{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T14:23:15Z","timestamp":1788445395278,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Experimental Path"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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\u2010term administration of ASP in various organ tissues. However, there is little evidence available about the nature and mechanisms of the adverse effects of long\u2010term 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\u2009mg\/kg, 80\u2009mg\/kg and 160\u2009mg\/kg ASP orally, for 90\u2009days. ASP at the doses of 80 and 160\u2009mg\/kg increased the serum content of malondialdehyde (MDA), but decreased serum nitric oxide (NO), creatine kinase (CK) and CK\u2010MB, as well as blood superoxide dismutase (SOD) levels. Serum level of total anti\u2010oxidant capacity (TAC) in blood was also reduced in serum at the dose of 80\u2009mg\/kg. Histochemical staining, including Periodic acid\u2010Schiff, Masson's trichrome and Verhoeff\u2010van Gieson staining, indicated that ASP at doses of 80 and 160\u2009mg\/kg reduced glycogen deposition and decreased the number of collagen and elastic fibres in the cardiac tissue. The cardiac expression of pro\u2010apoptotic genes, including P53, Bax, Bcl\u20102 and Caspase\u20103, was modulated at the dose of 160\u2009mg\/kg. Moreover, transcription of Caspase\u20103 was up\u2010regulated at the dose of 80\u2009mg\/kg. In conclusion, long\u2010term consumption of ASP any higher than the acceptable daily intake (40\u2009mg\/kg) appears to act by promoting oxidative stress, has the potential to alter both histopathological and biochemical parameters, and induces P53\u2010dependent apoptosis in cardiac tissue.<\/jats:p>","DOI":"10.1111\/iep.12458","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T16:45:52Z","timestamp":1666025152000},"page":"252-262","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Long\u2010term intake of <scp>aspartame\u2010induced<\/scp> cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and trigger <scp>P53\u2010dependent<\/scp> apoptosis in a mouse 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