Have a personal or library account? Click to login
The role of peroxisome proliferator-activated receptor in the treatment of non-alcoholic fatty liver disease Cover

The role of peroxisome proliferator-activated receptor in the treatment of non-alcoholic fatty liver disease

By: Xin Sun,  Yan Zhang and  Meilin Xie  
Open Access
|Feb 2017

References

  1. 1. G. Ganzetti, A. Campanati and A. Offidani, Non-alcoholic fatty liver disease and psoriasis: So far, so near, World J. Hepatol. 7 (2015) 315-326; DOI: 10.4254/wjh.v7.i3.315.10.4254/wjh.v7.i3.315438116025848461
  2. 2. A. Kotronen and H. Yki-Jarvinen, Fatty liver: a novel component of the metabolic syndrome, Arterioscler. Thromb. Vasc. Biol. 28 (2008) 27-38; DOI: ATVBAHA.107.147538.10.1161/ATVBAHA.107.14753817690317
  3. 3. M. Takeuchi, J. Takino, A. Sakasai-Sakai, T. Takata, T. Ueda, M. Tsutsumi, H. Hyogo and S. Yamagishi, Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies, World J. Hepatol. 6 (2014) 880-893; DOI: 10.4254/wjh.v6.i12.880.10.4254/wjh.v6.i12.880426990725544875
  4. 4. C. S. Hsu and J. H. Kao, Non-alcoholic fatty liver disease: an emerging liver disease in Taiwan, J. Formos. Med. Assoc. 111 (2012) 527-535; DOI: 10.1016/j.jfma.2012.07.002.10.1016/j.jfma.2012.07.00223089687
  5. 5. A. S. Bodzin and R. W. Busuttil, Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome, World J. Hepatol. 7 (2015) 1157-1167; DOI: 10.4254/wjh.v7.i9.1157.10.4254/wjh.v7.i9.1157443849126019732
  6. 6. P. Loria, A. Lonardo, L. Carulli, A. M. Verrone, M. Ricchi, S. Lombardini, A. Rudilosso, S. Ballestri and N. Carulli, Review article: the metabolic syndrome and non-alcoholic fatty liver disease, Aliment. Pharmacol. Ther. 22 (Suppl 2) (2005) 31-36; DOI: APT2592.
  7. 7. D. Papandreou and E. Andreou, Role of diet on non-alcoholic fatty liver disease: An updated narrative review, World J. Hepatol. 7 (2015) 575-582; DOI: 10.4254/wjh.v7.i3.575.10.4254/wjh.v7.i3.575438118025848481
  8. 8. C. P. Day and O. F. James, Steatohepatitis: a tale of two “hits”?, Gastroenterology 114 (1998) 842-845; DOI: S0016508598003564.
  9. 9. P. Angulo, Nonalcoholic fatty liver disease, N. Engl. J. Med. 346 (2002) 1221-1231; DOI: 10.1056/ NEJMra011775.10.1056/NEJMra01177511961152
  10. 10. A. Takaki, D. Kawai and K. Yamamoto, Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH), Int. J. Mol. Sci. 14 (2013) 20704-20728; DOI: 10.3390/ijms141020704.10.3390/ijms141020704382163924132155
  11. 11. H. Tilg and A. R. Moschen, Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis, Hepatology 52 (2010) 1836-1846; DOI: 10.1002/hep.24001.10.1002/hep.2400121038418
  12. 12. W. Tomeno, M. Yoneda, K. Imajo, Y. Ogawa, T. Kessoku, S. Saito, Y. Eguchi and A. Nakajima, Emerging drugs for non-alcoholic steatohepatitis, Expert Opin. Emerg. Drugs 18 (2013) 279-290; DOI: 10.1517/14728214.2013.811232.10.1517/14728214.2013.81123223848366
  13. 13. Y. Takahashi, K. Sugimoto, H. Inui and T. Fukusato, Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, World J. Gastroenterol. 21 (2015) 3777-3785; DOI: 10.3748/wjg.v21.i13.3777.10.3748/wjg.v21.i13.3777438552525852263
  14. 14. S. R. Pyper, N. Viswakarma, S. Yu and J. K. Reddy, PPARalpha: energy combustion, hypolipidemia, inflammation and cancer, Nucl. Recept. Signal. 8 (2010) e002; DOI: 10.1621/nrs.08002.10.1621/nrs.08002285826620414453
  15. 15. K. S. Kilgore and A. N. Billin, PPARbeta/delta ligands as modulators of the inflammatory response, Curr. Opin. Invest. Drugs 9 (2008) 463-469.
