Ciprofloxacin Modulates Cytokine/Chemokine Profile in Serum, Improves Bone Marrow Repopulation, and Limits Apoptosis and Autophagy in Ileum after Whole Body Ionizing Irradiation Combined with Skin-Wound Trauma

Abstract

Radiation combined injury (CI) is a radiation injury (RI) combined with other types of injury, which generally leads to greater mortality than RI alone. A spectrum of specific, time-dependent pathophysiological changes is associated with CI. Of these changes, the massive release of pro-inflammatory cytokines, severe hematopoietic and gastrointestinal losses and bacterial sepsis are important treatment targets to improve survival. Ciprofloxacin (CIP) is known to have immunomodulatory effect besides the antimicrobial activity. The present study reports that CIP ameliorated pathophysiological changes unique to CI that later led to major mortality. B6D2F1/J mice received CI on day 0, by RI followed by wound trauma, and were treated with CIP (90 mg/kg p.o., q.d. within 2 h after CI through day 10). At day 10, CIP treatment not only significantly reduced pro-inflammatory cytokine and chemokine concentrations, including interleukin-6 (IL-6) and KC (i.e., IL-8 in human), but it also enhanced IL-3 production compared to vehicle-treated controls. Mice treated with CIP displayed a greater repopulation of bone marrow cells. CIP also limited CI-induced apoptosis and autophagy in ileal villi, systemic bacterial infection, and IgA production. CIP treatment led to LD0/10 compared to LD20/10 for vehicle-treated group after CI. Given the multiple beneficial activities of CIP shown in our experiments, CIP may prove to be a useful therapeutic drug for CI.

Potent Antiedematous and Protective Effects of Ciprofloxacin in Pulmonary Ricinosis

“…It can increase survival by producing effective antiedematous activities, apparently via balancing cytokine levels toward inflammatory attenuation and by reducing neutrophil migration into the lungs. Finally, in contrast to the prosurvival effects of ciprofloxacin in sterile injuries published thus far (1 to 4 h before LPS challenges [9,10]; 2 h after combined irradiation/skin wound trauma [40]), in the present study, ciprofloxacin administration is shown to lead to increased survival even when the drug is first administered at late time points (24 h) following injury onset.…”

A signalome screening approach in the autoinflammatory disease TNF receptor associated periodic syndrome (TRAPS) highlights the anti-inflammatory properties of drugs for repurposing

“…Significant evidence of in vivo and in vitro antiinflammatory activities of fluoroquinolones has been reported previously [38][39][40][41][42]. In particular, with regard to the effects of fluoroquinolones on pro-inflammatory signaling intermediates, it has been reported that norfloxacin and gemifloxacin reduce NFkB expression and activation [43][44][45], and that garenoxacin inhibits Erk1/2 phosphorylation [46].…”

Therapeutic effect of Aloe vera and silver nanoparticles on acid-induced oral ulcer in gamma-irradiated mice

“…radiation exposure increase cell death, tissue damage, organ dysfunction, mortality, DNA damages, and severe and rapid loss of hematological components compared to radiation exposure alone. 3 The loss of oral mucosa cells is continuously compensated by proliferation of epithelial cells of the basal layer. 4 Irradiation significantly diminishes the barrier function of the epithelium against different insults (mechanical, chemical and microbial), impairing the balance between cell proliferation and death.…”