Atrophic remodeling of the heart during vitamin D deficiency and insufficiency in a rat model.

Vitamin D deficiency (VDD) is associated with skeletal muscle wasting and impaired cardiac function in humans and animals. However, the molecular events that cause cardiac dysfunction in VDD are poorly understood, and therefore, therapeutic approaches are limited. In the present study, we investigated the effects of VDD on heart function with an emphasis on signaling pathways that regulate anabolism/catabolism in cardiac muscle. Vitamin D insufficiency and deficiency led to cardiac arrhythmia, a decrease in heart weight, and an increase in apoptosis and interstitial fibrosis. Ex-vivo cultures of atria revealed an increase in total protein degradation and a decrease in de-novo protein synthesis. The catalytic activities of the major proteolytic systems: ubiquitin-proteasome system, autophagy-lysosome, and calpains were upregulated in the heart of VDD and insufficient rats. In contrast, the mTOR pathway that regulates protein synthesis was suppressed. These catabolic events were exacerbated by a decrease in the expression of myosin heavy chain and troponin genes, as well as decreased expression and activities of metabolic enzymes. These latter changes occurred despite the activation of the energy sensor, AMPK. Our results provide, compelling evidence for cardiac atrophy in Vitamin D deficient rats. Unlike the skeletal muscle, the heart responded to VDD by activating all three proteolytic systems.

Chemopreventive Effect of Cinnamon and Its Bioactive Compounds in a Rat Model of Premalignant Prostate Carcinogenesis.

Cinnamon and its bioactive compounds inhibit prostate cancer cell proliferation in vitro. The aim of the current study was to assess the chemopreventive efficacy of cinnamon (CN) and its bioactive compounds in vivo using N-methyl-N-nitrosourea (MNU) and testosterone (T) to induce prostate carcinogenesis in male Wistar/National Institute of Nutrition rats. Cancer-induced (CI) rats (n = 10) developed prostatic hyperplasia and prostatic intraepithelial neoplasia. These histopathologic changes were diminished in CI rats fed for 4 months with diets supplemented with either CN (n = 20) or its bioactive compounds (cinnamaldehyde, n = 10 and procyanidin B2, n = 10). Androgen receptor (AR) expression was lower in the prostates of CI rats than in control, but the AR target gene, probasin, was robustly upregulated. Treatment of CI rats with CN or its bioactive compounds upregulated AR expression but inhibited the expression of the 5-alpha reductase genes (Srd5a1 and Srd5a2) and did not further increase probasin expression, suggesting blunted transcriptional activity of AR due to the limited availability of dihydrotestosterone. MNU+T induced an altered oxidant status in rat prostate, which was reflected by an increase in lipid peroxidation and DNA oxidation. These changes were completely or partially corrected by treatment with CN or the bioactive compounds. CN and its active components increased the activity of the apoptotic enzymes caspase-8 and caspase-3 in the prostates of CI rats. In conclusion, our data demonstrate that CN and its bioactive compounds have inhibitory effects on premalignant prostate lesions induced by MNU + T and, therefore, may be considered for the chemoprevention of prostate cancer. PREVENTION RELEVANCE: The research work presented in this article demonstrates the chemopreventive efficacy of CN and its bioactive compounds in a rat model of premalignant prostate cancer.