The Effect of Sildenafil on Cisplatin Nephrotoxicity in Rats

Abstract

Sildenafil, the first drug for erectile dysfunction, has cardiopulmonary protective actions. A recent study has reported that sildenafil given intraperitoneally (i.p.) attenuated cisplatin (CP)-induced nephrotoxicity. Here, we evaluated whether sildenafil, given by two different routes and at two different doses, can attenuate CP-induced nephrotoxicity and would also affect renal haemodynamics in CP-treated rats. Six groups of rats were treated with saline (controls), CP [5 mg ⁄ kg, intraperitoneally (i.p.) once], sildenafil (0.4 mg ⁄ kg ⁄ day, i.p. for 5 days), sildenafil (0.4 mg ⁄ kg ⁄ day i.p. for 5 days) plus CP (5 mg ⁄ kg, i.p., once), sildenafil [10 mg ⁄ kg ⁄ day, subcutaneous (s.c.) for 5 days] or sildenafil (10 mg ⁄ kg ⁄ day, s.c. for 5 days) plus CP (5 mg ⁄ kg, i.p. once). Five days after the end of the treatments, urine was collected from all rats, which were then anaesthetized for blood pressure and renal blood flow monitoring. This was followed by intravenous (i.v.) injection of norepinephrine for the measurement of renal vasoconstrictor responses. Thereafter, blood and kidneys were collected for measurement of several biochemical, functional and structural parameters. CP reduced body-weight and renal blood flow but did not affect norepinephrine-induced renal vasoconstriction. It increased the plasma concentrations of urea and creatinine, and reduced creatinine clearance. CP caused extensive renal tubular necrosis, increased urine volume and N-acetyl-b-Dglucosaminidase activity. When sildenafil (0.4 mg ⁄ kg ⁄ day, i.p. for 5 days) was combined with cisplatin, there was a dramatic improvement in renal histopathology, reduction in N-acetyl-b-D-glucosaminidase and increase in renal blood flow. However, sildenafil (10 mg ⁄ kg ⁄ day, s.c. for 5 days) did not affect CP nephrotoxicity, suggesting the importance of dose and route selection of sildenafil as a nephroprotectant.

Epidermal Growth Factor Receptor Inhibition with Erlotinib Partially Prevents Cisplatin-Induced Nephrotoxicity in Rats

“…The dose of CP was selected based on a previous study [19]. To investigate the effect of erlotinib, 28 CP-N rats were divided into two groups.…”

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

“…Immediately after the surgical procedure was completed, the rats in the sham-operated and the SLDtreated CLP groups received 10-or 20-mg/kg doses of SLD, which were administered with an oral gavage suspended in saline. There are many sildenafil doses for rats, varying from 0·4 mg/kg to 90 mg/kg, with different administration routes [28][29][30][31][32][33]. The reason we selected 10-and 20-mg/kg doses of oral sildenafil is that 10 mg/kg/day of sildenafil would result approximately in the same plasma concentration as 50 mg in humans [34].…”

Abrogation of cisplatin‐induced nephrotoxicity by emodin in rats

“…The procedure involves mineralization of the kidney tissue with a mixture of concentrated HNO 3 and H 2 O 2 , followed by the determination of platinum in the extract, using inductively coupled plasma optical emission spectrometry at an emission wavelength of 265.945 nm. Platinum atomic absorption spectrophotometer standard solution (Sigma, St. Louis, MO, USA) was used to construct a standard curve, as described earlier [22].…”