Long‐term intake of aspartame‐induced cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and trigger P53‐dependent apoptosis in a mouse model

Abstract

Aspartame (ASP) is probably the best known artificial sugar substitute that is used widely in food. Many experimental studies have reported the toxicity of long‐term administration of ASP in various organ tissues. However, there is little evidence available about the nature and mechanisms of the adverse effects of long‐term consumption of ASP on the cardiovascular system. This study was conducted to evaluate the possible effects of ASP on heart tissue. For this study 36 mature male mice were divided into one control group and three groups which received respectively 40 mg/kg, 80 mg/kg and 160 mg/kg ASP orally, for 90 days. ASP at the doses of 80 and 160 mg/kg increased the serum content of malondialdehyde (MDA), but decreased serum nitric oxide (NO), creatine kinase (CK) and CK‐MB, as well as blood superoxide dismutase (SOD) levels. Serum level of total anti‐oxidant capacity (TAC) in blood was also reduced in serum at the dose of 80 mg/kg. Histochemical staining, including Periodic acid‐Schiff, Masson's trichrome and Verhoeff‐van Gieson staining, indicated that ASP at doses of 80 and 160 mg/kg reduced glycogen deposition and decreased the number of collagen and elastic fibres in the cardiac tissue. The cardiac expression of pro‐apoptotic genes, including P53, Bax, Bcl‐2 and Caspase‐3, was modulated at the dose of 160 mg/kg. Moreover, transcription of Caspase‐3 was up‐regulated at the dose of 80 mg/kg. In conclusion, long‐term consumption of ASP any higher than the acceptable daily intake (40 mg/kg) appears to act by promoting oxidative stress, has the potential to alter both histopathological and biochemical parameters, and induces P53‐dependent apoptosis in cardiac tissue.

Aspartame Safety as a Food Sweetener and Related Health Hazards

“…Several in vivo and in vitro studies revealed altered scavenging mechanisms, increased lipid peroxydation, and enhanced generation of ROS/RNS in the erythrocytes or serum of aspartame-treated animals [ 20 , 98 , 99 ] or in human neuroblastoma cells [ 100 ]. The imbalance in ROS/RNS neutralization induced by aspartame can affect neutrophil adhesion, the phagocytic index, as well as antibody titers and soluble immune complexes in phagocytic and immune system cells, including neutrophils and lymphocytes [ 99 ].…”

An in Vitro Model of Aspartame Cytotoxicity via Heterologous Expression of Nmda Receptors

“…Recent cohort studies also evidenced increased risk for cardiovascular diseases associated to high aspartame intake [15]. Several in vivo and in vitro studies have shown increased production of reactive oxygen/nitrogen species, lipid peroxydation and changes in scavenging systems in erythrocytes or serum of aspartame-treated animals [2,11,41] or in human neuroblastoma cells [21].…”