Interactions of Inorganic Mercury and Inorganic Cadmium with Biomimetic and Complex Biological Membranes and their Influence on Membrane Packing and Size

Inorganic mercury (Hg2+) and Inorganic Cadmium (Cd2+) are toxic heavy metals linked to the development of cancer, diabetes and neurological dysfunctions. The effect of these metals on the fluidity and phase transition (Tm) of biomimetic and polar extract membranes was investigated using Laurdan Generalized Polarization (GP) and Dynamic Light Scattering (DLS). Hg2+ and Cd2+ electrostatically target and induce rigidity in membranes containing cationic and anionic lipids respectively. Hg2+ also imparts rigidity by acting as a catalyst in the vinyl ether hydrolysis of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) plasmalogens. Cd2+-induced rigidity of anionic membranes results in a stabilization of the gel phase and a suppression of the Tm of membranes composed of phosphatidic acid (PA), cardiolipin (CL), phosphatidylserine (PS), phosphatidylglycerol (PG) and phosphatidylinositol (PI). Cd2+ induces more rigidity in rigid anionic membranes compared to more fluid anionic membranes. These results further our understanding of metal-lipid interactions

Binding Affinity of Inorganic Mercury and Cadmium to Biomimetic Erythrocyte Membranes

Inorganic mercury and cadmium are becoming increasingly prevalent due to industrial activity and have been linked to cardiovascular disease and diabetes. The binding affinity of Hg, Cd, and their mixtures to biomimetic erythrocyte membranes was investigated by isothermal titration calorimetry in physiologically relevant media (100 mM NaCl, pH 7.4, 37 °C). The thermodynamic parameters were not expressed per mole of lipid but as metals binding to liposomes. To our knowledge, this method is novel and provides a more intuitive approach to understand such interactions. The results demonstrated that Hg interacted with membranes in the following order: PC (phosphatidylcholine) > 85:15 PC/PE (phosphatidylethanolamine) > 85:15 PC/PS (phosphatidylserine), with the binding constants ranging from 10 to 233 M^–1. In contrast, Cd interacted most readily with negatively charged PC/PS membranes but not with the remaining systems. Metal mixtures bind less to PC/PE membranes than the individual constituents. The large entropy contribution from these interactions suggests possible water release and/or reorganization upon Hg and Cd binding to membranes. ζ-Potential data indicate that the process may be electrostatically driven. It is imperative to consider the chemical speciation of these metals in the presence of chloride to better understand metal–lipid interactions and their impact on biomembranes

Resveratrol and Resveratrol-Aspirin Hybrid Compounds as Potent Intestinal Anti-Inflammatory and Anti-Tumor Drugs

Resveratrol (3,4,5-Trihydroxy-trans-stilbene) is a naturally occurring polyphenol that exhibits beneficial pleiotropic health effects. It is one of the most promising natural molecules in the prevention and treatment of chronic diseases and autoimmune disorders. One of the key limitations in the clinical use of resveratrol is its extensive metabolic processing to its glucuronides and sulfates. It has been estimated that around 75% of this polyphenol is excreted via feces and urine. To possibly alleviate the extensive metabolic processing and improve bioavailability, we have added segments of acetylsalicylic acid to resveratrol in an attempt to maintain the functional properties of both. We initially characterized resveratrol-aspirin derivatives as products that can inhibit cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) activity, DNA methyltransferase (DNMT) activity, and cyclooxygenase (COX) activity. In this study, we provide a detailed analysis of how resveratrol and its aspirin derivatives can inhibit nuclear factor kappa B (NFκB) activation, cytokine production, the growth rate of cancer cells, and in vivo alleviate intestinal inflammation and tumor growth. We identified resveratrol derivatives C3 and C11 as closely preserving resveratrol bioactivities of growth inhibition of cancer cells, inhibition of NFκB activation, activation of sirtuin, and 5’ adenosine monophosphate-activated protein kinase (AMPK) activity. We speculate that the aspirin derivatives of resveratrol would be more metabolically stable, resulting in increased efficacy for treating immune disorders and as an anti-cancer agent