Omega-3 increased serum Resolvin E1 and catalase activity and improved aortic smooth muscle function but did not prevent doxorubicin-induced endothelial dysfunction and oxidative stress.
Does omega-3 fatty acid supplementation improve vascular function and reduce oxidative stress in rats treated with doxorubicin?
In a rat model, omega-3 fatty acid supplementation increased pro-resolving mediators but did not protect against doxorubicin-induced vascular endothelial dysfunction or oxidative stress.
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Abstract Background Vascular remodeling mediated by endothelial dysfunction is one of the earliest changes resulting from the use of doxorubicin (Dox). Omega-3 fatty acids are widely recognized for their beneficial effects in attenuating inflammation and improving vascular health, which results in a reduction in atherosclerosis. However, their effect on Dox-induced vascular injury is unknown. Purpose To evaluate the influence of omega-3 on vascular structure, regulation, and function in rats treated with Dox. Methods Sixty male Wistar rats were allocated into four groups: Control (C), Dox (D), omega-3 (O3), and Dox + omega-3 (DO3). Over six weeks, the O3 and DO3 groups received 400 mg/kg of omega-3 daily by gavage, while the C and D groups received filtered water. From the third week onward, Dox administration (4 mg/kg, intraperitoneal, once a week) was started and maintained for four weeks in the D and DO3 groups, while the C and O3 groups received saline. After six weeks, the rats were euthanized, and vascular function was analyzed. Resolvin E1 and D1 were measured by ELISA, and oxidative stress parameters were assessed by spectrophotometry. Statistical analysis: One-way and two-way ANOVA with a significance level of 5%. Results There was an increase in potassium chloride-induced contraction in rings with intact endothelium in the O3, D, and DO3 groups (Figure 1A-1B) and a decrease in contraction magnitude in DO3 group rings without endothelium. Impairment of endothelium-dependent vascular relaxation was observed in rings pre-contracted with phenylephrine and relaxed with acetylcholine in the D and DO3 groups (Figure 1C-1D). These findings suggest that Dox caused vascular dysfunction and that omega-3 may improve vascular smooth muscle function in rats, as evidenced by increased aortic wall thickness in these animals (Figure 1E) and no differences in aortic collagen deposition (Figure 1F). Additionally, omega-3 supplementation increased serum catalase activity (Figure 2A), but was not able to attenuate oxidative stress induced by Dox (Figure 2A-2B). Finally, omega-3 supplementation increased serum levels of the specialized pro-resolving mediator Resolvin E1 in rats treated with omega-3 compared to those that did not receive it (Figure 2E). Serum Resolvin D1 concentration was lower in the D group compared to the C group, and the DO3 group exhibited higher Resolvin D1 levels than the D group (Figure 2F). Conclusion Dox causes endothelial dysfunction and increases oxidative stress. Dox also decreases Resolvin D1, which is mitigated by omega-3 administration. Isolated omega-3 treatment increases Resolvin E1 and catalase activity and may improve aortic smooth muscle, but these effects are not maintained in the presence of Dox.Figure 1 Figure 2
Monte et al. (Sat,) reported a other. Omega-3 increased serum Resolvin E1 and catalase activity and improved aortic smooth muscle function but did not prevent doxorubicin-induced endothelial dysfunction and oxidative stress.