Vitamin D attenuates pro-inflammatory TNF-α cytokine expression by inhibiting NF-кB/p65 signaling in hypertrophied rat hearts.
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.
Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Nawal M
NM
Al-Rasheed
Nouf M
NM
Al-Rasheed
Yieldez A
YA
Bassiouni
Iman H
IH
Hasan
Maha A
MA
Al-Amin
Hanaa N
HN
Al-Ajmi
Raeesa A
RA
Mohamad
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002762:Cholecalciferol / Q000494:pharmacology*; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000009:adverse effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002316:Cardiotonic Agents; D020672:I-kappa B Proteins; D016328:NF-kappa B; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D020107:Troponin T; D014409:Tumor Necrosis Factor-alpha; D002762:Cholecalciferol; D007545:Isoproterenol