Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats
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Date
2020-10-23
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Oxidative Medicine and Cellular Longevity
Abstract
Cardiotoxicity as an off-target effect of doxorubicin therapy is a major limiting factor for its clinical use as a choice cytotoxic agent.
Seeds of Irvingia gabonensis have been reported to possess both nutritional and medicinal values which include antidiabetic, weight
losing, antihyperlipidemic, and antioxidative effects. Protective effects of Irvingia gabonensis ethanol seed extract (IGESE) was
investigated in doxorubicin (DOX)-mediated cardiotoxicity induced with single intraperitoneal injection of 15mg/kg of DOX
following the oral pretreatments of Wistar rats with 100-400mg/kg/day of IGESE for 10 days, using serum cardiac enzyme
markers (cardiac troponin I (cTI) and lactate dehydrogenase (LDH)), cardiac tissue oxidative stress markers (catalase (CAT),
malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px),
and reduced glutathione (GSH)), and cardiac histopathology endpoints. In addition, both qualitative and quantitative analyses
to determine IGESE’s secondary metabolites profile and its in vitro antioxidant activities were also conducted. Results revealed
that serum cTnI and LDH were significantly elevated by the DOX treatment. Similarly, activities of tissue SOD, CAT, GST, and
GSH levels were profoundly reduced, while GPx activity and MDA levels were profoundly increased by DOX treatment. These
biochemical changes were associated with microthrombi formation in the DOX-treated cardiac tissues on histological
examination. However, oral pretreatments with 100-400mg/kg/day of IGESE dissolved in 5% DMSO in distilled water
significantly attenuated increases in the serum cTnI and LDH, prevented significant alterations in the serum lipid profile and the
tissue activities and levels of oxidative stress markers while improving cardiovascular disease risk indices and DOX-induced
histopathological lesions. The in vitro antioxidant studies showed IGESE to have good antioxidant profile and contained 56
major secondary metabolites prominent among which are γ-sitosterol, Phytol, neophytadiene, stigmasterol, vitamin E,
hexadecanoic acid and its ethyl ester, Phytyl palmitate, campesterol, lupeol, and squalene. Overall, both the in vitro and in vivo
findings indicate that IGESE may be a promising prophylactic cardioprotective agent against DOX-induced cardiotoxicity, at
least in part mediated via IGESE’s antioxidant and free radical scavenging and antithrombotic mechanisms.