Role of N-Acetylcystein in Protection against Cisplatin Nephrotoxicity

Habib, Sahar; Ramzy, Maggie; Abd Elghany, Manal

doi:10.21608/besps.2010.36179

Role of N-Acetylcystein in Protection against Cisplatin Nephrotoxicity

Document Type : Original Article

Authors

¹ Forensic Med. And Toxicology Department, Faculty of Medicine, Minia University

² Biochemistry Department, Faculty of Medicine, Minia University

³ Pathology Department, Faculty of Medicine, Minia University

10.21608/besps.2010.36179

Abstract

Background: Cisplatin (CDDP) is a cytotoxic therapeutic agent that causes many
physiological adverse effects such as nephrotoxicity. Although N-acetylcystein (NAC)
a thiol containing antioxidant, has been documented to be effective in attenuating
CDDP induced renal injury, the precise mechanisms involved in its renoprotection
have not been completely clarified. Methods: Four groups of albino rats were used.
The first group injected by saline as control, the second by NAC (i.p.), the third by a
single bolus of cisplatin (i.v.), and the last by NAC/CDDP, after 5 days from CDDP
injection, investigations were conducted on the levels of serum urea and creatinine,
oxidant/antioxidant status by estimation of malondialdehyde, catalase and reduced
glutathione, and renal and systemic tumor necrosis factor-alpha (TNF-α). Also, renal
tissues were examined histopathologically. Results: Administration of cisplatin to rats
induced a significant increase in serum urea and creatinine levels in addition to
severe alterations in renal tissue architecture. Cisplatin also increased
malondialdehyde and decreased glutathione, and catalase in renal tissues. Also,
CDDP increased both renal and systemic TNF-α. Administration of NAC markedly
reduced the cisplatin-induced higher serum creatinine and urea levels and
counteracted the effects of cisplatin on oxidative stress markers, protected the tissues
from the cisplatin-induced lipid peroxidation, and increased TNF-α and improved
renal tissue architecture. Conclusion: NAC protection is mediated by preventing the
decline of antioxidant status, inhibit malondialdehyde and TNF-α and prevent
necrosis and apoptosis from kidneys. These results have implications in use of NAC in
human application for protecting against drug-induced nephrotoxicity.

Keywords