GAS CHROMATOGRAPHY- MASS SPECTROMETRY ANALYSIS AND EFFECT OF Amaranthus hybridus AQUEOUS LEAF EXTRACT ON PLASMA AND HEART LIPID PROFILE IN DOXORUBICIN INDUCED CARDIOTOXIC RAT

INTRODUCTION: Doxorubicin poisoning has been linked to organ damage, particularly the heart (Indu et al., 2014; Afsar et al, 2017; Zilinyi et al., 2018; Ahmed et al., 2019). A variety of pathways for doxorubicin-induced cardiotoxicity have been proposed in numerous research. Among those implicated are oxidative stress, inflammation, apoptosis, protein synthesis inhibition or abnormal protein processing, mitochondrial abnormalities, and lysosomal alterations (Abdalla et al., 2016; Kwatra et al., 2016; Wang et al., 2016; Cappetta et al., 2017; Zhao and Zhang, 2017; Zilinyi et al., 2018; Alghorabi et al., 2019; Zhang et al., 2019; Wallace et al., 2020). They also include increased myocardial lipid accumulation/dyslipidaemia, damage to cell membranes and lipid peroxidation, myocardial electrolytes imbalance, changes in adenylate cyclase, Na+,K+-adenosine triphosphatase (ATPase), Ca2+-ATPase, and creatine kinase impairment (Abdalla et al., 2016; Kwatra et al. Others include endothelin-1 upregulation, doxorubicin-iron complex formation, decreased myocardial adrenergic control, autophagy dysregulation, cellular toxicity of doxorubicin metabolites, and suppression of beta-oxidation of long chain fatty acids, which results in cardiac ATP depletion (Ashour et al., 2012; Octavia et al., 2012; Zilinyi et al., 2018).

Doxorubicin-induced cardiomyopathy is frequently associated with increased plasma lactate dehydrogenase and creatine kinase activity, as well as dyslipidaemia (Indu et al., 2014; Sharma et al., 2016; Abdo et al., 2017). Doxorubicin-induced dyslipidaemia is accompanied by increased lipid accumulation (e.g., cholesterol, triglycerides, free fatty acids, and phospholipids) in the myocardium; impaired cardiac fatty acid oxidation; and significant increases in plasma total cholesterol, triglyceride, low and very low density lipoproteins, with a decrease in high density lipoprotein levels (Subashini et al., 2007; Tatlidede et al., 2009).

The electrolyte imbalance caused by doxorubicin-induced cardiotoxicity is distinguished by cardiac sodium and calcium overload (Kwatra et al., 2016). This is usually due to doxorubicin or its metabolites interfering with membrane functions such as Na+,K+-dependent ATPase activity, calcium transport, and intracellular electrolyte balance, as well as doxorubicin-induced oxidative stress (Tatlidede et al., 2009).

Numerous phytochemicals and/or bioactive compounds derived from plants have been reported to prevent or mitigate doxorubicin cardiotoxicity via antioxidation. They include allicin, ascorbic acid, baicalein, carotenoids, catechin, p-coumaric acid, ellagic acid, epicatechin, epigallocatechin-3-gallate, gallic acid, isorhamnetin, kaempferol, lycopene, malvidin, naringenin, quercetin, saponins, and silymarin, all of which have been shown to exert cardioprotective effects by attenuation of doxorubicin-induced oxidative stress in the heart (Indu et al., 2014; Kulkarni and Swamy, 2015; Saeed et al., 2015; Warpe et al., 2015; Sahu et al., 2016; Abdel-Daim et al., 2017; Akolkar et al., 2017; Al-Shabanah et al., 2019).

Amaranthus hybridus L, also known as "Amaranth or pigweed," is an annual herbaceous plant that grows to be 1 to 6 feet tall. The leaves are alternate petioled, 3 - 6 inches long, dull green, rough, hairy, ovate or rhombic with wavy margins, and rough, hairy, ovate or rhombic with wavy margins. The flowers are small, with terminal panicles that are greenish or red. Tap root is long and fleshy red or pink in color. The seeds are small and lenticellular in shape, averaging 1 - 1.5 mm in diameter and weighing 0.6 - 1.2 g per 1000 seeds. It is a common species in landfills, cultivated fields, and barnyards. In Nigeria, A. hybridus leaves are combined with condiments to make soup (Ngoroyemoto et al., 2019; Montgomery et al., 2020). Their leaves are eaten as spinach or green vegetables in Congo (Kietlinski et al., 2014). In Mozambique and West Africa, these leaves are boiled and mixed with a groundnut sauce and eaten as a salad (Perotti et al., 2019; Paniagua-Zambrana et al., 2020). Squalene, a compound with both health and industrial benefits, has been found in high concentrations in A. hybridus (Adhikary and Pratt, 2015). Despite its use for such purposes, little is known about the nutritional and chemical composition of A. hybridus leaves. The purpose of this study is to document the gas chromatography-mass spectrometry analysis and effect of Amaranthus hybridus aqueous leaf extract on plasma and heart lipid profile in doxorubicin-induced cardiotoxic rat.

1.1 Statement of Problem

Natural crude extracts from plants have been used in traditional medicine to treat a variety of ailments, with Amaranthus being one of them; however, its full therapeutic potential remains unexplored. Scientific interest in Amaranthus and its health-promoting benefits has grown significantly in recent years, with numerous reviews presenting Amaranth's nutraceutical properties, composition, antioxidant properties, applications, and processing. It is widely acknowledged that amaranth has been underutilized due to a lack of knowledge about its nutritional and medicinal properties. There have been few studies on the effects of Amaranthus hybridus aqueous leaf extract on the plasma and heart lipid profile of doxorubicin-induced cardiotoxicity, resulting in either limited or scant information. Against this backdrop, the current study was conducted to determine the effect of Amaranthus hybridus aqueous leaf extract on plasma and heart lipid profiles in doxorubicin-induced cardiotoxic rats.