BIOCHEMICAL STUDY OF ACACIA SENEGAL EXTRACT AGAINST CARDIOTOXICITY-INDUCED BY DOXORUBICIN

BIOCHEMICAL STUDY OF ACACIA SENEGAL EXTRACT AGAINST CARDIOTOXICITY-INDUCED BY DOXORUBICIN

Mohamed M. Omran¹ ;Esraa K. Elshekh¹ ;Wael M. Aboulthana²

; Fatma A. Ibrahim² andMohga S. Abdalla^1, *

¹ Chemistry Department, Faculty of Science, Helwan University, Cairo 11795, Egypt.

² Genetic Engineering andBiotechnology Division, National Research Centre, Cairo, Egypt

Key Words: cardiovascular disease; Acacia senegal; Doxorubicin; antioxidant.

ABSTRACT

Heart disease one of the most dangerous disease and count many death all over world. Chemotherapy considered one the causes of cardiovascular disease.Cancer therapy depend on production of reactive oxygen species which effect on cancer cell and normal cell as well. Doxorubicin has a powerful usage in treatment of different type of cancer. Myocyte is the most affected by this free radical produced because of low antioxidant defense. Natural products provide a wide plants with different chemical compounds have the ability to protect hearts from side effect of chemotherapy. Acacia senegal L. (Fabaceae) known as gum Arabia rich source of poly phenol compound and antioxidant.AS may be considered promising candidates in the prevention cardiotoxicity induced by Doxorubicin in rats.

1. INTRODUCTION

Cardiac diseases and cancer are the world's most cause of death among chronic disease (Hoyert and Xu, 2012). In 2018, the world health organization reported that 17.9 million people die because of cardiovascular diseases (CVDs) whereas; 9.6 million people die because of cancer annually. Inspite of the essential advances in prevention and treatment, it was demonstrated that CVDsare considered as the largest contributor to the burden(Benjamin et al., 2017).Cancer treatments by mean of chemotherapy leads to many CVDs such as arrhythmias and heart failure (Geiger et al., 2010).

Doxorubicin (Dox), an anthracycline, is widely used as antineoplastic agent. It shows a broad range of antitumor activity.   A number of mechanisms have been proposed for cardiotoxic effects of Dox. It was postulated that increased oxidative stress and release of reactive oxygen radicals, including superoxide anion and other reactive oxygen intermediates as well as antioxidant deficits, have been suggested to play a major role in Dox-induced cardiomyopathy and heart damage.It was suggested that the traditional medication might lead to severe side effects (Miller and Arnold, 2019).

 It was emphasized that there is a growing interest in uses of natural antioxidants as a protective strategy against the cardiovascular-related problems such as ischemia-reperfusion and Dox-induced cardiotoxicity (Viswanatha Swamy et al., 2011). Acacia species is one of the richest resources of bioactive flavonoids, alkaloids, phenolics, saponins, polysaccharides, tannins, and terpenoids. Various previous studies documented that Acacia species exhibited various biological activities including hypoglycemic, anti-inflammatory, antitumor (Lam and Ng, 2010), antifungal, antiplatelet aggregation, spasmogenic, vasoconstrictor, antihypertensive, antihepatitic C virus, antioxidant potential (Singh et al., 2010), antinociceptive activity and chemopreventive(Lee et al., 2011). Moreover, Seif et al., (2017)showed thatAS extract exhibited ameliorative effect against the deleterious effect induced by di-(2-ethylhexyl phthalate) in liver and brain of rats.

Therefore, the present study aimed to describe the curative influences of AS gum extract against the adverse effects induced as a result of injection of Dox on heart tissues of rats.

1. MATERIALS AND METHODS

2.1.Extract preparation

Plant material of Acacia senegal gum was purchased from Haraz El Attar, Bab El Khalq, Cairo, Egypt. Before grinding the samples, it was dried at oven and crushed into mechanical size. The powder dissolved in two liquids; distilled water (aqueous solution) and corn oil (organic solution). Then 10-gram powdered material added to 100 ml distal water or corn oil to get 10% concentration.

2.2.Treatment dose

Based on the results obtained by (Meena et al., 2006) and supported by (Singh et al., 2009) who reported that no deaths or adverse effects were detected during the 24-hour observation period in rats treated with up to 3000 mg/kg.bw. The dose at the concentration of 250 mg/kg.bw was chosen for the therapeutic application during the experiment.

