2026-10-14T04:56:10Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33987436 2026-09-24T17:26:06Z category_7 category_8 category_12 category_19 category_873 category_46 category_734 category_64 category_106 category_132 portal_5 item_type_3 month_year_09_2026

<p>Rat groupings.</p> Sigurbergur Karason (11625806) Arni Asbjarnarson (13142367) Saevar Ingthorsson (398268) Kolbrun Bjork Jonasdottir (25104964) Jennifer Kricker (761200) Thorarinn Gudjonsson (207248) Jon Petur Joelsson (25104967) Medicine Microbiology Cell Biology Pharmacology Chemical Sciences not elsewhere classified Immunology Biological Sciences not elsewhere classified Cancer Science Policy Infectious Diseases seven days ), negligible antibacterial activity critically ill patients bronchoalveolar lavage fluid peak airway pressure conventional macrolide therapy div >< p induced lung injury compounds attenuated ventilation rats </ p induced pulmonary oedema pulmonary oedema induced increases pressure ventilation macrolide antibiotics lung wet lung damage eight rats whereas ventilation mechanical ventilation ventilated animals total protein systemic complications survival rates study investigated smaller increase six groups significantly reduced significant complication response pathways rat model promising alternative likely due kg daily findings suggest either unchanged dry ratio derived compound demonstrated anti cytokine profiling cytokine levels bacterial resistance animals subjected 5 mg 35 cmh <div><p>Ventilator-induced lung injury (VILI) is a significant complication of mechanical ventilation, contributing to morbidity and mortality in critically ill patients. Excessive mechanical stress triggers an inflammatory cascade, leading to lung damage, pulmonary oedema, and systemic complications. While macrolide antibiotics such as azithromycin (AZM) have demonstrated anti-inflammatory and epithelial barrier strengthening effects, their use is limited by concerns regarding antibiotic resistance. EP317, an azithromycin-derived compound with negligible antibacterial activity, was designed to retain the immunomodulatory and epithelial barrier enhancing effects of AZM while mitigating the risk of bacterial resistance. This study investigated the effects of AZM and EP317 in a rat model of VILI. Forty-eight rats were divided into six groups (N = 8 per group), receiving either placebo, AZM, or EP317 (5 mg/kg daily for seven days), with half of the animals subjected to mechanical ventilation with peak airway pressure at 35 cmH₂O. Both compounds attenuated ventilation-induced pulmonary oedema, reflected in a smaller increase in lung wet/dry ratio, whereas ventilation-induced increases in total protein in bronchoalveolar lavage fluid (BALF) were not significantly reduced by either treatment. Cytokine profiling in plasma (L-Selectin, PAI-1, RANTES, MCP-3, IL-6, SCF, IL-17a, RAGE, MIP-3α, IL-13, G-CSF, IL-10, M-CSF, IFN-γ, GRO-KC and MMP9) revealed that both treatments attenuated inflammatory responses, while cytokine levels in BALF in ventilated animals were either unchanged or increased. Survival rates were improved in the treatment groups. Histological analysis indicated increased oedema in ventilated animals, likely due to the high-pressure ventilation, while drug-treated groups exhibited reduced oedema. Global gene expression profiling by RNA sequencing revealed robust upregulation of inflammatory and stress-response pathways in ventilated animals, with partial attenuation following AZM or EP317 pre-treatment. These findings suggest that EP317 and AZM offer protective effects against VILI. EP317 presents a promising alternative to conventional macrolide therapy by circumventing antibiotic resistance concerns.</p></div> 2026-09-24T17:25:55Z Dataset Dataset 10.1371/journal.pone.0358745.t001 https://figshare.com/articles/dataset/_p_Rat_groupings_p_/33987436 CC BY 4.0