2014 Volume 40 Issue 1 Pages 17-27
Chemotherapy regimens using cisplatin (CDDP) have rarely been applied to outpatients because they require vigorous hydration to reduce CDDP-induced nephrotoxicity. In this study, we investigated the protective effect of oral rehydration solution (ORS) on CDDP-induced nephrotoxicity in rats, which could be applicable to outpatients for oral hydration.
Two mg/kg CDDP was intraperitoneally injected into male F344 rats (n = 8) once a week for 7 weeks. A total of 60 mL/kg/day water, ORS, or modified ORS (MOS: chloride-free ORS) was orally administered for hydration. Changes in renal functions were evaluated by plasma creatinine, creatinine clearance, and histopathological evaluation of the kidney. Urinary excretion of platinum and chloride was also measured.
Evaluations of body weight (205 ± 13 vs 238 ± 7 g, P = 0.002) (Mean ± SD, water vs ORS), serum creatinine (0.69 ± 0.19 vs 0.41 ± 0.05 mg/dL, P = 0.023), creatinine clearance (0.48 ± 0.22 vs 0.74 ± 0.23 mL/min, P = 0.044), and histopathological evaluation at the 7th week revealed that nephrotoxicity was prevented more effectively by oral hydration using ORS than using water. MOS did not show any protective effects. Urinary platinum excretion after CDDP administration was similar between water and ORS. Urinary chloride concentration was higher after ORS administration.
ORS reduced CDDP-induced nephrotoxicity in rats, probably through providing chloride ions to prevent CDDP activation in renal tubules and to promote CDDP excretion. As the clinical application of ORS in cisplatin regimens may contribute to release from infusion, the shortening of the bed residence time and patient's quality of life improvement, safety and usefulness of ORS during cisplatin chemotherapy need to be evaluated.