2.3.Experimental design

Experimental animals were obtained from the animal house of Medical Research Center of Ain Shams University, which included: Mature Wistar male rats weighting 150-200g body weight, about 40 animals were used this study and divided into 5 groups each one contains 8 rats, the five groups were presented in table 1.

Table1: Experimental animals

2.4.Sample collection

            After twenty-four hours of last treatment doserats were euthanized by cervical dislocation and dissected from the ventral side. Blood was collected and centrifuged at 3,000 rpm for 15 min to obtained serum. Serum was separated and kept in sterilized tube at -20°C.

2.5.Biochemical analysis

Cardiac enzymes tests such as aspartate aminotransferase (AST), Creatine kinase (CK) and lactate dehydrogenase (LDH) are measured in serum.

2.6.Statistical analysis

Data are expressed mean ± SEM (n = 6). One way analysis of variance (ANOVA) followed by Turkey’s test was used for analyzing the statistical differences between different treatment groups using Graph pad prism 5 software. Level of significance was set at p < 0.05.

1. RESULTS AND DISCUSSION

Effect of Acacia on serum cardiac enzymes

The levels of AST, CK and LDH in serum of each rat are illustrated in (Table 2). Dox-group showed a highly significant (P<0.001)increase in AST,CKand LDH level and ahighly significant (P<0.001). The cardiac tissue has been confirmed damage at this stage. Acacia-protected and acacia-treated groups demonstrated a highly significant (P<0.001) decrease in the level of AST, CK, and LDH.Protected group results were progress correspondingly to treated group. Acacia-group showed no alteration in cardiac enzymes.

Table2: Effect of Acacia extract against doxorubicin induced cardiac toxicity

^**   Highly Significant difference at p˂ 0.001 in comparison with control group.

^chighlySignificant difference at p˂ 0.001 in comparison with Dox group.

 We assumed that flavonoid-rich AS extract might be beneficial in alleviating oxidative cardiac damage caused by the drug. Hence, the effect of AS was assessed in a dose-dependent manner to study its protective effect against cardiotoxicity induced by DOX.Our results showed that the aqueous extract of AS contained higher levels of phenols which was agreed with and (Ayaz et al., 2017).

The present data illustrated that the mean value of AST, CK and LDH activity in DOX-group showed a highly significant elevation (p ˂ 0.001) compared to control group indicated a myocardial injury due to ROS generated. These results are in accordance with Gotama et al., (2019) and Zhou et al., (2018).The elevation of these biomarker levels in DOX-group seemed to be an oxidative damage to the heart tissues and consequent release of its inside’s substances into the circulation.The level of cardiac enzymes restored near to the normal level in both pre and post treated group which recorded a highly significant decrease compared to DOX group. These results coincides with (Afsar et al., 2017) and (Afsar et al., 2019).

1. CONCLUSION

Acacia senegalshowed a powerful effect against Doxorubicin-induced cardiotoxicity by amelioration of cardiac biomarker enzymes. AS can be used as anti-cardiotoxicity induced by Doxorubicin.

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" دراسات کیمیائیه حیویه لمستخلص نبات الاکاسیا السنغال ضد سمیه القلب المسبب بعقار الدکسروبیسین"

محمد مصطفى عمران ⁽¹⁾ ، اسراء کمال الشیخ ⁽²⁾ ، وائل محمود ابو الثنا ⁽³⁾ ،

 فاطمه عبد الحمید ابراهیم ⁽⁴⁾ ،مهجه شفیق عبد الله⁽⁵⁾

1-     استاذ مساعد الکیمیاء الحیویه – کلیه العلوم – جامعه حلوان.

2-     طالب بحث ماجستیر – کلیه العلوم – جامعه حلوان.

3-     باحث – قسم الهندسه الوراثیه والبیووجیا الحیویه – المرکز القومى لبحوث.

4-     استاذ مساعد – قسم الهندسه الوراثیه والبیولوجیا الحیویه – المرکز القومى للبحوث.

5-     استاذ دکتور الکیمیاء الحیویه – کلیه العلوم – جامعه حلوان.

مستخلص نبات الاکاسیا السنغال المعروف باسم الصمغ العربى ، تم دراسه فعالیه ضد سمیه القلب المسببه بعقار الدکسروبیسین المستخدم فى العلاج الکیماوى لمرضى السرطان . وقد اثبت النبات فعالیته بتحسین انزیمات القلب .