The Preventive Effects of N-Acetylcysteine on Tacrolimus Induced Nephrotoxicity
Journal Title: IOSR Journal of Pharmacy (IOSRPHR) - Year 2018, Vol 8, Issue 9
Abstract
Tacrolimus exhibits its nephrotoxic effect in relation to its inhibition of one of the antioxidant enzymes named catalase. Glutathione peroxidase catalysesa similar reaction done by catalase. The factor which increases GPx’s activity is Glutathione levels.Subsequently, Glutathione levelsare increased by N-Acetyl cysteine (NAC). Thus, it seems NAC can influence the prevention of Tacrolimus mediated nephrotoxicity. In this study,Sprague-Dawley ratsreceived1 mg/kg/day dose of tacrolimus in the control group while the three treatment groupsreceived 1mg/kg/day of tacrolimuswith NAC in 100,200 and 300 mg/kg/day doses respectivelyfor 28 days. Upon study completion, the biochemical markers of tacrolimus nephrotoxicity (urinary microalbumin,serum creatinine and BUN) showed dramatic increase in both the control group and in the three treatment groups. Urinary microalbumin levels showed significant decrease with 300 mg/kg NAC dosing (p<0.01). Furthermore, serum creatinine levels showed significant decrease in all three doses (p<0.05) while BUN showed significant decrease in NAC 100 and 200 mg/kg doses (p<0.01) and 300 mg/kg dose (p<0.001). In the control group on tacrolimus alone, an increase in interstitial fibrosis and tubular atrophy- two important markers of chronic tacrolimus nephrotoxicity- was observedwhereas in contrastthe NAC treatment groups revealed a significant decrease in interstitial fibrosis (p<0.05 in NAC 200 and 300) and tubular atrophy (p<0.05 for NAC 200 and 300). These findings confirm the nephroprotective effects of N-acetylcysteine in chronic tacrolimus nephrotoxicity which acts in a dose dependent manner.
Authors and Affiliations
Afsaneh Azhari, Atila Karaalp, Reza Fathi, Ranim Shartouni, Maryam Mahmoodi Momenabadi, Nilgun Uzun, Sukran Sarikaya, Nimet Karadayi, Hamed Jalilipour Nikvar
Keywords
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