  16. 16. S. J. Bensinger and P. Tontonoz, Integration of metabolism and inflammation by lipid-activated nuclear receptors, Nature 454 (2008) 470-477; DOI: 10.1038/nature07202.10.1038/nature0720218650918
  17. 17. L. Zeng, W. J. Tang, J. J. Yin and B. J. Zhou, Signal transductions and nonalcoholic fatty liver: a mini-review, Int. J. Clin. Exp. Med. 7 (2014) 1624-1631.
  18. 18. L. Michalik, J. Auwerx, J. P. Berger, V. K. Chatterjee, C. K. Glass, F. J. Gonzalez, P. A. Grimaldi, T. Kadowaki, M. A. Lazar, S. O’Rahilly, C. N. A. Palmer, J. Plutzky, J. K. Reddy, B. M. Spiegelman, B.Staels and W. Wahli, International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors, Pharmacol. Rev. 58 (2006) 726-741; DOI: 10.1124/pr.58.4.5 58/4/726 [pii ].10.1124/pr.58.4.517132851
  19. 19. D. Usuda and T. Kanda, Peroxisome proliferator-activated receptors for hypertension, World J. Cardiol. 6 (2014) 744-754; DOI: 10.4330/wjc.v6.i8.744.10.4330/wjc.v6.i8.744416370325228953
  20. 20. V. T. Samuel and G. I. Shulman, Mechanisms for insulin resistance: common threads and missing links, Cell 148 (2012) 852-871; DOI: 10.1016/j.cell.2012.02.017.10.1016/j.cell.2012.02.017329442022385956
  21. 21. F. Kim, M. Pham, E. Maloney, N. O. Rizzo, G. J. Morton, B. E. Wisse, E. A. Kirk, A. Chait and M. W. Schwartz, Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance, Arterioscler. Thromb. Vasc. Biol. 28 (2008) 1982-1988; DOI: 10.1161/ATVBAHA.108.169722.10.1161/ATVBAHA.108.169722257757518772497
  22. 22. S. H. Caldwell, E. E. Hespenheide, J. A. Redick, J. C. Iezzoni, E. H. Battle and B. L. Sheppard, A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis, Am. J. Gastroenterol. 96 (2001) 519-525; DOI: S0002-9270(00)02346-7.10.1111/j.1572-0241.2001.03553.x11232700
  23. 23. E. Frohlich and R. Wahl, Chemotherapy and chemoprevention by thiazolidinediones, Biomed. Res. Int. 2015 (2015) Article ID 845340; DOI: 10.1155/2015/845340.10.1155/2015/845340438343825866814
  24. 24. H. B. Bhatt and R. J. Smith, Fatty liver disease in diabetes mellitus, Hepatobil. Surg. Nutr. 4 (2015) 101-108; DOI: 10.3978/j.issn.2304-3881.2015.01.03.
