Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.
References
[1]
Qi, H.; Zhao, T.; Zhang, Q.; Li, Z.; Zhao, Z. Antioxidant activity of different molecular weight sulfated polysaccharides from Ulva pertusa Kjellm (Chlorophyta). J. Appl. Phycol. 2005, 17, 527–534, doi:10.1007/s10811-005-9003-9.
[2]
Yang, Y.F.; Fei, X.G.; Song, J.M.; Hu, H.Y.; Wang, G.C.; Chung, I.K. Growth of Gracilaria lemaneiformis under different cultivation conditions and its effects on nutrient removal in Chinese coastal waters. Aquaculture 2006, 254, 248–255, doi:10.1016/j.aquaculture.2005.08.029.
[3]
Jiao, G.; Yu, G.; Zhang, J.; Ewart, H.S. Chemical structures and bioactivities of sulfated polysaccharides from marine algae. Mar. Drugs 2011, 9, 196–223.
[4]
Almeida-Lima, J.; Costa, L.S.; Silva, N.B.; Melo-Silveira, R.F.; Silva, F.V.; Felipe, M.B.M.C.; Medeiros, S.R.B.M.; Leite, E.L.; Rocha, H.A.O. Evaluating the possible genotoxic, mutagenic and tumor cell proliferation-inhibition effects of a non-anticoagulant, but antithrombotic algal heterofucan. J. Appl. Toxicol. 2010, 30, 708–715, doi:10.1002/jat.1547.
Cumashi, A.; Ushakova, N.A.; Preobrazhenskaya, M.E.; D’incecco, A.; Picooli, A.; Totani, L.; Tinari, N.; Morozevich, G.E.; Berman, A.E.; Bilan, M.I. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology 2007, 17, 541–552.
[7]
Chaves, L.S.; Nicolau, L.A.D.; Silva, R.O.; Barros, F.C.N.; Freitas, A.L.P.; Aragao, K.S.; Ribeiro, R.A.; Souza, M.H.L.P.; Barbosa, A.L.R.; Medeiros, J.V.R. Anti-inflammatory and anti-nociceptive effects in mice of a sulfated polysaccharide fraction extracted from the marine red algae Gracilaria caudata. Immunopharmacol. Immunotoxicol. 2012. in press.
[8]
Knutsen, S.H.; Myslabodski, D.E.; Larsen, B.; Usov, A.I. A modified system of nomenclature for red algal galactans. Bot. Mar. 1994, 37, 163–170.
[9]
Rees, D.A. Biogenesis of 3,6-anhydro-l-galactose. Biochem. J. 1961, 81, 347–352.
[10]
Ye, H.; Wang, K.; Zhou, C.; Liu, J.; Zeng, X. Purification, antitumor and antioxidant activities in vitro of polysaccharides from the brown seaweed Sargassum pallidum. Food Chem. 2008, 111, 428–432, doi:10.1016/j.foodchem.2008.04.012.
[11]
11. Souza, B.W.S.; Cerqueira, M.A.; Bourbon, A.I.; Pinheiro, A.C.; Martins, J.T.; Teixeira, J.A.; Coimbra, M.A.; Vicente, A.A. Chemical characterization and antioxidant activity of sulfated polysaccharide from the red seaweed Gracilaria birdiae. Food Hydrocoll. 2012, 27, 287–292, doi:10.1016/j.foodhyd.2011.10.005.
[12]
Silva, R.O.; Santos, G.M.P.; Nicolau, L.A.D.; Lucetti, L.T.; Santana, A.P.M.; Chaves, L.S.C.; Barros, C.N.; Freitas, A.L.P.; Souza, M.H.L.P.; Medeiros, J.V.R. Sulfated-polysaccharide fraction from red algae Gracilaria caudata protects mice gut against ethanol-induced gastric damage. Mar. Drugs 2011, 9, 2188–2200, doi:10.3390/md9112188.
Villegas, I.; La Casa, C.; De la Lastra, C.A.; Motilva, V.; Herrerías, J.M.; Martín, M.J. Mucosal damage induced by preferential COX-1 and COX-2 inhibitors: Role of prostaglandins and inflammatory response. Life Sci. 2004, 74, 873–884, doi:10.1016/j.lfs.2003.07.021.
[15]
Beck, W.S.; Schneider, H.T.; Dietzel, K.; Nuernberg, B.; Brune, K. Gastrointestinal ulcerations induced by anti-inflammatory drugs in rats. Arch. Toxicol. 1990, 64, 210–217, doi:10.1007/BF02010727.
[16]
Tenembaum, J. The epidemiology of nonsteroidal anti-inflammatory drugs. Can. J. Gastroenterol. 1999, 13, 119–122.
