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

Abstract

SummarySepsis 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)-a 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 CLPinduced sepsis via maintenance of the oxidant-anti-oxidant status and decrease in the level of TNF-a.

Sepsis and Septic Shock: Current Treatment Strategies and New Approaches

“…The beneficial effects of propofol administration on the inflammation of lungs after intravenous endotoxin administration has been shown in rats [42][43][44][45][46][47][48][49][50].…”

The effects of Sildenafil in liver and kidney injury in a rat model of severe scald burn: A biochemical and histopathological study

“…Cadirci et al [32] reported effects of sildenafil (10 and 20 mg/ kg/p.o.) in remote organs, including the lung and kidneys, in a rat model of sepsis.…”

“…[20] Moreover, the beneficial effects of sildenafil have been shown in the balance of oxidation and antioxidation via decreasing oxidative and nitrosative stress in inflammatory events. [9,23,[30][31][32][33][34] However, there is no study in the literature focusing on the effects of sildenafil in remote organ injury induced by severe burn except our previous study focusing on acute lung injury. [9] The purpose of the present study was to evaluate the effects of different dosages of sildenafil in distant organs, such as liver and kidneys, due to severe scald burn injury in rats.…”

“…[23,[30][31][32][33][34]46,47] Histopathological evaluations of those studies also demonstrated the positive effects of various dosages of sildenafil administration (range 2±25 mg/kg) in decreased inflammation scores.…”

Phosphodiesterase type 5 inhibitors and kidney disease

“…Restoration of oxygen levels upon reperfusion causes a surge in the generation of reactive oxygen species and pro-inflammatory mediators and cells to exacerbate ischemic injury [33]. PDE5 inhibitors have been reported to increase antioxidant defenses and decrease inflammation [34] and apoptosis [35]. Indeed, these agents were shown to decrease I/R injury in renal tissue [35,36].…”