Kinin B1 Receptor Antagonist BI113823 Reduces Acute Lung Injury*

Nasseri, Saeed; Gurusamy, Malarvizhi; Jung, Birgit; Lee, Dongwon; Khang, Gilson; Doods, Henri; Wu, Dongmei

doi:10.1097/ccm.0000000000001268

Cited by 27 publications

(34 citation statements)

References 33 publications

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“…Smoking is more frequent in males than females which is consistent with our study as males represented profoundly larger population of smokers than females (p < 0.001) (1,16). Male's smoking rate in a meta-analysis has shown to be 8.9 times higher than female's one (11). In some Arab countries, however, studies shed light on new facts as female university students are more interested in WP smoking than males in part due to their traditional beliefs (14).…”

Section: Discussionsupporting

confidence: 90%

“…Smoking, especially WP, can cause or accelerate the rate of pulmonary and cardiovascular complications as well as cancer and new anti-inflammatory drugs with higher specificity and lesser side effects are routinely investigated to elucidate their potential role in curing or decreasing the inflammatory responses in lungs, mediated via cigarette and other stimulatory factors (11,12). Majority of WP smoking mortalities have been reported from developing countries (13).…”

Section: Introductionmentioning

confidence: 99%

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Higher prevalence of water pipe compared to cigarette smoking among medical students in Southeast Iran

Miri-Moghaddam¹,

Sheikhi²,

Nasseri³

et al. 2019

Cent Eur J Public Health

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Objectives: Smoking of water pipe (WP) and cigarettes has recently turned into a major global health burden. The present study aimed at assessing WP and cigarette smoking among Zahedan University of Medical Sciences (ZUMS) students in Iran. Methods: A cross-sectional survey was conducted on 500 students in ZUMS (182 males, 318 females). The subjects were selected through randomized cluster sampling. Morgan's chart was applied to calculate the sample size; 96.6% of the attendees completed a questionnaire designed to address the aims of the study. Results: The mean age of the subjects was 21.2 ± 2.4 years. WP and cigarette smoker rates were at 31.2% and 15.2%, respectively. The age of smoking initiation ranged between 15 and 20 years. Friends played crucial roles in triggering the smoking in both groups of WP and cigarette smokers (78% and 54%, respectively). The main reasons for WP and cigarette smoking were entertainment followed by curiosity. Furthermore, males used more cigarette (26.5 vs. 8.7%) and WP (50.6 vs. 20.4%) than females. Among father and mother smokers, respectively, 54.2% and 60% of children were also WP smokers (p = 0.001). Also, 21.9% and 60% of children smoking cigarettes had father and mother smokers, respectively (p = 0.05). Conclusion: Tobacco use, especially for WP seems to be at alarming rates among medical students in Iran. It is highly recommended to control the progressive prevalence of WP smoking by governmental/academic preventive measures as educational and smoking cessation activities.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Higher prevalence of water pipe compared to cigarette smoking among medical students in Southeast Iran

Miri-Moghaddam¹,

Sheikhi²,

Nasseri³

et al. 2019

Cent Eur J Public Health

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“…Even if significant, the fall in MAP in this group before CLP and at 30 h may not be linked to sepsis, but to initial hypertension. The other organs showed a decrease in permeability in the R-954 group as reported in the literature [21,38,39]. Moreover, the significant decrease in extravasation of EBD in the lungs is partially explained by the action of B1R in the pulmonary vascular bed.…”

Section: Discussionsupporting

confidence: 76%

“…This was consistent with two recent studies that used a B1R antagonist, BI113823, administered orally. This molecule attenuated lung injuries secondary to LPS or CLP [20,21]. In another model of acute lung injury caused by lipopolysaccharide inhalation, R-954 counteracts the role of B1R and prevented the airway hyperreactivity, the increased cellular infiltration and protein content in the bronchoalveolar lavage fluid, and inhibited the expression of cytokines/chemokines [22].…”