  25. 25. M. O. Rakoski, A. G. Singal, M. A. Rogers and H. Conjeevaram, Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis, Aliment. Pharmacol. Ther. 32 (2010) 1211-1221; DOI: 10.1111/j.1365-2036.2010.04467.x.10.1111/j.1365-2036.2010.04467.x20955440
  26. 26. A. S. Laganá, S. G. Vitale, A. Nigro, V. Sofo, F. M. Salmeri, P. Rossetti, A. M. C. Rapisarda, S. La Vignera, R. A. Condorelli, G. Rizzo and M. Buscema, Pleiotropic Actions of peroxisome proliferator-activated receptors (PPARs) in dysregulated metabolic homeostasis, inflammation and cancer: Current evidence and future perspectives, Int. J. Mol. Sci. 17 (2016) Article ID 999 (10 pp); DOI: 10.3390/ijms17070999.10.3390/ijms17070999496437527347932
  27. 27. C. Ning, L. Liu, G. Lv, Y. Yang, Y. Zhang, R. Yu, Y. Wang and J. Zhu, Lipid metabolism and inflammation modulated by vitamin D in liver of diabetic rats, Lipids Health Dis. 14 (2015) Article ID 31 (9 pages); DOI: 10.1186/s12944-015-0030-5.10.1186/s12944-015-0030-5440621925899686
  28. 28. G. Sabio, M. Das, A. Mora, Z. Zhang, J. Y. Jun, H. J. Ko, T. Barrett, J. K. Kim and R. J. Davis, A stress signaling pathway in adipose tissue regulates hepatic insulin resistance, Science 322 (2008) 1539- 1543; DOI: 10.1126/science.1160794.10.1126/science.1160794264302619056984
  29. 29. J. H. Peng, T. Cui, Z. L. Sun, F. Huang, L. Chen, L. Xu, Q. Feng and Y. Y. Hu, Effects of Puerariae radix extract on endotoxin receptors and TNF-alpha expression induced by gut-derived endotoxin in chronic alcoholic liver injury, Evid. Based Complement. Alternat. Med. 2012 (2012) Article ID 234987; DOI: 10.1155/2012/234987.10.1155/2012/234987348552023133491
  30. 30. Y. Ma, M. Gao, H. Sun and D. Liu, Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice, Biochim. Biophys. Acta 1852 (2015) 1001-1011; DOI: 10.1016/j.bbadis.2015.01.017.10.1016/j.bbadis.2015.01.01725660446
  31. 31. G. Paredes-Turrubiarte, A. González-Chavez, R. Pérez-Tamayo, B. Y. Salazar-Vázquez, V. S. Hernández, N. Garibay-Nieto, J. M. Fragoso and G. Escobedo, Severity of non-alcoholic fatty liver disease is associated with high systemic levels of tumor necrosis factor alpha and low serum interleukin 10 in morbidly obese patients, Clin. Exp. Med. 16 (2016) 193-201; DOI: 10.1007/s10238-015-0347-4.10.1007/s10238-015-0347-425894568
  32. 32. X. Lin, Z. Zhang, J. M. Chen, Y. Y. Xu, H. R. Ye, J. Cui, Y. Fang, Y. Jin, D. R. Zhu and L. Yuan, Role of APN and TNF-alpha in type 2 diabetes mellitus complicated by nonalcoholic fatty liver disease, Genet. Mol. Res. 14 (2015) 2940-2946; DOI: 10.4238/2015.April.10.1.10.4238/2015.April.10.125966055
  33. 33. Q. Lv, Q. Zhen, L. Liu, R. Gao, S. Yang, H. Zhou, R. Goswami and Q. Li, AMP-kinase pathway is involved in tumor necrosis factor alpha-induced lipid accumulation in human hepatoma cells, Life Sci. 131 (2015) 23-29; DOI: 10.1016/j.lfs.2015.03.003.10.1016/j.lfs.2015.03.00325817233
  34. 34. C. Wang, G. Zhou and Z. Zeng, Effects of peroxisome proliferator-activated receptor-beta/delta on sepsis induced acute lung injury, Chin. Med. J. 127 (2014) 2129-2137.
