Neurotoxic Effect of Aspartame on the Sciatic Nerve of Adult Male Albino Rat and the Possibility of Spontaneous Recovery: Light and Electron Microscopic Study

Abstract

Background: Aspartame is considered the most widely used nocaloric artificial sweetener. It is used in a variety of food products and beverages. However, the consumption of aspartame has been controversial as several studies have reported an association between its use and many serious diseases.

Can Aspartame Induce Reversible Cerebellar Changes?

“…While many researchers found partial improvement in the recovery groups for one month, such as Mohamed [24], who stated that the recovery from aspartame was partial and explained this recovery by the scavenging of free radicals that are naturally present in cells, which are the antioxidant process that neurons may activate. which matched with the ndings of another author who claimed that microglial cells may aid brain repair by releasing cytokines and growth factors [25]. Moreover, Omar [24] reported improvement in necrosis index, anti-NSE immunostaining and the amount of GFAP in frontal cortex four weeks after dosing of aspartame.…”

“…In the liver, Methanol forms about 10% of aspartame is transformed into formaldehyde [25]. They are neurotoxic and cause DNA destruction [26].…”

“…Moreover, Omar [24] reported improvement in necrosis index, anti-NSE immunostaining and the amount of GFAP in frontal cortex four weeks after dosing of aspartame. Bekheet et al [25] demonstrated that After four weeks without aspartame, spontaneous healing wasn't complete and recommended longer recovery for evaluation.…”

The Protective Effect of L-Arginine against Aspartame-Induced Toxicity on Adrenal Cortex of Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study

“…So, adrenal gland is sensitive to different noxious compounds (21) Egyptian Journal of Cell and Tissue Research (EJCTR), Volume 2, Issue 1, January, 2024 ___________________________________________________________________________ https://ejctr.journals.ekb.eg/ Additionally, according toEnciu etal., 2020 (44) , the decreased activity of reduced Glutathione and increased that of MDA lasted for 42 days after the cessation ofaspartame treatment. This was also reported byBekheet and Rady, 2020 (15) who stated that aspartame termination treatment for four weeks was insufficient for restoring the frontal cortex to its normal histologicalfeatures after chronic aspartame consumption in rats. Therefore, it is crucial to note that even when daily consumption of aspartame has stopped, aspartame-induced Aldosterone plays a role in controlling electrolyte and fluid homeostasis through the mineralocorticoid receptor activation, which leads to increased muscle tone of the blood vessels with subsequent increased renal absorption of water and sodium, so the primary aldosteronism is considered the leading cause of secondary hypertension (52).…”

“…The excess cytoplasmic vacuolation observed in the aspartame group (III) was apparently decreased after the administration of L-arginine resulting in significant decrease in themean thickness of ZF in group (IV). Effectiveness of L-arginine in preventing fat accumulation in adrenal cortical cells was most likely due its role in attenuating the oxidative stress which impairs the utilization of cholesterol in steroidogenesisand hence decreasing the release of ACTH and cortisol responsible for the hypertrophy of zona fasciculata (ZF) (33).In the current work, recovery group (V)showed incomplete improvement in the histological and biochemical aspects after 4 weeks of aspartame consumption's stoppage.Egyptian Journal of Cell and Tissue Research (EJCTR), Volume 2, Issue 1, January, 2024 ___________________________________________________________________________ https://ejctr.journals.ekb.eg/ These results were supported byBekheet and Rady, 2020(15) who reported that 4 weeks' cessation of aspartame consumption by the rats was insufficient to retain the sciatic nerve histological organization.By Masson's Trichrome stain, the capsule in the aspartame group(III) appeared detached and distorted with decreased thickness resulting in significant decrease in the mean area % of collagen fibrescompared to the other This mimics the observation ofMcKay etal., 2021 (34) who stated that L-arginine supplementation could influence all extra cellular matrix protein secretion especially collagen I secretion from the fibroblast. Aspartame group(III) showed upregulation of Caspase-3 expression inthe immunohistochemical stained sections, with many cells exhibiting +ve reaction in all zones of adrenal cortex.Morphometric analysis proved a significant increase in their mean area as compared with other groups.…”