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Abstract
The in vitro effects of detergent sclerosants, sodium tetradecylsulphate (STS) and
polidocanol (POL) on cell activation, cytokine release, apoptosis and oncosis were
investigated. The general hypothesis of this thesis was that detergent sclerosants at low
concentrations induce the release of proinflammatory and proangiogenic cytokines.
Leukocytes, platelets, and endothelial cells (ECs) were incubated with varying concentrations
(0%, 0.075%, 0.15%, 0.30%, 0.60% and 1.2%) of sclerosants. ELISA was used to detect the
release of proinflammatory and proangiogenic cytokines. Interferon-g and tumour necrosis
factor-a were released from STS-stimulated polymorphonuclear cells (PMNC). Both
sclerosants induced the release of vascular endothelial growth factor (VEGF).
Morphological changes were analysed using fluorescence microscopy. Nuclear and
cytoplasmic changes consistent with cell activation, apoptosis, oncosis and senescence
were found with both STS and POL at low concentrations (< 0.3%).
Leukocyte and EC apoptosis was assessed using confocal microscopy and flow cytometry.
Lactadherin and PI were used to stage apoptosis and Caspase-3, -8, -9 and Bax to assess
apoptotic pathways. Porimin was used to assess oncosis. STS induced activation of
caspase-3, -8, -9 and increase in Bax expression. POL only induced activation of Caspase
-3, -9 and Bax. Active Caspase 3, 8 and 9 but not Bax were increased in EC stimulated with
low concentrations of both STS and POL. Both agents increased the activation of porimin
at all concentrations.
In Conclusion, detergent sclerosants induce cell activation and the release of proinflammatory
and proangiogenic cytokines. Sclerosants at low concentrations are also capable of inducing
cell apoptosis and cell oncosis in leukocytes and EC.