The protective role evaluation of N-acetyl-cysteine and folic acid against aspartame-induced hepatotoxicity in albino rats

Abstract

Aspartame (ASP) is a synthetic sweetener consumed by more than half the adult population in 75 countries. Its metabolites can be toxic, principally to the retina, and there are a few studies on the effect of aspartame use in the liver. The present study was designed to examine the ability of N-acetylcysteine (NAC) and folic acid (FA),naturally occurring antioxidants, to attenuate ASP-induced hepatotoxicity in adult albino rats. Forty adult male Wistar rats, weighing 150-170 g, were randomly divided into four groups as follows: first group was given distilled water and served as control group I, Group II: received aspartame (ASP) dissolved in distilled water in a dose of 500 mg /kg. b.wt./day, Group III: received both NAC and FA dissolved in distilled water in a dose of 600 mg /kg b.wt./day and 12 mg/kg b.wt./day, respectively, and Group IV:  Rats received and both NAC and FA dissolved in distilled water in a dose of 600 mg /kg b.wt./day and 12 mg/kg b.wt./day, respectively and aspartame (ASP).Administration of ASP at a dose level of500 mg/kg b.wt. to rats for 42 days significantly elevated the levels of serum alanine   aminotransferase (ALT), aspartate  aminotransferase (AST), gamma-glutamyltransferase(GGT),tumor necrosis factor (TNF-α) and hepatic alphafetoprotein (AFP) activity which indicate injury to the liver function. Also, total cholesterol, triglycerides and low-density lipoprotein (LDL) increased significantly. On the other hand ASP decreased serum protein, albumin, high-density lipoprotein (HDL) and liver glutathione (GSH) and superoxide dismutase (SOD). While, ASP induced lipid peroxidation as indicated by markedly increased of malondialdehyde (MDA), these results reflects that ASP intoxication induced marked alterations in liver functions and caused liver atrophy. Combination of NAC (600 mg/kg b.wt.) and FA(12mg/kg b.wt), which administered 1h before ASP ameliorated the hepatotoxicity induced by ASP. This was evidenced by a significant reduction in serum ALT, AST, GGT, TNF-α and hepatic AFP activity and a significant restoration in serum protein, albumin, HDL, GSH and SOD.  Also, MDA decreased significantly after treatment with combination of NAC and FA. These results indicate that combination of N-acetylcysteine and folic acid has a strong potential effect against Aspartame-induced damage to liver. This reflects the beneficial role of N-acetylcysteine and folic acid in treatment of liver injury.