  35. 35. L. M. Jiménez-Flores, S. López-Briones, M. H. Macías-Cervantes, J. Ramírez-Emiliano and V. Pérez-Vázquez, A PPARy, NF-kB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver, Molecules 19 (2014) 8289-8302; DOI: 10.3390/molecules19068289.10.3390/molecules19068289627162024945581
  36. 36. Y. Shiomi, T. Yamauchi, M. Iwabu, M. Okada-Iwabu, R. Nakayama, Y. Orikawa, Y. Yoshioka, K. Tanaka, K. Ueki and T. Kadowaki, A novel peroxisome proliferator-activated receptor (PPAR)alpha agonist and PPARgamma antagonist, Z-551, ameliorates high-fat diet-induced obesity and metabolic disorders in mice, J. Biol. Chem. 290 (2015) Article ID 14567-81; DOI: jbc.M114.622191.
  37. 37. K. L. Lannan, J. Sahler, N. Kim, S. L. Spinelli, S. B. Maggirwar, O. Garraud, F. Cognasse, N. Blumberg and R. P. Phipps, Breaking the mold: transcription factors in the anucleate platelet and platelet- derived microparticles, Front. Immunol. 6 (2015) Article ID 48; DOI: 10.3389/fimmu.2015.00048.10.3389/fimmu.2015.00048432762125762994
  38. 38. M. Capanni, F. Calella, M. R. Biagini, S. Genise, L. Raimondi, G. Bedogni, G. Svegliati-Baroni, F. Sofi, S. Milani, R. Abbate, C. Surrenti and A. Casini, Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study, Aliment. Pharmacol. Ther. 23 (2006) 1143-1151; DOI: 10.1111/j.1365-2036.2006.02885.x.10.1111/j.1365-2036.2006.02885.x16611275
  39. 39. L. Li, L. Chen, X. Lin, Y. Xu, J. Ren, J. Fu and Y. Qiu, Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats, J. Pharmacol. Sci. 127 (2015) 244-250; DOI: 10.1016/j.jphs.2014.12.001.10.1016/j.jphs.2014.12.00125837920
  40. 40. N. Zhang, Y. Lu, X. Shen, Y. Bao, J. Cheng, L. Chen, B. Li and Q. Zhang, Fenofibrate treatment attenuated chronic endoplasmic reticulum stress in the liver of nonalcoholic fatty liver disease mice, Pharmacology 95 (2015) 173-180; DOI: 10.1159/000380952.10.1159/00038095225896720
  41. 41. P. Patel and H. Barkate, Comparison of efficacy and safety of choline fenofibrate (fenofibric acid) to micronized fenofibrate in patients of mixed dyslipidemia: A randomized, open-label, multicenter clinical trial in Indian population, Indian J. Endocrinol. Metab. 20 (2016) 67-71; DOI: 10.4103/2230-8210.172243.10.4103/2230-8210.172243474338726904471
  42. 42. S. M. El-Haggar and T. M. Mostafa, Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease, Hepatol. Int. 9 (2015) 471-479; DOI: 10.1007/s12072-015-9633-1.10.1007/s12072-015-9633-125956613
  43. 43. T. Kopf, H. L. Schaefer, M. Troetzmueller, H. Koefeler, M. Broenstrup, T. Konovalova and G. Schmitz, Influence of fenofibrate treatment on triacylglycerides, diacylglycerides and fatty acids in fructose fed rats, PLOS ONE 9 (2014) e106849; DOI: 10.1371/journal.pone.0106849.10.1371/journal.pone.0106849415781125198467
  44. 44. R. L. Attridge, C. R. Frei, L. Ryan, J. Koeller and W. D. Linn, Fenofibrate-associated nephrotoxicity: a review of current evidence, Am. J. Health Syst. Pharm. 70 (2013) 1219-1225; DOI: 10.2146/ajhp120131.10.2146/ajhp12013123820458
