The present study evaluated the beneficial effect of cranberry extract on the cardiotoxicity caused by metaproterenol in laboratory mice.
Similar to some of their reported antitumor activities, the antioxidant properties of phenolics in cranberry fruit play a major role in the observed ability to reduce cardiovascular and age-related diseases. Cranberry’s role in preventing oxidative processes included a decrease in the oxidation of lipoproteins. Cranberry ranks high among fruits in antioxidant quality and quantity for their inherent flavonoid content, including proanthocyanidins, anthocyanins, flavonols, and phenolic acids [11].
The diagnosis of heart damage and myocardial infarction is made by evaluating cardiac marker enzymes, including CK, CK-MB, AST, alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and cholesterol [12, 13]. These enzymes do not include contractile proteins and are not found in the bloodstream. In the case of myocardial necrosis, these are released into the blood [14].
In previous studies, the induction of ISO, MET, and allylamine to rats caused heart damage [6]. In the present study, the induction of MET in rats increased parameters indicating cardiac damage. In some cases, increased cTnI represents ischemic damage induced by increased oxygen consumption, decreased blood pressure (perfusion), and decreased oxygen supply to the heart muscle [15]. The superiority of measuring cardiac troponins compared to other commonly-used indicators has made them a gold standard for diagnosing myocardial infarction. Troponins are sensitive and specific indicators even for small amounts of myocardial necrosis [16]. In the present study, cTnI levels significantly increased in the negative control group compared to the positive control group in the fourth and sixth weeks.
Compared to the control group, an excessive increase in CK and CKMB concentrations caused by DOX in serum indicates myocardial damage. The present findings are consistent with Afsar et al.'s reports, indicating that MET, including DOX, increases the serum activity of the mentioned parameters (the most basic biomarkers of myocardial cell damage) [17].
The normalization of CK, CK-MB, and AST serum values in the tested groups receiving cranberry compared to those receiving heart-damaging drugs suggested that cranberry extract could improve cardiac function. The findings of this study are in line with previous findings regarding the protective effect of plant extracts on cardiotoxicity caused by DOX [18].
Many studies have reported that rutin has a protective effect on the heart in cases of myocardial infarction caused by the ISO induction [19]. In the present study, cranberry extract had favorable protective effects on the heart in rats damaged by metaproterenol. This healing effect on the heart can be justified by reducing serum parameters in the groups receiving the extract.
Troponin 1 is one of the cardiac regulatory proteins and improves the contractile function of the heart [20]. In the present study, cTnI was present only in the myocardium; therefore, it was used as a marker of cardiac damage. When the heart cell dies, this protein is released from the heart into the bloodstream. Hence, the level of this serum parameter was higher in animals receiving MET than in the group not receiving this drug. The level of cTnI, however, was low in the groups receiving both heart-damaging drugs and cranberry extract, suggesting that the cranberry extract can improve cardiac function.
Cardiac marker enzymes include AST, CK-MB, and cTnI and act as markers for diagnosing myocardial damage [21]. Our study showed a significant decrease in the levels of these serum parameters in the groups receiving cranberry extract with a dose of 150 mg/kg compared to the negative control group. Cranberry extract has an effect even in a low dose; as the dose increases, its effect on improving cardiac function also increases. Accordingly, cranberry plays a comprehensive role in preventing cardiac damage and reducing the parameters of cardiac damage.
This study also showed the oxidative damage caused by increased free radicals in the heart tissues after the MET administration. Damage to the heart myocardium leads to the release of serum parameters of cardiac indicators such as AST, CK-MB, and cTnI in the blood, leading to the diagnosis of cardiac damage [22].
Cardiac cell damage significantly decreased in rats receiving different doses of cranberry extract reduced compared to those receiving MET. As a result of heart damage, the level of cTnI, one of the most reliable and common biomarkers, increased. However, the effects and longevity of cranberry extract were not permanent. After stopping the administration of this extract, the values of the cTnI parameter were higher in the group receiving 150 doses of this extract in the sixth week than in the negative control group. This implies that the stability of cranberry extract is short, and it should be consumed for a more prolonged period [23, 24].
In Kharadi et al.’s study, the administration of Allium cepa aqueous extract at a dose of 400 mg/kg resulted in the recovery of increased parameters (troponin I, CK-MB, and AST) [25]. In our study, the administration of cranberry extract in 75, 100, and 150 doses led to the recovery of the aforementioned parameters, especially in the fourth week. The recovery of troponin I, CK-MB, and AST by this extract was significant in the present study.
CK enzymes, especially CK-MB, convert ATP into ADP and transfer energy to cardiac myosin filaments. The sensitivity of CK-MB measurement is 95% in many studies, and it is a highly specific marker in confirming cardiac damage [26, 27]. A remarkable increase in this enzyme was observed in the studied rats with heart damage. While the level of this enzyme decreased in rats receiving different doses of cranberry extract. This implies that cranberry extract is a strong cardiac protector inhibiting cardiac necrosis caused by MET.