The NACHT, LRR and PYD Domains-Containing protein 3 (NLRP3) Inflammasome Mediates Inflammation and Voiding Dysfunction in a Lipopolysaccharide-Induced Rat Model of Cystitis

Baicalein has been shown to have chondroprotective potential in vitro. However, its effect on disease modification in osteoarthritis (OA) is largely unknown. The present study is aimed at determining whether baicalein could slow the progression of OA and inhibit OA-related inflammation in a rat model of destabilization of the medial meniscus (DMM) and the underlying mechanisms. The rats subjected to DMM surgery were treated with baicalein (0.8, 1.6, and 3.2 μg/L, 50 μL, once a week) by intra-articular injection for 6 weeks. Dexamethasone (0.4 mg/mL, 50 μL, once a week) was used as a positive control. Histologic grading of cartilage degeneration was performed using the Osteoarthritis Research Society International (OARSI) recommended grading system (on a scale of 0-6). The expression levels of molecules associated with cartilage homeostasis and inflammatory cytokines were analyzed; moreover, the NLRP3 inflammasome activation and cartilage oxidative stress-associated molecules were determined. Baicalein treatment reduced the OARSI score and slowed OA disease progression in a dose-dependent manner within a certain range. Compared with DMM rats, intra-articular injection of baicalein led to (1) reduced levels of inflammatory mediates such as IL-1β and TNF-α, (2) reduced immunochemical staining of MMP-13 and ADAMTS-5, (3) suppressed immunochemical staining loss of type II collagen, (4) reduced expression of cartilage degradation markers including CTX-II and COMP in urine, and (5) inhibited NLRP3 inflammasome activation rather than regulated expression of SOD, GSH, and MDA. In contrast to the administration of baicalein, dexamethasone injection showed similar effects to slow OA progression, while dexamethasone inhibited NLRP3 inflammasome partly through decreasing levels of SOD, GSH, and MDA. This study indicated that baicalein may have the potential for OA prevention and exerts anti-inflammatory effects partly via suppressing NLRP3 inflammasome activation without affecting oxidative stress-associated molecules, and inhibition of cartilage catabolism enzymes in an OA rat model.

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428: A Type II Diabetic Rat Model of Diabetic Voiding Dysfunction

The Journal of Urology ◽

10.1016/s0022-5347(18)30681-5 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 143-143

Author(s):

Surat Phonsombat ◽

Kavirach Tantiwongse ◽

Thomas M. Fandel ◽

Guifang Wang ◽

Guiting Lin ◽

...

Keyword(s):

Rat Model ◽

Voiding Dysfunction ◽

Diabetic Rat ◽

Type Ii ◽

Diabetic Rat Model

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TRPV4 receptor activation in the bladder improves voiding dysfunction in a rat model of detrusor underactivity induced by pelvic nerve crush injury

10.26226/morressier.59b63e3fd462b80292389280 ◽

2017 ◽

Author(s):

Eiichiro Takaoka

Keyword(s):

Rat Model ◽

Voiding Dysfunction ◽

Receptor Activation ◽

Crush Injury ◽

Detrusor Underactivity ◽

Pelvic Nerve ◽

Nerve Crush ◽

Nerve Crush Injury

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URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion

Journal of Neuroinflammation ◽

10.1186/s12974-019-1668-0 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 8

Author(s):

Shao-Hua Su ◽

Yi-Fang Wu ◽

Qi Lin ◽

Da-Peng Wang ◽

Jian Hai

Keyword(s):

Proinflammatory Cytokines ◽

Rat Model ◽

Nlrp3 Inflammasome ◽

Therapeutic Potential ◽

Artery Occlusion ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Ultrastructural Changes ◽

Inflammasome Activation ◽

Related Proteins

Abstract Background Previous studies reported that URB597 (URB) had therapeutic potential for treating chronic cerebral hypoperfusion (CCH)-induced neuroinflammation and autophagy dysfunction. However, the interaction mechanisms underlying the CCH-induced abnormal excessive autophagy and neuroinflammation remain unknown. In this study, we investigated the roles of impaired autophagy in nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 inflammasome activation in the rat hippocampus and the underlying mechanisms under the condition of induced CCH as well as the effect of URB treatment. Methods The CCH rat model was established by bilateral common carotid artery occlusion (BCCAo), and rats were randomly divided into 11 groups as follows: (1) sham-operated, (2) BCCAo; (3) BCCAo+autophagy inhibitor 3-methyladenine (3-MA), (4) BCCAo+lysosome inhibitor chloroquine (CQ), (5) BCCAo+microglial activation inhibitor minocycline, (6) BCCAo+ROS scavenger N-acetylcysteine (NAC), (7) BCCAo+URB, (8) BCCAo+URB+3-MA, (9) BCCAo+URB+CQ, (10) BCCAo+URB+minocycline, (11) BCCAo+URB+NAC. The cell localizations of LC3, p62, LAMP1, TOM20 and NLRP3 were assessed by immunofluorescence staining. The levels of autophagy-related proteins (LC3, p62, LAMP1, BNIP3 and parkin), NLRP3 inflammasome-related proteins (NLRP3, CASP1 and IL-1β), microglial marker (OX-42) and proinflammatory cytokines (iNOS and COX-2) were evaluated by western blotting, and proinflammatory cytokines (IL-1β and TNF-a) were determined by ELISA. Reactive oxygen species (ROS) were assessed by dihydroethidium staining. The mitochondrial ultrastructural changes were examined by electron microscopy. Results CCH induced microglial overactivation and ROS accumulation, promoting the activation of the NLRP3 inflammasome and the release of IL-1β. Blocked autophagy and mitophagy flux enhanced the activation of the NLRP3-CASP1 inflammasome pathway. However, URB alleviated impaired autophagy and mitophagy by decreasing mitochondrial ROS and microglial overactivation as well as restoring lysosomal function, which would further inhibit the activation of the NLRP3-CASP1 inflammasome pathway. Conclusion These findings extended previous studies indicating the function of URB in the mitigation of chronic ischemic injury of the brain.

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