Conclusion
Cisplatin decreased the gene expression of PPAR-γ and -β/δ, while the rosiglitazone treatment inhibited these effects via PPAR-γ independent pathway. Rosiglitazone did not show improvement in modulation of TNF-α or CGRP release impaired by cisplatin.
Methods
Dorsal Root Ganglia (DRG) were harvested from Wistar rats (Rattus norvegicus), the cells were dissociated, plated, and maintained with nerve growth factor for 9 days. On day 8, the cells were treated with cisplatin, rosiglitazone and/or T0070907 (PPAR-γ antagonist) for 24 h. The cell viability was measured by trypan blue exclusion method, the mRNA was quantified by real-time RT-PCRq and the release of TNF-α and calcitonin gene-related peptide (CGRP) was evaluated by ELISA.
Results
Cisplatin, rosiglitazone or T0070907 treatments did not decreased the cell viability on the primary DRG cultures cells. Cisplatin treatment induced a decrease of PPAR-γ and -β/δ mRNA, while the co-treatment with rosiglitazone inhibited this cisplatin-induced effect. Moreover, T0070907 did not change the observed results, indicating that the rosiglitazone's effect could be due to mechanisms beyond PPAR-γ activation. Also, the rosiglitazone effect is not exclusively to DRG cells since there was an increase of PPAR-γ mRNA expression in 3T3-L1 cells. Furthermore, rosiglitazone did not modulate the cisplatin decrease neuronal function of DRG cells (TNF-α and CGRP release).