[Protective effect of amifostine on cisplatin-induced nephrotoxicity and its mechanism].
OBJECTIVE
To investigate the sites and pattern of renal toxicity in rats treated with cisplatin and the protective effect of amifostine, and to understand whether Fas/FasL system is involved in cisplatin-induced nephrotoxicity.


METHODS
Forty-eight Sprague-Dawley rats were randomly divided into 3 groups: control group (0.9% saline solution), cisplatin group (6 mg/kg) and amifostine group (cisplatin 6 mg/kg + amifostine 200 mg/kg). Serum BUN and creatinine were measured by automatic biochemiscal analysis. Renal histopathological lesions were examined by light microscopy. TUNEL method was used for counting apoptotic cells. Immunohistochemistry and image analysis system were used for observing the expression of Fas/FasL system in renal tissues.


RESULTS
Compared with control group and amifostine group, serum BUN and creatinine were significantly elevated on day 3 (P < 0.05) and day 5 (P < 0.01 and P < 0.05, respectively), and recovered to normal on day 10. Severe necrosis and apoptosis of renal proximal tubular cells were revealed by elevated number of positively staining apoptotic cells examined by TUNEL method. Increased immunostaining intensity of Fas/FasL system in renal tissues in cisplatin-treated group was detected by immunohistochemistry and image analysis system.


CONCLUSIONS
Amifostine can reduce cisplatin-induced nephrotoxicity and its mechanism is probably associated with the suppression of Fas/FasL expression in renal tissues.
Guo
Ye
Y
Department of Chemotherapy, Tumor Hospital, Fudan University, Shanghai 200032, China.
Liu
Ye
Y
Xu
Li-gong
LG
Guo
Mu-yi
MY
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D053222:Fas Ligand Protein / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009336:Necrosis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor; D003404:Creatinine; D004999:Amifostine; D002945:Cisplatin