EPCs and Bacillus subtilis-derived surfactin attenuate LPS-induced hepatic injury in mice

Abstract

Lipopolysaccharide (LPS)-induced endotoxemia promotes systemic inflammation, oxidative stress, endothelial dysfunction, and hepatic injury. Endothelial progenitor cells (EPCs) may support vascular repair and immunomodulation, whereas surfactin, a cyclic lipopeptide derived from Bacillus subtilis , has reported anti-inflammatory and antioxidant properties. This study evaluated the effects of EPCs, surfactin, and their combined administration on LPS-associated injury in mice. Male C57BL/6 mice were assigned to control, LPS + vehicle, LPS, LPS + EPCs, LPS + surfactin, and LPS + EPCs + surfactin groups. Serum TNF-α was measured 2 h after LPS exposure to confirm early systemic inflammation. Antioxidant indices, inflammatory mediators, serum hepatic biochemical markers, liver histopathology, and total NF-κB p65 and Nrf2 protein abundance were evaluated at day 5. LPS impaired antioxidant defense and increased inflammatory, biochemical, and histopathological indices of hepatic injury. EPCs and surfactin each partially attenuated these changes, whereas combined treatment produced the broadest recovery across the evaluated endpoints. The combined intervention was also associated with lower total NF-κB p65 abundance and higher total Nrf2 abundance relative to untreated LPS-challenged mice. These protein-expression findings were treated as exploratory, semi-quantitative measurements and do not establish pathway activation, inhibition, or causal involvement. Overall, EPC and surfactin co-administration was associated with greater attenuation of LPS-induced hepatic injury than either monotherapy.