Pharmacologic targeting of bacterial β-glucuronidase alleviates nonsteroidal anti-inflammatory drug-induced enteropathy in mice

Journal of Pharmacology and Experimental Therapeutics

Volumn 341, Issue 2, 2012, Pages 447-454

  LoGuidice, Amanda ^a   Wallace, Bret D ^b   Bendel, Lauren ^a   Redinbo, Matthew R ^b   Boelsterli, Urs A ^a  

^a UNIVERSITY OF CONNECTICUT   (United States)

^b University of North Carolina at Chapel Hill   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 ((6,8 DIMETHYL 2 OXO 1,2 DIHYDROQUINOLIN 3 YL)METHYL) 3 (4 ETHOXYPHENYL) 1 (2 HYDROXYETHYL)THIOUREA; AGLYCONE; BACTERIAL ENZYME; BETA GLUCURONIDASE; DICLOFENAC; FLUORESCEIN ISOTHIOCYANATE DEXTRAN; GASTROINTESTINAL AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG MECHANISM; DRUG STRUCTURE; DRUG TARGETING; ENZYME INHIBITION; ENZYME RELEASE; ENZYME SUBSTRATE; ESCHERICHIA COLI; IC 50; IN VITRO STUDY; IN VIVO STUDY; INTESTINE INJURY; INTESTINE MUCOSA PERMEABILITY; INTESTINE ULCER; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN HYDROLYSIS; TIME TO MAXIMUM PLASMA CONCENTRATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; DICLOFENAC; ENTEROCYTES; ESCHERICHIA COLI; ESCHERICHIA COLI PROTEINS; GLUCURONIDASE; GLYCOPROTEINS; INTESTINAL DISEASES; INTESTINAL MUCOSA; INTESTINE, SMALL; MALE; MICE; MICE, INBRED C57BL; ULCER;

EID: 84859987078     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.111.191122     Document Type: Article

References (38)

