Citrus aurantium for cardiovascular support -
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Clin Pharmacol Ther ;76 5 — Keogh AM, Baron DW. Sympathomimetic abuse and coronary artery spasm. Br Med J ; It is also used to treat colds, coughs, Please Note: The articles on this database are automatically generated by our AI system. While we strive for accuracy, these articles may not contain verified information and should be used for informational purposes only.
We recommend consulting verified sources or experts for accurate and reliable information. It is also used to treat colds, coughs, and other respiratory illnesses. Bitter orange is a dietary supplement that is used to help with weight loss, to reduce appetite, and to increase energy levels.
It is also used to treat digestive problems, colds, and headaches. Bitter orange is a dietary supplement that is commonly used in the food industry as a flavoring agent. It is often used to add a citrusy flavor to dishes, as well as to enhance the flavor of other ingredients.
It is also used as a natural preservative, as it has antimicrobial properties that can help to extend the shelf life of food products. Additionally, bitter orange is sometimes used as a colorant to give food a more vibrant hue.
Bitter orange is a dietary supplement that is known to have many health benefits. It is rich in antioxidants, which can help protect the body from free radical damage and reduce inflammation. It is also known to help boost the immune system, improve digestion, and reduce cholesterol levels.
Additionally, it may help to reduce the risk of certain types of cancer, as well as help to regulate blood sugar levels. Amid nutrients of citrus fruits, flavonoids have been more lately documented as having several benefits that contain antioxidant, antimicrobial, anti-inflammatory, and anti-cancer properties [11,12].
The flavonoids extracted from citrus fruit containing c itrus aurantium L. are mostly consisted of hesperidin, naringenin, and nobiletin. These flavonoids have been stated to have some properties that adjust the inflammatory response and halts carcinogenesis [13].
According to that, since the inflammatory process and antioxidant system involves MI induced by ISO, we hypothesized that this plant extract may have cardio protective effects. The purpose of this study was to explore the possible antioxidant effect of c itrus aurantium flower extract and cardio protection against MI induced by ISO through electrocardiographic, myocardial marker injury, lipid profile changes as well as peroxidation of lipids, changes in antioxidant system and histopathological parameters.
Isoproterenol hydrochloride was purchased from Sigma Aldrich Chemical Company, St. Louis, MO, USA. Lipid peroxidation product MDA and antioxidant assay kits SOD, GSH, CAT, GP X were bought from Zell Bio Company, Germany.
Other biochemical substances were of analytical grade and purchased from Pars-Azmoon Company, Iran. All experiment and procedures defined in this study were approved by the local ethics committee of Zahedan University of Medical Sciences.
Animals were fed with standard pellet diet and water ad libitum. at 24 h interval for 2 days to experimental myocardial infarction induction [16]. After acclimatization, the animals were allocated randomly into 4 groups 6 in each group.
The volume of solution injected was same in all groups. Total duration of experiment was two weeks and all experiments started at 9 am every day. ECG recordings obtained through computerized Power Lab system AD Instruments, Australia and analyzed with chart7 software.
After recording the ECG, the animals were sacrificed and blood samples were taken. Samples were centrifuged at rpm for ten minutes. Serum was taken and kept at 0C, and then CK-MB, LDH, ALP, AST, ALT, and lipid profile were measured using routine laboratory kits Pars Azmoon, Tehran. Serum LDL-cholesterol was calculated by the Friedewald formula.
MDA, SOD, GP X , GSH, and CAT were measured using Zell Bio kit Zell Bio GmbH, Deutschland and ELISA method.
The fixed tissues were inserted in paraffin, sectioned at 5 µm and stained with hematoxylin and eosin [17]. The samples were observed under light microscope, and then photomicrographs were taken. It should also be mentioned that grading of histopathological changes was classified by a blind pathologist as: low, mild focal myocytes injury or multifocal deterioration with a mild degree of inflammation , moderate myofibrillar degeneration or moderate inflammatory process and severe necrosis with extensive inflammatory process.
Citrus aurantium flowers were taken from Shiraz, Iran, in The plant was recognized and authenticated by the botany department of Sistan and Baluchistan University. During the time of experiments, the extract was dissolved in saline and animals were forced-fed with above-mentioned doses [14].
Data is expressed as mean ± SE. Statistical analysis was done by SPSS software version The effects of ISO and citrus aurantium extract treatment on pattern of ECG are depicted in Figure 1 and Table 1.
Control and citrus aurantium treated rats showed normal pattern of ECG, whereas rats treated with ISO showed a significant increase in S-T voltage, decrease in R amplitude as compared to control rats, suggestive of myocardial infarction.
ISO treated rats likewise displayed the pathological Q wave, demonstrating transmural myocardial infarction induction. Also, a significant decrease in QRS and R-R interval and a significant increase in heart rate were detected in rats treated with ISO.
Figure 1: Electrocardiographic patterns in control A , ISO B , pretreated with citrus aurantium extract then treated with ISO C and citrus aurantium alone D groups. Table 1: Effect of citrus aurantium pretreatment on electrocardiographic parameters in ISO induced myocardial infarction in rats.
Table 2 represents the effects of ISO and citrus aurantium extract treatment on cardiac marker enzymes such as CK-MB, LDH, ALP, AST and ALT.
ISO treated rats showed an increased significantly in activities of these enzymes as compared to the control group. ISO treated animals that pre-treated with citrus aurantium extract exhibited significantly decrease the CK-MB, LDH, ALP, AST and ALT activities.