[17]
Kim, J.H.; Kim, Y.S.; Song, G.G.; Park, J.J.; Chang, H.I. Protective effect of astaxanthin on naproxen-induced gastric antral ulceration in rats. Eur. J. Pharmacol. 2005, 514, 53–59, doi:10.1016/j.ejphar.2005.03.034.
[18]
Parks, D.A. Oxygen radicals: Mediators of gastrointestinal pathophysiology. Gut 1989, 30, 293–298, doi:10.1136/gut.30.3.293.
[19]
Yoshikawa, T.; Naito, Y.; Ueda, S.; Oyamada, H.; Takemura, T.; Yoshida, N.; Sugino, S.; Kondo, M. Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. J. Clin. Gastroenterol. 1990, 12, 65–71, doi:10.1097/00004836-199001001-00012.
[20]
Maciel, J.S.; Chaves, L.S.; Souza, B.W.S.; Teixeira, D.I.A.; Freitas, A.L.P.; Feitosa, J.P.A.; De Paula, R.C.M. Structural characterization of cold extracted fraction of soluble sulfated polysaccharide from red seaweed Gracilaria birdiae. Carbohydr. Polym. 2008, 71, 559–565, doi:10.1016/j.carbpol.2007.06.026.
[21]
Regula, J.; Butruk, E.; Dekkers, C.P.; de Boer, S.Y.; Raps, D.; Simon, L.; Terjung, A.; Thomas, K.B.; Luhmann, R.; Fischer, R. Prevention of NSAID-associated gastrointestinal lesions: A comparison study pantoprazole versus omeprazole. Am. J. Gastroenterol. 2006, 101, 1747–1755, doi:10.1111/j.1572-0241.2006.00686.x.
[22]
Nishida, T.; Tsujii, M.; Tsujii, S. Are COX-2 inhibitors truly able to prevent NSAIDs-associated ulcers? Nippon Rinsho 2004, 62, 561–565.
[23]
Wallace, J.L. NSAID gastroenterophaty: Past, present and future. Can. J. Gastroenterol. 1996, 10, 451–459.
[24]
Kameda, N.; Higuchi, K.; Shiba, M. A prospective, single-blind trial comparing wireless capsule endoscopy and double-balloon enteroscopy in patients with obscure gastrointestinal bleeding. Gastroenterology 2008, 43, 434–440, doi:10.1007/s00535-008-2182-9.
[25]
Pemberton, R.E.; Strand, L.J. A review of upper-gastrointestinal effects of the newer nonsteroidal antiinflammatory agents. Dig. Dis. Sci. 1979, 24, 53–64, doi:10.1007/BF01297239.
[26]
Higuchi, K.; Umegaki, E.; Watanabe, T.; Yoda, Y.; Morita, E.; Murano, M.; Tokioka, S.; Arakawa, T. Present status and strategy of NSAIDs-induced small bowel injury. J. Gastroenterol. 2009, 44, 879–888, doi:10.1007/s00535-009-0102-2.
[27]
Takeuchi, K.; Miyazawa, T.; Tanaka, A.; Kato, S.; Kunikat, T. Pathogenic importance of intestinal hypermotility in NSAID-induced small intestinal damage in rats. Digestion 2002, 66, 30–41, doi:10.1159/000064419.
[28]
Reuter, B.K.; Davies, N.M.; Wallace, J.L. Nonsteroidal anti-inflammatory drug enteropathy in rats: Role of permeability, bacteria and enterohepatic circulation. Gastroenterology 1997, 112, 109–117, doi:10.1016/S0016-5085(97)70225-7.
[29]
Chen, D.; Wu, X.Z.; Wen, Z.Y. Sulfated polysaccharides and immune response: Promoter or inhibitor? Panminerva Med. 2008, 50, 177–183.
[30]
Suzuki, M.; Mori, M.; Miura, S.; Suematsu, M.; Fukumura, D.; Kimura, H.; Ishii, H. Omeprazole attenuates oxygen-derived free radical production from human neutrophils. Free Radic. Biol. Med. 1996, 21, 727–731, doi:10.1016/0891-5849(96)00180-3.
[31]
Zhang, X.; Tajima, K.; Kageyama, K.; Kyoi, T. Irsogladine maleate suppresses indomethacin-induced elevation of proinflammatory cytokines and gastric injury in rats. World J. Gastroenterol. 2008, 14, 4784–4790, doi:10.3748/wjg.14.4784.
