The Effect of Testosterone and Estradiol on Renal Function Markers in Two Protocols of Cisplatin Induced Nephrotoxicity Models in Surgically Orchiectomized and Ovariectomized Rats

Abstract

Background: The major side effect of cisplatin (CP) therapy in patients with cancer is nephrotoxicity, which limits the treatment. In two protocols of CP treatments, we tested 3 weeks of hormone therapy against CP induced nephrotoxicity in bilateral orchiectomized (OR) and ovariectomized (OV) rats. Methods: A total of 101 OR and OV rats were subjected to receive 3 weeks of testosterone (Ts, 10 mg/kg/week) and estradiol (Es, 250 mu g/kg/week), respectively, followed by two protocols of CP therapies; continuous (divided) doses (3 mg/kg/day for period of 5 days) as protocol 1 and single dose (7.5 mg/kg) as protocol 2. The measurements were performed by the end of the 4th week. Results: CP increased the serum levels of blood urea nitrogen (BUN) and creatinine (Cr) in both OR and OV rats, which were related to the protocols of CP treatments. Es (not Ts) in protocol 2 attenuated the serum levels of BUN and Cr. Ts significantly increased body weight loss in protocol 1 compared with control group (P < 0.05). Es did not attenuate kidney tissue damage score (KTDS) in protocol 1 treated animal, but KTDS was decreased by Es in protocol 2 treated Rats. Hormone replacement therapy did not alter Cr clearance compared with control group. Conclusions: It seems that hormone therapy could not protect the kidney against CP induced nephrotoxicity.