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Thermal Steam Aerosolization Protects Against Lipopolysaccharide-Induced Sepsis in Rats

Udomlak Matsathit MSc*, Chantana Mekseepralard PhD**, Orapin Wongsawatkul PhD*, Piyanee Ratanachamnong MSc***, Prasit Upapan MD****, Laddawal Phivthong-Ngam PhD*

Affiliation : * Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand ** Department of Microbiology, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand *** Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand **** Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Nakhon Nayok, Thailand

Background : Sepsis is a severe systemic inflammatory state in response to infection. The induction of heat shock protein 70 (HSP70) by heat stress has been reported to protect against lethal effects of sepsis. In clinical situation, inhalation of thermal water has been used empirically in the treatment of chronic diseases of respiratory tract. Thus, thermal steam aerosolization may have beneficial effects on sepsis via HPS70 induction.
Objective : The present study tested the hypothesis that thermal steam aerosolization could protect against lipopolysaccharide- induced sepsis in rats. Material and Method: Male Spraque-Dawley rats were subjected to steam aerosolization at 40°C for 1 hour before intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS). Blood pressure, heart rate and core temperature were recorded in two hours interval. At the end of the study period, vascular response to vasoconstrictor of isolated aortic rings ex vivo was assessed. Serum proinflammatory cytokines, IL-1beta and IL-6, were analyzed using ELISA technique. Plasma nitric oxide was determined using nitrate/nitrite fluorometric assay Kit. HSP70 expression, heat shock factor-1 (HSF-1) mRNA level and nuclear factor-kappa B (NF-kappa B) activity in the lungs of rats were investigated using western blot analysis, real-time quantitative PCR and transcription factor kits for NF-kappa B p65, respectively.
Results : Thermal steam aerosolization treatment prevented the fall in systolic, diastolic, mean arterial blood pressures induced by LPS and restored the vascular response to adrenaline. LPS significantly increased plasma nitrate/nitrite concentration, serum IL-1 beta and IL-6 levels, and NF-kappa B activity in rat lung lysate which were reduced by thermal steam aerosolization. Thermal steam aerosolization induced both HSP70 and HSF-1 mRNA expression.
Conclusion : The present study suggests that thermal steam aerosolization can delay the stage of shock in LPS-induced septic rats. It shows a beneficial therapeutic effect and may be applied to the clinical approach for septic shock patient.

Keywords : Heat shock protein 70, Hypotension, Lipopolysaccharide, Proinflammatory cytokines, Sepsis, Shock, Steam aerosolization


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