Abstract
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.
Highlights
Forskolin (FSK) is a labdane diterpene contains some unique functional elements, including the presence of a tetrahydropyranderived heterocyclic ring, it is commonly to raise levels of cyclic AMP in the study and research of cell physiology
To explore the effect of FSK on cardiotoxicity, FOXO transcription factors play a role in the response to oxidative stress
We investigate the change of oxidative stress and determine the relationship between FoxO1 and oxidative stress in cardiotoxic rats
Summary
Forskolin (FSK) is a labdane diterpene contains some unique functional elements, including the presence of a tetrahydropyranderived heterocyclic ring, it is commonly to raise levels of cyclic AMP (cAMP) in the study and research of cell physiology. FSK activates the adenyl cyclase and increases intracellular levels of cyclic AMP (cAMP) [1]. Class O1 ( FOXO1) is one of transcription family factor It is conserved as a DNA binding domains subjected to posttranslational modification. Such modifications can increase or decrease the transcriptional activity of FOXO1 and play important role in oxidative stress and regulating cellular metabolism [3]. Forkhead transcription factor O1 (FOXO1) plays an important role in regulating metabolism and oxidant stress. 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
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