N-acetylcysteine is effective in ameliorating nephrotoxicity induced by low dose but not large dose of 5-Fluorouracil in rats.

Abstract

5-Fluorouracil (5-FU) is a common chemotherapy drug with demonstrated effectiveness in treating human cancer. However, hepatotoxic and nephrotoxic side effects limit its therapeutic value. This investigation exhibited the therapeutic influence of N-acetylcysteine (NAC) in 5-FU (20 and 50 mg) kidney injury in rats. For this purpose, 40 male rats were assigned into 5 groups. The 1st group was used as a control. The 2nd group was injected with 20 mg/kg of 5-FU i.p. for 6 days. The 3rd group received 5-FU at a dose of 50 mg/kg i.p. for 6 days. The 4th group received 5-FU 20 mg +NAC 40 mg/kg for 6 days. The 5th group supplied with 5-FU 50 mg + NAC 40 mg/kg. Biochemical assessment for serum urea, creatinine, uric acid, albumin, and inflammatory markers as TNF-α and IL-1β, and oxidative stress parameters as GSH and MDA were measured. 5‑FU nephrotoxicity was noticed by significant elevation of all renal parameters, such as creatinine, urea, uric acid, MDA, TNF-α and IL-1β, with a remarkable decline in albumin and GSH levels. NAC treatment improved the kidney status, especially induced by 20 mg 5-FU. So, NAC exhibited a remarkable effect in protecting nephrotoxicity caused by the low dose of 5-FU rather than using it with a high dose of 5-FU.