Abstract
Backgrounds Cisplatin (CP) still is a novel choice for solid tumor therapy, but it is accompanied with the side effect of nephrotoxicity. Hydration may reduce the risk of CP-induced nephrotoxicity, while the issue is still challenging. In this study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy. Methods Seventy-six male and female Wistar rats in 14 groups of experiments were subjected to CP therapy, and five types of hydration protocols were implemented, and the induced nephrotoxicity was evaluated via biochemical markers, kidney function parameters, and pathology investigation. Results Male and female rats had different responses to hydration protocol types. The higher mortality rate was seen in female rats that received mannitol or dextrose hydration types. In addition, the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) and sodium excretion fraction (ENa%) increased and the clearance of Cr (ClCr) decreased significantly (P < 0.05) in female rats hydrated with saline plus furosemide or mannitol plus saline-treated groups. The worsened condition in male rats is observed in the mannitol hydration group with a significant decrease of ClCr and significant increase of serum BUN and Cr and ENa% (P < 0.05). The higher kidney tissue damage score (KTDS) in the mentioned groups verified the findings. Conclusion Hydration with mannitol or dextrose promotes the risk of nephrotoxicity during CP therapy with more intensity on the female.
Highlights
Nowadays, cisplatin (CP) is recognized as a choice treatment for a wide range of solid tumors in clinic
Nephrotoxicity has still remained as the most common and important usage limiter of CP [2]. e kidney eliminates CP, while the main site of injury is in the renal epithelial cells of proximal tubule where the CP concentration increases to three times the serum concentration. erefore, the nuclear and mitochondrial DNA injury and cells death were performed, and the reactive oxygen species generation and inflammatory mechanisms are related in the CP-induced nephrotoxicity process [1, 3,4,5]
There are some risk factors for CP-induced nephrotoxicity including sex, history of renal dysfunction, drug dose, and the frequency of drug administration, older Journal of Toxicology age, female gender, and hypoalbuminemia [1, 5, 6], while diabetes and organic cation transporter 2 (OCT2) polymorphisms are considered as decreased risks factors for CPinduced nephrotoxicity [1]
Summary
Cisplatin (CP) is recognized as a choice treatment for a wide range of solid tumors in clinic. There are some risk factors for CP-induced nephrotoxicity including sex, history of renal dysfunction, drug dose, and the frequency of drug administration, older. By hydration with or without diuretic, the renal excretion is increased, and the contact duration of drug with the renal tubules is decreased, and the risk of CP-induced nephrotoxicity may attenuate, but the issue is still challenging. In this current study, five types of hydration protocols including saline, mannitol, dextrose saline, saline plus furosemide, and saline plus mannitol were examined in both sexes of rats during CP therapy, and the induced nephrotoxicity was evaluated
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