Document Type : Original Article

Authors

• Annamaria Marton ¹
• Csongor Kolozsi ¹
• Erzsebet Kusz ¹
• Zoltan Olah ^{2, 3}
• Tamas Letoha ^{2, 4}
• Csaba Vizler ¹
• Laszlo Pecze ^{1, 5}

¹ Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences

² Molecular Surgery Unit, Institute of Pharmaceutical Analysis, University of Szeged

³ Acheuron Hungary Ltd.

⁴ Pharmacoidea Ltd., Szeged, Hungary

⁵ Department of Medicine, University of Fribourg, Fribourg, Switzerland

Abstract

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.

Keywords

• Inflammation
• NF-KB
• Propylene-Glycol
• Sepsis