No significant difference was detected in rats treated with the extract alone when compared to control rats. Table 2: Effect of citrus aurantium pretreatment on cardiac marker enzymes in ISO induced myocardial infarction in rats.
The levels of MDA and GSH along with the activities of the enzymes GP X , SOD, and catalase in normal and experimental rats are listed in Table 3.
The value of MDA, end product of lipid peroxidation and marker for oxidative stress, showed significantly increase in ISO treated rats, as compared to the control group.
ISO treatment also caused in the significant decrease in the level of GSH, an endogenous antioxidant in comparison with normal control rats. Activities of glutathione-dependent antioxidant enzyme and antiperoxidative enzymes were significantly lowered in ISO treated rats as compared to the control group.
Pre and co-treatment with citrus aurantium in MI induced by ISO rats significantly decreased the level of MDA as compared to rats treated with ISO alone. The pre-treatment of citrus aurantium for 14 days resulted in a significant rise in the level of GSH and activities of GP X , SOD and catalase.
Normal rats that receive citrus aurantium alone did not display any substantial alteration when compared with other normal rats, indicating that it does not per se have any adverse effects.
Table 3: Effect of citrus aurantium pretreatment on lipid peroxidation, endogenous antioxidant and antioxidant enzymes in ISO induced myocardial infarction in rats. Table 4 lists the levels of total cholesterol, HDL, LDL and triglycerides in the serum of all groups of animals.
Rats treated with ISO only exhibited a significant rise in these parameters with the levels of HDL-cholesterol being an exception where there was a significant decrease. Pre-treatment of citrus aurantium for 14 days beside with ISO administration on 13 th and 14 th days considerably reduced the levels of LDL and triglycerides with a following noteworthy increase in the levels of HDL-cholesterol as compared to ISO alone treated rats.
No significant change in total cholesterol was observed when compared to ISO treated group. In the citrus aurantium alone group, there was no substantial alteration detected in serum lipoproteins and triglycerides levels in comparison to those of the control rats.
Figure 2 illustrates the histological photographs of heart tissues of all studied groups. Histopathological analysis of myocardial tissue achieved from normal control animals displayed clear integrity of membrane of myocardial cells. Normal untreated rats indicated typical cardiac tissues without any infarction and infiltration of inflammatory cells was not seen in this group.
Histopathological results revealed that the ISO caused induction of MI in cardiac muscle. Tissues sample from myocardial infarction induced by ISO, exhibited extensive myocardial structure abnormality and subendocardial necrosis with capillary dilatation and leukocyte infiltration as compared to the control group.
Prior administration of citrus aurantium showed reduced grade of infiltration of inflammatory cells and the appearance of myocardial cells was comparatively well conserved with no evidence of focal necrosis. Extract treated group rats displayed no change in morphology of heart tissue as compared to the normal control group.
The pathophysiology mechanism of MI has not been fully revealed. Although catecholamines have regulatory effect on contraction and metabolism of myocardial muscle, these substances may be responsible for cell damages in the long term. The same situation can be observed in clinical situations such as angina, temporary myocardial hypoxia, acute inadequacy in coronary blood flow and subendocardial infarction.
Isoproterenol, a potent synthetic catecholamine, can improve injuries like myocardial infarction when injected in animals. These lesions are apparently same to those of coagulative myocytolysis or myofibrillar deterioration.
This is one of the findings during acute MI and unexpected death in man [18,19]. Different mechanisms have been reported as responsible for induction of myocardial infarction by ISO.
Previous reports recommended that coronary inadequacy, sarcoplasmic calcium excess, changed metabolic and electrolyte balancing system and oxidative stress are the main causative factors in catecholamine induced cardiac insufficiency [20].
Imbalance between oxygen delivery and request of myocytes after coronary hypotension and cardiac muscle hyperactivity due to augmented heart rate and contractility could cause myocardial damage [21].
Interaction of ISO with β1 and β2 adrenoceptors, activation of which causes to positive inotropic and chronotropic effects on heart, which produce relative ischemia due to myocardial hyperactivity and coronary hypotension [22].
ECG deliberated the single most important primary clinical exam for diagnosis of infarction and ischemia in cardiac muscle and. In our study, ISO administration causes pathological Q wave in rats, the most characteristic finding of transmural MI of the left ventricle.
Administration of ISO also showed a decline in R-R interval, and increase in QRS time and heart rate. These changes could be due to the damage of cell membrane in injured cardiac muscle [23]. It has been exposed that a rise in heart rate is responsible for augmented oxygen consumption causing to enhanced necrosis of myocardial tissue [24].
ISO also increased ST-segment voltage and decreased R- wave voltage. This is favorable with the comments of earlier reports. ST-segment elevation reproduces the potential difference in the border between ischemic and non-ischemic regions and consequences in loss of cell membrane function whereas decrease in R-wave voltage might be due to the start of myocardial edema subsequent ISO treatment [25].
Citrus aurantium pre-treatment in ISO treated rats prohibited the pathological changes in the ECG, which suggest s protective effect for its cell membrane. Cardiac muscle contains different diagnostic markers of MI and when heart metabolism injured, it discharges its contents into the extracellular fluid [26].
Cytotoxic enzymes such as CK-MB, LDH, AST, ALT and ALP, which serve as diagnostic markers, could be released from tissues damaged in the circulation due to permeable or disagreement of cell membrane and reflect the changes in plasma membrane integrity [27].
Our data confirmed significant increase in the levels of these enzymatic biomarkers of serum in ISO treated rats, which were in same direction with previous reports.
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