1-Methylnicotinamide (MNA), the major endogenous metabolite of nicotinic acid (NicA), may partially contribute to the vasoprotective properties of NicA. Here we compared the antiatherosclerotic effects of MNA and NicA in apolipoprotein E (ApoE)/ low-density lipoprotein receptor (LDLR)-deficient mice. ApoE/ LDLR 2/2 mice were treated with MNA or NicA (100 mg/kg). Plaque size, macrophages, and cholesterol content in the brachiocephalic artery, endothelial function in the aorta, systemic inflammation, platelet activation, as well as the concentration of MNA and its metabolites in plasma and urine were measured. MNA and NicA reduced atherosclerotic plaque area, plaque inflammation, and cholesterol content in the brachiocephalic artery. The antiatherosclerotic actions of MNA and NicA were associated with improved endothelial function, as evidenced by a higher concentration of 6-keto-prostaglandin F 1a and nitrite/nitrate in the aortic ring effluent, inhibition of platelets (blunted thromboxane B 2 generation), and inhibition of systemic inflammation (lower plasma concentration of serum amyloid P, haptoglobin). NicA treatment resulted in an approximately 2-fold higher concentration of MNA and its metabolites in urine and a 4-fold higher nicotinamide/MNA ratio in plasma, compared with MNA treatment. In summary; MNA displays pronounced antiatherosclerotic action in ApoE/LDLR 2/2 mice, an effect associated with an improvement in prostacyclin-and nitric oxide-dependent endothelial function, inhibition of platelet activation, inhibition of inflammatory burden in plaques, and diminished systemic inflammation. Despite substantially higher MNA availability after NicA treatment, compared with an equivalent dose of MNA, the antiatherosclerotic effect of NicA was not stronger. We suggest that detrimental effects of NicA or its metabolites other than MNA may limit beneficial effects of NicA-derived MNA.
Raman optical activity (ROA) spectroscopy has been applied for the first time to study the interaction of cisplatin with DNA. The knowledge about the structure of DNA-metal ion cross-links and hence the mechanism of the drug action is fundamental for the development of new antitumor drugs. At the same time, there is an urgent need to search for new methods for monitoring of this effect at the therapeutic dose of a drug. We have demonstrated that ROA spectroscopy is a sensitive technique with the capability to follow the structural alteration of the whole DNA molecule upon drug binding via a direct observation of transformation undergoing within chiral sugar moieties. A ROA profile delivers clear evidence of a partial transition from the B-DNA to the A-form due to the formation of cisplatin-DNA cross-links.
This work shows the application of vibrational spectroscopy supported by other complementary techniques in analysis of tissues altered by vascular diseases, in particular atherosclerosis. The analysis of atherosclerotic plaque components, as well as label-free imaging of vessels and identification of biochemical markers of endothelial dysfunction are reported. Additionally, the potential of vibrational spectroscopy imaging in following the disease progression (including calcification) and pathological changes in heart valves is described. The presented research shows the effectiveness of techniques used in the biochemical studies of altered tissues and summarizes their capabilities in research on vascular diseases. The scope of the paper is to collect previously published work connected with the application of Raman spectroscopy, FT-IR spectroscopy and complementary methods for the investigation of vascular diseases ex vivo and presenting it in a comprehensive overview.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.