Abstract
Adriamycin (Adr) is a cytotoxic anthracycline agent that is utilized to manage many types of tumors, but its clinical use is undesirable due to severe cardiotoxicity. The present study aimed to investigate the cardioprotective effect of Achillea fragrantissima (A. fragrantissima) against Adr-induced cardiotoxicity through the antioxidant and anti-inflammatory metabolic pathways. A single dose of Adr was injected in rats to induce cardiotoxicity. Rats are divided into 5 groups, control, A. fragrantissima 800, Adr, A. fragrantissima 400 + Adr, and A. fragrantissima 800 + Adr. 72 h after Adr administration, electrocardiographic (ECG) study was performed for all rats. Serum and hearts were then collected for biochemical and histopathological studies. A. fragrantissima ameliorated Adr-induced ST-segment elevation. It reduced Adr-induced elevation in lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), thiobarbituric acid reactive substance (TBARS), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6. It also protected against Adr-induced histopathological changes. Pretreatment with the extract increased heart tissue contents of glutathione peroxidase (GSH-PX) and reduced glutathione (GSH). Phytochemical analysis of the extract revealed that it is rich in phenolic and flavonoid active constituents. The results of this study revealed that A. fragrantissima extract ameliorates Adr-induced cardiotoxicity via an antioxidant and anti-inflammatory mechanisms. Further studies are warranted in order to recognize the precise active constituents of this natural extract which are responsible for the antioxidant and anti-inflammatory actions.
Highlights
Adriamycin (Adr) is a cytotoxic anthracycline antibiotic that is used to treat a wide variety of cancers including, leukaemia and lymphoma, besides breast, lung, and other solid cancers
Since oxidative stress and inflammation have become accepted as a suitable target for early therapeutic intervention in Adr-induced cardiotoxicity, the present study addressed the cardioprotective effect of A. fragrantissima against Adrinduced cardiotoxicity through the antioxidant and antiinflammatory metabolic pathways
Phytochemical analysis of A. fragrantissima extract indicated that it contains adequate amounts of flavonoids, phenolics, glycosides, lignans, and terpenes (Table 1)
Summary
Adriamycin (Adr) is a cytotoxic anthracycline antibiotic that is used to treat a wide variety of cancers including, leukaemia and lymphoma, besides breast, lung, and other solid cancers. Its clinical application is restricted due to its dangerous cardiotoxicity that may be aggravated to heart failure [1,2,3]. The underlying mechanism of Adrinduced acute cardiotoxicity is based on the production of free radicals and reactive oxygen species (ROS) that damage the cell membrane lipids and caused the liberation of lipid peroxides products [4, 5]. There is growing evidence that Adr elicits inflammatory effects in the vasculature and the myocardium that subsequently induces the production of several proinflammatory mediators such as tumor necrosis factor-alpha (TNF-α) [6]. Research has found that cardiac toxicity of Adr is associated with an increase in IL-1β production. Il1B causes cardiomyocytes apoptosis by increasing the calcium storage of the heart muscle cells [8]
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