Background: Reactive Oxygen Species (ROS) production has been established
as an essential contributor in the development cardiotoxicity. The increase of
ROS production simultaneously leads to the inhibition of anti-oxidant systems.
Forkhead transcription factor O1 (FOXO1) plays an important role in regulating
metabolism and oxidant stress. Clozapine was used to induce cardiotoxicity.
Forskolin the well-known anti-oxidant and anti-inflammatory agent was used to
modulate the effect on both FOXO1 gene and its target gene catalase and to what
extent it may protect against clozapine-induced cardiotoxicity.
Methods: The animals were classified into: control group, forskolin group; forskolin
was administered for 8 weeks; clozapine group, and forskolin + clozapine group;
forskolin was pre-administered for 5 weeks then continued along with clozapine
for the last 3 weeks. RT-qPCR and gel electrophoresis were done. We analyzed the
relation between FoxO1 gene and oxidative stress.
Results: These effects are achieved by the ability of Forskolin to modulate the
expression of Foxo-1 and catalase, the levels of CKMB, troponin I, GST, MDA, and
TNF- α, Caspase-3 were decreased, histopathological changes were improved.
Forskolin reduce cardiomyocytes damage, and improve cardiac function by
decreasing oxidative stress.
Conclusion: Forkolin with its biological activities and anti-oxidative effects control
cardiotoxicity induced by ROS in addition to its anti-inflammatory activity. This
may be considered as therapy in cardiac problems management