[32]
Naito, Y.; Yoshikawa, T.; Matsuyama, K.; Yagi, N.; Arai, M.; Nakamura, Y.; Nishimura, S.; Yoshida, N.; Kondo, M. Effects of oxygen radical scavengers on the quality of gastric ulcer healing in rats. J. Clin. Gastroenterol. 1995, 21, 82–86, doi:10.1097/00004836-199509000-00002.
[33]
Wallace, J.L. Pathogenesis of NSAID-induced gastroduedenal mucosal injury. Best Pract. Res. Clin. Gastroenterol. 2001, 15, 691–703, doi:10.1053/bega.2001.0229.
[34]
Odabasoglu, F.; Cakir, A.; Suleyman, H.; Aslan, A.; Bayir, Y.; Halici, M.; Kazaz, C. Gastroprotective and antioxidant effects of usnic acid on indomethacine-induced gastric ulcer in rats. J. Ethnopharmacol. 2006, 103, 59–65, doi:10.1016/j.jep.2005.06.043.
[35]
Basiviredy, J.; Jacob, M.; Ramamoorthy, P.; Pulimood, A.B.; Balasubramanian, K.A. Indomethacin-induced free radical-mediated changes in the intestinal brush border membranes. Biochem. Pharmacol. 2003, 65, 683–695.
[36]
Medeiros, J.V.; Gadelha, G.G.; Lima, S.J.; Garcia, J.A.; Soares, P.M.; Santos, A.A.; Brito, G.A.; Ribeiro, R.A.; Souza, M.H. Role of the NO/cGMP/KATP pathway in the protective effects of sildenafil against ethanol-induced gastric damage in rats. Br. J. Pharmacol. 2008, 153, 721–727, doi:10.1038/sj.bjp.0707605.
[37]
Das, D.; Bandyopadhyay, D.; Bhattacharjee, M.; Banerjee, R.K. Hydroxyl radical is the major cousative factor in stress-induced gastric ulceration. Free Radic. Biol. Med. 1997, 23, 8–18, doi:10.1016/S0891-5849(96)00547-3.
[38]
Bradley, P.P.; Christensen, R.D.; Rothstein, G. Cellular and extracellular myeloperoxidase in pyogenic inflammation. Blood 1982, 60, 618–622.
[39]
Cuzzocrea, S.; Riley, D.P.; Caputi, A.P.; Salvemini, D. Antioxidant therapy: A new pharmacological approach in shock, inflammation and ischemia/reperfusion injury. Pharmacol. Rev. 2001, 53, 135–159.
[40]
Zhao, B. Natural antioxidants protect neurons in Alzheimer’s disease and Parkinson’s disease. Neurochem. Res. 2009, 34, 630–638, doi:10.1007/s11064-008-9900-9.
[41]
Xing, R.; Yu, H.; Liu, S.; Zhang, W.; Zhang, Q.; Li, Z.; Li, P. Antioxidant activity of differently regioselective chitosan sulfates in vitro. Bioorg. Med. Chem. 2005, 13, 1387–1392, doi:10.1016/j.bmc.2004.11.002.
[42]
Farias, W.R.L.; Valente, A.P.; Pereira, M.S.; Mour？o, P.A.S. Structure and anticoagulant activity of sulfated galactans. Isolation of a unique sulfated galactan from the red alga Botryocladia occidentalis and comparison of its anticoagulant action with that of sulfated galactans from invertebrates. J. Biol. Chem. 2000, 275, 29299–29307.
[43]
Dubois, M.; Gillis, K.A.; Hamilton, J.K.; Rebers, P.A.; Smith, F. Colorimetric method for determination of sugars and related substances. Anal. Chem. 1956, 28, 350–356.
[44]
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248–254.
Stevenson, T.T.; Furneaux, R.H. Chemical methods for the analysis of sulphated galactans from red algae. Carbohydr. Res. 1991, 210, 277–298, doi:10.1016/0008-6215(91)80129-B.
[47]
Sedlak, J.; Lindsay, R.H. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal. Biochem. 1968, 24, 1992–2005.
[48]
Mihara, M.; Uchiyama, M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal. Biochem. 1978, 86, 271–278, doi:10.1016/0003-2697(78)90342-1.
[49]
Bradley, P.P.; Priebat, D.A.; Christensen, R.D.; Rothstein, G. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. J. Invest. Dermatol. 1982, 78, 206–209, doi:10.1111/1523-1747.ep12506462.
[50]
Morris, G.P.; Beck, P.L.; Herridge, M.S.; Depew, W.T.; Szewczuk, M.R.; Wallace, J.L. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989, 96, 795–803.
[51]
Laine, L.; Weinstein, W.M. Histology of alcoholic hemorrhagic “gastritis”: A prospective evaluation. Gastroenterology 1988, 94, 1254–1262.
