Faculty of Health Sciences
School of Medicine
Department of Physiology
Selected Highlights from Research Findings
Mammalian cells often use the extracellular signal regulated protein kinase (ERK) cascades to transmit intracellular instructions, including apoptosis. Since 2-methoxyestradiol (2ME) and prostaglandin A2 (PGA2) play a key role in the induction of apoptosis, their influence was investigated on ERK1/2 expression levels in three cancer cell lines. PGA2 exposure lead to a statistically significant increase in ERK1/2 expression levels of HeLa (cervical carcinoma) and WHCO3 (squamous oesophageal carcinoma) cells. In contrast to the HeLa and WHCO3 cancer cell lines, no effect on ERK1/2 expression levels was observed after exposure of PGA2 to MCF-7 (breast carcinoma) cells. 2ME caused a statistically significant increase in ERK1/2 expression levels in all three cancer cell lines. The characteristics of both PGA2 and 2ME render them as possible anti-tumor agents. Understanding the functional role of signaling events will provide new insights into mechanisms involved in malignant cell proliferation.
Contact person: Dr AM Joubert.
In response to mounting concerns about the influence of environmental chemicals on human health a cross-sectional epidemiological study was initiated by Prof Tiaan de Jager to specifically investigate the effects of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane) (DDT) on male reproductive health. One hundred and seventy men from Venda in the Limpopo province, where DDT is still sprayed, participated in the project. Semen analyses, toxicological target analyses, and hormone profiles were included. Various sperm parameters were affected and very high concentrations of DDT and metabolites were detected in the blood serum. The effects of DDT on seminal parameters may not be ignored and the project will be extended. In addition to the epidemiological approach, reproductive toxicology studies were performed. A general trend in decreased fertility parameters was observed after exposure of rats to a mixture of DDT, deltamethrin, nonylphenol and phytoestrogens. DDT and deltamethrin at environmentally relevant concentrations had negative effects on reproductive health, with phytoestrogens in combination with other EDCs showing synergistic effects.
Prof Bornman focuses on urogenital birth defects in newborns and the transfer of chemicals to the unborn baby during pregnancy. In collaboration with Prof Una MacIntyre from the University of Limpopo, the nutritional status and dietary intakes of men, women and children were first addressed. The nutritional value of the diets was described and the food intakes identified, which could contribute as exposure route.
These are the first studies in the world to be conducted in currently DDT-sprayed high-risk malaria areas. Although DDT has been banned for international use, countries like South Africa have restricted use for malaria vector control. South Africa is a signatory to the Stockholm Convention on the control of Persistent Organic Pollutants (POP's) including DDT, and now has the obligation to limit and control the release of substances like DDT into the environment. The studies provide invaluable data on human health effects of people currently exposed to DDT and will support the Department of Environmental Health and Tourism and National Government in assessing health risk. The findings have already lead to a pilot intervention project by the Agricultural Research Council to improve dietary quality in Resource Poor Farmers and again confirm the need for safer alternatives for malaria control.
Contact person: Prof MS Bornman.
The incidence of lifestyle diseases such as depression, cardiovascular disease, obesity, Type 2 diabetes and osteoporosis is escalating to alarming proportions in countries that have adopted a western lifestyle. Polyunsaturated (omega-3 and -6) fatty acids are increasingly used as a successful therapeutic strategy in these conditions. Research has focused on elucidating fatty acid action mechanisms in two areas, namely osteoporosis and diabetes type 2. In the first focus, a PhD study by Ms M Coetzee under supervision of Prof Marlena Kruger, Massey University, New Zealand and Haag has shown differential effects of arachidonic acid (omega-6) and docosahexaenoic acid (omega-3) on bone cell culture growth, differentiation and balance between osteoblast and osteoclast activity. In the second area, in which we co-operate with Drs Arnold Mouton of the Department of Gynaecology and Marcel Groot from Eugene Marais Hospital, we have shown that these fatty acids have major effects on insulin action in isolated fat cells obtained from human abdominal adipose tissue.
Contact person: Prof M Haag.
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