Effect of long term-administration of aspartame on adrenal gland histomorphometry and histochemistry in adult male NMRI mice

Aspartame is an artificial sweetener which is being consumed by over 200 million people in the world and also is widely used in foodstuffs and medicines in more than 90 countries. On the other hand, there are a great number of contradictory reports about its toxic effect on variety of tissues. However, there is a few of information about the adverse effects of aspartame on adrenal glands, so the present study has been conducted to evaluate the effects of aspartame on the adrenal glands in male mice. A total of 36 adult male NMRI mice weighing between 20 to 25 g were randomly divided into four groups of nine each. For three groups, aspartame was administered orally with the doses of 40 (low dose), 80 (medium dose) and 160 (high dose) mg/kg.BW respectively for 90 days by gavage. Also a control group was considered. 24 hours after the last treatment, histological and histomorphometrical alterations were evaluated by digital microscope. Also, specific stains of periodic acid schiff, trichrome masson and toluidine blue were used to determine carbohydrate compounds, amount of fibrosis and the number of mast cells in adrenocortical tissue. In the high dose group, aspartame led to disorganization of cellular orders in zona glomerulosa, and zona reticularis. Besides, aspartame could induce cellular disorganization and disintegration in cellular columns of zona fasciculata in medium and high dose groups, and also inflammatory and necrotizing centers of zona fasciculata were observable. There were some necrotizing centers in central region of adrenal gland, in medium and high dose groups. Histometric changes revealed a significant increase in the number of mast cells, the size of spongiocytes, and the thickness of zona fasciculate and zona reticularis. Also it caused a significant decrease in the larger diameter of medulla of the adrenal gland in medium and high dose groups. There were no significant changes in the thickness of zona glomerulosa and adrenal capsule. Histochemical study with masson's trichrome revealed that aspartame could induce increase in fibrose tissue in the high dose group. Also with periodic acid schiff staining, there were no sensible changes in relation with carbohydrate compounds in all groups. The findings of this study showed that aspartame as an oxidant, in medium and high dose groups, could induce negative effects on histomofometric parameters and caused tissue damage in the adrenal gland. It also increased the number of mast cells and fibrosis of the adrenocortical tissue.