scholarly journals Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway

2021 ◽  
Vol 22 (12) ◽  
pp. 6471
Author(s):  
Ramona D’Amico ◽  
Roberta Fusco ◽  
Rosalba Siracusa ◽  
Daniela Impellizzeri ◽  
Alessio Filippo Peritore ◽  
...  
Keyword(s):  
Microglial Activation ◽  
Purinergic Receptor ◽  
Male Rats ◽  
Inflammasome Activation ◽  
Sprague Dawley ◽  
Behavioral Deficits ◽  
Positive Effects ◽  
Nlrp3 Inflammasome Activation ◽  
Purinergic P2x7 Receptor

Fibromyalgia is a chronic condition characterized by persistent widespread pain that significantly reduces quality of life in patients. The purinergic P2X7 receptor (P2X7R) seems to be involved in different pain states and neuroinflammation. The purpose of this study is to investigate the positive effects of P2X7R inhibition by the antagonist Brilliant Blue G (BBG) in a rat model of reserpine-induced fibromyalgia. Sprague–Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days. Later, animals were administered BBG (50 mg/kg) intraperitoneally for seven days. Reserpine injections induced a significant increase in pain pro-inflammatory mediators as well as a significant increase in neuroinflammation. Chronic pain, in turn, led to depressive-like symptoms and reduced neurogenesis. Blockage of P2X7R by BBG administrations is able to attenuate the behavioral deficits, pain mediators and microglial activation induced by reserpine injection. Additionally, BBG prevents NLRP3 inflammasome activation and consequently the release of active interleukin (IL)-1 and IL-18, involved in the activation of nociceptors. In conclusion, these results suggest that inhibition of P2X7R should be further investigated to develop a potential approach for the management of fibromyalgia.

scholarly journals Effects of Shizhifang on NLRP3 Inflammasome Activation and Renal Tubular Injury in Hyperuricemic Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-19 ◽  
Author(s):  
Yansheng Wu ◽  
Fei He ◽  
Yingqiao Li ◽  
Huiling Wang ◽  
Liqiang Shi ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Factors ◽  
Control Group ◽  
Inflammasome Activation ◽  
Tubular Injury ◽  
Sprague Dawley ◽  
Positive Effects ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
Renal Tubular

Objective. Uric acid (UA) activates the NLRP3-ASC-caspase-1 axis and triggers cascade inflammatory that leads to hyperuricemic nephropathy and hyperuricemia-induced renal tubular injury. The original study aims to verify the positive effects of the traditional Chinese medicinal formula Shizhifang (SZF) on ameliorating the hyperuricemia, tubular injury, and inflammasome infiltration in the kidneys of hyperuricemic lab rats. Method. Twenty-eight male Sprague-Dawley rats were divided into four groups: control group, oxonic acid potassium (OA) model group, OA + SZF group, and OA + Allopurinol group. We evaluated the mediating effects of SZF on renal mitochondrial reactive oxygen species (ROS) and oxidative stress (OS) products, protein expression of NLRP3-ASC-caspase-1 axis, and downstream inflammatory factors IL-1β and IL-18 after 7 weeks of animals feeding. Result. SZF alleviated OA-induced hyperuricemia and inhibited OS in hyperuricemic rats (P<0.05). SZF effectively suppressed the expression of gene and protein of the NLRP3-ASC-caspase-1 axis through accommodating the ROS-TXNIP pathway (P<0.05). Conclusion. Our data suggest that SZF alleviates renal tubular injury and inflammation infiltration by inhibiting NLRP3 inflammasome activation triggered by mitochondrial ROS in the kidneys of hyperuricemic lab rats.

scholarly journals Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/ NLRP3 signaling in rat

2020 ◽  
Author(s):  
Hetao Bian ◽  
Gaohua Wang ◽  
Junjie Huang ◽  
Liang Liang ◽  
Yage Zheng ◽  
...  
Keyword(s):  
Sickness Behavior ◽  
Ros Generation ◽  
Inflammasome Activation ◽  
Preventive Effect ◽  
Sprague Dawley ◽  
Behavioral Deficits ◽  
Dihydrolipoic Acid ◽  
Nlrp3 Inflammasome Activation ◽  
Sprague Dawley Rats ◽  
Related Proteins

