Pharmacology
Permanent URI for this community
Browse
Browsing Pharmacology by Author "Abeywardena, Mahinda Y."
Now showing 1 - 8 of 8
Results Per Page
Sort Options
Item Metadata only Depressed prostanoid-induced contractility of the gut in spontaneously hypertensive rats (SHR) is not affected by the level of dietary fat(American Society for Nutritional Sciences, 2004) Patten, Glen Stephen; Adams, Michael J.; Dallimore, Julie A.; Abeywardena, Mahinda Y.; School of Medical Sciences : PharmacologyItem Metadata only Dietary fats, carbohydrates and vascular disease: Sri Lankan perspectives(Elsevier Sci Ireland Ltd, 2003) Abeywardena, Mahinda Y.Item Metadata only Dietary fish oil dose-response effects on ileal phospholipid fatty acids and contractility(Amer Oil Chemists Soc A O C S Press, 2005) Patten, Glen Stephen; Adams, Michael J.; Dallimore, Julie A.; Abeywardena, Mahinda Y.; School of Medical Sciences : PharmacologyWe have reported that dietary fish oil (FO) leads to the incorporation of long-chain n−3 PUFA into the gut tissue of small animal models, affecting contractility, particularly of rat ileum. This study examined the FO dose response for the incorporation of n−3 PUFA into ileal tissue and how this correlated with in vitro contractility. Groups of ten to twelve 13-wk-old Wistar-Kyoto rats were fed 0, 1, 2.5, and 5% FO-supplemented diets balanced with sunflower seed oil for 4 wk, after which ileal total phospholipid FA were determined and in vitro contractility assessed. For the total phospholipid fraction, increasing the dietary FO levels led to a significant increase first evident at 1% FO, with a stepwise, nonsaturating six-fold increase in n−3 PUFA as EPA (20∶5n−3), DPA (docosapentaenoic acid, 22∶5n−3), and DHA, but mainly as DHA (22∶6n−3), replacing the n−6 PUFA linoleic acid (18∶2n−6) and arachidonic acid (20∶4n−6) over the dosage range. There was no difference in KCl-induced depolarization-driven contractility. However, a significant increase in receptor-dependent maximal contractility occurred at 1% FO for carbachol and at 2.5% FO for prostaglandin E2, with a concomitant increase in sensitivity for prostaglandin E2 at 2.5 and 5% FO. These results demonstrate that significant increases in ileal membrane n−3 PUFA occurred at relatively low doses of dietary FO, with differential receptor-dependent increases in contractility observed for muscarinic and prostanoid agonists.Item Metadata only Dietary fish oil increases acetylcholine- and eicosanoid-induced contractility of isolated rat ileum(Amer Inst Nutrition, 2002) Patten, Glen S.; Abeywardena, Mahinda Y.; McMurchie, Edward J.; Jahangiri, AnisaItem Metadata only Inhibition of low-density lipoprotein oxidation and up-regulation of low-density lipoprotein receptor in HepG2 cells by tropical plant extracts(American Chemical Society, 2002) Salleh, Mohammed Nizar; Runnie, Irine; Roach, Paul D.; Mohamed, Suhaila; Abeywardena, Mahinda Y.Twelve edible plant extracts rich in polyphenols were screened for their potential to inhibit oxidation of low-density lipoprotein (LDL) in vitro and to modulate LDL receptor (LDLr) activity in cultured HepG2 cells. The antioxidant activity (inhibition of LDL oxidation) was determined by measuring the formation of conjugated dienes (lag time) and thiobarbituric acid reagent substances (TBARS). Betel leaf (94%), cashew shoot (63%), Japanese mint (52%), semambu leaf (50%), palm frond (41%), sweet potato shoot, chilli fruit, papaya shoot, roselle calyx, and maman showed significantly increased lag time (>55 min, P < 0.05) and inhibition of TBARS formation (P < 0.05) compared to control. LDLr was significantly up-regulated (P < 0.05) by Japanese mint (67%), semambu (51%), cashew (50%), and noni (49%). Except for noni and betel leaf, most plant extracts studied demonstrated a positive association between antioxidant activity and the ability to up-regulate LDL receptor. Findings suggest that reported protective actions of plant polyphenols on lipoprotein metabolism might be exerted at different biochemical mechanisms.Item Metadata only Naturally derived micelles for rapid in vitro screening of potential cholesterol-lowering bioactives(Amer Chemical Soc, 2005) Kirana, Chandra; Rogers, Paul F.; Bennett, Louise E.; Abeywardena, Mahinda Y.; Patten, Glen Stephen; School of Medical Sciences : PharmacologyA high plasma cholesterol level, especially low-density lipoprotein cholesterol, indicates increased risk of cardiovascular diseases. Plasma cholesterol levels are influenced by diet and cholesterol biosynthesis, uptake, and secretion. Cholesterol uptake involves solubilization into complex phospholipid spherical bodies termed micelles that facilitate the transport of lipids through the gut brush border membrane into enterocytes. In vitro assays reported to date to determine potential