Akademik Veri Yönetim Sistemi
PAKISTAN VETERINARY JOURNAL, cilt.24, sa.1, ss.1-10, 2024 (SCI-Expanded)
Cilomilast is an oral phosphodiesterase-4 (PDE4) inhibitor recommended for
treating COPD. However, its side effects and low therapeutic index remain an
unresolved problem in clinical practice. This study aimed to evaluate the effects of
cilomilast on the spleen and thymus tissues of rats. For experimental studies, 24
male Sprague-Dawley rats weighing 200-220 g were randomly divided into three
experimental groups: The procedures were repeated for 7 days for the control, sham,
and cilomilast groups. Blood and tissue samples were collected from the rats under
anesthesia on day 8 of the experiment for analysis. p<0.05 at a 95% confidence
level was considered to indicate statistical significance. Severe tissue damage in the
thymus and spleen was observed in the cilomilast group. In the thymus and spleen
tissues of the control and sham groups, CD4+
and CD8+
cell immunopositivity were
more intense, while the density of these cells was significantly reduced in the
cilomilast group. In addition, glutathione (GSH) levels decreased, and nitric oxide
levels increased in both tissues of the cilomilast group. However, in-silico results
showed that the decrease in GSH levels is due to the enzymes γ-glutamylcysteine
synthase and glutathione synthase, which act as catalysts in the two-step GSH
biosynthesis mechanism. Suppression of the immune system targets both harmful
and compensatory pathways so that both beneficial mechanisms and pathological
changes can be blocked. To eliminate these cilomilast-induced side effects and
enable more effective clinical application, it may be recommended to develop
formulations such as lipid-based inhaled forms or nano-drug delivery systems
including dendrimers, reverse micelle systems, polymeric or lipid-based carriers as
an alternative to conventional application