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


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



01 February 2023 : Editorial  

Editorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.939580

Med Sci Monit 2023; 29:e939580


19 January 2023 : Clinical Research  

Evaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...

Med Sci Monit In Press; DOI: 10.12659/MSM.938892  

27 December 2022 : Clinical Research  

Effect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...

Med Sci Monit 2022; 28:e938926

10 December 2022 : Clinical Research  

Retrospective Study to Identify Risk Factors for Severe Disease and Mortality Using the Modified Early Warn...

Med Sci Monit 2022; 28:e938647

In Press

03 Feb 2023 : Clinical Research  

Treatment of Gingival Recession Defects with Pouch and Tunnel Technique Using Connective Tissue Graft and L...

Med Sci Monit In Press; DOI: 10.12659/MSM.938865  

02 Feb 2023 : Clinical Research  

Online Questionnaire-Based Study to Evaluate the Attitudes and Use of Rubber Dental Dams by Saudi Dental Pr...

Med Sci Monit In Press; DOI: 10.12659/MSM.938672  

02 Feb 2023 : Database Analysis  

Prognostic-Related Biomarkers in Pancreatic Ductal Adenocarcinoma Correlating with Immune Infiltrates Based...

Med Sci Monit In Press; DOI: 10.12659/MSM.938785  

01 Feb 2023 : Clinical Research  

Comparison of 3 Enzyme-Linked Immunoassay Methods to Evaluate Serum Concentrations of Infliximab and Antibo...

Med Sci Monit In Press; DOI: 10.12659/MSM.939084  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

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

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