Conjugated linoleic acid, but not rosiglitazone and pioglitazone increase apoptosis/reduce viabillity in a monocytic cell line
Cardiff Metropolitan University
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Thiazolidinediones (TZDs) are a class of oral chemotherapeutics used in the treatment of type 2 diabetes mellitus (TTDM). TZDs improve insulin sensitivity in TTDM by modulating the transcriptional effects of peroxisome proliferator activated receptor-y (PPAR-y). Recent concern over the negative cardiovascular effects of the TZD, rosiglitazone, led to its withdrawal from US and European drug markets. Previous studies have investigated the effect of rosiglitazone on intracellular calcium storage as a possible mechanism for these side effects. This study investigated the effect of rosiglitazone and other PPAR-y ligands on cell viability and apoptosis at pharmacological and suprapharmacological concentrations. The drugs were either administered as a single dose or as serial treatments, administered every 3 days, over a 14 day period to an established monocytic cell line (THP1). As expected, the positive control thapsigargin increased apoptosis levels and decreased cell viability (P = 0.027), confirming this agent as cytotoxic. Pioglitazone and rosiglitazone had no effect on cell viability and apoptosis under all experimental conditions (P =0.429 and P = 0.570 respectively). Conjugated linoleic acid had no effect on cell viability and apoptosis at concentrations of 20µM and 100µM when administered as a single dose and no effect when serial treatments of 20µM were administered. However, serial treatment with suprapharmacological concentrations (100µM) of conjugated linoleic acid appeared to reduce cell viability and/or increase apoptosis (P=0.008). The results pertaining to pioglitazone reflect positively on the safety profile of this drug. However, susceptibility to toxic effects varies between cell types and in vitro observations on a single (transformed) cell type may not accurately reflect the effect of these compounds in vivo.
BSc (Hons) Biomedical Science
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