Modulation of the Acute Inflammatory Response Induced by the <i>Escherichia coli</i> Lipopolysaccharide through the Interaction of Pentoxifylline and Florfenicol in a Rabbit Model

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dc.contributor.authorCazanga, Victoria
dc.contributor.authorPalma, Cristina
dc.contributor.authorCasanova, Tomas
dc.contributor.authorRojas, Daniela
dc.contributor.authorBarrera, Karin
dc.contributor.authorValenzuela, Cristhian
dc.contributor.authorAcevedo, Aracelly
dc.contributor.authorAscui-Gac, Gabriel
dc.contributor.authorPerez-Jeldres, Tamara
dc.contributor.authorPerez-Fernandez, Ruben
dc.date.accessioned2025-01-20T20:14:55Z
dc.date.available2025-01-20T20:14:55Z
dc.date.issued2023
dc.description.abstractBackground: Experimental reports have demonstrated that florfenicol (FFC) exerts potent anti-inflammatory effects, improving survival in a murine endotoxemia model. Considering the anti-inflammatory and immunomodulatory properties of pentoxifylline (PTX) as an adjuvant to enhance the efficacy of antibiotics, the anti-inflammatory effects of the interaction FFC/PTX over the E. coli Lipopolysaccharide (LPS)-induced acute inflammatory response was evaluated in rabbits. Methods: Twenty-five clinically healthy New Zealand rabbits (3.8 +/- 0.2 kg body weight: bw), were distributed into five experimental groups. Group 1 (control): treated with 1 mL/4 kg bw of 0.9% saline solution (SS) intravenously (IV). Group 2 (LPS): treated with an IV dose of 5 mu g/kg of LPS. Group 3 (pentoxifylline (PTX) + LPS): treated with an oral dose of 30 mg/kg PTX, followed by an IV dose of 5 mu g/kg of LPS 45 min after PTX. Group 4 (Florfenicol (FFC) + LPS): treated with an IM dose of 20 mg/kg of FFC, followed by an IV dose of 5 mu g/kg of LPS 45 min after FFC administration. Group 5 (PTX + FFC + LPS): treated with an oral dose of 30 mg/kg of PTX, followed by an IM dose of 20 mg/kg of FFC, and, 45 min after an IV dose of 5 mu g/kg of LPS was administered. The anti-inflammatory response was evaluated through changes in plasma levels of interleukins (TNF-alpha, IL-1 beta and IL-6), C-reactive protein (CRP), and body temperature. Results: It has been shown that each drug produced a partial inhibition over the LPS-induced increase in TNF-alpha, IL-1 beta, and CRP. When both drugs were co-administered, a synergistic inhibitory effect on the IL-1 beta and CRP plasma concentrations was observed, associated with a synergic antipyretic effect. However, the co-administration of PTX/FFC failed to modify the LPS-induced increase in the TNF-alpha plasma concentrations. Conclusions: We concluded that the combination of FFC and PTX in our LPS sepsis models demonstrates immunomodulatory effects. An apparent synergistic effect was observed for the IL-1 beta inhibition, which peaks at three hours and then decreases. At the same time, each drug alone was superior in reducing TNF-alpha levels, while the combination was inferior. However, the peak of TNF-alpha in this sepsis model was at 12 h. Therefore, in rabbits plasma IL-1 beta and TNF-alpha could be regulated independently, thus, further research is needed to explore the effects of this combination over a more prolonged period.
dc.description.funderGrant FONDECYT from National Agency for Research and Development of Chilean government (ANID-CHILE)
dc.fuente.origenWOS
dc.identifier.doi10.3390/antibiotics12040639
dc.identifier.issn2079-6382
dc.identifier.urihttps://doi.org/10.3390/antibiotics12040639
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/92229
dc.identifier.wosidWOS:000978860700001
dc.issue.numero4
dc.language.isoen
dc.revistaAntibiotics-basel
dc.rightsacceso restringido
dc.subjectanti-inflammatory
dc.subjectcytokines
dc.subjectantibiotics
dc.subjectpentoxifylline
dc.subjectflorfenicol
dc.subjectdrug interactions
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleModulation of the Acute Inflammatory Response Induced by the <i>Escherichia coli</i> Lipopolysaccharide through the Interaction of Pentoxifylline and Florfenicol in a Rabbit Model
dc.typeartículo
dc.volumen12
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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