Abstract Background: Recently, depression has been identified as prevalent and severe mental disorder. However, the mechanisms underlying the depression risk remain elusive. The neuroinflammation and NLRP3 inflammasome activation are known to be involved in the pathology of depression. Dihydrolipoic acid (DHLA) has been reported as a strong antioxidant and exhibits anti-inflammatory properties in various diseases, albeit the direct relevance between DHLA and depression is yet unknown. The present study aimed to investigate the preventive effect and potential mechanism of DHLA in the Lipopolysaccharide (LPS)-induced sickness behavior in rats. Methods: Adult male Sprague–Dawley rats were utilized. LPS and DHLA were injected intraperitoneally every 2 days and daily, respectively. Fluoxetine (Flu) was injected intraperitoneally daily. PD98059, an inhibitor of ERK, was injected intraperitoneally one hour before DHLA injection daily. Small interfering ribonucleic acid (siRNA) for nuclear factor erythroid 2-like (Nrf2) was injected into the bilateral hippocampus 14 days before the DHLA injection. Depression-like behavior tests were performed. Western blot and immunofluorescence staining detected the ERK/Nrf2/HO-1/ROS/NLRP3 pathway-related proteins.Results: The DHLA and fluoxetine treatment exerted preventive effects in LPS-induced sickness behavior rats. The DHLA treatment increased the expression of ERK, Nrf2, and HO-1 but decreased the ROS generation levels and reduced the expression of NLRP3, caspase-1, and IL-1b in LPS-induced sickness behavior rats. PD98059 abolished the effects of DHLA on preventive effect as well as the levels of Nrf2 and HO-1 proteins. Similarly, Nrf2 siRNA reversed the preventive effect of DHLA administration via the decreased expression of HO-1.Conclusions: These findings suggested that DHLA exerted a preventive effect via ERK/Nrf2/HO-1/ROS/NLRP3 pathway in LPS-induced sickness behavior rats. Thus, DHLA may serve as a potential therapeutic strategy for depression.

scholarly journals Electroacupuncture Stimulation Regulates Adipose Lipolysis via Catecholamine Signaling Mediated by NLRP3 Suppression in Obese Rats

2022 ◽  
Vol 12 ◽  
Author(s):  
Mengjiang Lu ◽  
Ziwei Yu ◽  
Qian Li ◽  
Meirong Gong ◽  
Li An ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Therapeutic Potential ◽  
Monoamine Oxidase A ◽  
Male Rats ◽  
Inflammatory Factors ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Sprague Dawley ◽  
Nlrp3 Inflammasome Activation ◽  
Visceral Adipose

Chronic low-grade inflammation of visceral adipose tissue can cause obesity-associated insulin resistance, leading to metabolic syndrome. However, anti-inflammatory drugs and those for obesity management can lead to serious side effects such as abnormal heart rate and blood pressure. Consequently, this study aimed to explore the therapeutic potential of electroacupuncture stimulation (ES) for obesity and associated chronic inflammation. Sprague-Dawley male rats were fed a high-fat diet (HFD) for ten weeks to build an obesity model, and half of the diet-induced obesity (DIO) rats were received ES. The levels of inflammatory factors were detected by ELISA and qPCR analysis. The nerve-associated macrophages were marked with immunofluorescence staining. The molecular mechanism of NLRP3 inflammasome in ES was determined by the NLRP3 inflammasome activation model. Compared to HDF rats, ES showed decreased body weight and chronic inflammatory damage. Specifically, this occurred via a decrease in monoamine oxidase-A (MAOA) expression, which suppressed noradrenaline degradation. MAOA is expressed in nerve-associated macrophages (NAMs), and ES attenuated NAMs by suppressing the NLRP3 inflammasome. The NLRP3 agonist blocked the noradrenaline degradation-reducing effect of ES, and an increase in lipolysis via the inhibition of the NLRP3 inflammasome attenuated NAMs. Thus, our findings suggest that ES induced lipolysis via activation of the NLRP3 inflammasome in nerve-associated macrophages (NAMs), independently of sympathetic nervous system activity.

