Protective Effects of Chrysin against Cyclophosphamide‐Induced Cardiotoxicity in Rats: A Biochemical and Histopathological Approach

Abstract

Mounting evidences have indicated that cyclophosphamide (CyC)a potent anticancer and cytotoxic agent is associated with various organ and systemic toxicities and the cytotoxic effects observed after administration of CyC still challenges its clinical use. Chrysin (Chy) is a dietary flavonoid with prevailing antioxidant and antiinflammatory properties. This study evaluated the protective properties of Chy against CyC-induced cardiotoxicity in rats. The animals were orally treated with Chy (25 and 50 mg/kg/day) for 35 days and exposed to CyC (i. p., 100 mg/kg) once a week for four weeks. The results indicated that CyC caused significant cardiotoxicity as manifested by notable increases in heart weight, cardiac function biomarkers such as lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), troponin T and aspartate transaminase (AST). In addition, cardiac malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1β (IL1 β) and interleukin 6 (IL-6) levels were considerably increased. Meanwhile, cardiac antioxidant enzymes activities such as superoxide dismutase (SOD) and catalase (CAT), as well as glutathione (GSH) level were suppressed, while H&E stained histopathological assessment showed marked alterations in cardiac tissues. CyC also significantly lowered red blood cells (RBC) and white blood cells (WBC) parameters, whereas treatment with Chy significantly restored the altered biochemical and histopathological features. Conclusively, aforementioned results inferred that Chy offered cardioprotective potentials against CyC-induced cardiotoxicity which may be due to its antioxidant, and anti-inflammatory properties.

Asperuloside attenuates cadmium-induced toxicity by inhibiting oxidative stress, inflammation, fibrosis and apoptosis in rats

“…However, in the evident of cardiac damage or insult, these enzymes are also released into the blood stream leading to their elevated levels in the serum. As such, these biomarkers are considered as an indicator of myocardial damage 24 , 25 . The co-administration of ASP with Cd notably reduced the levels of these cardiac biomarkers.…”

Role of hypoxia inducible factor/vascular endothelial growth factor/endothelial nitric oxide synthase signaling pathway in mediating the cardioprotective effect of dapagliflozin in cyclophosphamide-induced cardiotoxicity

“…These results are in line with different previous studies. [30][31][32] Release of free radicals and stimulation of oxidative stress associated with imbalance between oxidants and antioxidants leads to membrane lipid peroxidation which was detected by measuring its sensitive indicator, MDA level. Furthermore, intracellular antioxidants, such as GSH, serve as the first line of defense system to rescue the myocardium and prevent oxidative injury.…”

Role and molecular mechanism of traditional Chinese medicine in preventing cardiotoxicity associated with chemoradiotherapy

“…Quercetin (QUE) has strong antioxidant activity and attenuates CyC-induced cardiotoxicity by inhibiting ROS accumulation in CMs; interestingly, it also enhances the antitumor activity of CyC ( 78 ). Another TCM that combats CyC-effects, chrysin increases enzyme levels that combat ROS and decreases levels of lipid peroxidation products in CyC-injured hearts, all of which protect against cardiotoxicity ( 79 ).…”