الفهرس 
1.Introduction and Aim of The WorkOnly 14 pages are availabe for public view
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Abstract
5-Flurouracil -induced cardiotoxicity represent a serious obstacle that faces its use in clinical practice. Different pathological mechanisms are included in it. In a trial for examining the role of bosentan and nebivolol in 5-FU-induced cardiotoxicity. The current study explored the possible protective effect of bosentan and nebivolol in cardiotoxicity induced by 5-FU in rats.
The current research involved two sets of 32 rats in each one.
In the first set, rats were divided into the following groups (n=8): control group: that were given saline as a vehicle daily for 7 consecutive days with oral gavage and on the 5th day, they injected with a single dose of i.p. saline. Bosentan group: were administered bosentan 50 mg /kg/day for 7 consecutive days with oral gavage and on the 5th day, they injected with a single dose of i.p. saline. 5-FU group: were given saline daily for 7 consecutive days with oral gavage and on the 5th day, rats were injected with a single i.p. dose of 5-FU (150 mg/kg). 5-FU/bosentan group: were administered bosentan (50 mg /kg/day) for 7 consecutive days with oral gavage and on the 5th day, rats were injected with a single i.p. dose of 5-FU (150 mg/kg).
In the second set, rats were allocated into the following groups (n=8): control group: that were given saline as a vehicle daily for 7 consecutive days with oral gavage and on the 5th day, rats were injected with a single i.p. dose of normal saline. Nebivolol group: were administered nebivolol 10 mg /kg/ day for 7 consecutive days with oral gavage and on the 5th day, rats were injected with a single i.p. dose of normal saline. 5-FU group: were given normal saline daily for 7 consecutive days with oral gavage and on the 5th day rats will be injected with single i.p. dose of 5-FU 150 mg/kg. 5-FU/ Nebivolol group: were administered nebivolol 10 mg /kg daily for 7 consecutive days with oral gavage and on the 5th day rats were injected with single i.p. dose of 5-FU 150 mg/kg.
Blood samples were taken when we finished the experiment to assess cardiac enzymes such as tropnin I, CK-MB, and LDH, as well as TAC. GSH, MDA, caspase 3, TLR 4, MYD88, NF-κB, eNOS, and ETA receptors, as well as histopathological evaluation and scoring, were all assessed in heart tissue. The results of this research revealed that the 5-FU group resulted in an increase in serum cardiac enzymes levels (CK-MB, tropnin I and LDH), MDA, NF-κB, TLR 4, MYD88, caspase 3, ETA receptor and caused significant histopathological cardiac damage. But it decreased the levels of TAC, GSH and eNOS expression.
Both bosentan and nebivolol showed cardioprotective activity manifested by decreased cardiac enzyme levels and confirmed by improvement of cardiac histopathology when compared to 5-FU non-treated group. This cardioprotective activity was indicated by restoration of oxidative stress/antioxidant balance (decreased level of MDA and increased both GSH and TAC), regression of inflammatory biomarkers level (decreased NF-κB, TLR4, MYD88), decreased apoptotic marker caspase-3, decreased ETA receptor level, and increased cardiac eNOS expression. So, the cardioprotective effects of either bosentan or nebivolol were indicated by their antioxidant, anti-inflammatory, antiapoptotic, and ET receptor modulatory effect.