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Vitamin D attenuates pro-inflammatory TNF-α cytokine expression by inhibiting NF-кB/p65 signaling in hypertrophied rat hearts

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Abstract

A growing body of evidence suggests that immune activation and inflammatory mediators may play a key role in the development and progression of left ventricle (LV) hypertrophy. The present study was designed to test the hypothesis that the cardioprotective effect of cholecalciferol (Vit-D3) is mediated via the regulation of messenger RNA (mRNA) expression of pro-inflammatory cytokines. Rats were randomly divided into four groups: control group received normal saline (0.9 % NaCl) i.p. for 14 days; Vit-D3 group received Vit-D3 at a dose of 12 μg/kg/day by gavage for 14 days; ISO group received saline for 7 days, and at day 7, ISO (5 mg/kg/day) was injected i.p. for 7 consecutive days to induce cardiac hypertrophy; and Vit-D3 + ISO group was treated with Vit-D3 for 14 days, and at day 7, ISO was administered for 7 consecutive days. Heart/body weight ratio, troponin-T, creatine kinase-MB, and tumor necrosis factor-α (TNF-α) levels of LV tissue were estimated. Levels of mRNA expression of NF-кB (NF-кB)/p65 and inhibitory kappa B (IкB)-α were determined by real-time PCR. Vit-D3 administration before and during induction of cardiac hypertrophy significantly reduced (P < 0.001) cardiac biomarkers. The histopathological examination further confirmed these results. In addition, Vit-D3 significantly decreased (P < 0.001) NF-кB-p65 mRNA expression and increased (P < 0.01) IкB-α mRNA expression in LV tissues compared to ISO group. Based on these findings, it was concluded that the administration of cholecalciferol markedly attenuated the development of ISO-induced cardiac hypertrophy likely through downregulation of TNF-α /NF-кb/p65 signaling pathways. However, it should be pointed out that other signaling pathways may contribute to the cardioprotective effect of Vit-D3 which requires further investigation.

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Acknowledgments

This research project was supported by a grant from the “Research Center of the Female Scientific and Medical Colleges”, Deanship of Scientific Research, King Saud University.

Conflict of interest

The authors declare that they have no conflict of interest.

Authors’ contribution

NMA and NA participated in the experimental design and revised the final manuscript. YA wrote and revised the all results of the manuscript. IH carried out the molecular genetic studies, performed the statistical analysis, and participated in the sequence alignment and drafted the manuscript. MA and HN designed the experimental and participated in the biochemical analysis and data collections. RA carried out the histological and immunoassays. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia

    Nawal M. Al-Rasheed, Nouf M. Al-Rasheed, Yieldez A. Bassiouni, Iman H. Hasan, Maha A. Al-Amin & Hanaa N. Al-Ajmi

  2. Department of Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Yieldez A. Bassiouni

  3. Department of Anatomy, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Raeesa A. Mohamad

  4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Saud University, Riyadh, 11495, P.O. Box. 22452, Saudi Arabia

    Iman H. Hasan

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  1. Nawal M. Al-Rasheed
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Correspondence to Iman H. Hasan.

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Al-Rasheed, N.M., Al-Rasheed, N.M., Bassiouni, Y.A. et al. Vitamin D attenuates pro-inflammatory TNF-α cytokine expression by inhibiting NF-кB/p65 signaling in hypertrophied rat hearts. J Physiol Biochem 71, 289–299 (2015). https://doi.org/10.1007/s13105-015-0412-1

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  • DOI: https://doi.org/10.1007/s13105-015-0412-1

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