Abstract
This study aimed to investigate the effect of age on natural ulcer healing and delayed ulcer healing induced by nonsteroidal antiinflammatory drugs, using a rat model. Gastric ulcers were induced in young, adult, and aged rats using serosal or mucosal (kissing ulcers) application of acetic acid. Rats were treated with indomethacin 1 mg/kg/day subcutaneously or vehicle for two weeks. Ulcers were assessed by macroscopic and histological measurements of ulcer size. Ulcer induction was affected by age. Aged rats developed significantly smaller ulcers when induced by serosal application of acetic acid and significantly larger ulcers from mucosal application of acetic acid. However, measurements of ulcer size from both models showed no age-related differences in natural ulcer healing. Similarly, indomethacin-induced delayed gastric ulcer healing was not effected by age. We conclude that there are age-related differences in the development of gastric ulcers but there are no age-related differences in natural or delayed ulcer healing in rats.
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References
Bonnevie O: The incidence of gastric ulcer in Copenhagen County. Scand J Gastroenterol 10:231–239, 1975
Levrat M, Pasquier J, Lambert R, Tissot A: Peptic ulcer in patients over 60. Am J Dig Dis 11:279–283, 1966
Steinheber F: Ageing and the stomach. Clin Gastroenterol 14:657–688, 1985
Roth SH, Bennett RE: Nonsteroidal anti-inflammatory drug-associated gastropathy: Recognition and response. Arch Intern Med 147:2093–2100, 1987
Lancaster-Smith MJ, Jaderberg ME, Jackson DA: Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers. Gut 32:252–255, 1991
Fries JF, Williams CA, Bloch DA, Michel BA: Nonsteroidal anti-inflammatory drug-associated gastropathy: Incidence and risk factor models. Am J Med 91:213–222, 1991
Cox DA, Kunz S, Cerletti N, McMaster GK, Burk RR: Wound healing in aged animals—effects of locally applied transforming growth factor beta 2 in different model systems.In Angiogenesis: Key Principles. R Steiner, PB Weisz, iLanger R (eds). Basel, Birkhauser Verlag 1992, pp 287–295
Grove GL: Age-related differences in healing of superficial skin wounds in humans. Arch Dermatol Res 272:381–395, 1982
Holt DR, Kirk SJ, Regan MC, Hurson M, Lindblad WJ, Barbul A: Effect of age on wound healing in healthy human beings. Surgery 112:293–298, 1992
Eaglstein WH: Wound healing and aging. Clin Geriatr Med 5:183–188, 1989
Holm-Pedersen P, Zederfeldt B: Strength development of skin incisions in young and old rats. Scand J Plast Reconstr Surg 5:7–12, 1971
Yamaura H, Matsuzawa T: Decrease in capillary growth during aging. Exp Gerontol 15:145–150, 1980
Petersen TI, Kissmeyer-Nielsen P, Laurberg S, Christensen H: Impaired wound healing but unaltered colonic healing with increasing age: An experimental study in rats. Eur Surg Res 27:250–257, 1995
Gottrup F: Healing of incisional wounds in stomach and duodenum. The influence of aging. Acta Chir Scand 147:363–369, 1981
Tsukimi Y, Okabe S: Changes in gastric function and healing of chronic gastric ulcers in aged rats. Jpn J Pharmacol 68:103–111, 1995
Penney AG, Andrews FJ, O'Brien PE: Effects of misoprostol on delayed ulcer healing induced by aspirin. Dig Dis Sci 39:934–939, 1994
Wang JY, Yamasaki S, Takeuchi K, Okabe S: Delayed healing of acetic acid-induced gastric ulcers in rats by indomethacin. Gastroenterology 96:393–402, 1989
Tsukimi Y, Okabe S: Validity of kissing gastric ulcers induced in rats for screening of antiulcer drugs. J Gastroenterol Hepatol 9:S60-S65, 1994
Hollander D, Tarnawski A, Stachura J, Gergely H: Morphologic changes in gastric mucosa of aging rats. Dig Dis Sci 34:1692–1700, 1989
Pare WP: Strain, age, but not gender, influence ulcer severity induced by water-restraint stress. Physiol Behav 45:627–632, 1989
Majumdar APN, Moshier JA, Arlow FL, Luk GD: Biochemical changes in the gastric mucosa after injury in young and aged rats. Biochim Biophys Acta 992:35–40, 1989
Lee M, Feldman M: Age-related reductions in gastric mucosal prostaglandin levels increase susceptibility to aspirin-induced injury in rats. Gastroenterology 107:1746–1750, 1994
Uchida M, Misaki N, Kawano O, Yano S, Watanabe K: Change in formation of gastric lesions by aspirin during aging in rats. J Pharmacobiodyn 13:493–496, 1990
Pare WP, Vincent GP: Cimetidine and stress ulcer in aged rats. Physiol Behav 33:305–308, 1984
Goldstein R, Wozniak DF: Effect of age, food deprivation and stress on gastric erosions in the rat. Physiol Behav 23:1011–1015, 1979
Ohno T, Uramoto H, Masuda Y, Kubota H, Ishihara T: Influence of aging on stress ulcer formation in rats. Scand J Gastroenterol 24(suppl 162):95–99, 1989
Krasinski SD, Russell RM, Samloff IM: Fundic atrophic gastritis in an elderly population. Am J Geriatr Soc 34:800–806, 1986
Kekki M, Samloff IM, Ihamaki T, Varis K, Siurala M: Age- and sex-related behaviour of gastric acid secretion at the population level. Scand J Gastroenterol 17:737–743, 1982
Russell RM: Changes in gastrointestinal function attributed to aging. Am J Clin Nutr 55:1203S-1207S, 1992
Taniguchi Y, Kimura K, Yoshida Y, Seki M, Kumakura Y, Satoh K, Kihira K, Ido K, Mato M: Age-related changes in the microvessels of the human stomach: An ultrastructural study. J Clin Gastroenterol 17(suppl 1):S92-S98, 1993
Holt PR: Approach to gastrointestinal problems in the elderly.In Textbook of Gastroenterology. T Yamada, DH Alpers, C Owyang (eds). New York, JB Lippincott, 1991, pp 886–889
Masuda Y, Ohno T, Uramato H, Ishihara T: Effects of aging on gastric secretion and blood flow in rats.In Mechanisms of Injury, Protection and Repair of the Upper Gastrointestinal Tract. A Garner, PE O'Brien (eds). Chichester, John Wiley & Sons, 1991, pp 309–317
Cryer B, Faust TW, Goldschmiedt M, Redfern JS, Lee E, Feldman M: Gastric and duodenal mucosal prostaglandin concentration in gastric or duodenal ulcer disease: Relationships with demographics, environmental, and histological factors, includingHelicobacter pylori: Am J Gastroenterol 87:1747–1754, 1992
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This study was supported by grants from the Sandoz Foundation for Gerontological Research, Australia and Perpetual Trustees, Australia.
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Penney, A.G., Andrews, F.J. & O'Brien, P.E. Influence of age on natural and delayed healing of experimentally-induced gastric ulcers in rats. Digest Dis Sci 41, 1838–1844 (1996). https://doi.org/10.1007/BF02088755
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DOI: https://doi.org/10.1007/BF02088755