Author + information
- Ipek Komsuoglu1,
- Sevgi Turker2,
- Umut Celikyurt3,
- Oguz Mutlu1,
- Esen Gumuslu4,
- Furuzan Yıldız Akar1 and
- Dilek Ural3
Rolipram is a prototypic inhibitor of phosphodiesterase 4 (PDE4) which contributes to the regulation of cAMP levels in cardiac myocytes. Recent studies are focused on the effects of PDE inhibitors on cardiovascular function. Controversial results exist for the effect of PDE4 on cardiovascular system. Recent studies have shown that PDE4 inactivation can trigger arrhythmias and lead to the development of heart failure in mice, but contradictory findings are also present.
In the current study, our aim was to investigate the molecular effects of a PDE4 inhibitor, rolipram, on naive mice heart tissue by Fourier Transform Infrared (FTIR) Spectroscopy. This method monitors vibration groups of different molecules present in the biological samples so that it gives detailed information about molecular structure of the system.
Material and Methods
For the experimental part of the study, male Balb-c mice (totally n=25) were divided into three groups as control, rolipram 0.1 mg/kg and rolipram 0.05 mg/kg. Animals treated with subchronic intraperitoneal administration of rolipram for 15 days. The mice were then sacrificed and the heart tissues were collected for FTIR analysis. The isolated heart samples were studied in 4000-400 cm-1 frequency range with 4 cm-1 resolution. Subsequently, the changes in the FTIR spectral parameters upon administration of the agents were determined and statistical analysis was performed.
In this study, both doses of rolipram caused a decrease in lipid, carbohydrate and protein content of heart indicating breakdown of these biomolecules, which may be attributed to high cellular activation. Alterations in protein structure were also observed in treated groups. In addition, heart membrane lipids were more ordered and more fluid as indicated by the lower frequency and the higher bandwidth values of CH2 asymmetric stretching, implicating an abnormally increased membrane transportation. Detailed analysis of =CH olefinic band showed that rolipram caused a decrease in the amount of unsaturated lipids in the membrane possibly due to lipid peroxidation. Another effect of rolipram was observed in hydrogen bonded phospholipids of the membrane structures from frequency changes of the PO2 and the C=O modes.
Hence, according to the FTIR spectral parameters subchronic rolipram treatment led to severe molecular alterations in biomolecules of heart tissue and membranes. These molecular variations offer molecular information for the action mechanisms of rolipram on mice heart. Consequently, the findings of the present study may suggest that, PDE4 inhibition, could affect the heart tissue which may result in heart dysfunction and failure.