Section a pharma proposal

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Section a pharma proposal

  1. 1. Pharmacology Proposal SECTION A SPECIAL CLASS
  2. 2. Toxic metal pollution of surface, groundwater and agricultural products has become a major concern in many countries, including Philippines. Many studies have been conducted on finding the treatment for toxic metal poisoning.
  3. 3. <ul><li>Common name : Turmeric, Indian-saffron </li></ul><ul><li>Scientific name : Curcuma longa Linn. </li></ul><ul><li>Plant family : Zingiberaceae </li></ul>
  4. 4. A yellow phenolic compound, curcumin is one of the three main curcuminoids extracted from the rhizomes of turmeric plants.
  5. 6. Curcumin inhibits lipid peroxidation and cyclooxygenase-2 (COX-2) expression and induces glutathione S-transferase (GSH) enzymes. After 14 days of curcumin supplement in rodent, the total GSH activity and malondialdehyde (MDA), which reflects endogenous lipid peroxidation, were measured in liver. The curcumin diet increased hepatic GSH by 16% and decreased MDA levels by 36% when compared with controls. (Sharma, R. et. al. 2001)
  6. 7. Cadmium is one of the heavy metal . Toxic metal or heavy metals are chemical elements with a specific gravity that is at least 5 times greater than the specific gravity of water. Transition metal
  7. 8. Cadmium Physical Properties Chemical symbol Cd Form White, Soft metal Characteristics Malleable, Ductile and Flexible Found In compound form with sulfide Atomic weight 112.41
  8. 9. Cadmium Human activities Environmental N ickel-cadmium batter y manufactories Cigarette smoking Plating, coating metal industries Accumulated in rivers, lakes Car exhaust fumes Soil, Fertilizers Earth’s crust Sources of Cadmium
  9. 10. <ul><li>Target organs </li></ul><ul><li>Acute oral LD 50 </li></ul><ul><li>Route of exposure </li></ul><ul><li>Health Effects </li></ul>Liver, kidney, lung, bone and small intestine. Itai - Itai disease Osteomalacia, Osteoporosis Ingestion and inhalation Kidney failure, other organ failure. 225 mg/ kg BW (Material Safety Data Sheet, http//www.Science Lab.com)
  10. 11. Absorbed Cadmium Intestinal lumen Organs Liver Bind to Metallothionin (MT) Cd -- MT Kidney Cd -- MT Cadmium free form MT released Mucosal cells Systemic circulation
  11. 12. <ul><li>MDA Level (product of lipid peroxidation) </li></ul><ul><li>Glutathione Level </li></ul><ul><li>Histopathological change in the liver cell </li></ul>
  12. 13. <ul><li>Lipid peroxidation has been established as a major mechanism of cellular injury for cadmium toxicity . (Manca et al., 1991; Yiin et al., 1999). </li></ul><ul><li> The mechanism involves a process whereby free radicals &quot;steal&quot; electrons from the lipids in cell membranes, resulting in cell damage. It most often affects polyunsaturated fatty acids . </li></ul>
  13. 14. Product : MDA
  14. 15. <ul><ul><li>Glutathione (GSH), a powerful antioxidant found within every cells, contains –SH group. </li></ul></ul><ul><ul><li>Their main function is the activity as an antioxidant protecting the cells from damage caused by the free radical, H 2 O 2 . </li></ul></ul><ul><ul><li>GSH is produced mainly from liver. </li></ul></ul><ul><ul><li>Glutathione exists in reduced (GSH) and oxidized (GSSG) states. </li></ul></ul>
  15. 16. <ul><ul><li>Liver cell Hepatocyte </li></ul></ul><ul><ul><li>Arranged into cord . </li></ul></ul><ul><ul><li>Lobule shape Hexagonal </li></ul></ul><ul><ul><li>At the corners between adjacent lobules are the portal triads. </li></ul></ul><ul><ul><li>Central vein – centre of each lobule, which is a branch of the hepatic vein. </li></ul></ul>Bile duct Portal vein Hepatic artery
  16. 17. Hepatic Lobule
  17. 18. PORTAL TRIAD
  18. 19. The liver tissue consists of epithelial hepatocytes, arranged into cords , separated by vascular sinusoids. SINUSOID
  19. 20. Functionally, the liver can be divided into 3 zones, based upon oxygen supply. Zone 1 encircles the portal tracts where the oxygenated blood from hepatic arteries enters. Zone 3 is located around central veins, where oxygenation is poor. Zone 2 is located in between.
  20. 21. <ul><li>To study acute toxicity of Cd acetate. </li></ul><ul><li>To evaluate the protective effect of curcumin on lipid peroxidation, glutathione and histopathological change in rat liver, induced by Cd acetate. </li></ul>
  21. 22. <ul><ul><li>If found to be preventive, curcumin can be used as a prevention for cadmium poisoning. </li></ul></ul><ul><ul><li>If curcumin is found to be preventive, it may be further used in studies concerning other free radical agent or other heavy metals. </li></ul></ul><ul><ul><li>The database concerning curcumin can be used for further studies Eg : Effect of curcumin on disease that causes free radical. </li></ul></ul>
  22. 23. PHASE I Protective effect of Curcumin against Cd toxicity
  23. 25. <ul><li>Cd acetate solution of dose 100, 200, 300 mg/kg BW was prepared by dissolving it in distilled water. </li></ul><ul><li>The curcumin extracted from turmeric plant was provided by the Government Pharmaceutical Organization (GPO). The curcumin dose 250 mg/kg BW will be dissolved in glycerol. </li></ul>
  24. 26. <ul><ul><li>Adult Wistar male rats 200-220 g </li></ul></ul><ul><ul><li>Acclimatization 5 days </li></ul></ul><ul><ul><li>12 hr light / dark cycle </li></ul></ul><ul><ul><li>Standard pellet diet + drinking water </li></ul></ul>
  25. 27. 32 Wistar Rats
  26. 28. Treated (Oral administration) Sacrificed by anesthesia 10% formalin buffer 1.00 gm of Liver Remainder of liver Frozen in -70 . c 5 days
  27. 29. Liver Homogenate (1.5 ml) Add TCA- TBA- HCl solution (3 mL) Centrifuge 1,000 rpm 10 min Pipette supernatant Spectrophotometer (Absorbance at 535 nm) Heat in boiling water 15 minutes
  28. 30. Liver Homogenate (0.5 mL) Add 4% Sulfosalicylic acid (0.5 mL ) Supernatant (0.5 mL) <ul><ul><li>Add 0.1 mM dithiobenzoic acid (4.5 mL) </li></ul></ul>Spectrophotometer (Absorbance at 412 nm ) Centrifugue at 1,000 rpm 10 min
  29. 32. FIXATION DEHYDRATION
  30. 33. INFILTRATION EMBEDDING
  31. 34. SECTIONING BY MICROTOME STAINING H & E
  32. 35. MOUNTING SLIDE MICROSCOPIC EXAMINATION

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