Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

20 August 2019 : Animal Research  

Carbon Monoxide Attenuates Lipopolysaccharides (LPS)-Induced Acute Lung Injury in Neonatal Rats via Downregulation of Cx43 to Reduce Necroptosis

Wanwei Li1BDE, Fang Wu2DF, Long Chen3C, Qian Li1BC, Juan Ma1BF, Mengchun Li1B, Yuan Shi13AE*

DOI: 10.12659/MSM.917751

Med Sci Monit 2019; 25:6255-6263

Abstract

BACKGROUND: Acute lung injury (ALI) is one of major causes of death in newborns, making it urgent to improve therapy. Administration of low dose carbon monoxide (CO) plays a protective role in ALI but the mechanisms are not fully understood. This study was designed to test the therapeutic effect of monoxide-releasing molecule 3 (MORM3) in lipopolysaccharide (LPS) induced neonatal ALI and the possibly associated molecular mechanisms.

MATERIAL AND METHODS: For this study, 3- to 8-day old Newborn Sprague-Dawley rats were subjected to intraperitoneal injection of 3 mg/kg LPS to induce ALI. Then animals received intraperitoneal injection of carbon monoxide-releasing molecules 3 (CORM3) (8 mg/kg) or inactive CORM3 (iCORM3) for 7 consecutive days. Lung tissues were collected for histological examination and total cell counts and protein content in bronchoalveolar lavage fluid (BALF) were measured. Expression of Cx43 and necroptosis-related markers were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot.

RESULTS: LPS exposure induced significant lung injury indicated by histological damage, increased lung wet/dry weight ratio (W/D) and increased total cell counts and protein concentration in BALF. These changes were significantly ameliorated by administration of CORM3 but not iCORM3. LPS also increased necroptosis-related markers RIP1, RIP3, and MLKL and their elevation was blocked by CORM3. CORM3 administration ameliorated LPS induced elevation of Cx43 expression and adenoviral overexpression of Cx43 abolished lung protective effect of CORM3. CORM3 administration attenuated LPS induced activation of extracellular-signal-regulated kinase (ERK) and its protection against necroptosis was abolished by ERK inhibitor U0126.

CONCLUSIONS: CORM3 attenuates LPS-Induced ALI in neonatal rats and its lung protective effect might be through downregulation of Cx43 to attenuate ERK signaling and ameliorate necroptosis, suggesting CORM3 as a potential therapeutic drug for ALI in neonates.

Keywords: acute lung injury, Carbon Monoxide, Animals, Newborn, Bronchoalveolar Lavage Fluid, Connexin 43, Down-Regulation, Extracellular Signal-Regulated MAP Kinases, Lipopolysaccharides, Lung, Necroptosis

Add Comment 0 Comments

Editorial

01 March 2024 : Editorial  

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-Thalassemia

Dinah V. Parums

DOI: 10.12659/MSM.944204

Med Sci Monit 2024; 30:e944204

0:00

In Press

18 Mar 2024 : Clinical Research  

Sexual Dysfunction in Women After Tibial Fracture: A Retrospective Comparative Study

Med Sci Monit In Press; DOI: 10.12659/MSM.944136  

0:00

21 Feb 2024 : Clinical Research  

Potential Value of HSP90α in Prognosis of Triple-Negative Breast Cancer

Med Sci Monit In Press; DOI: 10.12659/MSM.943049  

22 Feb 2024 : Review article  

Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943168  

23 Feb 2024 : Clinical Research  

A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943732  

Most Viewed Current Articles

16 May 2023 : Clinical Research  

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

17 Jan 2024 : Review article  

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750