scholarly journals Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/ NLRP3 signaling in rat

2020 ◽  
Author(s):  
Hetao Bian ◽  
Gaohua Wang ◽  
Junjie Huang ◽  
Liang Liang ◽  
Yage Zheng ◽  
...  
Keyword(s):  
Ros Generation ◽  
Inflammasome Activation ◽  
Preventive Effect ◽  
Sprague Dawley ◽  
Behavioral Deficits ◽  
Dihydrolipoic Acid ◽  
Nlrp3 Inflammasome Activation ◽  
Sprague Dawley Rats ◽  
Sickness Behaviors ◽  
Related Proteins

Abstract Background: Recently, depression has been identified as prevalent and severe mental disorder. However, the mechanisms underlying the depression risk remain elusive. The neuroinflammation and NLRP3 inflammasome activation are known to be involved in the pathology of depression. Dihydrolipoic acid (DHLA) has been reported as a strong antioxidant and exhibits anti-inflammatory properties in various diseases, albeit the direct relevance between DHLA and depression is yet unknown. The present study aimed to investigate the preventive effect and potential mechanism of DHLA in the Lipopolysaccharide (LPS)-induced sickness behaviors in rats. Methods: Adult male Sprague–Dawley rats were utilized. LPS and DHLA were injected intraperitoneally every 2 days and daily, respectively. Fluoxetine (Flu) was injected intraperitoneally daily. PD98059, an inhibitor of ERK, was injected intraperitoneally one hour before DHLA injection daily. Small interfering ribonucleic acid (siRNA) for nuclear factor erythroid 2-like (Nrf2) was injected into the bilateral hippocampus 14 days before the DHLA injection. Depression-like behavior tests were performed. Western blot and immunofluorescence staining detected the ERK/Nrf2/HO-1/ROS/NLRP3 pathway-related proteins. Results: The DHLA and fluoxetine treatment exerted preventive effects in LPS-induced sickness behaviors rats. The DHLA treatment increased the expression of ERK, Nrf2, and HO-1 but decreased the ROS generation levels and reduced the expression of NLRP3, caspase-1, and IL-1b in LPS-induced sickness behaviors rats. PD98059 abolished the effects of DHLA on preventive effect as well as the levels of Nrf2 and HO-1 proteins. Similarly, Nrf2 siRNA reversed the preventive effect of DHLA administration via the decreased expression of HO-1. Conclusions: These findings suggested that DHLA exerted a preventive effect via ERK/Nrf2/HO-1/ROS/NLRP3 pathway in LPS-induced sickness behaviors rats. Thus, DHLA may serve as a potential therapeutic strategy for depression.

scholarly journals Dihydrolipoic acid protects against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-1/ NLRP3 signaling in rat

2020 ◽  
Author(s):  
Hetao Bian ◽  
Gaohua Wang ◽  
Junjie Huang ◽  
Liang Liang ◽  
Yage Zheng ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Ros Generation ◽  
Inflammasome Activation ◽  
Sprague Dawley ◽  
Behavioral Deficits ◽  
Dihydrolipoic Acid ◽  
Depression Risk ◽  
Nlrp3 Inflammasome Activation ◽  
Sprague Dawley Rats ◽  
Related Proteins

