Cardioprotective Effects of Curcumin-Nisin Based Poly Lactic Acid Nanoparticle on Myocardial Infarction in Guinea Pigs.

Myocardial infarction (MI) is the most prevalent cause of cardiovascular death. A possible way of preventing MI maybe by dietary supplements. The present study was thus designed to ascertain the cardio-protective effect of a formulated curcumin and nisin based poly lactic acid nanoparticle (CurNisNp) on isoproterenol (ISO) induced MI in guinea pigs. Animals were pretreated for 7 days as follows; Groups A and B animals were given 0.5 mL/kg of normal saline, group C metoprolol (2 mg/kg), groups D and E CurNisNp 10 and 21 mg/kg respectively (n = 5). MI was induced on the 7th day in groups B-E animals. On the 9th day electrocardiogram (ECG) was recorded, blood samples and tissue biopsies were collected for analyses. Toxicity studies on CurNisNp were carried out. MI induction caused atrial fibrillation which was prevented by pretreatment of metoprolol or CurNisNp. MI induction was also associated with increased expressions of cardiac troponin I (CTnI) and kidney injury molecule-1 (KIM-1) which were significantly reduced in guinea pig's pretreated with metoprolol or CurNisNp (P < 0.05). The LC50 of CurNisNp was 3258.2 µg/mL. This study demonstrated that the formulated curcumin-nisin based nanoparticle confers a significant level of cardio-protection in the guinea pig and is nontoxic.

Thermal adaptation in biological membranes: functional significance of changes in phospholipid molecular species composition.

Quantities of 1-palmitoyl 2-docosahexaenoyl phosphatidylcholine (16:0/22:6-PC or PDPC) increase from 24 to 40 weight percent as a consequence of cold acclimation in mitochondrial membranes of rainbow trout liver (J. Comp. Physiol. 156, 665-674, 1986). The present study was undertaken to assess the impact of such a large change in the proportions of a single molecular species on the fluidity, lateral packing (as sensed by phospholipase A2), and permeability of biological membranes. These properties were examined in multilamellar liposomes prepared from binary mixtures of dipalmitoyl phosphatidylcholine (DPPC) and PDPC in proportions increasing from 10 to 40 mole% PDPC. Glucose permeability was positively correlated with both assay temperature and PDPC content. The temperature dependence of Na+ permeability declined steadily as the mole fraction of PDPC increased; consequently, sodium permeability was positively correlated with PDPC content at 5 degrees C, but inversely correlated at 20 degrees C. Phospholipase A2 activity was independent of both assay temperature and vesicle composition. Vesicles of all compositions displayed a single transition in the temperature dependence of 1,6 diphenyl-1,3,5-hexatriene (DPH) fluorescence polarization, which shifted to lower temperature and broadened as proportions of PDPC increased. At temperatures below the transition, fluidity was positively correlated with the mole fraction of PDPC, but interfacial and deeper regions of the bilayer were affected differently by variations in PDPC content. Nonelectrolyte permeability was the only index of membrane structure or function to be significantly correlated with the fluidity of the bilayer interior. The tendencies of PDPC to both fluidize the membrane and to reduce the temperature sensitivity of electrolyte permeation may promote the adaptation of membrane function to low temperature.

The curvature and cholesterol content of phospholipid bilayers alter the transbilayer distribution of specific molecular species of phosphatidylethanolamine.

The curvature, cholesterol content, and transbilayer distribution of phospholipids significantly influence the functional properties of cellular membranes, yet little is known of how these parameters interact. In this study, the transbilayer distribution of phosphatidylethanolamine (PE) is determined in vesicles with large (98 nm) and small (19 nm) radii of curvature and with different proportions of PE, phosphatidylcholine, and cholesterol. It was found that the mean diameters of both types of vesicles were not influenced by their lipid composition, and that the amino-reactive compound 2,4,6-trinitrobenzenesulphonic acid (TNBS) was unable to cross the bilayer of either type of vesicle. When large vesicles were treated with TNBS, approximately 40% of the total membrane PE was derivatized; in the small vesicles 55% reacted. These values are interpreted as representing the percentage of total membrane PE residing in the outer leaflet of the vesicle bilayer. The large vesicles likely contained approximately 20% of the total membrane lipid as internal membranes. Therefore, in both types of vesicles, PE as a phospholipid class was randomly distributed between the inner and outer leaflets of the bilayer. The proportion of total PE residing in the outer leaflet was unaffected by changes in either the cholesterol or PE content of the vesicles. However, the transbilayer distributions of individual molecular species of PE were not random, and were significantly influenced by radius of curvature, membrane cholesterol content, or both. For example, palmitate- and docosahexaenoate-containing species of PE were preferentially located in the outer leaflet of the bilayer. Membrane cholesterol content affected the transbilayer distributions of stearate-, oleate-, and linoleate-containing species. The transbilayer distributions of palmitate-, docosahexaenoate-, and stearate-containing species were significantly influenced by membrane curvature, but only in the presence of high levels of cholesterol. Thus, differences in membrane curvature and cholesterol content alter the array of PE molecules present on the surfaces of phospholipid bilayers. In cells and organelles, these differences could have profound effects on a number of critical membrane functions and processes.