cholesterol-lowering effects of various compounds require artificial micelle preparations that are elaborate and time-consuming to prepare. The aims of this study were to compare the efficacy of artificially prepared micelles with naturally derived micelles from pig's bile and to test their ability to assess potential inhibitors of cholesterol uptake. The suitability of pig's bile-derived micelles was tested both at the level of the micelle and at cellular uptake using cultured Caco-2 cells. Known cholesterol uptake inhibitors at the micelle (green tea catechins) and at the Caco-2 cell (β-lactoglobulin-derived peptide, IIAEK) were used as reference inhibitory compounds. It was concluded that pig's bile was a rapid, reproducible, convenient, and cost-effective source of micelles for cholesterol micelle solubility and cellular uptake assay systems and is suitable for screening purposes focused on identifying potential cholesterol-lowering agents.Item Metadata only Rapid screening for potential cholesterol-lowering peptides using naturally derived micelle preparation(Australian Society of Dairy Technology, 2005) Kirana, Chandra; Rogers, P. F.; Bennett, Louise E.; Abeywardena, Mahinda Y.; Patten, Glen Stephen; School of Medical Sciences : PharmacologySeveral food constituents have been shown to reduce blood cholesterol levels and promote cardiovascular health via different mechanisms, such as inhibition of cholesterol synthesis and suppression of cholesterol uptake. Inhibition of cholesterol solubilization into micelles and cellular cholesterol absorption are target sites of interventions for cholesterol reduction. Artificial micelles have been used as a model system for in vitro cholesterol solubilization and/or cholesterol absorption assays to evaluate hypocholesterolemic activity of potential bioactive compounds, including milk whey protein. This study aimed to compare the efficacy of artificially prepared micelles with naturally derived micelles from pig's bile on micellar solubility of cholesterol and cellular cholesterol absorption assays to identify potential cholesterol-lowering compounds. Green tea catechins and IIAEK with previously reported inhibitory effects on cholesterol uptake were used as reference compounds. Tea catechins, e.g. epigallocatechin gallate (EGCG), significantly reduced the solubility of cholesterol in pig's bile-derived micelle preparations (56%, p<0.001), which was comparable with those in artificially prepared micelles (65%, p<0.001). Suppression of cholesterol absorption in Caco-2 cells by IIAEK was also noted when using either artificially-prepared or pig's bile-derived micelle preparations (24%, p<0.01). We conclude that pig's bile is a rapid, reproducible, convenient and cost-effective source of micelles for cholesterol micelle solubility and cellular uptake assay systems and is suitable for screening purposes focused on identifying potential cholesterol-lowering agents.Item Metadata only Site specific delivery of microencapsulated fish oil to the gastrointestinal tract of the rat(Kluwer Academic, 2009) Patten, Glen Stephen; Augustin, Mary Ann; Sanguansri, Luz; Head, Richard J.; Abeywardena, Mahinda Y.; School of Medical Sciences : PharmacologyThe aim of this study was to design food grade matrices to deliver microencapsulated fish oil to the large bowel of the rat where the potential exists to retard inflammation and cancer development. Digestion in simulated gastric fluid and intestinal fluid demonstrated that only 4–6% of oil was released from the following dried emulsion formulations: 50% fish oil encapsulated in heated caseinglucose- dried glucose syrup (1:1:1) (Cas-Glu-DGS-50); 25% fish oil in casein-modified resistant starch (Hylon VII) (1:1) (Cas-Hylon-25); or 25% fish oil in Cas-Glu-Hylon (1:1:1) (Cas-Glu-Hylon-25). A short-term gavage study (0–12 h) with fish oil and Cas-Glu-DGS-50 demonstrated the appearance of fish oil long chain (LC) n-3 polyunsaturated fatty acids (PUFA) into the plasma indicating specific small intestinal absorption with little LC n-3 PUFA reaching the large bowel. In a 2-week-long term, daily gavage study, the bioavailability of fish oil and fish oil in Cas-Glu-DGS-50 or Cas-Hylon-25 demonstrated that fish oil and Cas-Glu-DGS- 50 LC n-3 PUFA were incorporated into the tissue of the small intestine and colon, whereas Cas-Hylon-25 was resistant to degradation in the small intestine. The use of modified Hylon VII for targeted colonic delivery was confirmed in the final short-termgavage study (0–14 h) using Cas-Glu-Hylon- 25 with [14C]-trilinolenin as a marker incorporated into the microcapsules, where up to 60% of the labeled oil reached the large bowel. Depending on the microencapsulating matrix employed, fish oil can be delivered selectively to the small intestine or to a high degree to the large bowel.