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Comparative Clinical Pathology

Erschienen in:

14.10.2016 | Original Article

Gastroprotective potential of melatonin versus melatonin loaded niosomes on gastric ulcer healing in rats

verfasst von: Ebtehal Ahmed, Nasser Anwar, Omyma Galal, Mahmoud El-sabahy, Mokhtar Taha

Erschienen in: Comparative Clinical Pathology | Ausgabe 1/2017

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Abstract

The present study was conducted to investigate the therapeutic effects of melatonin and melatonin-loaded niosomes on ethanol-induced gastric lesions. Morphological and biochemical changes associated with each drug were investigated. Seventy apparently healthy female albino rats, weighting about 200–250 g were randomly assigned to 4 experimental groups. The first group (induction group) included 10 rats that were given 1 ml 70 % ethanol and sacrificed after 1 and 1/2 hour. The second group (melatonin-treated group) included 25 rats that were administrated with 2 mg/rat melatonin by gastric tube daily after induction of ulcer by ethanol. Five rats were sacrificed after 3, 7, 14, 21, and 28 days post-treatment. The third group (melatonin-loaded niosomes treated group) consisted of 25 rats that were given melatonin-loaded niosomes in the same dose and route as the third group. Five rats were sacrificed after 3, 7, 14, 21, and 28 days post-treatment. The fourth group (control group) consisted of 10 rats that administrated only the vehicle in a similar dose and route as other groups (5 rats were given 1 ml of saline and the other 5 rats were given 1 ml of niosomes polymer daily via gastric tube). The rats were kept throughout the time of the study and were sacrificed by cervical dislocation at the end of the experiment. Gross lesions were carried out, and ulcer index was calculated for each subgroup. Tissue samples were fixed in 10 % neutral buffered formalin and stained with Hx&E stain for conventional histological examination. Biochemical analysis of tissue homogenate for determination of lipid peroxidation and total antioxidants was performed. Melatonin-loaded niosomes showed early impressive gastroprotection as early as 7 days post-treatment while unloaded melatonin therapy exerted their effects after 14 days respectively. In addition, melatonin-loaded niosomes improved the micro-vascular damages after 14 days compared to the other melatonin-treated group which showed improved gastric alterations after 21 days. Biochemically, the cases of melatonin-loaded niosomes achieved the lowest mean values of lipid peroxidation and highest mean values of total antioxidants compared to other values recorded in case of unloaded melatonin therapy, and these results are in accordance with that of the histopathological findings.

Al-Attar AM (2011) Protective effect of Avicennia alba leaves extract on gastric mucosal damage induced by ethanol. Research Journal of Medicinal Plant 5(4):477–490CrossRef

Allegra M, Reiter R, Tan DX, Gentile C, Tesoriere L, Livrea M (2003) The chemistry of melatonin's interaction with reactive species. J Pineal Res 34(1):1–10PubMedCrossRef

Arab HH, Salama SA, Omar HA, Arafa E-SA, Maghrabi IA (2015) Diosmin protects against ethanol-induced gastric injury in rats: novel anti-ulcer actions. PLoS One 10(3):e0122417PubMedPubMedCentralCrossRef

Araki Y, Sugihara H, Hattori T (2006) The free radical scavengers edaravone and tempol suppress experimental dextran sulfate sodium-induced colitis in mice. Int J Mol Med 17(2):331–334PubMed

Bandyopadhyay D, Biswas K, Bandyopadhyay U, Reiter RJ, Banerjee RK (2000) Melatonin protects against stress-induced gastric lesions by scavenging the hydroxyl radical. J Pineal Res 29(3):143–151PubMedCrossRef

Bandyopadhyay D, Biswas K, Reiter R, Banerjee R (2001) Gastric toxicity and mucosal ulceration induced by oxygen-derived reactive species: protection by melatonin. Curr Mol Med 1(4):501–513PubMedCrossRef

Bandyopadhyay D, Biswas K, Bhattacharyya M, Reiter RJ, Banerjee RK (2002) Involvement of reactive oxygen species in gastric ulceration: protection by melatonin. Indian J Exp Biol 40(6):693–705PubMed

