Changes in the Mucus Barrier During Cisplatin-induced Intestinal Mucositis in Rats

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2014 Jan 24

PMID 24455680

Citations 20

Authors

Hajime Yamamoto

Kazuhiko Ishihara

Yuko Takeda

Wasaburo Koizumi

Takafumi Ichikawa

Affiliations

Soon will be listed here.

Abstract

Aim: Gastrointestinal mucositis is a frequent complication of antineoplastic chemotherapy, but the effects of chemotherapy on mucosal defense mechanisms remain poorly understood. We studied the effects of cisplatin on mucin, one of the principal defense factors of the gastrointestinal mucosa, and evaluated the efficacy of two different types of H2-receptor antagonists against cisplatin-induced mucositis.

Methods: Cisplatin (6 mg/kg) was administered intravenously to rats (day 0). The rats were sacrificed 1, 3, 7, and 11 days after treatment, and their stomach, jejunum, ileum, and colon were removed. Immunoreactivity of the mucosa was compared with the use of anti-mucin monoclonal antibody. To evaluate the efficacy of H2-receptor antagonists, either famotidine (3 mg/kg) or lafutidine (30 mg/kg) was given orally once daily on days 0, 1, and 2. Histological and biochemical findings were compared among the groups to assess effects on cisplatin-induced injury.

Results: Cisplatin significantly altered the immunoreactivity and content of mucin in the small intestinal mucosa, especially in the ileum. Lafutidine protected against cisplatin-induced mucosal injury and attenuated decreased mucin accumulation.

Conclusion: Cisplatin appears to alter the mucus barrier function in the intestinal mucosa. Lafutidine might effectively prevent chemotherapy-induced mucositis by activating intestinal mucus cells.

Citing Articles

Prebiotics counteract the morphological and functional changes secondary to chronic cisplatin exposition in the proximal colon of mice.

Biagioni C, Traini C, Faussone-Pellegrini M, Idrizaj E, Baccari M, Vannucchi M J Cell Mol Med. 2024; 28(6):e18161.

PMID: 38445787 PMC: 10915824. DOI: 10.1111/jcmm.18161.

Animal Model of Cisplatin-Induced Oral Mucositis: Dose Optimization.

Kadarullah O, Tamtomo D, Wasita B, Setiamika M Acta Med Acad. 2024; 52(3):188-194.

PMID: 38407085 PMC: 10945320. DOI: 10.5644/ama2006-124.422.

Attenuates Cisplatin-Induced Intestinal Mucositis in Mice via Modulating the Gut Microbiota and Improving Intestinal Inflammation.

Alsholi D, Yacoub G, Rehman A, Ullah H, Khan A, Deng T Pathogens. 2023; 12(11).

PMID: 38003804 PMC: 10674506. DOI: 10.3390/pathogens12111340.

Chemotherapy induced gastrointestinal toxicities.

Akbarali H, Muchhala K, Jessup D, Cheatham S Adv Cancer Res. 2022; 155:131-166.

PMID: 35779873 PMC: 10033220. DOI: 10.1016/bs.acr.2022.02.007.

Dioscin Alleviates Cisplatin-Induced Mucositis in Rats by Modulating Gut Microbiota, Enhancing Intestinal Barrier Function and Attenuating TLR4/NF-κB Signaling Cascade.

Jin S, Guan T, Wang S, Hu M, Liu X, Huang S Int J Mol Sci. 2022; 23(8).

PMID: 35457248 PMC: 9025408. DOI: 10.3390/ijms23084431.

References

Vickers A, Rose K, Fisher R, Saulnier M, Sahota P, Bentley P . Kidney slices of human and rat to characterize cisplatin-induced injury on cellular pathways and morphology. Toxicol Pathol. 2004; 32(5):577-90. DOI: 10.1080/01926230490508821. View

Korenaga D, Honda M, Yasuda M, Inutsuka S, Nozoe T, Tashiro H . Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue tegafur in rats. Eur Surg Res. 2002; 34(5):351-6. DOI: 10.1159/000064001. View

Sartori S, Trevisani L, Nielsen I, Tassinari D, Panzini I, Abbasciano V . Randomized trial of omeprazole or ranitidine versus placebo in the prevention of chemotherapy-induced gastroduodenal injury. J Clin Oncol. 2000; 18(3):463-7. DOI: 10.1200/JCO.2000.18.3.463. View

Miyamoto Y, Miyamoto M . Immunohistochemical localizations of secretin, cholecystokinin, and somatostatin in the rat small intestine after acute cisplatin treatment. Exp Mol Pathol. 2004; 77(3):238-45. DOI: 10.1016/j.yexmp.2004.05.007. View

