Dimethyl Sulfoxide as a Novel Therapy in a Murine Model of Acute Lung Injury

Sharven Taghavi; David Engelhardt; Alexandra Campbell; Inna Goldvarg-Abud; Juan Duchesne; Farhana Shaheen; Derek Pociask; Jay Kolls; Olan Jackson-Weaver

doi:10.1097/TA.0000000000004293

Dimethyl Sulfoxide as a Novel Therapy in a Murine Model of Acute Lung Injury

J Trauma Acute Care Surg. 2024 Mar 6. doi: 10.1097/TA.0000000000004293. Online ahead of print.

Authors

Sharven Taghavi¹, David Engelhardt¹, Alexandra Campbell¹, Inna Goldvarg-Abud¹, Juan Duchesne¹, Farhana Shaheen¹, Derek Pociask², Jay Kolls³, Olan Jackson-Weaver¹

Affiliations

¹ Tulane University School of Medicine, Department of Surgery, New Orleans, Louisiana.
² Tulane University School of Medicine, Department of Medicine, New Orleans, Louisiana.
³ Tulane University School of Medicine, Center for Translational Research in Infection and Inflammation, New Orleans, LA.

PMID: 38444065
DOI: 10.1097/TA.0000000000004293

Abstract

Introduction: The endothelial glycocalyx (EGX) on the luminal surface of endothelial cells contributes to the permeability barrier of the pulmonary vasculature. Dimethyl sulfoxide (DMSO) has a disordering effect on plasma membranes, which prevents the formation of ordered membrane domains important in the shedding of the EGX. We hypothesized that DMSO would protect against protein leak by preserving the EGX in a murine model of acute respiratory distress syndrome (ARDS).

Methods: C57BL/6 mice were given ARDS via intra-tracheally administered lipopolysaccharide (LPS). DMSO (220 mg/kg) was administered intravenously for 4 days. Animals were sacrificed post-injury day 4 after bronchoalveolar lavage (BAL). BAL cell counts and protein content was quantified. Lung sections were stained with FITC-labelled wheat germ agglutinin (FITC-WGA) to quantify the EGX. Cultured endothelial cells (HUVECs) were exposed to LPS. EGX was measured using FITC-WGA, and co-immunoprecipitation was performed to measure interaction between sheddases and syndecan-1.

Results: DMSO treatment resulted in greater EGX staining intensity in the lung when compared to sham (9,641 vs. 36,659 A.U. p < 0.001). Total BAL cell counts were less for animals receiving DMSO (6.93 x 106 vs. 2.49 x 106 cells, p = 0.04). The treated group had less BAL macrophages (189.2 vs. 76.9 cells, p = 0.02) and lymphocytes (527.7 vs. 200.0 cells, p = 0.02). Interleukin-6 levels were lower in DMSO treated. Animals that received DMSO had less protein leak in BAL (1.48 vs. 1.08 ug/ul, p = 0.02). DMSO prevented LPS-induced EGX loss in HUVECs, and reduced the interaction between Matrix Metalloproteinase (MMP) 16 and syndecan-1.

Conclusions: Systemically administered DMSO protects the EGX in the pulmonary vasculature, mitigating pulmonary capillary leak after acute lung injury. DMSO also results in decreased inflammatory response. DMSO reduced the interaction between MMP16 and Syndecan-1 and prevented LPS-induced glycocalyx damage in cultured endothelial cells. DMSO may be a novel therapeutic for ARDS.

Level of evidence: Not applicable (animal studies).