الفهرس 
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Abstract
CVD is the leading global cause of death that accounts 31% of global death. CH is a type of CVD that is defined as an adverse remodelling process of the cellular architecture of the heart, which arises initially as an adaptive mechanism towards stressful conditions that on prolonged state leads to the critical intermediate stage that advances into different cardiovascular complications. The characteristic features of CH are fibrosis (enhanced sarcomere organization and extracellular matrix deposition) and inflammation, accompanied by increase in cardiomyocytes size, protein synthesis, and thickening of left ventricle.
Lignans are a large group of bioactive, non-nutrient, phenolic plant compounds that are found in the highest concentrations in flaxseeds and sesame seeds. Flaxseeds show significant protective effect in a variety of cardiovascular diseases, due to its anti-inflammatory, antioxidant, anti-apoptotic, antihypertensive, and anti-atherosclerotic activities. Thus, the present work was designed to investigate the therapeutic effect of flaxseed lignans to ameliorate CH, and to assess the mechanism of its action.
In the current study, a total of forty healthy adult male mice were used. For the experiments, the animals were randomly assigned into five groups, as follows:
group I (negative control group, n= 7): normal mice, neither treated with lignans nor injected with isoproterenol.
group II (Lignans control group, n= 7): mice orally treated with lignans at a daily dose of 200 mg/kg b.wt for 4 weeks.
group III (ISO group, n= 12): ISO-injected mice. CH was induced by subcutaneous injections with isoproterenol (5 mg/kg in 0.9% saline), once daily for 14 consecutive days.
group IV (ISO+ Lignans100 group, n= 7): ISO-injected mice, then orally treated with lignans (100 mg/kg b.wt) daily for 4 weeks.
group V (ISO+ Lignans200 group, n= 7): ISO-injected mice, then orally treated with lignans (200 mg/kg b.wt) daily for 4 weeks.
At the end of the experiment, blood and heart samples was collected and subjected to different analysis according to the following protocol:
Echocardiography studies to assess alterations in cardiac structure and function. Heart relative weight results to assess the changes in the heart weight. Biochemical analyses to assess the effect of lignans on CK-MB, MDA and TAC. Histopathological studies to assess the effect of lignans on the pathological characteristics of cardiac tissue of hypertrophic mice. Ultrastructural studies to assess the effect of lignans on the ultrastructure of cardiac tissue of hypertrophic mice.
Quantitative data were analyzed statistically using One-way ANOVA followed by post hoc multiple comparisons (Tukey’s test) for comparative analysis between the groups. P< 0.05 was regarded as statistically significant.
Echocardiography results, mice injected with ISO showed significant increase in LVM, IVS, and LVPW as well as significant decrease in LVID. These structural alterations consequently affected the cardiac function as manifested by significant decrease in the measurements of EF and FS. Most of these cardiac impairments were absent in lignans-treated group. This was evidenced by significant decrease in LVM, IVS, and LVPW, and significant increase in LVID as well as, significant increase in the measurements of EF and FS.
Heart relative weight results, mice injected with ISO showed the relative weight and gross morphology of the heart were significantly increased. However, after treating ISO-injected mice with lignans, the relative heart weights of the treated groups were significantly decreased compared with that of the ISO-injected group.
In the biochemical results, mice injected with ISO showed significant increase in serum CK-MB, tissue MDA concentrations, as well as significant decrease in TAC concentrations compared with those of the negative control group. However, treating ISO- injected mice with lignans significantly ameliorated the biochemical results. Lignans treatment significantly reduced CK-MB, and MDA, and increased the level of TAC.
Histological results, all cardiac hypertrophic mice showed increase in the size of IVS, LVW, decrease in the size of LVID and showed abnormal architecture of heart wall with damaged striations, infiltration of inflammatory cells, edema, hyper-eosinophilic cytoplasm, in addition to severe fibrosis. The ISO-injected group treated with lignans showed decrease in the size of IVS, LVW, increase the size of LVID and reguraly-arranged striations, with no inflammation, edema and very little fibrosis.
Ultrastructural results showed mice injected with ISO showed disarrayed myofibrils with obvious fragmentation and dissolution, ruptured sarcomeres, and disrupted Z lines. Mitochondria were swollen with damaged cristae, disruption of mitochondrial membranes and vacuolations. The ISO-injected group treated with lignans showed many intact myofibrils with repeated sarcomeres and well-arranged Z lines were seen. Few swelling mitochondria with fragmented cristae were seen. And the structure is relatively better organized.
ISO-injected treated mice with low and high dose of lignans nearly gave the same results, but high dose of lignans improved CH better.
In conclusion, flaxseed lignans decreased heart relative weight, CK-MB, and MDA as well as increased the level of TAC. In addition, lignans effectively attenuated the histological and ultrastructural changes in cardiac tissue, and fibrosis. Lignans restored echocardiography parameters to normal. This is attributed to the anti-inflammatory, antifibrotic and antioxidant effects of flaxseed lignans.