20 August 2019 : Animal Research
Carbon Monoxide Attenuates Lipopolysaccharides (LPS)-Induced Acute Lung Injury in Neonatal Rats via Downregulation of Cx43 to Reduce NecroptosisWanwei Li1BDE, Fang Wu2DF, Long Chen3C, Qian Li1BC, Juan Ma1BF, Mengchun Li1B, Yuan Shi13AE*
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 : EditorialEditorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread
Med Sci Monit 2023; 29:e939580
19 January 2023 : Clinical ResearchEvaluation 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
19 January 2023 : Clinical ResearchDetermining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Q...
Med Sci Monit 2023; 29:e939238
27 December 2022 : Clinical ResearchEffect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...
Med Sci Monit 2022; 28:e938926
03 Feb 2023 : Clinical ResearchTreatment 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 ResearchOnline 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 AnalysisPrognostic-Related Biomarkers in Pancreatic Ductal Adenocarcinoma Correlating with Immune Infiltrates Based...
Med Sci Monit In Press; DOI: 10.12659/MSM.938785
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292