Research on the effect of rosiglitazon on telomere dynamics with molecular methods in rats

Abstract

Rosiglitazone that is a drug for the treatment of type II diabetes mellitus, belong to the class of thiazolidinediones. Drugs of this class act as ligands for the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), which is involved in the regulation of genes controlling carbohydrate and lipid metabolism. Telomeres are composed of specialized DNA and protein complexes. Telomeric DNA consist of guanine-rich sequences, such as TTAGGG in vertebrates. In normal cells, telomeres shorten by ?50-150 bp with each round of DNA replication. In addition to this, unrepaired oxidative DNA damage can also contribute to telomere shortening. There is no study that shows the effect of rosiglitazone on telomere length in literature. Because of this, we aimed to research on the effect of rosiglitazone on the telomere length in our study. We used sixteen male Sprague-Dawley rats that at 7-8 weeks of age and weighing 248-275 g in our study. The rats were divided into four groups, four rats in each group, and dosed once a day for 14 days by oral gavage with doses of 0.0, 0.5, 1.0, and 2.0 mg/kg rosiglitazone. Genomic DNA was extracted from rat liver, small intestine, pancreas tissue and lymphocytes. The 36B4 gene was chosen as single copy gene for determine the number of genom in the samples. The number of genome copies were found in a rat tissue by qPCR that is used the 36B4 gene-specific primers. This sample, that is used as rat genom standarts, was used for find the number of genome in all samples. The qPCR was performed for telomere (T) and 36B4 (S) in all samples. The T/S ratio was calculated by the ratio of the products derived from two studies to each other, and then the relative T/S ratio was calculated by using a calibrator sample for each sample. In addition, telomere lengths of the samples were also calculated as kilobase by using 10,2 kb long telomere standard. We did not found statistically any significant difference between doses of rosiglitazone and control groups for telomere length (p>0.05). This result has showed that rosiglitazone doesn't lead to telomere shortening. © 2011 OMÜ Tüm haklari saklidir.