Sildenafil treatment attenuates lung and kidney injury due to overproduction of oxidant activity in a rat model of sepsis: a biochemical and histopathological study

Summary Sepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on...

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Bibliographic Details
Published in:Clinical and experimental immunology 2011-12, Vol.166 (3), p.374-384
Main Authors: Cadirci, E., Halici, Z., Odabasoglu, F., Albayrak, A., Karakus, E., Unal, D., Atalay, F., Ferah, I., Unal, B.
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Animal models
Animals
Bacterial diseases
Bacterial sepsis
Biological and medical sciences
Cecal Diseases - drug therapy
Cyclic GMP
Fundamental and applied biological sciences. Psychology
Glutathione
Glutathione - metabolism
Human bacterial diseases
Infection
Infectious diseases
Inflammation
Inflammation - drug therapy
Injuries
Kidney
Kidney - drug effects
Kidney - pathology
Kidneys
Lipid peroxidation
Lipid Peroxidation - drug effects
Lung
Lung - drug effects
lung injury
Lung Injury - drug therapy
Medical sciences
Morbidity
Mortality
Oxidants
oxidative stress
Oxidative Stress - drug effects
Peroxidase
Peroxidase - metabolism
phosphodiesterase
Piperazines - administration & dosage
Piperazines - pharmacology
polymicrobial sepsis
Purines - administration & dosage
Purines - pharmacology
rat
Rats
Rats, Wistar
Rodents
Sepsis
Sepsis - drug therapy
Sepsis - metabolism
Sepsis - pathology
Sildenafil
Sildenafil Citrate
Sulfones - administration & dosage
Sulfones - pharmacology
Superoxide dismutase
Superoxide Dismutase - metabolism
Translational Studies
Tumor necrosis factor- alpha
Tumor Necrosis Factor-alpha - blood
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Summary:Summary Sepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)‐induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD‐treated CLP group; (ii) 20 mg/kg SLD‐treated CLP group; (iii) CLP group; and (iv) sham‐operated control group. A CLP polymicrobial sepsis model was applied to the rats. All groups were killed 16 h later, and lung, kidney and blood samples were analysed histopathologically and biochemically. Sildenafil increased glutathione (GSH) and decreased the activation of myeloperoxidase (MPO) and of lipid peroxidase (LPO) and levels of superoxide dismutase (SOD) in the septic rats. We observed a significant decrease in LPO and MPO and a decrease in SOD activity in the sildenafil‐treated CLP rats compared with the sham group. In addition, 20 mg/kg sildenafil treatment in the sham‐operated rats improved the biochemical status of lungs and kidneys. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups, except the CLP + sildenafil 10 mg/kg group. The CLP + sildenafil 20 mg/kg group had the lowest inflammation score. Sildenafil treatment decreased the serum tumour necrosis factor (TNF)‐α level when compared to the CLP group. Our results indicate that sildenafil is a highly protective agent in preventing lung and kidney damage caused by CLP‐induced sepsis via maintenance of the oxidant–anti‐oxidant status and decrease in the level of TNF‐α.
ISSN:0009-9104
1365-2249
DOI:10.1111/j.1365-2249.2011.04483.x