الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 142 |  |  |
| | | from | 142 | | |
Abstract
Aspartame is one of the most widely used artificial sweeteners in over 90 countries worldwide in over 6000 products. It is found in carbonated and powdered soft drinks, hot chocolate, chewing gum, candy, desserts, yogurt and tabletop sweeteners, as well as some pharmaceutical products like vitamins and sugar-free cough drops.
Chronic exposure to aspartame has been shown to induce oxidative stress and lipid peroxidation. For this reason, it shows species and organ toxicity such as liver, kidney, brain and testis.
The present study was designed to study the chronic toxic effects of aspartame and the possible protective role of NAC and vit C. The study lasted for 90 days.
It was conducted on 70 sexually mature male albino rats divided into seven groups, ten rats each. group I was considered as negative control group, group II received NAC dissolved in distilled water in a dose of 600 mg/kg body weight (b.wt)/day. group III, animals received ascorbic acid dissolved in distilled water in a dose of 200 mg/kg b.wt./day. group IV received ASP dissolved in distilled water was given in a dose of 100 mg/kg b.wt./day. group V received aspartame dissolved in distilled water was given in a dose of 100 mg/kg b.wt./day plus NAC dissolved in distilled water in a dose of 600 mg/kg b.wt./day. group VI received ASP dissolved in distilled water was given in a dose of 100 mg/kg b.wt./day plus ascorbic acid dissolved in distilled water in a dose of 200 mg/kg b.wt/day. GroupVII received ASP dissolved in distilled water was given in a dose of 100 mg/kg b.wt./day plus a combination of NAC and ascorbic acid.
At the end of the experiment, blood samples were taken from retro-orbital blood vessels. Each sample was divided into 2 parts; one for measurement of serum ALT and AST and the other part was used for measurement of serum testosterone level.
After sacrification of the animals by cut throat, liver and testicular biopsies were routinely processed, formalin fixed and paraffin embedded according to the usual schedule used in the laboratory.
The biochemical results of the present study of liver enzymes showed a statistical significant rise of serum level of ALT (95.50±19.69 u/l) and AST (203.20±34.51u/l) in aspartame treated group (IV) as compared to the negative control group (I) which were (49..60± 15.05 u/l), (126.80± 41.25 u/l) respectively, and the positive control groups treated with NAC (II) or vit C (III) as ALT values were (48.80±14.66 u/l, 50.20±13.77 u/l) respectively and AST values were (120.60±16.53 u/l, 121.20±39.76 u/l) respectively.
Antioxidant administration of NAC, vit C or together to aspartame treated rats resulted in significant decrease in liver enzymes compared to aspartame treated group.
In the present study, rat group treated with aspartame plus NAC (group V) showed nearly normal levels of ALT (67.40±20.13 u/l) and AST (159.20±36.56 u/l) compared to aspartame treated group (IV).
In aspartame plus vit C treated group (group VI), there was a statistical significant decrease in the mean value of serum ALT and AST compared to aspartame treated group (IV) (76.20±17.5 u/l, 164.80±38.16 u/l respectively) reporting the hepatoprotective effect of vit C against various oxidants including aspartame.
In the present study, it was found that prophylactic therapy by dual antioxidants like NAC and vit C showed marked decrease in the mean values of ALT (64.40±17.52 u/l) and AST (158.80±50.33 u/l) compared to aspartame treated group with ALT (95.50±19.69 u/l) and AST (203.20±34.51 u/l) reflecting its potent hepatoprotection.
Testosterone is the main secretary product of testis and acts as both an endocrine and local factor within the testis. In the present study, aspartame was given to male albino rats in a dose of 100 mg/kg/b.wt. for 90 days. A significant statistical decrease in the mean value of testosterone level was detected (1.694±0.406 nmol/ml) as compared to the control group (3.226±0.73 nmol/l).
Testosterone level of aspartame treated rats showed a significant decrease in serum testosterone (1.694±0.406 nmol/l) compared to control groups II and III (3.290±0.987 nmol/l and 3.464±0.832 nmol/l) respectively.
Administration of NAC, vit C either separate or together prior to aspartame administration resulted in significant increase in the mean value of serum testosterone level compared to aspartame treated group as they showed a significant rise in serum testosterone level in NAC (V) or vit C treated (VI) (2.720±0.497 nmol/l and 2.40± 0.774 nmol/l respectively) compared to aspartame treated group (1.694±0.41 nmol/l). Regarding the combination of both NAC and vit C with aspartame, it showed restoration of normal or near normal serum testosterone levels (2.804±0.78 nmol/l) as compared to aspartame treated group (1.694±0.41 nmol/l) reflecting the antioxidant role of NAC, vit C or both in preventing oxidative damage to the testes by aspartame.
In the present study, pathological changes were observed in the liver when aspartame was given orally in a dose of 100mg∕kg daily for 90 days. These pathological changes were in the form of disorganization of hepatic parenchyma. Vascular dilatation and congestion were observed particularly in the portal area with portal mononuclear infiltrate and peripheral necrosis of hepatocyte with pyknotic nuclei. The histopathological lesions observed were corresponding to the change in transaminases level, however the control groups I, II and III showed a normal hepatic architecture.
Light microscopic examination of aspartame plus NAC and vit C or both (V, VI, VII) groups revealed improvement of hepatic architecture. Normal hepatic cords radiating from centrilobular veins with restoration of normal appearance of hepatocytes (acidophilic cytoplasm and vesicular basophilic nuclei). Mild congested centrilobular venule and mild portal mononuclear infiltration were observed when compared to aspartame treated group. These results were in accordance with the biochemical results of the present study which partially normalized when NAC, vit C separate or together were given prior to aspartame ingestion.
Histopathological examination of testis specimen stained by H&E, animals treated with aspartame showed disorganization of seminiferous tubules, sometimes with reduced sperm count and intertubular hemorrhage compared to a normal microscopic picture of the testis regarding seminiferous tubules and interstitial tissues in control groups.
Histopathological alterations were markedly reduced with improvement of seminiferous tubules and increased number of sperms within it when NAC, vit C or both were administered to aspartame treated groups (V, VI, VII). These results were in accordance with the biochemical results of the present study with the rise of serum testosterone levels in these study groups showing the protective effect of these antioxidants against aspartame damage to the testes.
Conclusion
o Aspartame intake for 90 days was associated with hepatic damage and biochemical changes in liver function regarding elevation of serum transaminases (ALT and AST) with disorganization of hepatic parenchyma, tissue necrosis and congested hepatic veins.
o Aspartame intake for 90 days was associated with a significant decrease in testosterone levels with degenerative changes in seminiferous tubules.
o Administration of NAC and vit C either separate or combined resulted in protection to larger extent of hepatic biochemical parameters and preservation of hepatic architecture.
o A significant increase of testosterone level with preservation of normal structure of seminiferous tubules and testicular architecture were observed when NAC and vit C were administered either separate or combined to aspartame treated rats.
Recommendations
The daily dose of aspartame should be less than the FDA approved dose 50 mg/kg.bw.day, this dose should be reviewed.
Further studies should be carried out on aspartame in different doses to show their effects upon other body organs as brain, kidney, pancreas….etc
Further studies should be carried out on chronic aspartame toxicity and its effects on testes regarding the quality of semen parameters in humans.
Antioxidants like NAC and vit C have a free radical scavenging effects, so they showed protective effects on the liver and testes, so more studies should be done to judge their effects against other oxidants.
Studying the effect of antioxidants other than vit C and NAC should be conducted specially those found naturally in food.