanitz ◽  
M. Tuchscherer ◽  
G. Nürnberg

AbstractStudies in rodents and primates strongly indicate that prenatal stress affects the survival, behaviour and physiology of the offspring. Stressful stimuli during gestation may have a direct or hormone mediated effect on the development of stress systems in the foetal organism, resulting in an altered coping during stressful situations. The present study was conducted to elucidate prenatal stress effects in domestic pigs on the responses of the hypothalamicpituitary- adrenocortical (HPA) axis and the sympatho-adrenomedullary (SAM) system as well as on morbidity, mortality and growth of the offspring. Pregnant sows were subjected to a restraint stress for five minutes daily during the last five weeks of gestation. Endocrine reactions of the piglets were tested at 3, 7, 21 and 35 days of age using an immobilization test and an ACTH challenge test. Prenatally stressed piglets showed lower basal plasma cortisol and increased corticosteroid binding globulin (CBG) concentrations at 3 days of age, indicating decreased free cortisol concentrations after birth. Cortisol levels after ACTH stimulation and catecholamine levels after immobilization were not affected by the stress treatment of the sows. Piglets from stressed sows tended to have lower noradrenaline : adrenaline ratios at three days of age compared with the control piglets. In addition, stressed sows tended to have lower litter weights after birth. The morbidity and mortality during the suckling period was higher in the prenatally stressed litters, as shown by a higher frequency of diseased and perished piglets per litter. We suppose that prenatal stress during late gestation in pigs alters the development of the HPA system and impairs the vitality of the offspring.


Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Fenglian He ◽  
Guanghui Zheng ◽  
Juntao Hu ◽  
Weiwei Ge ◽  
Xianfei Ji ◽  
...  

Introduction: Gasdermin D (GSDMD), a previously unknown protein, serves as a key effector in pyroptosis and its inhibition has protective effects during cerebral ischemia and reperfusion. Necrosulfonamide (NSA) specifically blocks the mixed lineage kinase domain-like pseudo kinase (MLKL), which directly binds to GSDMD preventing pyroptotic cell death and interleukin-1 (IL-1) release. In this study, we investigated the effects of NSA on survival and neurological function after cardiac arrest and resuscitation. Hypothesis: Administration of NSA following cardiopulmonary resuscitation (CPR) will improve survival and neurological function in a rat model of cardiac arrest. Methods: Twelve male Sprague-Dawley rats weighting between 450-550g were utilized. Ventricular fibrillation was induced and untreated for 6 min followed by defibrillation after 8 min of CPR. Animals were then randomized into two groups: NSA and control. NSA (10mg/kg) or vehicle was administered 5 minutes after restoration of spontaneous circulation (ROSC) by intraperitoneal injection. Duration of survival and neurological deficit scores were recorded at 24, 48, and 72 hours after ROSC. Results: All animals were resuscitated successfully. Duration of survival was significantly longer in the NSA group compared to control (p<0.05, Figure 1). The severity of post-resuscitation cerebral dysfunction was significantly reduced in the NSA group compared to control (p<0.05, Figure 2). Conclusion: Administration of NSA after ROSC improves post-resuscitation survival and neurological function in a rat model of cardiac arrest.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Pin-Kuei Fu ◽  
Chieh-Liang Wu ◽  
Tung-Hu Tsai ◽  
Ching-Liang Hsieh

Paeonol is an active component of Moutan Cortex Radicis and is widely used as an analgesic, antipyretic, and anti-inflammatory agent in traditional Chinese medicine. We wanted to determine the role of paeonol in treating adult respiratory distress syndrome (ARDS). We established an acute lung injury (ALI) model in Sprague-Dawley rats, which was similar to ARDS in humans, using intratracheal administration of lipopolysaccharide (LPS). The intraperitoneal administration of paeonol successfully reduced histopathological scores and attenuated myeloperoxidase-reactive cells as an index of polymorphonuclear neutrophils infiltration and also reduces inducible nitric oxide synthase expression in the lung tissue, at 16 h after LPS administration. In addition, paeonol reduced proinflammatory cytokines in bronchoalveolar lavage fluid, including tumor-necrosis factor-α, interleukin-1β, interleukin-6, and plasminogen-activated inhibition factor-1. These results indicated that paeonol successfully attenuates inflammatory and coagulation reactions to protect against ALI.