1. Allison MC, Howatson AG, Torrance CJ, Lee FD, and Russell RI (1992) Gastrointestinal damage associated with the use of nonsteroidal antiinflammtory drugs. New Engl J Med 327:749-754.
2. Bailey MJ and Dickinson RG (1996) Chemical and immunochemical comparison of protein adduct formation of four carboxylate drugs in rat liver and plasma. Chem Res Toxicol 9:659-666. (Pubitemid 26123969)
3. Bjarnason I, Hayllar J, MacPherson AJ, and Russell AS (1993) Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 104:1832-1847. (Pubitemid 23235480)
4. Boelsterli UA and Ramirez-Alcantara V (2011) NSAID acyl glucuronides and enteropathy. Curr Drug Metab 12:245-252.
5. Davies NM, Saleh JY, and Skjodt NM (2000) Detection and prevention of NSAID-induced enteropathy. J Pharm Pharm Sci 3:137-155.
6. Dickinson RG and King AR (2001) Rearrangement of diflunisal acyl glucuronide into its β-glucuronidase-resistant isomers facilitates transport through the small intestine to the colon of the rat. Life Sci 70:25-36. (Pubitemid 33124354)
7. Fortun PJ and Hawkey CJ (2007) Nonsteroidal antiinflammatory drugs and the small intestine. Curr Opin Gastroenterol 23:134-141. (Pubitemid 46192967)
8. Hotz-Behofsits C, Simpson RJ, Walley M, and Bjarnason IT (2010) Role of COX-2 in nonsteroidal anti-inflammatory drug enteropathy in rodents. Scand J Gastroenterol 45:822-827.
9. Klaassen CD and Watkins JB 3rd (1984) Mechanisms of bile formation, hepatic uptake, and biliary excretion. Pharmacol Rev 36:1-67. (Pubitemid 14128249)
10. Koga H, Matsumoto T, and Iida M (2008) Epidemiology, diagnosis and treatments of non-steroidal anti-inflammatory drug-induced enteropathy: a review of the literature. Gastroenterol Endosc 50:189-198. (Pubitemid 351427611)
11. Kumar S, Samuel K, Subramanian R, Braun MP, Stearns RA, Chiu SH, Evans DC, and Baillie TA (2002) Extrapolation of diclofenac clearance from in vitro microsomal metabolism data: role of acyl glucuronidation and sequential oxidative metabolism of the acyl glucuronide. J Pharmacol Exp Ther 303:969-978. (Pubitemid 35424378)
12. Lagas JS, Sparidans RW, Wagenaar E, Beijnen JH, and Schinkel AH (2010) Hepatic clearance of reactive glucuronide metabolites of diclofenac in the mouse is dependent on multiple ATP-binding cassette efflux transporters. Mol Pharmacol 77: 687-694.
13. LoGuidice A, Ramirez-Alcantara V, Proli A, Gavillet B, and Boelsterli UA (2010) Pharmacologic targeting or genetic deletion of mitochondrial cyclophilin D protects from NSAID-induced small intestinal ulceration in mice. Toxicol Sci 118:276-285.
14. Maiden L (2009) Capsule endoscopic diagnosis of nonsteroidal antiinflammatory drug-induced enteropathy. J Gastroenterol 44:64-71.
15. McConnell EL, Basit AW, and Murdan S (2008) Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments. J Pharm Pharmacol 60:63-70.
16. Napolitano LM, Koruda MJ, Meyer AA, and Baker CC (1996) The impact of femur fracture with associated soft tissue injury on immune function and intestinal permeability. Shock 5:202-207. (Pubitemid 126727651)
17. Oleson L and Court MH (2008) Effect of the beta-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDPglucuronosyltransferases. J Pharm Pharmacol 60:1175-1182.
18. Ramirez-Alcantara V, LoGuidice A, and Boelsterli UA (2009) Protection from diclofenac-induced small intestinal injury by the JNK inhibitor SP600125 in a mouse model of NSAID-associated enteropathy. Am J Physiol Gastrointest Liver Physiol 297:G990-G998.
19. Regan SL, Maggs JL, Hammond TG, Lambert C, Williams DP, and Park BK (2010) Acyl glucuronides: the good, the bad and the ugly. Biopharm Drug Dispos 31:367-395.
20. Sarda S, Page C, Pickup K, Schulz-Utermoehl T, and Wilson I (2012) Diclofenac metabolism in the mouse: novel in vivo metabolites identified by high performance liquid chromatography coupled to linear ion trap mass spectrometry. Xenobiotica 42:179-194.
21. Scarpignato C (2008) NSAID-induced intestinal damage: are luminal bacteria the therapeutic target? Gut 57:145-148.
22. Scarpignato C and Hunt RH (2010) Nonsteroidal antiinflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin North Am 39:433-464.
23. Seitz S and Boelsterli UA (1998) Diclofenac acyl glucuronide, a major biliary metabolite, is directly involved in small intestinal injury in rats. Gastroenterology 115: 1476-1482. (Pubitemid 28545998)
24. Seitz S, Kretz-Rommel A, Oude Elferink RP, and Boelsterli UA (1998) Selective protein adduct formation of diclofenac glucuronide is critically dependent on the rat canalicular conjugate export pump (Mrp2). Chem Res Toxicol 11:513-519. (Pubitemid 28242496)
25. Sidhu R, Brunt LK, Morley SR, Sanders DS, and McAlindon ME (2010) Undisclosed use of nonsteroidal anti-inflammatory drugs may underlie small-bowel injury observed by capsule endoscopy. Clin Gastroenterol Hepatol 8:992-995.
26. Sigthorsson G, Simpson RJ, Walley M, Anthony A, Foster R, Hotz-Behoftsitz C, Palizban A, Pombo J, Watts J, Morham SG, et al. (2002) COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice. Gastroenterology 122:1913-1923. (Pubitemid 34651435)
27. Smith PC, McDonagh AF, and Benet LZ (1990) Effect of esterase inhibition on the disposition of zomepirac glucuronide and its covalent binding to plasma proteins in the guinea pig. J Pharmacol Exp Ther 252:218-224. (Pubitemid 20067716)
28. Somasundaram S, Rafi S, Hayllar J, Sigthorsson G, Jacob M, Price AB, Macpherson A, Mahmod T, Scott D, Wrigglesworth JM, et al. (1997) Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine. Gut 41:344-353. (Pubitemid 27428194)
29. Spahn-Langgut H, Li C, and Benet LZ (2007) Mechanistic role of acyl glucuronides, in Drug-Induced Liver Disease (Kaplowitz N and DeLeve L eds), pp 125-157, Informa Healthcare, New York.
30. Stierlin H, Faigle JW, Sallmann A, Küng W, Richter WJ, Kriemler HP, Alt KO, and Winkler T (1979) Biotransformation of diclofenac sodium (Voltaren) in animals and in man. I. Identification and isolation of principal metabolites. Xenobiotica 9:601-610.
31. Tanaka A, Hase S, Miyazawa T, and Takeuchi K (2002) Up-regulation of cyclooxygenase-2 by inhibition of cyclooxygenase-1: a key to nonsteroidal anti-inflammatory drug-induced intestinal damage. J Pharmacol Exp Ther 300:754-761. (Pubitemid 34164976)
32. Treinen-Moslen M and Kanz MF (2006) Intestinal tract injury by drugs: importance of metabolite delivery by yellow bile road. Pharmacol Ther 112:649-667. (Pubitemid 44596214)
33. Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, Venkatesh M, Jobin C, Yeh LA, Mani S, et al. (2010) Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science 330:831-835.
34. Wallace JL, Syer S, Denou E, de Palma G, Vong L, McKnight W, Jury J, Bolla M, Bercik P, Collins SM, et al. (2011) Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology 141:1314-1322, 1322.e1-5.
35. Watanabe T, Higuchi K, Kobata A, Nishio H, Tanigawa T, Shiba M, Tominaga K, Fujiwara Y, Oshitani N, Asahara T, et al. (2008) Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent. Gut 57: 181-187. (Pubitemid 351158044)
36. Whittle BJ (2004) Mechanisms underlying intestinal injury induced by anti-inflammatory COX inhibitors. Eur J Pharmacol 500:427-439.
37. Wolfe MM, Lichtenstein DR, and Singh G (1999) Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. New Engl J Med 340:1888-1899. (Pubitemid 29272670)
38. Yamada S, Naito Y, Takagi T, Mizushima K, Hirai Y, Horie R, Fukumoto K, Inoue K, Harusato A, Yoshida N, et al. (2011) Reduced small-intestinal injury induced by indomethacin in interleukin-17A-deficient mice. J Gastroenterol Hepatol 26:398-404.