Abstract Background: Recently, depression has been identified as prevalent and severe mental disorder. However, the mechanisms underlying the depression risk remain elusive. The neuroinflammation and NLRP3 inflammasome activation are known to be involved in the pathology of depression. Dihydrolipoic acid (DHLA) has been reported as a strong antioxidant and exhibits anti-inflammatory properties in various diseases, albeit the direct relevance between DHLA and depression is yet unknown. The present study aimed to investigate the anti-depressant effects and potential mechanism of DHLA in the Lipopolysaccharide (LPS)-induced depression animal model. Methods: Adult male Sprague–Dawley rats were utilized. LPS and DHLA were injected intraperitoneally every 2 days and daily, respectively. Fluoxetine(Flu) was injected intraperitoneally daily. PD98059, an inhibitor of ERK, was injected intraperitoneally one hour before DHLA injection daily. Small interfering ribonucleic acid (siRNA) for nuclear factor erythroid 2-like (Nrf2) was injected into the bilateral hippocampus 14 days before the DHLA injection. Depression-like behavior tests were performed. Western blot and immunofluorescence staining detected the ERK/Nrf2/HO-1/ROS/NLRP3 pathway-related proteins. Results: The DHLA and fluoxetine treatment exerted anti-depressant effects in LPS-induced depression rats. The DHLA treatment increased the expression of ERK, Nrf2, and HO-1 but decreased the ROS generation levels and reduced the expression of NLRP3, caspase-1, and IL-1b in LPS-induced depression rats. PD98059 abolished the effects of DHLA on anti-depression as well as the levels of Nrf2 and HO-1 proteins. Similarly, Nrf2 siRNA reversed the anti-depressant effect of DHLA administration via the decreased expression of HO-1. Conclusions: These findings suggested that DHLA exerted anti-depressant-like effects via ERK/Nrf2/HO-1/ROS/NLRP3 pathway in LPS-induced depression rats. Thus, DHLA may serve as a potential therapeutic strategy for depression.

scholarly journals The Role of NLRP3 Inflammasome in Cerebrovascular Diseases Pathology and Possible Therapeutic Targets

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110181
Author(s):  
Rongrong Bai ◽  
Yue Lang ◽  
Jie Shao ◽  
Yu Deng ◽  
Reyisha Refuhati ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Purinergic Receptor ◽  
Cerebrovascular Diseases ◽  
New Drugs ◽  
Signalling Pathways ◽  
Inflammasome Activation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nlrp3 Inflammasome Activation ◽  
Pathological Mechanism

Cerebrovascular diseases are pathological conditions involving impaired blood flow in the brain, primarily including ischaemic stroke, intracranial haemorrhage, and subarachnoid haemorrhage. The nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3) inflammasome is a protein complex and a vital component of the immune system. Emerging evidence has indicated that the NLRP3 inflammasome plays an important role in cerebrovascular diseases. The function of the NLRP3 inflammasome in the pathogenesis of cerebrovascular diseases remains an interesting field of research. In this review, we first summarised the pathological mechanism of cerebrovascular diseases and the pathological mechanism of the NLRP3 inflammasome in aggravating atherosclerosis and cerebrovascular diseases. Second, we outlined signalling pathways through which the NLRP3 inflammasome participates in aggravating or mitigating cerebrovascular diseases. Reactive oxygen species (ROS)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), ROS/thioredoxin-interacting protein (TXNIP) and purinergic receptor-7 (P2X7R) signalling pathways can activate the NLRP3 inflammasome; activation of the NLRP3 inflammasome can aggravate cerebrovascular diseases by mediating apoptosis and pyroptosis. Autophagy/mitochondrial autophagy, nuclear factor E2-related factor-2 (Nrf2), interferon (IFN)-β, sirtuin (SIRT), and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) reportedly alleviate cerebrovascular diseases by inhibiting NLRP3 inflammasome activation. Finally, we explored specific inhibitors of the NLRP3 inflammasome based on the two-step activation of the NLRP3 inflammasome, which can be developed as new drugs to treat cerebrovascular diseases.

scholarly journals Thymoquinone enhances sperm DNA integrity in nicotineinduced infertile male rats

2021 ◽  
Vol 18 (6) ◽  
pp. 1219-1225
Author(s):  
Farah Dayana Rosli ◽  
Noor Hashida Hashim ◽  
Yusmin Mohd Yusuf ◽  
Khairul Osman ◽  
Siti Fatimah Ibrahim ◽  
...  
Keyword(s):  
Normal Saline ◽  
Quantitative Polymerase Chain Reaction ◽  
Male Rats ◽  
Control Group ◽  
Dna Integrity ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Sperm Dna ◽  
Potential Benefits