Section: Discussionmentioning

confidence: 98%

Kinin B1 receptor: a potential therapeutic target in sepsis-induced vascular hyperpermeability

et al. 2020

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Background: In sepsis, the endothelial barrier becomes incompetent, with the leaking of plasma into interstitial tissues. VE-cadherin, an adherens junction protein, is the gatekeeper of endothelial cohesion. Kinins, released during sepsis, induce vascular leakage and vasodilation. They act via two G-protein coupled receptors: B1 (B1R) and B2 (B2R). B1R is inducible in the presence of pro-inflammatory cytokines, endotoxins or after tissue injury. It acts at a later stage of sepsis and elicits a sustained inflammatory response. The aim of our study was to investigate the relationships between B1R and VE-cadherin destabilization in vivo in a later phase of sepsis. Methods: Experimental, prospective study in a university research laboratory. We used a polymicrobial model of septic shock by cecal ligation and puncture in C57BL6 male mice or C57BL6 male mice that received a specific B1R antagonist (R-954). We studied the influence of B1R on sepsis-induced vascular permeability 30 h after surgery for several organs, and VE-cadherin expression in the lung and kidneys by injecting R-954 just before surgery. The 96-h survival was determined in mice without treatment or in animals receiving R-954 as a "prophylactic" regimen (a subcutaneous injection of 200 µg/kg, prior to CLP and 24 h after CLP), or as a "curative" regimen (injection of 100 µg/kg at H6, H24 and H48 post-surgery). Results: B1R inactivation helps to maintain MAP above 65 mmHg but induces different permeability profiles depending on whether or not organ perfusion is autoregulated. In our model, VE-cadherin was destabilized in vivo during septic shock. At a late stage of sepsis, the B1R blockade reduced the VE-cadherin disruption by limiting eNOS activation. The survival rate for mice that received R-954 after sepsis induction was higher than in animals that received an antagonist as a prophylactic treatment. Conclusions: B1R antagonizing reduced mortality in our model of murine septic shock by limiting the vascular permeability induced by VE-cadherin destabilization through maintenance of the macrohemodynamics, consequently limiting organ dysfunctions.

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“…Acute lung injury is characterized by lung edema, endothelial and epithelial injury and an excessive infiltration of neutrophils into the interstitium and bronchoalveolar space ( 59 ). Neutrophils play a key role in the progression of ALI ( 60 ).…”

Section: Purinergic Signaling Shapes Neutrophil Immunity In Pathologimentioning

confidence: 99%

Purinergic Regulation of Neutrophil Function

Wang

Chen

2018

Front. Immunol.

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Purinergic signaling, which utilizes nucleotides (particularly ATP) and adenosine as transmitter molecules, plays an essential role in immune system. In the extracellular compartment, ATP predominantly functions as a pro-inflammatory molecule through activation of P2 receptors, whereas adenosine mostly functions as an anti-inflammatory molecule through activation of P1 receptors. Neutrophils are the most abundant immune cells in circulation and have emerged as an important component in orchestrating a complex series of events during inflammation. However, because of the destructive nature of neutrophil-derived inflammatory agents, neutrophil activation is fine-tuned, and purinergic signaling is intimately involved in this process. Indeed, shifting the balance between P2 and P1 signaling is critical for neutrophils to appropriately exert their immunologic activity. Here, we review the role of purinergic signaling in regulating neutrophil function, and discuss the potential of targeting purinergic signaling for the treatment of neutrophil-associated infectious and inflammatory diseases.

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Kinin B1 Receptor Antagonist BI113823 Reduces Acute Lung Injury*

Abstract: Administration of B1 receptor antagonist BI113823 significantly reduced endotoxin-induced direct lung injury and also reduced sepsis-induced lung inflammatory response. Most importantly, BI113823 improved survival following severe polymicrobial sepsis.

Cited by 27 publications

References 33 publications

Higher prevalence of water pipe compared to cigarette smoking among medical students in Southeast Iran

Higher prevalence of water pipe compared to cigarette smoking among medical students in Southeast Iran

Kinin B1 receptor: a potential therapeutic target in sepsis-induced vascular hyperpermeability

Purinergic Regulation of Neutrophil Function

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