PURPOSE: Cisplatin (CCDP), an indispensable agent of several chemotherapy protocols, has serious dose limiting side effects, including nephrotoxicity. In this experimental study, we used deferoxamine mesilate (DFO), an iron chelating agent, to ameliorate cisplatin-induced nephrotoxicity. MATERIALS AND METHODS: Sixty adult male bulb-c mice were divided in 6 equal groups. Group 1 received distilled water, group 2 received 100 mg/kg DFO, group 3 received 0.9 mg/kg CCDP, group 4 received 100 mg/kg DFO one hour before 0.9 mg/kg CCDP, group 5 received 1.8 mg/kg CCDP, and group 6 received 200 mg/kg DFO one hour before 1.8 mg/kg CCDP transperitoneally for 10 days. The next day, blood and urine samples were obtained, and all the animals were sacrificed, the kidneys and testes were removed, and histopathologic and biochemical analyses were performed. RESULTS: Low-dose and high-dose CCDP treated mice had significantly more extensive proximal tubular degeneration (p < 0.001) when compared to control animals. Moreover, these changes were significantly less extensive in the mice taking DFO than mice taking CCDP. DFO showed no effect on cisplatin induced testicular histopathology. The cisplatin administration significantly increased the serum urea and plasma creatinin concentrations, and DFO administration prior to CCDP significantly decreased serum urea and plasma creatinin concentrations. CONCLUSION: Our findings suggest that DFO administration may be safe and useful for ameliorating cisplatin-induced nephrotoxicity.
PURPOSE:Cisplatin (CCDP), an indispensable agent of several chemotherapy protocols, has serious dose limiting side effects, including nephrotoxicity. In this experimental study, we used deferoxamine mesilate (DFO), an iron chelating agent, to ameliorate cisplatin-induced nephrotoxicity. MATERIALS AND METHODS: Sixty adult male bulb-c mice were divided in 6 equal groups. Group 1 received distilled water, group 2 received 100 mg/kg DFO, group 3 received 0.9 mg/kg CCDP, group 4 received 100 mg/kg DFO one hour before 0.9 mg/kg CCDP, group 5 received 1.8 mg/kg CCDP, and group 6 received 200 mg/kg DFO one hour before 1.8 mg/kg CCDP transperitoneally for 10 days. The next day, blood and urine samples were obtained, and all the animals were sacrificed, the kidneys and testes were removed, and histopathologic and biochemical analyses were performed. RESULTS: Low-dose and high-dose CCDP treated mice had significantly more extensive proximal tubular degeneration (p < 0.001) when compared to control animals. Moreover, these changes were significantly less extensive in the mice taking DFO than mice taking CCDP. DFO showed no effect on cisplatin induced testicular histopathology. The cisplatin administration significantly increased the serum urea and plasma creatinin concentrations, and DFO administration prior to CCDP significantly decreased serum urea and plasma creatinin concentrations. CONCLUSION: Our findings suggest that DFO administration may be safe and useful for ameliorating cisplatin-induced nephrotoxicity.
Authors: G Daugaard; U Abildgaard; N H Holstein-Rathlou; I Bruunshuus; D Bucher; P P Leyssac Journal: Clin Pharmacol Ther Date: 1988-08 Impact factor: 6.875
Authors: O A Badary; M N Nagi; O A al-Shabanah; H A al-Sawaf; M O al-Sohaibani; A M al-Bekairi Journal: Can J Physiol Pharmacol Date: 1997-12 Impact factor: 2.273