African Vegetables (Clerodendrum volibile Leaf and Irvingia gabonensis Seed Extracts) Effectively Mitigate Trastuzumab Induced Cardiotoxicity in Wistar Rats
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Date
2020-10-15
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Oxidative Medicine and Cellular Longevity
Abstract
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. 400mg/kg/day CVE and IGE dissolved in 5% DMSO in sterile water were
investigated in Wistar rats injected with 2.25mg/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 400mg/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.