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

• Published in: Clinical and experimental immunology Vol. 166; no. 3; pp. 374 - 384
• Main Authors: Cadirci, E., Halici, Z., Odabasoglu, F., Albayrak, A., Karakus, E., Unal, D., Atalay, F., Ferah, I., Unal, B.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-2011; Blackwell; Oxford University Press; Blackwell Science Inc
• 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; Animal model; Oxidative stress; Rat; 3',5'-Cyclic-GMP phosphodiesterase; Esterases; Biochemistry; Phosphoric diester hydrolases; Oxidant; Kidney; Sepsis syndrome; Histopathology; lung injury; polymicrobial sepsis; Lung disease; Enzyme; Respiratory disease; Rodentia; Enzyme inhibitor; Biological activity; Bacteremia; Infection; Phosphodiesterase inhibitor; Phosphodiesterase 5 inhibitor; Vertebrata; Anatomic pathology; Mammalia; Treatment; Urinary system; Animal; Bacteriosis; Hydrolases; Sildenafil; Molecular biology
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2011.04483.x

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.