Perinatal Administration of C-Phycocyanin Protects Against Atherosclerosis in apoE-Deficient Mice by Modulating Cholesterol and Trimethylamine-N-Oxide Metabolisms

Abstract

Objective: Gestational hypercholesterolemia concomitantly with a highly oxidative environment is associated with higher atherosclerosis in human and animal offspring. This work aimed to determine whether perinatal administration of a C-phycocyanin concentrate, a powerful antioxidant, can protect against atherosclerosis development in genetically hypercholesterolemic mice in adult life. Approach and Results: C-Phycocyanin was administered during gestation solely or gestation and lactation to apolipoprotein E-deficient mice. Male and female offspring were studied until 25 weeks old. Progenies born to supplemented mothers displayed significantly less atherosclerotic root lesions than control group in all groups excepted in male supplemented during gestation and lactation. Female born to supplemented mothers had a greater gallbladder total bile acid pool, lower secondary hydrophobic bile acid levels such as lithocholic acid, associated with less plasma trimethylamine N -oxide at 16 weeks old compared with control mice. Regarding male born to C-Phycocyanin administrated mothers, they expressed a higher high-density lipoprotein cholesterol level, more soluble bile acids such as β-muricholic acids, and a decreased plasma trimethylamine at 16 weeks old. Liver reduced-to-oxidized glutathione ratio were increased and liver gene expression of superoxide dismutase and glutathione peroxidase were significantly decreased in male born to gestational supplemented mothers. No difference in the composition of cecal microbiota was found between groups, regardless of sex. Conclusions: Our findings suggest a protective effect of perinatal antioxidant administration on atherosclerosis development in apolipoprotein E-deficient mice involving sex-specific mechanisms.

Antioxidant Efficacy of a Spirulina Liquid Extract on Oxidative Stress Status and Metabolic Disturbances in Subjects with Metabolic Syndrome

“…The mean plasma triglycerides level decreased significantly in the Spirulysat ® group compared to the placebo, while HDL-cholesterol levels increased at all visits in this group. Thus, these results suggest a protective effect of Spirulysat ® against cardiovascular disease and are consistent with our data obtained in mice [ 24 ] and hamsters [ 23 ], fed hyperenergetic diets. Indeed, Spirulysat ® supplementation of apolipoprotein E-deficient mice, a model of a human atherosclerosis, during gestation and lactation, decrease atherosclerosis development in adult offspring [ 24 ].…”

“…Thus, these results suggest a protective effect of Spirulysat ® against cardiovascular disease and are consistent with our data obtained in mice [ 24 ] and hamsters [ 23 ], fed hyperenergetic diets. Indeed, Spirulysat ® supplementation of apolipoprotein E-deficient mice, a model of a human atherosclerosis, during gestation and lactation, decrease atherosclerosis development in adult offspring [ 24 ]. Similarly, we showed in hamsters fed with a high-fat diet, that Spirulysat ® supplementation improves sphingolipids profile and protects from lipid accumulation in aorta, suggesting a protective effect against cardiovascular disease [ 23 ].…”

“…The effect of Arthrospira on urinary isoprostanes has not been reported in the literature in patients with metabolic syndrome but data from some studies [ 35 , 40 ] have shown a favourable effect of Arthrospira on oxidative stress and inflammation. [ 24 ]. A review from Spahis et al enumerated several types of connection between metabolic disturbances and oxidative stress in metabolic syndrome [ 41 ].…”

“…Hemodynamic measurements appeared stable throughout the study in both groups and in the entire study population. Using a higher dose of Spirulysat ® in hamsters for 12 weeks and in mice for 25 weeks, we did not observe deleterious effects on biological parameters or mortality [ 22 , 24 ]. No adverse effects are reported in previous studies using higher doses of phycocyanin, notably in mice [ 32 , 50 ] and in rats [ 51 ].…”

“…In high fat high sucrose fed mice, Spirulysat ® supplementation protects against non-alcoholic steatohepatitis [ 22 ]. We also reported that Spirulysat ® supplementation prevent metabolic syndrome-associated metabolic disturbances in hamsters [ 23 ] and atherosclerosis development in apolipoprotein E-deficient mice [ 24 ].…”