Purpose: To assess the effects of thymoquinone (TQ) on the integrity of sperm DNA in nicotineinduced sperm impairment in rats. Methods: Adult male Sprague Dawley rats were randomized into four equal groups: control group received normal saline orally for 60 days; nicotine group was subcutaneously injected with 5 mg/kg/day nicotine for 30 days and then given normal saline for the next 30 days; TQ group was given normal saline for 30 days followed by TQ at 5 mg/kg/day for 30 days; and nicotine-TQ group received 5 mg/kg of nicotine for 30 days and 5mg/kg of TQ for another 30 days. Sperm DNA breakages were evaluated using Comet assay. The expression levels of protamine 1 (PT1) and transition nuclear protein 2 (Tnp2) genes which are essential for the proper compaction of the sperm DNA were analyzed by quantitative polymerase chain reaction (qPCR). Results: Thymoquinone significantly decreased DNA fragmentation in the sperm of nicotine-treated rats. However, there was no change in PT1 gene expression. Tnp2 was downregulated in the nicotine group and slightly upregulated in nicotine-TQ group (p < 0.05). Conclusion: The results demonstrate the potential benefits of TQ in improving sperm DNA quality of nicotine-induced male infertility.

FTY720 Inhibits MPP+-Induced Microglial Activation by Affecting NLRP3 Inflammasome Activation

2019 ◽  
Vol 14 (3) ◽  
pp. 478-492 ◽  
Author(s):  
Shu Yao ◽  
Longjun Li ◽  
Xin Sun ◽  
Jun Hua ◽  
Keqi Zhang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Microglial Activation ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation

scholarly journals Activation of purinergic receptors (P2) in the renal medulla promotes endothelin-dependent natriuresis in male rats

2016 ◽  
Vol 311 (2) ◽  
pp. F260-F267 ◽  
Author(s):  
Eman Y. Gohar ◽  
Joshua S. Speed ◽  
Malgorzata Kasztan ◽  
Chunhua Jin ◽  
David M. Pollock
Keyword(s):  
Mrna Expression ◽  
Purinergic Receptor ◽  
Purinergic Signaling ◽  
Renal Medulla ◽  
P2 Receptors ◽  
Male Rats ◽  
Urine Collection ◽  
Sprague Dawley ◽  
Signaling Systems

Renal endothelin-1 (ET-1) and purinergic signaling systems regulate Na+ reabsorption in the renal medulla. A link between the renal ET-1 and purinergic systems was demonstrated in vitro, however, the in vivo interaction between these systems has not been defined. To test whether renal medullary activation of purinergic (P2) receptors promotes ET-dependent natriuresis, we determined the effect of increased medullary NaCl loading on Na+ excretion and inner medullary ET-1 mRNA expression in anesthetized adult male Sprague-Dawley rats in the presence and absence of purinergic receptor antagonism. Isosmotic saline (NaCl; 284 mosmol/kgH2O) was infused into the medullary interstitium (500 μl/h) during a 30-min baseline urine collection period, followed by isosmotic or hyperosmotic saline (1,800 mosmol/kgH2O) for two further 30-min urine collection periods. Na+ excretion was significantly increased during intramedullary infusion of hyperosmotic saline. Compared with isosmotic saline, hyperosmotic saline infused into the renal medulla caused significant increases in inner medullary ET-1 mRNA expression. Renal intramedullary infusion of the P2 receptor antagonist suramin inhibited the increase in Na+ excretion and inner medullary ET-1 mRNA expression induced by NaCl loading in the renal medulla. Activation of medullary P2Y2/4 receptors by infusion of UTP increased urinary Na+ excretion. Combined ETA and ETB receptor blockade abolished the natriuretic response to intramedullary infusion of UTP. These data demonstrate that activation of medullary P2 receptors promotes ET-dependent natriuresis in male rats, suggesting that the renal ET-1 and purinergic signaling systems interact to efficiently facilitate excretion of a NaCl load.

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