The protective role of fosfomycin in lung injury due to oxidative stress and inflammation caused by sepsis

Abstract

Aim: Early and prompt treatment of sepsis by effective antibiotics against susceptible organisms may be lifesaving. However, increased antibiotic resistance and side effects of chemotherapeutic agents limiting their tolerability result in a restricted use of medications. This has led to an increased search for solution oriented novel treatments and therapeutic targets, as well as investigations on the pathogenesis and physiology of sepsis. In this study, we aimed to examine the antioxidant and anti-inflammatory effects of fosfomycin in sepsis resulting from other causes.

Main methods: Sprague Dawley rats were assigned into three groups. Randomly selected control rats received intraperitoneal saline solution only. Only caecal puncture and ligation were carried out in the caecal ligation and puncture (CLP) group, while in the CLP + fosfomycin group (CLP + FOS), together with sepsis due to caecal puncture and ligation, 500 mg/kg of FOS was administered intraperitoneally (i.p.).

Key findings: As compared to the control group, elevated TBARS and TNF-α levels as well as increased expression of NF-kB/p65 and TLR-4 and reduced -SH levels were found in the lung tissue of CLP rats. On the other hand, TBARS and TNF-α levels were reduced and NF-kB/p65 and TLR-4 expressions were decreased together with increase in total -SH levels among CLP + FOS (500 mg/kg i.p.) rats.

Significance: FOS treatment may represent a promising agent in terms of reducing the sepsis-related lung injury due to its antimicrobial effects as well as its antioxidant and anti-inflammatory properties.

Keywords: Fosfomycin; Inflammation; Lung; Oxidative stress; Rat; Sepsis.