Bilici D, Süleyman H, Banoğlu ZN, Kiziltunç A, Avci B, Çiftçioğlu A, Bilici S (2002) Melatonin prevents ethanol-induced gastric mucosal damage possibly due to its antioxidant effect. Dig Dis Sci 47(4):856–861PubMedCrossRef

Blanchard B, Pompon D, Ducrocq C (2000) Nitrosation of melatonin by nitric oxide and peroxynitrite. J Pineal Res 29(3):184–192PubMedCrossRef

Boutin JA, Audinot V, Ferry G, Delagrange P (2005) Molecular tools to study melatonin pathways and actions. Trends Pharmacol Sci 26(8):412–419PubMedCrossRef

Brzozowska I, Konturek PC, Brzozowski T, Konturek SJ, Kwiecien S, Pajdo R, Drozdowicz D, Pawlik M, Ptak A, Hahn EG (2002) Role of prostaglandins, nitric oxide, sensory nerves and gastrin in acceleration of ulcer healing by melatonin and its precursor, L-tryptophan. J Pineal Res 32(3):149–162PubMedCrossRef

Brzozowska I, Strzalka M, Drozdowicz D, Konturek SJ, Brzozowski T (2014) Mechanisms of esophageal protection, gastroprotection and ulcer healing by melatonin. Implications for the therapeutic use of melatonin in gastroesophageal reflux disease (GERD) and peptic ulcer disease. Curr Pharm Des 20(30):4807–4815PubMedCrossRef

Brzozowski T, Konturek PC, Zwirska-Korczala K, Konturek SJ, Brzozowska I, Drozdowicz D, Sliwowski Z, Pawlik M, Pawlik WW, Hahn EG (2005) Importance of the pineal gland, endogenous prostaglandins and sensory nerves in the gastroprotective actions of central and peripheral melatonin against stress-induced damage. J Pineal Res 39(4):375–385PubMedCrossRef

Buckton G (2000) Interfacial phenomena in drug delivery and targeting, CRC press

Cabeza J, Motilva V, Martı́n MAJ, de la Lastra CA (2001) Mechanisms involved in gastric protection of melatonin against oxidant stress by ischemia-reperfusion in rats. Life Sci 68(12):1405–1415PubMedCrossRef

Christian P, Von der Kammer F, Baalousha M, Hofmann T (2008) Nanoparticles: structure, properties, preparation and behaviour in environmental media. Ecotoxicology 17(5):326–343PubMedCrossRef

Chu B, Dopico AM, Lemos JR, Treistman SN (1998) Ethanol potentiation of calcium-activated potassium channels reconstituted into planar lipid bilayers. Mol Pharmacol 54(2):397–406PubMed

Coşkun, Ö., M. Kanter, F. Armutçu, K. Çetin, B. Kaybolmaz and Ö. Yazgan (2004). Protective effects of quercetin, a flavonoid antioxidant, in absolute ethanol-induced acut gastric ulcer

Das MK, Palei NN (2011) Sorbitan ester niosomes for topical delivery of rofecoxib. Indian J Exp Biol 49:438–445PubMed

de Souza Pereira R (2006) Regression of an esophageal ulcer using a dietary supplement containing melatonin. J Pineal Res 40(4):355–356PubMedCrossRef

Dellegar SM, Murphy SA, Bourne AE, DiCesare JC, Purser GH (1999) Identification of the factors affecting the rate of deactivation of hypochlorous acid by melatonin. Biochem Biophys Res Commun 257(2):431–439PubMedCrossRef

des Rieux A, Fievez V, Garinot M, Schneider Y-J, Préat V (2006) Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release 116(1):1–27PubMedCrossRef

Dokmeci D, Akpolat M, Aydogdu N, Doganay L, Turan FN (2005) L-carnitine inhibits ethanol-induced gastric mucosal injury in rats. Pharmacol Rep 57(4):481–488PubMed

