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 15 mg/kg of DOX following the oral pretreatments of Wistar rats with 100-400 mg/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 100-400 mg/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.