A Combined Therapy of Pegylated G-CSF with Ciprofloxacin Mitigates Damage Induced by Lethal Ionizing Radiation to the Bone Marrow, Spleen, and Ileum by Increasing AKT Activation but Decreasing IL-18, C3, and miR-34a

• DOI: 10.1667/rade-24-00266.1
• Publication Date: 2025-04-05T00:31:37Z
• Authors: Juliann G. Kiang; Georgetta Cannon; Min Zhai; Matthew G. Olson; Akeylah K. Woods; Katherine S. Clev...; Hengying Ellery; Feng Xu; Mang Xiao
• Keywords: Splenocyte

Ciprofloxacin (CIP) was found to enhance pegylated G-CSF therapy (PEG, Neulasta®)-induced survival from 30% 85% after ionizing radiation exposure. This combined significantly mitigated radiation-induced brain hemorrhage through its capability improve platelet recovery. study tested whether this treatment also gastrointestinal damage radiation. B6D2F1 female mice were exposed 60Co γ CIP fed daily for up 14 days. PEG injected on day 1, and then weekly 14. For the early time point study, blood, femurs, spleen, ileum collected days 2, 4, 9, 15 postirradiation. Bone marrow cells counted; spleen weights splenocyte counts measured; histopathology examined analyzed. AKT, ERK, JNK, p38, claudin NF-kB, Bax, Bcl-2, gasdermin D measured in lysates using Western blotting while miR-34a by reverse transcription followed real-time-PCR, citrulline colorimetric assay. In serum, interleukin-18 (IL-18) Luminex assay complement protein 3 (C3) detected ELISA. The bacterial DNA load livers real-time PCR. Radiation depleted bone femurs beginning 2 postirradiation, which or CIP+PEG 9 15, respectively. exposure led decreased weight reduction 15. reduced but that Ileum histology showed villus height 15; whereas PEG+CIP it Villus widths increased effectively them 4 Crypt depth returned baseline transiently only 4. regardless of individual drugs combinations. Citrulline data confirmed pro-inflammatory cytokine IL-18 alone PEG+CIP, not alone. C3 serum. serum positively associated with levels negatively correlated crypt depth. Radiation-induced decreases (a tight junction marker) increases PEG+CIP. did reduce NF-kB activation Bcl-2 expression, recovered any drug combination. However, combination NF- kB BAX. contrast, cleaved D, mitigated. immunohistochemistry. results taken together suggest effective mitigating marrow, injury. mitigative effect mediated suppress miR-34a, thereby probably leading D-mediated pyroptosis.