The Therapeutic Applications of Medium-Chained Saturated Fatty Acids in the Treatment and Prevention of Intestinal Protozoal Infections
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Giardia duodenalis is a protozoal, intestinal parasite that is a common aetiological agent of infectious diarrhoea in humans worldwide. Chemotherapeutic intervention presently offers a limited range of drugs and these are usually only employed after clinical diagnosis. Moreover, these drugs are ineffective against the infectious cysts, can produce unpleasant side effects, and are expensive with limited availability in developing countries. Frequent reports of drug toxicity, treatment failure and parasite drug resistance have, in some instances, also resulted in the increasing reluctance to over-prescribe synthetic anti-microbials. Alternatively, there is now mounting evidence to suggest that some of the naturally derived, mediumchain, saturated fatty acids (MCSFAs) possess anti-microbial and antiparasitic properties. I have therefore examined the effects of four different fatty acids on G. duodenalis trophozoites in vitro. Cytotoxicity was determined using fluorescence, scanning and transmission electron microscopic techniques and standard cytotoxicity assays. My studies have confirmed that the MCSFA, dodecanoic acid (C:12; common name lauric acid; DA), is anti-giardial with an LD50 concentration comparable to that of metronidazole, the drug of choice in the treatment of giardiasis. DA appears to induce trophozoite death by accumulating within the parasite cytoplasm resulting in rupture of the cell membrane. In vivo trials in mice using DA and coconut oil (which consists of 45-55% DA) as dietary supplements have also appeared promising against G. duodenalis infection, however the water soluble derivative, monolaurin (C:15; dodecanoic acid, 2,3-dihydroxypropyl ester) did not. These studies have opened fresh avenues for development of natural drug therapy in which food supplementation may augment, or even replace, some of the standard chemotherapeutic agents presently employed in the treatment of giardiasis and possibly other infectious intestinal diseases. In order to develop an alternate model to further our research goals, 3-D tissues grown in vitro were used to explore disease pathogenesis, which could possibly replace expensive experimental animal models. Tissue engineering is a relatively modern and expanding field of medical research working to develop appropriate models and technologies to promote the regeneration of human tissues. This includes the restoration of tissue and organ function via creating biological substitutes in place of harvested tissues, artificial implants and prostheses. Full clinical regeneration of a tissue encompasses the source of suitable cell types, encouraging these cells to grow into an appropriate, fully functioning, three-dimensional (3-D) tissue, and incorporating this tissue successfully into the recipient. Likewise, three dimensional tissues employed in medical research would reduce the need for several animal experimentation protocols, particularly in the fields of tropical medicine with emphasis on parasitology.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
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