Protective Effect of Omega-3 Fatty Acid Supplementation against Immobilization Stress-Induced Cardiac Morphological and Functional Abnormalities in the Menopausal Rat Model

Menopause increased the vulnerability of women to stress, which affects most of the body tissues, especially the brain and heart. The goal of this study was to explore whether omega-3 fatty acid supplementation can help to reduce stress-related heart problems in menopausal rats. Female Wistar rats (n = 32) were divided into four groups: control, ovariectomy, ovariectomy + immobilization stress (2 h daily for 2 weeks), and ovariectomy + immobilization stress (IMO, 2 h daily for 14 consecutive days) plus oral supplementation of omega-3 fatty acids (400 mg/kg BW/d for 14 consecutive days). In these groups, we investigated cardiac function by echocardiography and analysed serum level of IGF-1 and estrogen, in addition to some local cardiac parameters such as troponin-T (cTnT) levels, as well as serum protein levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CKMB). We also measured serum levels of heat-shock proteins (HSP), atrial natriuretic peptide (ANP), and B-type natriuretic peptide (BNP). The cardiac tissue was also examined histologically and immunohistochemically for iNOS and caspase-3. The data obtained demonstrated a significant change in cardiac weights, abnormal deposition of excess collagen, and dyslipidemia in stressed rats. In addition, we found elevated cardiac CK-MB and LDH activities and cTnT levels, together with a reduction of systolic function of the heart by decreasing EF% and FS%. Importantly, both caspase-3 and nitric oxide synthase expression were markedly increased in the ST-OVX group. Furthermore, stressed rats showed low serum IGF-1 and decreased local compensatory peptides like HSP, ANP, and BNP. Omega-3 supplementation improved these parameters; however, they were still lower than those of control rats. The present study suggests that the anti-stress effect of omega-3 supplements is mediated by normalization of stress-induced changes in the circulating IGF-1 and dyslipidemia. In addition, it possesses an antiapoptotic effect by decreasing local expression of caspase-3, thereby returning the body to normal homeostasis. These data showed that the response to chronic restraint stress-induced cardiac dysfunction was modulated by the omega-3 fatty acid supply.