Irvingia gabonensis Seed Extract: An Effective Attenuator of Doxorubicin-Mediated Cardiotoxicity in Wistar Rats

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 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.

Ferulic Acid Alleviates Myocardial Ischemia Reperfusion Injury Via Upregulating AMPKα2 Expression-Mediated Ferroptosis Depression

“…The activities of endogenous antioxidant enzyme systems consisting of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were estimated with spectrophotometry separately. Heart tissue homogenates were prepared to detect MDA levels, CAT, SOD, and GSH-Px activities 22 strictly according to the instructions provided with the kits (Jiancheng, Nanjing, China).…”

Phytochemical Identification and Analgesic Potential of the Seed Extract of Irvingia gabonensis

“…The chemical composition of Irvingia gabonensis ethanol seeds extract was reported by Olorundare and coworkers in 2020 [13] and it was revealed that 4,6-di-O-methyl-alpha-dgalactose, Neophytadiene, 4-Methyl-2,5dimethoxybenzaldehyde, Cycloheptasiloxane, tetradecamethyl-, Pyrrolidine, 1-(1-cyclohexen-1yl)-, Naphthalen-4a,8a-imine, octahydro-, Cyclotetrasiloxane, octamethyl-, Z,Z-7,11-Hexadecadien-1-ol, Cyclotetrasiloxane, octamethyl-,1,2-Cyclopentanedione, Ethanol, 2-(ethylamino)-and Oxime-, methoxy-phenyl-were the common compounds. While quercetin, kaempferol, ellagic acid, mono-, di-, and tri-Omethyl-ellagic acids, and their glycosides were reported earlier [6,14].…”

Beta vulgaris‐derived exosome‐like nanovesicles alleviate chronic doxorubicin‐induced cardiotoxicity by inhibiting ferroptosis

“…[28] Pisum sativum peel or Irvingia gabonensis seed extract were also candidates as natural agents to protect against Dox toxicity. [29,30] However, the juice or extract was generally given at a high dose (up to 500 mg/kg bodyweight per day). Although this is close to dietary intake, it's difficult to clinically translate.…”