Sildenafil, a phosphodiesterase-5-inhibitor decreased the oxidative stress induced by carbon tetrachloride in the rat kidney: A preliminary study

Carbon tetrachloride (CCl4) is a well-established nephrotoxin. Free radical generation has been described as one of the mechanisms of inducing its nephrotoxicity. This preliminary study investigated the protective effect of sildenafil (SILD) in CCl4-induced oxidative stress in rat kidney. Thirty male albino wistar rats weighing between 150–200g were randomly divided into five groups, each consisting of 6 rats. Control group received physiological saline (10ml/kg, p.o.), another group received 0.5 ml/kg/i.p. of CCl4 while three separate groups were pretreated with SILD at 5mg, 10mg and 20mg/kg respectively before CCl4 challenge. Animals were sacrificed 24 hours after CCl4 administration. Renal biomarkers were measured in the serum. In addition, antioxidant assays and histopathological studies were carried out. CCl4 treatment produced no significant change in the serum levels of creatinine and BUN (p>0.05). However, CCl4 significantly (p<0.05) reduced GSH level by 43.8% and increased lipid peroxidation by 37.5% (p<0.05) when compared to the group that received saline. Pretreatment with 10mg and 20mg/kg doses of SILD significantly raised GSH level by 28.0% and 35.7% respectively while lipid peroxidation was reduced by 50% (p<0.05) at 10mg/kg dose of SILD. Low dose of SILD (5mg/kg) was not effective as it caused a significant reduction of about 33.3% in GSH level (p<0.05). CCl4 significantly lowered the activities SOD, CAT and GST by 63.5%, 60.0% and 47.5% respectively when compared with the control group while GPx activity was decreased slightly by 17.0% (p>0.05). SILD treatment at 10mg/kg significantly elevated the activities of SOD, CAT, GPx, and GST (by 30.9%, 56.0%, 26.9% and 76.5% respectively) as compared with the CCl4-administered group while SILD at 5mg/kg led to reductions of 71.8%, 18.0%, 5.6% in the enzyme activities of SOD, CAT and GPx respectively. Sildenafil at highest dose of 20mg/kg significantly produced a further increase in the activities of SOD and CAT by 33.0% and 64.0% respectively. Data generated from this preliminary study suggested that high dose of sildenafil may protect against the oxidative stress induced by CCl4 in the kidney of rats.