Dubey V, Mishra D, Jain N (2007) Melatonin loaded ethanolic liposomes: physicochemical characterization and enhanced transdermal delivery. Eur J Pharm Biopharm 67(2):398–405PubMedCrossRef

El-Gibaly I, Meki A, Abdel-Ghaffar S (2003) Novel B melatonin-loaded chitosan microcapsules: in vitro characterization and antiapoptosis efficacy for aflatoxin B1-induced apoptosis in rat liver. Int J Pharm 260(1):5–22PubMedCrossRef

Fasinu P, Pillay V, Ndesendo VM, du Toit LC, Choonara YE (2011) Diverse approaches for the enhancement of oral drug bioavailability. Biopharm Drug Dispos 32(4):185–209PubMedCrossRef

Favero G, Rodella LF, Reiter RJ, Rezzani R (2014) Melatonin and its atheroprotective effects: a review. Mol Cell Endocrinol 382(2):926–937PubMedCrossRef

Fornai, M., L. Antonioli, R. Colucci, M. Tuccori and C. Blandizzi (2014). Pathophysiology of gastric ulcer development and healing: molecular mechanisms and novel therapeutic options.

Ganguly K, Kundu P, Banerjee A, Reiter RJ, Swarnakar S (2006) Hydrogen peroxide-mediated downregulation of matrix metalloprotease-2 in indomethacin-induced acute gastric ulceration is blocked by melatonin and other antioxidants. Free Radic Biol Med 41(6):911–925PubMedCrossRef

Ganguly K, Sharma AV, Reiter RJ, Swarnakar S (2010) Melatonin promotes angiogenesis during protection and healing of indomethacin-induced gastric ulcer: role of matrix metaloproteinase-2. J Pineal Res 49(2):130–140PubMed

Gonzalez F, Portela T, Stipp E, Di Stasi L (2001) Antiulcerogenic and analgesic effects of Maytenus aquifolium, Sorocea bomplandii and Zolernia ilicifolia. J Ethnopharmacol 77(1):41–47PubMedCrossRef

Hafner A, Lovrić J, Voinovich D, Filipović-Grčić J (2009) Melatonin-loaded lecithin/chitosan nanoparticles: physicochemical characterisation and permeability through Caco-2 cell monolayers. Int J Pharm 381(2):205–213PubMedCrossRef

Holzer P (2006) Efferent-like roles of afferent neurons in the gut: blood flow regulation and tissue protection. Auton Neurosci 125(1):70–75PubMedPubMedCentralCrossRef

Jadhav SM, Morey P, Karpe M, Kadam V (2012) Novel vesicular system: an overview. J Appl Pharm Sci 2(01):193–202

Jahanshahi M, Zhang Z, Lyddiatt A (2005) Subtractive chromatography for purification and recovery of nano-bioproducts IEE Proceedings-Nanobiotechnology, IET

Kahraman A, Erkasap N, Köken T, Serteser M, Aktepe F, Erkasap S (2003) The antioxidative and antihistaminic properties of quercetin in ethanol-induced gastric lesions. Toxicology 183(1):133–142PubMedCrossRef

Kanter M, Coskun O, Uysal H (2006) The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol 80(4):217–224PubMedCrossRef

Konturek PC, Konturek SJ, Burnat G, Brzozowski T, Brzozowska I, Reiter RJ (2008) Dynamic physiological and molecular changes in gastric ulcer healing achieved by melatonin and its precursor L-tryptophan in rats. J Pineal Res 45(2):180–190PubMedCrossRef

Konturek P, Konturek S, Celinski K, Slomka M, Cichoz-Lach H, Bielanski W, Reiter R (2010) Role of melatonin in mucosal gastroprotection against aspirin-induced gastric lesions in humans. J Pineal Res 48(4):318–323PubMedCrossRef

Koracevic D, Koracevic G, Djordjevic V, Andrejevic S, Cosic V (2001) Colorimetric method for determination of total antioxidant capacity. J Clin Pathol 54:356–361PubMedPubMedCentralCrossRef

La Casa C, Villegas I, De La Lastra CA, Motilva V, Calero MM (2000) Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol 71(1):45–53PubMedCrossRef

