Limited effect of surfactant protein D ablation on doxorubicin-induced intestinal toxicity in mice

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Introduction Surfactant protein (SP-D) is an anti-inflammatory host defense molecule, produced by epithelial cells and present on mucosal surfaces throughout the human and mouse body. In the present study, we investigated whether SP-D attenuates chemotherapy-induced gastrointestinal toxicity and inflammation in mice. Methods SP-D knockout (KO, Sftpd -/- ) mice and wild type (WT, Sftpd +/+ ) littermates were treated with doxorubicin (20mg/kg) or saline and sacrificed at day 3 o rat day 7, post-administration. Gastrointestinal toxicity was evaluated by weight change, citrulline levels, and histopathology. Genetic expression of genes related to chemotherapy-induced mucositis, inflammation, apoptosis, and repair of the damaged epithelium was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) on jejunal and colonic samples. Results Doxorubicin significantly reduced bodyweight, and KO mice lost significantly more weight relative to WT mice. Transcriptional analyses showed a significant SP-D-dependent increase of gasdermin genes ( Gsdmc2/3 and Gsdmc4 ) in the small intestine. The doxorubicin challenge did not alter intestinal SP-D expression. Discussion In conclusion, SP-D had a limited but significant impact on mouse gastrointestinal toxicity after chemotherapy-induced mucositis, which primarily involved weight loss of unknown cause and had no or limited effects on intestinal morphology and inflammation.

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