Abstract:
The therapeutic efficacy of anthracycline antibiotic, doxorubicin (Dox), is hampered due to the dose-dependent cardiotoxicity. The
objective of the study was to explore the counteraction of aqueous bark extract of Nauclea orientalis in Dox-induced cardiotoxicity
in Wistar rats. The acute and subchronic toxicity study performed with 2.0 g/kg of the plant extract revealed biochemical and
haematological parameters to be within the physiological range, and no histological alterations were observed in any organs
isolated. Screening of plant extract for the protection of the myocardium from Dox-induced oxidative stress, inflammation, and
apoptosis was performed on five groups of rats: control, plant extract control, Dox control (distilled water (D.H2O) 2 weeks +
on the 11th day single injection of Dox, 18 mg/kg), plant + Dox (2.0 g/kg plant extract 2 weeks + on the 11th day Dox, 18 mg/
kg), and positive control, dexrazoxane. A significant increase in cardiac biomarkers and lipid peroxidation (p < 0:001) and a
significant decrease in antioxidant parameters (p < 0:001) were observed in the Dox control group. All these parameters were
reversed significantly (p < 0:05) in the plant-pretreated group. The histopathological assessment of myocardial damage provided
supportive evidence for the biochemical results obtained. Inflammatory markers, myeloperoxidase, expression of TNFα and
caspase-3, and DNA fragmentation (TUNEL positive nuclei) were significantly elevated (p < 0:05), and expression of Bcl-2 was
significantly decreased (p < 0:05) in the Dox control; however, all these parameters were significantly reversed in the plant
extract-treated group. In conclusion, the aqueous bark extract of Nauclea orientalis (2.0 g/kg) has the ability to attenuate the
Dox-induced oxidative stress, inflammation, apoptosis, and DNA fragmentation in Wistar rats.
