BACKGROUNDS: Cisplatin (CP) as an anticancer drug may affect the plasma glucose level while diabetic subjects are protected against CP-induced nephrotoxicity. In the current study, the role of dextrose hydration during CP therapy on CP-induced nephrotoxicity was evaluated.METHODS: Sixty-nine male and female rats were divided into 12 groups. The rats were hydrated with 15 mL/kg vehicle or different doses of 2%, 10% and 20% dextrose before and after 7.5 mg/kg CP administration. One week later, the biochemical and kidney function markers, and histology finding were determined.RESULTS: All the animals co-treated with CP and 20% dextrose, were dead during one week of the experiment. Administration of CP alone increased kidney tissue damage score (KTDS) and kidney weight (KW). It also elevated the blood urea nitrogen (BUN) and BUN-creatineine ratio (BUN/Cr) levels in the serum. In addition, CP decreased body weight and creatinine (Cr) clearance (ClCr) significantly in both male and female rats (p<0.05). However, 2% and 10% dextrose did not alter the mentioned parameters in male, but 10% dextrose supplement increased the serum levels of BUN, Cr and BUN/Cr ratio, KW and KTDS significantly in female rats (p<0.05).CONCLUSION: Our data suggest that not only do not support the nephro-protective role of dextrose hydration during CP therapy, the dextrose hydration can act as risk factor to promote CP-induced nephrotoxicity in female rats. Prohibition of high carbohydrate (glucose) diet during CP therapy is recommended.KEYWORDS: cisplatin, nephrotoxicity, dextrose, rat, gender
Introduction: Cisplatin (CP) is an anti-cancer drug with the most common side effects of nephrotoxicity. Losartan, an angiotensin II type 1 receptor (AT1R) antagonist and angiotensin 1-7 (Ang1-7) protects the kidney against CP administration in males Moreover, the activity of the renin angiotensin system (RAS) and the incidence of CP induced nephrotoxicity are gender related. Objectives: The role of Ang1-7 and losartan against CP induced nephrotoxicity in female rats was examined. Methods: Thirty-two female Wistar rats in five experimental groups were treated with vehicle, single dose of CP (7.5 mg/kg), CP+losartan (10 ), CP+Ang1-7 (30 μg/kg/d) or CP+Ang1-7+A779 (Mas receptor antagonist, 100 μg/kg/d). The biochemical and histology measurements were conducted one week later. Results: The levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in serum increased insignificantly by CP alone administration. However co-treatment of CP with losartan, Ang1-7, or Ang1-7 plus A779 showed an increase of the serum levels of BUN and Cr, and kidney tissue damage score (KTDS) (P < 0.05) when compared with control groups. Conclusion: The AT1R and Mas receptor (MasR) antagonists and Ang1-7 administration promote the CP induced damage of kidney in female rats, and special attention is needed during CP therapy in hypertensive patients who are treating with anti-hypertensive drug of losartan.
Background: Cyclosporine (CYC) is an immunosuppressant drug used widely in kidney transplant patient. The major side effect of CYC is nephrotoxicity. In this study, three different doses of CYC alone or accompanied with zinc (Zn) supplement were administrated in male and female rats to determine the kidney tissue damages and functions. Methods: Male and female rats were treated with 10, 50 or 100 mg/kg/day of CYC alone or accompanied with 10 mg /kg/day of Zn sulfate for 10 days. The parameters related to renal function were determined and the kidney tissues were subjected to histological evaluation. Results: All male and female animals were treated with high dose CYC (100 mg/kg/day) alone or accompanied with Zn supplement during the experiment. The data obtained for the serum levels of creatinine (Cr) and blood urea nitrogen/Cr ratio, clearance of Cr, kidney weight (KW), sodium (Na) filtration rate, Na excretion rate and Na excretion fraction (%) in surviving animals suggest a role of gender in the variation of these factors. The kidney tissue damage score (KTDS) was increased as the dosage of CYC was elevated, and the Zn supplement attenuated the KTDS in animals treated with low dose CYC (10 mg/kg/day). Conclusion: The CYC-induced nephrotoxicity may be gender-related, and the 10 mg/kg dose of Zn sulphate as a supplement may possibly prevent the induced nephrotoxicity in males due to its antioxidant effects.
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