The effects of the combination of dietary flaxseed oil or fish oil with cyclosporine in a rat cardiac allograft model
Othman, Rgia A.
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The discovery of new immunosuppressive drugs has resulted in an improvement of short-term graft survival. Despite this achievement, long-term cardiac allograft survival has not been correspondingly improved. Cyclosporine A (CsA), an effective immunosuppressive drug, has been shown to increase the risk of hyperlipidemia, hypertension, kidney injuries and chronic rejection despite its extensive use in the clinical setting. Therefore, these side-effects of CsA, may further contribute to graft failure over long-term. Early studies have shown that fish oil may reduce side-effects of CsA. These beneficial effects of fish oil may be related to n-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Flaxseed oil is another major source of an n-3 FA, namely α-linolenic acid (ALA). However, its impact on heart transplantation has not been fully explored. The current study aimed to investigate whether dietary flaxseed oil and fish oil reduce post-transplant complications and prolong graft function in a rat cardiac allograft model. Male Fischer and Lewis rats were used as donors and recipients, respectively, to generate a heterotopic cardiac allograft model. After transplant, animals were randomly assigned into 3 groups and fed a diet supplemented with: a) 5% w/w safflower oil (control n=7), b) 5% w/w flaxseed oil (n=8) or c) 2% w/w fish oil (n=7) and an intraperitoneal injection of cyclosporine A (CsA) (1.5 mg/kg/d) over 12 weeks. Body weight, blood pressure (BP), plasma levels of lipids, CsA, and select cytokines, fatty acid profile of hearts (native and graft) and liver tissues as well as graft function and chronic rejection features were assessed. Body weight and blood CsA levels were similar among the groups. As compared to controls, both diet treated groups demonstrated a significantly lower systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (pressure (DBP) (p<0.001), mean arterial pressure (MAP) (p<0.001), heart rate (p<0.05), abdominal fat (p<0.05) and plasma levels of macrophage chemoattractant protein-1 (MCP-1) (p<0.05). Moreover, the fish oil group had significantly (p<0.05) lower plasma levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL), as compared to the control group. High-density lipoprotein cholesterol (HDL) concentrations were significantly higher (P<0.05) in the flaxseed oil-treated group as compared to the other two groups. Data of this study suggest that both flaxseed oil and fish oil may provide similar biochemical, hemodynamic and inflammatory improvements after heart transplantation; however, these apparent beneficial changes were not accompanied with significant reductions in chronic rejection states or apparent histological evidence of cyclosporine-induced nephrotoxicity in this model.