Open AccessNauclea orientalis (L.) Bark Extract Protects Rat Cardiomyocytes from Doxorubicin-Induced Oxidative Stress, Inflammation, Apoptosis, and DNA Fragmentation
Author(s) -
Jayasinghe Arachchige Nirosha Sandamali,
Ruwani Punyakanthi Hewawasam,
Kamani Ayoma Perera Wijewardana Jayatilaka,
Lakmini Mudduwa
Publication year - 2022
Publication title -
oxidative medicine and cellular longevity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.494
H-Index - 93
eISSN - 1942-0900
pISSN - 1942-0994
DOI - 10.1155/2022/1714841
Subject(s) - cardiotoxicity , oxidative stress , pharmacology , doxorubicin , dna fragmentation , apoptosis , tunel assay , antioxidant , chemistry , lipid peroxidation , inflammation , anthracycline , dna damage , toxicity , biology , medicine , biochemistry , immunology , chemotherapy , cancer , programmed cell death , dna , organic chemistry , breast cancer
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.