Modulation of cyclophosphamide-induced cardiotoxicity by methyl palmitate.

Dina S El-Agamy, Mohamed A Elkablawy, Hany M Abo-Haded

Cancer chemotherapy and pharmacology 2017 Feb

filter terms:

Cyclophosphamide (CP) is a frequently used anticancer and immunosuppressant although its use has been associated with severe cardiotoxicity. The present study examined the ability of methyl palmitate (MP) to counteract CP-induced cardiotoxicity. Adult male Wistar rats were divided into four groups. The first one served as control while the second received a single injection of CP (200 mg/kg, i.p.). The other two groups were administered MP at two different dose levels (300, 400 mg/kg) for 10 days before and 7 days after CP single injection. CP injection resulted in marked cardiac injury as presented by ECG abnormal changes, elevation of serum creatine kinase-MB (CK-MB), cardiac troponin I, troponin T and lactate dehydrogenase (LDH) and enormous histopathological lesions. Moreover, CP-induced oxidative stress as it elevated malondialdehyde (MDA) and diminished superoxide dismutase activity and glutathione content in heart tissue. Additionally, CP-induced overexpression of toll-like receptors-4 (TLR-4) and nuclear factor kappa-B (NF-κB) accompanied by overproduction of inflammatory cytokines (TNF-α, NO). CP activated cardiomyocyte apoptosis as it increased apoptosis parameters (Bax and caspase-3) and decreased anti-apoptotic marker (Bcl-2). On the other hand, MP treatment attenuated all of the measured parameters of CP-induced cardiotoxicity. MP counteracted CP-induced oxidative stress and suppressed TLR-4 and NF-κB overexpression. Also, levels of cytokines and apoptotic markers were declined while Bcl-2 was elevated in MP treated animals. MP may serve as a new cardioprotective candidate. The cardioprotective effects of MP may be attributed to its ability to suppress oxidative stress and interrupt TLR4/NF-κB signaling pathway with subsequent amelioration of apoptosis.

Citation

Dina S El-Agamy, Mohamed A Elkablawy, Hany M Abo-Haded. Modulation of cyclophosphamide-induced cardiotoxicity by methyl palmitate. Cancer chemotherapy and pharmacology. 2017 Feb;79(2):399-409