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The importance of doxorubicin, as a potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy. It has been shown that free radicals are involved in doxorubicin-induced toxicity. Doxorubicin causes the generation of free radicals and the induction of oxidative stress, associated with cellular injury. Phenolic compounds are a chemical family whose members have one or more hydroxyl groups attached directly to an aromatic ring. phenolic compounds can frequently act as free-radical scavengers.
This study was undertaken to investigate the cardioprotective potential of some phenolic compounds namely caffeic acid, ferulic acid and syringic acid in doxorubicin induced cardiotoxicity.
The rats were randomized into 5 equal groups each of six. Group 1 sham group, which received no treatment, group 2, received doxorubicin at a dose 3 mg/kg IP every other 2 days plus normal saline as vehicle orally and considered as Cardiotoxic Control, Group 3 received doxorubicin plus ferulic acid 10 mg/day p.o for 2 weeks, group 4 received doxorubicin plus caffeic acid 40 mg/day p.o for 2 weeks, group 5 received doxorubicin plus syringic acid 100 mg/day p.o for 2 weeks. Left venrricular function was measured by volume flow meter.
At the end of experiment and after recording the final body weight, blood samples were collected from the heart for measurement of plasma level of cardiac troponin I (cTn I) and serum level of oxidative stress parameter malondialdehyde (MDA) and also for measurement of high sensitive c-reactive protein (hs-CRP). The heart were weighted and then harvested. The apical side was fixed in 10% formalin for histological examination and the basal side was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and interleukin-10 (IL-10).
Compared with sham group, levels of myocardial TNF-α, IL-1βand IL-10; plasma cTnI were significantly increased (p<0.001) in Doxorubicin treated group with significant increase (p<0.001) in MDA, hs-CRP and significant impairment of left ventricular ejection fraction and cardiac out put (p<0.001). Caffeic acid, ferulic acid and syringic acid significantly counteracted the increase in myocardial TNF-alfa,IL-1-beta, IL-10, serum cTnI, hs-CRP and MDA. Additionally these compounds significantly (p,0.001) counteracted the decrease in ejection fraction and cardiac out put.
The results of the present study reveal that phenolic compounds (caffeic acid,ferulic acid and syringic acid have been shown to decrease doxorubicin-induced cardiotoxicity via interfering with inflammatory reactions and also prophylactic use of these compounds may ameliorate the left ventricular function which deteriorate by doxorubicin administration.