The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin induced nephrotoxicity: A rat model.

Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers. Besides its chemotherapeutic effectiveness, cisplatin administration was associated with numerous side effects. Of these, the most clinically significant and common effect is nephrotoxicity. Recent studies reported that oxidative stress and inflamation are probably the most important mechanisms that contribute to the nephrotoxicity. N-acetylcysteine (NAC) is an antioxidant and anti-inflammatory agent. In the present study, the effects of NAC on cisplatin induced nephrotoxicity were investigated. Materials nad Methods: Rats were divided into four groups including eight rats: CONT, NAC-250, CP, CP+NAC. Rats in experimental groups were treated with a single dose intraperitoneally (i.p.) cisplatin (10 mg/kg body weight) and i.p. NAC (250 mg/kg body weight) for three consequitive days. Nephrotoxicity was determined by plasma BUN and creatinine levels. In tissue samples myeloperoxidase (MPO), nuclear factor-kappa B (NF-kB) and high mobility group box-1 (HMGB-1), Total oxidant status (TOS) and total antioxidant status (TAS) levels were measured. Kidneys were analyzed histopathologically as well.It was revealed that cisplatin was not effective on MPO, HMGB-1 and NF-kB levels but increased TOS levels and decreased TAS levels in tissue samples, interestingly NAC elevated MPO and HMGB-1 levels significantly. Nevertheless NAC ameliorated histological and functional changes in kidney tissues.It is suggested that inflammation has limited effect on cisplatin nephrotoxicity in this experimental design and as reflected by decreased BUN and creatinine levels NAC can be used as an additional therapeutic agent to standard cisplatin treatment protocols.