Abstract

Background: This study investigates the role of MMPs and TIMPs in sepsis pathogenesis. We aim to assess multiple potential biomarkers including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-13, TIMP-1, TIMP-2, TIMP-3 in serum, brain and kidney tissue samples. To this date, there is not such extensive assessment of MMP and TIMP in sepsis pathogenesis. Methods: Experimental sepsis was generated using an LPS-induced endotoxemia model in rats. After 24 h, serum, brain and kidney samples were collected. Levels of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-13, and TIMP-1, TIMP-2, TIMP-3 were measured by ELISA. Inflammatory cytokines (TNF-α, IL-6, IL-10, and IFN-γ) were analyzed to assess the inflammatory response. Results: Analysis revealed that MMP-1 concentrations were elevated in kidney and brain tissues, as well as in serum in the sepsis group. MMP-2 levels exhibited statistically significant increases in brain tissues compared to controls. Elevations in MMP-3 were observed across brain, kidney and serum samples. MMP-8 levels were significantly increased in the serum. MMP-9 concentrations were higher in serum and kidney samples of septic rats compared with controls, while MMP-13 levels were elevated in kidney tissues of the sepsis group. TIMP measurements also revealed tissue-specific elevations in sepsis. TIMP-1 was significantly increased in kidney; TIMP-2 showed significant rises in brain tissue and serum; and TIMP-3 was markedly elevated in kidney tissues. Conclusions: A major strength of our study is the simultaneous assessment of multiple parameters. Our findings offer preliminary evidence of tissue-specific MMP and TIMP responses in sepsis and may guide future research exploring their biomarker potential. We anticipate that these results will inform both future clinical and pharmacological research and assist in the interpretation of subsequent studies.

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