Trastuzumab (TZM) is a humanized
monoclonal antibody that has been approved for the clinical management of HER2-positive metastatic breast and
gastric cancers but its use is limited by its cumulative dose and off-target
cardiotoxicity. Unfortunately, till date, there is no approved
antidote to this off-target toxicity. Therefore, an acute study was designed at investigating the protective potential and mechanism(s) of CVE and
IGE in TZM-induced
cardiotoxicity utilizing cardiac
enzyme and oxidative stress markers and histopathological endpoints. 400 mg/kg/day CVE and
IGE dissolved in 5%
DMSO in sterile water were investigated in Wistar rats injected with 2.25 mg/kg/day/i.p. route of TZM for 7 days, using serum cTnI and LDH, complete
lipid profile, cardiac tissue oxidative stress markers assays, and histopathological examination of TZM-intoxicated heart tissue. Results showed that 400 mg/kg/day CVE and
IGE profoundly attenuated increases in the serum cTnI and LDH levels but caused no significant alterations in the serum
lipids and
weight gain pattern in the treated rats. CVE and
IGE profoundly attenuated alterations in the cardiac tissue oxidative stress markers' activities while improving TZM-associated cardiac histological lesions. These results suggest that CVE and
IGE could be mediating its cardioprotection via
antioxidant,
free radical scavenging, and antithrombotic mechanisms, thus, highlighting the therapeutic potentials of CVE and
IGE in the management of TZM-mediated
cardiotoxicity.