Lamprecht A, Ubrich N, Yamamoto H, Schäfer U, Takeuchi H, Maincent P, Kawashima Y, Lehr C-M (2001) Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease. J Pharmacol Exp Ther 299(2):775–781PubMed

Lamprecht A, Yamamoto H, Takeuchi H, Kawashima Y (2005) Nanoparticles enhance therapeutic efficiency by selectively increased local drug dose in experimental colitis in rats. J Pharmacol Exp Ther 315(1):196–202PubMedCrossRef

Lee M, Kim SW (2005) Polyethylene glycol-conjugated copolymers for plasmid DNA delivery. Pharm Res 22(1):1–10PubMedCrossRef

MacAllister C, Andrews F, Deegan E, Ruoff W, Olovson SG (1997) A scoring system for gastric ulcers in the horse. Equine Vet J 29(6):430–433PubMedCrossRef

Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65(1):271–284PubMedCrossRef

Maity P, Bindu S, Dey S, Goyal M, Alam A, Pal C, Reiter R, Bandyopadhyay U (2009) Melatonin reduces indomethacin-induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis. J Pineal Res 46(3):314–323PubMedCrossRef

Malhotra S, Sawhney G, Pandhi P (2004) The therapeutic potential of melatonin: a review of the science. MedGenMed 6(2)

Mayo J, Sainz R, Antolin I, Herrera F, Martin V, Rodriguez C (2002) Melatonin regulation of antioxidant enzyme gene expression. Cellular and Molecular Life Sciences CMLS 59(10):1706–1713PubMedCrossRef

Moghassemi S, Hadjizadeh A (2014) Nano-niosomes as nanoscale drug delivery systems: an illustrated review. J Control Release 185:22–36PubMedCrossRef

Moghimi SM, Szebeni J (2003) Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res 42(6):463–478PubMedCrossRef

Nasir A, Harikumar S, Amanpreet K (2012) Niosomes: an excellent tool for drug delivery. IJRPC 2(2):479–487

Netweera V, Priprem A, Limsitthichaikoon S, Johns NP (2013) Melatonin encapsulated niosomes permeation characteristics. Int J Sci Adv Technol 12–17

Noda Y, Mori A, Liburdy R, Packer L (1999) Melatonin and its precursors scavenge nitric oxide. J Pineal Res 27(3):159–163PubMedCrossRef

Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358PubMedCrossRef

Pablos MI, Reiter RJ, Ortiz GG, Guerrero JM, Agapito MT, Chuang J-I, Sewerynek E (1998) Rhythms of glutathione peroxidase and glutathione reductase in brain of chick and their inhibition by light. Neurochem Int 32(1):69–75PubMedCrossRef

Priano L, Esposti D, Esposti R, Castagna G, De Medici C, Fraschini F, Gasco MR, Mauro A (2007) Solid lipid nanoparticles incorporating melatonin as new model for sustained oral and transdermal delivery systems. J Nanosci Nanotechnol 7(10):3596–3601PubMedCrossRef

Reiter R, Tan D-X, Cabrera J, D'Arpa D, Sainz R, Mayo J, Ramos S (1998) The oxidant/antioxidant network: role of melatonin. Biol Signals Recept 8(1–2):56–63

Rodriguez C, Mayo JC, Sainz RM, Antolin I, Herrera F, Martin V, Reiter RJ (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36(1):1–9PubMedCrossRef

Ruckmani K, Sankar V (2010) Formulation and optimization of zidovudine niosomes. AAPS PharmSciTech 11(3):1119–1127PubMedPubMedCentralCrossRef

Salim A (1990) Removing oxygen-derived free radicals stimulates healing of ethanol-induced erosive gastritis in the rat. Digestion 47(1):24–28PubMedCrossRef

Sánchez-Fidalgo S, Martín-Lacave I, Illanes M, Motilva V (2004) Angiogenesis, cell proliferation and apoptosis in gastric ulcer healing. Effect of a selective cox-2 inhibitor. Eur J Pharmacol 505(1):187–194PubMedCrossRef

