Effects of aspartame on the blood coagulation system of the rabbit

Abstract

Aspartame is a dipeptide sweetener that can be found in most of the sugar-free products available on the market today. The FDA approved the use of aspartame, but ever since the safety of the consumption of aspartame has been questioned. Thus the aim of this thesis was to determine the effects of aspartame ingestion on the blood coagulation system and the blood filtering organs (liver and kidneys) of the rabbit. The protocol for obtaining blood from a rabbit as well as successful administration of aspartame was perfected. The rabbit was proven as best experimental model, when compared to a mouse, for studying the effects of aspartame on coagulation and haemostasis. The effects of aspartame were determined by: 1.) measuring the factors from the different coagulation pathways, namely the common pathway (factors II, V, X and fibrinogen); factors in the intrinsic pathway (factors VIII, IX), as well as factor VII, found in the extrinsic pathway. The prothrombin time (PT; measures how long blood takes to form a clot) and activated partial thromboplastin time (aPTT; measures recalcification time of plasma) was also measured; 2.) The ultrastructure of the fibrin networks, platelet morphology and endothelial lining were studied; 3.) The histological morphology of the leukocytes, liver and kidney were examined. Results obtained indicated that F VII, X and VIII were decreased with a prolonged prothrombin time. The concentration of circulating fibrinogen increased significantly, which corroborated with results obtained for the ultrastructure of the fibrin networks. The degree of fibrin fibre formation increased the higher the concentration of aspartame and the degree of platelet aggregation occurring, decreased with the increase of aspartame concentration. It is hypothesized that the amount of circulating serotonin decreased. The endothelial lining of the rabbits were damaged with the nuclei appearing apoptotic. The endothelial lining and their tight junctions play an integral part in the functioning of the BBB, in synchronization with cAMP (complexity of tight junctions, decreased due to decreased amount of serotonin), thus it appeared as though the BBB was compromised. The morphology of the leukocytes were altered, specifically that of the eosinophils and heterophils. The granules inside the eosinophils of the aspartame treated rabbit appeared to have increased and were more clearly visible, while the granules in the heterophils appeared to have decreased. The total number of leukocytes also decreased. Thenormal histological morphology of both the liver and kidney were affected by aspartame. Damage to the hepatocytes and their subsequent arrangement were noted. The visceral layer of the capsule of Bowman appeared thickened and the cuboidal epithelium lining the proximal convoluted tubule was also damaged The final judgment and conclusion of the results obtained in this thesis regarding the consumption of abuse doses of aspartame, was that aspartame could lead to bleeding disorders (especially in genetically predisposed individuals), suppressed immunity and a compromised BBB. Trouble can occur with formation of the glomerular filtrate and absorption of fluid from the proximal convoluted tubule, which could result in high blood pressure and an increased probability of dehydration respectively.