Gerdes J, Lemke H, Baisch H, Wacker H, Schwab U, STEIN H . Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984; 133(4):1710-5. View

Ishihara K, Kurihara M, Goso Y, Ota H, Katsuyama T, Hotta K . Establishment of monoclonal antibodies against carbohydrate moiety of gastric mucins distributed in the different sites and layers of rat gastric mucosa. Glycoconj J. 1996; 13(5):857-64. DOI: 10.1007/BF00702350. View

Ota H, Katsuyama T . Alternating laminated array of two types of mucin in the human gastric surface mucous layer. Histochem J. 1992; 24(2):86-92. DOI: 10.1007/BF01082444. View

Hesketh P, Gandara D . Serotonin antagonists: a new class of antiemetic agents. J Natl Cancer Inst. 1991; 83(9):613-20. DOI: 10.1093/jnci/83.9.613. View

Rubenstein E, Peterson D, Schubert M, Keefe D, McGuire D, Epstein J . Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer. 2004; 100(9 Suppl):2026-46. DOI: 10.1002/cncr.20163. View

10.

Saegusa Y, Ichikawa T, Iwai T, Goso Y, Okayasu I, Ikezawa T . Changes in the mucus barrier of the rat during 5-fluorouracil-induced gastrointestinal mucositis. Scand J Gastroenterol. 2008; 43(1):59-65. DOI: 10.1080/00365520701579662. View

11.

Azuumi Y, OHara S, Ishihara K, Okabe H, Hotta K . Correlation of quantitative changes of gastric mucosal glycoproteins with aspirin-induced gastric damage in rats. Gut. 1980; 21(6):533-6. PMC: 1419663. DOI: 10.1136/gut.21.6.533. View

12.

Tazuke Y, Maeda K, Wasa M, Satoko N, Fukuzawa M . Protective mechanism of glutamine on the expression of proliferating cell nuclear antigen after cisplatin-induced intestinal mucosal injury. Pediatr Surg Int. 2010; 27(2):151-8. DOI: 10.1007/s00383-010-2798-8. View

13.

Slavin R, Dias M, Saral R . Cytosine arabinoside induced gastrointestinal toxic alterations in sequential chemotherapeutic protocols: a clinical-pathologic study of 33 patients. Cancer. 1978; 42(4):1747-59. DOI: 10.1002/1097-0142(197810)42:4<1747::aid-cncr2820420413>3.0.co;2-t. View

14.

Sonis S, Elting L, Keefe D, Peterson D, Schubert M, Hauer-Jensen M . Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004; 100(9 Suppl):1995-2025. DOI: 10.1002/cncr.20162. View

15.

Saegusa Y, Ichikawa T, Iwai T, Goso Y, Ikezawa T, Nakano M . Effects of acid antisecretory drugs on mucus barrier of the rat against 5-fluorouracil-induced gastrointestinal mucositis. Scand J Gastroenterol. 2008; 43(5):531-7. PMC: 2430178. DOI: 10.1080/00365520701811693. View

16.

Sartori S, Trevisani L, Nielsen I, Tassinari D, Abbasciano V . Misoprostol and omeprazole in the prevention of chemotherapy-induced acute gastroduodenal mucosal injury. A randomized, placebo-controlled pilot study. Cancer. 1996; 78(7):1477-82. DOI: 10.1002/(sici)1097-0142(19961001)78:7<1477::aid-cncr15>3.0.co;2-x. View

17.

Singh G . A possible cellular mechanism of cisplatin-induced nephrotoxicity. Toxicology. 1989; 58(1):71-80. DOI: 10.1016/0300-483x(89)90105-4. View

18.

Elting L, Cooksley C, Chambers M, Cantor S, Manzullo E, Rubenstein E . The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003; 98(7):1531-9. DOI: 10.1002/cncr.11671. View

19.

Ichikawa T, Ota H, Sugiyama A, Maruta F, Ikezawa T, Hotta K . Effects of a novel histamine H2-receptor antagonist, lafutidine, on the mucus barrier of human gastric mucosa. J Gastroenterol Hepatol. 2007; 22(11):1800-5. DOI: 10.1111/j.1440-1746.2006.04721.x. View

20.

Tsubokawa D, Goso Y, Sawaguchi A, Kurihara M, Ichikawa T, Sato N . A monoclonal antibody, PGM34, against 6-sulfated blood-group H type 2 antigen, on the carbohydrate moiety of mucin. FEBS J. 2007; 274(7):1833-48. DOI: 10.1111/j.1742-4658.2007.05731.x. View