Quantification of Cellular Accumulation and Lipid Binding Properties for Phospholipidosis Inducing Drugs and Bioaccumulationg Environmental Toxicants
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesisAlternative title
Kvantifiering av ackumulering i celler och bindning till lipider för läkemedel som inducerar fosfolipidos och för miljögifter som bioackumuleras (Swedish)
Highly accumulating compounds in human body are found ubiquitously around the world, and can originate from the industry or from costumers. Depending on their physicochemical properties, they will tend to accumulate by different mechanisms. For example, cationic amphiphilic drugs (CADs) have been reported to accumulate in great extent in lysosomes, whereas fat tissue is the primary accumulation site for organic pollutants. Therefore, understanding the rules that govern their accumulation is fundamental for the creation of accurate screening methods and understanding the mechanisms of their biological effects. Here we describe the interaction of a group of compounds with cells and cell-free chromatographic systems. The interaction with cells was analyzed through the comparison of accumulation and retention of the studied compounds in lung epithelial cells and adipocytes. For understanding the interaction with lipids in cell-free systems, C18 and IAM PC columns were used to calculate LogD and CHIIAM, which represent the binding to neutral lipids and phospholipids, respectively. High Spearman correlation was found in accumulation and retention among the different cell types (r=0.869 and 0.9441, respectively). It was observed that interaction with phospholipids is strongly correlated to cellular accumulation and retention in both cell lines (r = 0.893 and 0.915, respectively). Finally, we found that one of environmental pollutants (PFOS) presented cellular accumulation and phospholipid binding behavior similar to CADs.
Place, publisher, year, edition, pages
2016. , 53 p.
CADs, PFOS, PFBS, logD, CHI IAM, accumulation, retention, adipocytes, chromatography
Engineering and Technology
IdentifiersURN: urn:nbn:se:kth:diva-190867OAI: oai:DiVA.org:kth-190867DiVA: diva2:953399