Investigation of the effect of the TLR4-interacting SPA4 peptide against lung, liver, and kidney tissue injury caused by experimentally induced endotoxemia via escherichia coli (E. Coli) lipopolysaccharide (LPS)

Recent studies have demonstrated that the surfactant protein A-derived SPA4 peptide, effectively reduces lung inflammation and tissue damage, decreases bacterial load, and enhances bacterial phagocytosis in both bacterial infection and lipopolysaccharide (LPS) models. The aim of this research was to assess the protective tissue effects of SPA4, extending beyond the lungs to include liver and kidney tissues. Accordingly, the histopathological effects of low (2.5 µg/g) and high (10 µg/g) doses of SPA4 on lung, liver, and kidney tissues were investigated following a systemic inflammatory response induced by a single intraperitoneal dose of LPS in rats. The study utilized 72 male Wistar-Albino rats, randomized into control, LPS, LPS+low-dose SPA4, LPS+high-dose SPA4, and groups receiving only low-dose or only high-dose SPA4. SPA4 was administered one hour post-LPS injection, and rats were euthanized six hours later for tissue sampling. Histopathological evaluations were conducted using Hematoxylin-Eosin (H-E), PAS, Masson-Goldner Trichrome, and immunohistochemical (NF-κB p65) staining techniques. Additionally, rats' general conditions were monitored throughout the experiment using the "Murine Sepsis Score." The findings indicated that symptoms induced by LPS improved significantly only with the high dose of SPA4, while the low dose showed only insignificant improvement. Lung inflammation and damage caused by LPS notably decreased with the high dose of SPA4, reaching levels similar to control, whereas moderate improvement was observed with the low dose. Similarly, high-dose SPA4 significantly mitigated atelectasis, inflammation, and hemorrhage in lung tissue. In the liver, a significant protective effect was observed only with the high dose, whereas the low dose only show insignificant improvement. Kidney tissues also exhibited significant reduction in tubular damage and congestion with high-dose SPA4, with only moderate improvement observed at the low dose. Moreover, high-dose SPA4 administration substantially decreased LPS-induced NF-κB activation in all tissues, whereas the decrease with low-dose SPA4 was moderate and statistically insignificant. No differences were observed in groups treated exclusively with SPA4 compared to control. In conclusion, the SPA4 peptide, particularly at a high dose, demonstrated significant protective effects by reducing LPS-induced damage not only in lung tissue but also in liver and kidney tissues, without any observed toxicity in SPA4-only groups. This study is the first to examine the therapeutic effectiveness of SPA4 outside the lungs, specifically in liver and kidney tissues. However, further studies at the molecular level are necessary to elucidate changes in proinflammatory cytokines in non-pulmonary organs following SPA4 administration.