Objective To investigate whether calcium supplementation at different times of the day affects myocardial health, providing a scientific basis for calcium supplementation. Methods Sixty SPF-grade female ICR mice were divided into four groups: morning control (MC), evening control (EC), morning calcium supplementation (MS), and evening calcium supplementation (ES). The calcium-supplemented groups were fed a 0.15% calcium diet and orally administered 6.75 g/(kg·d) of calcium carbonate solution, while the control groups were fed a 1.5% calcium diet and given an equal volume of water. After 10 weeks, the mice were euthanized, and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cardiac troponin (cTNT), superoxide dismutase (SOD), malondialdehyde (MDA), and calcium kinetics were measured. The heart-to-body weight ratio was calculated, and cardiac pathology was assessed via histopathological staining. Transcriptome sequencing, real-time quantitative PCR (RT-qPCR), and Western blot were performed to analyze changes in myocardial-related gene and protein expression. Results Compared with the ES group, the MS group exhibited a significantly increased heart-to-body weight ratio (P<0.01). Both MS and ES groups showed elevated serum MDA levels (P<0.05), with a more pronounced increase in the MS group, while SOD activity tended to decrease in the MS group. Serum TNF-α, cTNT, and IL-6 levels were significantly higher in the MS group (P<0.05). Histopathological analysis revealed disordered myocardial cell arrangement, hypertrophic nuclei, inflammatory cell infiltration, and necrosis in the MS group. Differentially expressed genes between morning and evening calcium-supplemented groups were primarily enriched in the PI3K-Akt, MAPK, and calcium signaling pathways. RT-qPCR and Western blot analyses demonstrated that, compared with the ES group, the MS group exhibited upregulated expression of Gadd45b and Plcb4 and downregulated expression of Cacna1g. Conclusion Morning calcium supplementation activates oxidative stress, exacerbates inflammation, and promotes myocardial hypertrophy and cardiac injury.
Key words
calcium /
circadian rhythm /
cardiac damage /
chrononutrition /
transcriptomics
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