Author(s):  
Yamila Raquel Juárez ◽  
Sofía Quiroga ◽  
Andrés Prochnik ◽  
Miriam Wald ◽  
Mariana Lorena Tellechea ◽  
...  

Abstract Prenatal insults during fetal development result in increased likelihood of developing chronic disease. Obesity, the biggest risk factor for the development of metabolic disease, is affected by several genetic and environmental factors. High-fat diet (HFD) consumption is usually linked with the development of obesity. The main goal of this study was to analyze the impact of the exposure to a HFD in prenatally stressed animals. For this purpose, we subjected pregnant BALB/c mice to restraint stress for 2 h a day between gestational day (GD) 14 and GD 21. Prenatally stressed and control offspring of both sexes were postnatally exposed to a HFD for 24 weeks. We found that prenatal stress (PS) per se produced disturbances in males such as increased total blood cholesterol and triglycerides, with a decrease in mRNA expression of sirtuin-1. When these animals were fed a HFD, we observed a rise in glucose and insulin levels and an increase in visceral adipose tissue gene expression of leptin, resistin, and interleukin-1 beta. Although females proved to be more resilient to PS consequences, when they were fed a HFD, they showed significant metabolic impairment. In addition to the changes observed in males, females also presented an increase in body weight and adiposity and a rise in cholesterol levels.


2013 ◽  
Vol 280 (1753) ◽  
pp. 20122368 ◽  
Author(s):  
Floriane Guibert ◽  
Sophie Lumineau ◽  
Kurt Kotrschal ◽  
Erich Möstl ◽  
Marie-Annick Richard-Yris ◽  
...  

The prenatal environment is a source of phenotypic variability influencing the animal's characteristics. Prenatal stress affects not only the development of offspring, but also that of the following generation. Such effects have been best documented in mammals but can also be observed in birds, suggesting common processes across phylogenetic orders. We found previously that Japanese quail females stressed during laying produced offspring with higher fearfulness, probably related to modulation of testosterone levels in their eggs. Here, we evaluated long-term effects of prenatal stress by analysing reproductive traits of these F 1 offspring and, then, the development of their subsequent (F 2 ) offspring. The sexual behaviour of F 1 prenatally stressed (F1PS) males was impaired. F1PS females' eggs contained less yolk and more albumen, and higher yolk testosterone and progesterone levels than did F 1 prenatal control females. The fearfulness of F 2 prenatally stressed quail was greater than that of F 2 prenatal control quail. These F 2 behavioural differences paralleled those evidenced by their parents, suggesting trans-generational transmission of prenatal stress effects, probably mediated by egg compositions of F1PS females.


2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
WaiJiao Tang ◽  
Lu Zeng ◽  
JinJin Yin ◽  
YuFa Yao ◽  
LiJuan Feng ◽  
...  

Ethnopharmacological Relevance. The Hugan Qingzhi tablet (HQT) is a traditional Chinese medicine used for treating NAFLD (nonalcoholic fatty liver disease). The present study evaluated the anti-inflammatory effects of HQT in rats with NAFLD.Materials and Methods. HQT was administered daily to the NAFLD experimental groups. Biochemical markers, histopathological data, and oxidative stress/antioxidant biomarkers were determined. Proinflammatory cytokines interleukin-1β(IL-1β), tumor necrosis factorα(TNF-α), and interleukin-6 (IL-6) were detected by enzyme-linked immunoassay. Expressions of silent information regulator 1 (SIRT1) and acetylated-nuclear-factor kappaB-p65 (Ac-NF-κB-p65) were performed by western blotting.Results. At high and moderate doses, HQT was highly effective in decreasing serum alanine aminotransferase (P<0.01), aspartate aminotransferase (P<0.01), hepatic total cholesterol (P<0.01), triglycerides (P<0.01), and free fatty acid levels (P<0.01). Moreover, high and moderate doses of HQT reduced hepatic levels of the proinflammatory cytokines TNF-α(P<0.01), IL-1β(P<0.01), and IL-6 (P<0.01), enhanced SIRT1 expression, and depressed Ac-NF-κB-p65 expression at protein level.Conclusions. In our NAFLD rat model, HQT exerted substantial anti-inflammatory and antioxidant activities, possibly involving the regulation of SIRT1 and Ac-NF-κB-p65 expression.


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