1Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences
2Molecular Surgery Unit, Institute of Pharmaceutical Analysis, University of Szeged
3Acheuron Hungary Ltd.
4Pharmacoidea Ltd., Szeged, Hungary
5Department of Medicine, University of Fribourg, Fribourg, Switzerland
Background : Propylene glycol (1,2-propanediol, PG) is a commonly used solvent for oral, intravenous, as well as topical pharmaceutical preparations. While PG is generally considered to be safe, it has been known that large intravenous doses given over a short period of time can be toxic. Objective: To evaluate the effect of PG in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS). Methods: Balb/c mice were treated with LPS (1 mg/kg b.w., i.p.) with or without PG (5 g/kg b.w. i.v.). The survival rate and the production of inflammatory cytokines were measured. In RAW264.7 mouse macrophages encoding NF- B-luc reporter gene, the nuclear transcription factor kappa- B (NF- B) activation was measured. Results: We found that intravenous PG increased the mortality rate in sepsis induced by the bacterial endotoxin lipopolysaccharide (LPS) in mice. In accordance with that, PG enhanced LPS -induced production of inflammatory cytokines, including tumor necrosis factor-α (TNF -α) and interleukin-6 (IL -6) in vivo. PG also increased the LPS-induced macrophage activation in vitro as detected by measuring NF- B activation. Conclusion: Our results indicate that drugs containing high doses of PG can pose a risk when administered to patients suffering from or prone to Gram negative bacterial infection.