  45. 45. X. M. Xin, M. X. Zhong, G. L. Yang, Y. Peng, Y. L. Zhang and W. Zhu, GW4064, a farnesoid X receptor agonist, upregulates adipokine expression in preadipocytes and HepG2 cells, World J. Gastroenterol. 20 (2014) 15727-15735; DOI: 10.3748/wjg.v20.i42.15727.10.3748/wjg.v20.i42.15727422953725400456
  46. 46. K. Chehaibi, L. Cedo, J. Metso, X. Palomer, D. Santos, H. Quesada, M. Naceur Slimane, W. Wahli. J. Julve, M. Vazquez-Carrera, M. Jauhiainen, F. Blanco-Vaca and J. C. Escola-Gil, PPAR-beta/delta activation promotes phospholipid transfer protein expression, Biochem. Pharmacol. 94 (2015) 101-108; DOI: 10.1016/j.bcp.2015.01.016.10.1016/j.bcp.2015.01.01625662586
  47. 47. L. Salvado, E. Barroso, A. M. Gomez-Foix, X. Palomer, L. Michalik, W. Wahli and M. Vazquez- Carrera, PPARbeta/delta prevents endoplasmic reticulum stress-associated inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism, Diabetologia 57 (2014) 2126-2135; DOI: 10.1007/s00125-014-3331-8.10.1007/s00125-014-3331-825063273
  48. 48. Y. M. Attia, E. F. Elalkamy, O. A. Hammam, S. S. Mahmoud and A. S. El-Khatib, Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection, Parasit. Vectors 6 (2013) Article ID 199; DOI: 10.1186/1756-3305-6-199.10.1186/1756-3305-6-199373392823829789
  49. 49. T. Izumi, F. Tsuruta, T. Ishizuka, K. Nakamura, M. Kothuma and M. Takahashi, Stereoselectivity in pharmacokinetics of rivoglitazone, a novel peroxisome proliferator-activated receptor gamma agonist, in rats and monkeys: model-based pharmacokinetic analysis and in vitro-in vivo extrapolation approach, J. Pharm. Sci. 102 (2013) 3174-3188; DOI: 10.1002/jps.23586.10.1002/jps.2358623686684
  50. 50. R. L. Koffarnus, K. A. Wargo and H. M. Phillippe, Rivoglitazone: a new thiazolidinedione for the treatment of type 2 diabetes mellitus, Ann. Pharmacother. 47 (2013) 877-885; DOI: 10.1345/aph.1R754.10.1345/aph.1R75423632280
  51. 51. B. Staels, A. Rubenstrunk, B. Noel, G. Rigou, P. Delataille, L. J. Millatt, M. Baron, A. Lucas, A. Tailleux, D. W. Hum, V. Ratziu, B. Cariou and R. Hanf, Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, Hepatology 58 (2013) 1941-1952; DOI: 10.1002/hep.26461.10.1002/hep.2646123703580
  52. 52. R. Hanf, L. J. Millatt, B. Cariou, B. Noel, G. Rigou, P. Delataille, V. Daix, D. W. Hum and B. Staels, The dual peroxisome proliferator-activated receptor alpha/delta agonist GFT505 exerts anti-diabetic effects in db/db mice without peroxisome proliferator-activated receptor gamma-associated adverse cardiac effects, Diab. Vasc. Dis. Res. 11 (2014) 440-447; DOI: 10.1177/1479164114548027.10.1177/147916411454802725212694
  53. 53. X. Zhao, J. Xue, X. L. Wang, Y. Zhang, M. Deng and M. L. Xie, Involvement of hepatic peroxisome proliferator-activated receptor alpha/gamma in the therapeutic effect of osthole on high-fat and high-sucrose-induced steatohepatitis in rats, Int. Immunopharmacol. 22 (2014) 176-181; DOI: 10.1016/j. intimp.2014.06.032.
