fosfomycin and Inflammation

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.. 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.).. 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.. 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.

Topics: Acute Lung Injury; Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Fosfomycin; Inflammation; Male; Oxidative Stress; Protective Agents; Rats; Rats, Sprague-Dawley; Sepsis

We examined the effect of fosfomycin (FOM) on the inflammatory response induced by carrageenan in the rat. Air pouches were induced subcutaneously on the backs of rats and injected with carrageenan. The rats were treated with either vehicle or FOM at a dose of 100 mg/kg 1 h before carrageenan challenge. After carrageenan challenge (48 h), the air pouches were removed and analyzed. The volume, protein amounts and cell counts in the exudate obtained from FOM-treated animals were significantly reduced compared with that from vehicle-treated animals. The contents of PGE(2) and TNF-alpha, and mRNA for cyclooxygenase-2 were also markedly suppressed in FOM-treated rats. Histological examination showed suppression of the inflammatory response in the pouch tissues from FOM-treated rats.

Topics: Animals; Anti-Inflammatory Agents; Chemokine CCL5; Dinoprostone; Disease Models, Animal; Exudates and Transudates; Fosfomycin; Inflammation; Models, Animal; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

To determine the mechanisms of immunomodulating action of fosfomycin (FOF), we examined its effect on the production of inflammatory cytokines in mice injected with lipopolysaccharide (LPS). Treatment with FOF significantly lowered the peak serum levels of tumor necrosis factor alpha and interleukin-1 beta, indicating that FOF alters inflammatory cytokine production after LPS stimulation.

Topics: Animals; Anti-Bacterial Agents; Cytokines; Dose-Response Relationship, Drug; Endotoxins; Escherichia coli; Fosfomycin; Inflammation; Interleukin-1; Lipopolysaccharides; Male; Mice; Time Factors; Tumor Necrosis Factor-alpha

Topics: Adolescent; Adult; Aged; Child; Female; Fosfomycin; Gingivitis; Humans; Inflammation; Male; Middle Aged; Periodontal Diseases