The Protective Effects Of N-acetylcysteine On Cisplatin-induced Nephrotoxicity In Mice

Objective The purpose of our study is to discuss the role of N-acetyl cysteine on cisplatin-induced nephrotoxicity in mice.Methods Adult male C57/BL6 mice(20-25g)were randomly divided into six gr oups as follows(1) saline-treated control group(2) cisplatin group(3) cisplatin + N- acetylcysteine group(4) N-acetylcysteine group(5) Cisplatin + cimetidine g roup(6) cimetidine group. Groups(2),(3),(5) were treated with 22 mg/kg body weight of cisplatin by intraperitoneal injection on the first day of our experimen t. Group(1) was given saline by intraperitoneal injection for 3 days, Groups(3),(4) were treated with N-acetylcysteine daily for 3 days,and Groups(5),(6) were gi ven cimetidine for 3 days. We collect the serum to test the level of creatinine a nd urea nitrogen reflecting kidney fuction after 72 h. PAS staining was used to ob serve the pathology of the kidney. C5 a R were tested by Immunohistochemistry(I HC) and immunofluorescence(IF). RT-PCR was conducted for C5 a R,TNF-a,I CAM-1,IL-1? expression. Western blot(WB) was used to detect the expression C5 a R.Result The test results of creatinine and urea nitrogen showed that cisplatin induced acute renal failure, N-acetylcysteine intervention group indicated less renal damage,cimetidine intervention group showed no significant changes in renal function. Immunohistochemistry and immunofluorescence suggested that N-acetylcysteine treatment can reduce the expression of C5 a R after cisplatin-induced kidney injury. RT-PCR showed that N- acetyl cysteine intervention group reduced the amount of m RNA expression of TNF-a, ICAM-1, IL-1 ?and C5 a R. We also found that Nacetylcysteine intervention group decreased expression of C5 a R by Western Blot.Conclusion N-acetylcysteine could ameliorate cisplatin-induced nephrotoxicity in mice and the protective effects maybe be conducted by inhibiting the activation of kidney inflammation and the complement system.But further studies are needed to clarify the specific mechanism how N-acetyl cysteine affects inflammation and the complement system.