  54. 54. M. Bhaswant, H. Poudyal and L. Brown, Mechanisms of enhanced insulin secretion and sensitivity with n-3 unsaturated fatty acids, J. Nutr. Biochem. 26 (2015) 571-584; DOI: S0955-2863(15)00030-3.10.1016/j.jnutbio.2015.02.00125841249
  55. 55. T. D. Filippatos and M. S. Elisaf, Safety considerations with fenofibrate/simvastatin combination, Expert Opin. Drug Safety 14 (2015) 1481-1493; DOI: 10.1517/14740338.2015.1056778.10.1517/14740338.2015.105677826134595
  56. 56. G. Derosa and P. Maffioli, Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists on glycemic control, lipid profile and cardiovascular risk, Curr. Mol. Pharmacol. 5 (2012) 272-281; DOI: EPub-Abstract-CMP-51.10.2174/187446721120502027222122457
  57. 57. K. Wallenius, A. Kjellstedt, P. Thalén, L. Löfgren and N. D. Oakes, The PPARα/γ agonist, tesaglitazar, improves insulin mediated switching of tissue glucose and free fatty acid utilization in vivo in the obese zucker rat, PPAR Res. 2013 (2013) Article ID 305347 (14 pages); DOI: 10.1155/2013/305347.10.1155/2013/305347382632624285952
  58. 58. F. Gilardi, M. Giudici, N. Mitro, O. Maschi, U. Guerrini, G. Rando, A. Maggi, G. Cermenati, A. Laghezza, F. Loiodice, G. Pochetti, A. Lavecchia, D. Caruso, E. De Fabiani, K. Bamberg and M. Crestani, LT175 is a novel PPARalpha/gamma ligand with potent insulin-sensitizing effects and reduced adipogenic properties, J. Biol. Chem. 289 (2014) 6908-6920; DOI: 10.1074/jbc.M113.506394.10.1074/jbc.M113.506394394535224451380
  59. 59. L. S. Mackenzie and L. Lione, Harnessing the benefits of PPARbeta/delta agonists, Life Sci. 93 (2013) 963-967; DOI: 10.1016/j.lfs.2013.10.022. 10.1016/j.lfs.2013.10.02224184294
  60. 60. H. J. Gim, H. Li, J. H. Jeong, S. J. Lee, M. K. Sung, M. Y. Song, B. H. Park, S. J. Oh, J. H. Ryu and R. Jeon, Design, synthesis, and biological evaluation of a series of alkoxy-3-indolylacetic acids as peroxisome proliferator-activated receptor γ/δ agonists, Bioorg. Med. Chem. 23 (2015) 3322-3336; DOI: 10.1016/j.bmc.2015.04.046.10.1016/j.bmc.2015.04.04625982078
  61. 61. G. Gupta, G. Krishna, D. K. Chellappan, K. S. Gubbiyappa, M. Candasamy and K. Dua, Protective effect of pioglitazone, a PPARgamma agonist against acetaminophen-induced hepatotoxicity in rats, Mol. Cell. Biochem. 393 (2014) 223-228; DOI: 10.1007/s11010-014-2064-9.10.1007/s11010-014-2064-924771068
  62. 62. A. M. Lincoff, J. C. Tardif, G. G. Schwartz, S. J. Nicholls, L. Ryden, B. Neal, K. Malmberg, H. Wedel, J. B. Buse, R. R. Henry, A. Weichert, R. Cannata, A. Svensson, D. Volz and D. E. Grobbee, Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial, JAMA 311 (2014) 1515-1525; DOI: 10.1001/jama.2014.3321.10.1001/jama.2014.332124682069
  63. 63. X. C. Bao, Y. Q. Fang, P. You, S. Zhang and J. Ma, Protective role of peroxisome proliferator-activated receptor-beta/delta against pulmonary oxygen toxicity mediated through changes in NOS expression levels, Exp. Lung Res. 40 (2014) 105-116; DOI: 10.3109/01902148.2013.879497.10.3109/01902148.2013.87949724624894
DOI: https://doi.org/10.1515/acph-2017-0007 | Journal eISSN: 1846-9558 | Journal ISSN: 1330-0075
Language: English
Page range: 1 - 13
Accepted on: Oct 6, 2016
Published on: Feb 21, 2017
Published by: Croatian Pharmaceutical Society
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Related subjects:

© 2017 Xin Sun, Yan Zhang, Meilin Xie, published by Croatian Pharmaceutical Society
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.