Schaffazick S, Pohlmann A, De Cordova C, Creczynski-Pasa T, Guterres S (2005) Protective properties of melatonin-loaded nanoparticles against lipid peroxidation. Int J Pharm 289(1):209–213PubMedCrossRef

Sener G, Paskaloglu K, Ayanoglu-Dülger G (2004) Protective effect of increasing doses of famotidine, omeprazole, lansoprazole, and melatonin against ethanol-induced gastric damage in rats. Indian Journal of Pharmacology 36(3):171

Sheeba M, Asha V (2006) Effect of Cardiospermum halicacabum on ethanol-induced gastric ulcers in rats. J Ethnopharmacol 106(1):105–110PubMedCrossRef

Shirsand S, Para M, Nagendrakumar D, Kanani K, Keerthy D (2012) Formulation and evaluation of ketoconazole niosomal gel drug delivery system. International journal of pharmaceutical investigation 2(4):201PubMedPubMedCentralCrossRef

Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70(1):1–20PubMedCrossRef

Swarnakar S, Ganguly K, Kundu P, Banerjee A, Maity P, Sharma AV (2005) Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer. J Biol Chem 280(10):9409–9415PubMedCrossRef

Swarnakar S, Mishra A, Ganguly K, Sharma AV (2007) Matrix metalloproteinase-9 activity and expression is reduced by melatonin during prevention of ethanol-induced gastric ulcer in mice. J Pineal Res 43(1):56–64PubMedCrossRef

Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ (2007) One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res 42(1):28–42PubMedCrossRef

Tarnawski AS (2010) Cellular and molecular mechanisms of gastrointestinal ulcer healing: state of the art 2010. Gastroenterologia Polska/Gastroenterology 17(3)

Tarnawski A, Ahluwalia A (2012) Molecular mechanisms of epithelial regeneration and neovascularization during healing of gastric and esophageal ulcers. Curr Med Chem 19(1):16–27PubMedCrossRef

Tarnawski A, Ahluwalia A, Jones MK (2013) Gastric cytoprotection beyond prostaglandins: cellular and molecular mechanisms of gastroprotective and ulcer healing actions of antacids. Curr Pharm Des 19(1):126–132PubMed

Torchilin V (1998) Polymer-coated long-circulating microparticulate pharmaceuticals. J Microencapsul 15(1):1–19PubMedCrossRef

Torchilin VP (2012) Multifunctional nanocarriers. Adv Drug Deliv Rev 64:302–315CrossRef

Volti GL, Musumeci T, Pignatello R, Murabito P, Barbagallo I, Carbone C, Gullo A, Puglisi G (2012) Antioxidant potential of different melatonin-loaded nanomedicines in an experimental model of sepsis. Exp Biol Med 237(6):670–677CrossRef

Yeo M, Kim D-K, Cho SW, Do Hong H (2008) Ginseng, the root of Panax ginseng CA Meyer, protects ethanol-induced gastric damages in rat through the induction of cytoprotective heat-shock protein 27. Dig Dis Sci 53(3):606–613PubMedCrossRef

Zhang L, Gong JT, Zhang HQ, Song QH, Xu GH, Cai L, Tang XD, Zhang HF, Liu F-E, Jia ZS (2015) Melatonin attenuates noise stress-induced gastrointestinal motility disorder and gastric stress ulcer: role of gastrointestinal hormones and oxidative stress in rats. Journal of neurogastroenterology and motility 21(2):189PubMedPubMedCentralCrossRef

Titel: Gastroprotective potential of melatonin versus melatonin loaded niosomes on gastric ulcer healing in rats
verfasst von: Ebtehal Ahmed
Nasser Anwar
Omyma Galal
Mahmoud El-sabahy
Mokhtar Taha
Publikationsdatum: 14.10.2016
Verlag: Springer London
Erschienen in: Comparative Clinical Pathology / Ausgabe 1/2017
Print ISSN: 1618-5641
Elektronische ISSN: 1618-565X
DOI: https://doi.org/10.1007/s00580-016-2344-8

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