The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats
The role of nitric oxide (NO) on intestinal mucosal injury induced by single or consecutive administration of methotrexate was investigated in a rodent model. Rats received methotrexate intraperitoneally either as a single administration (50 mg/kg) or as a consecutive administration (12.5 mg/kg/day)...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861320300189 |
| _version_ | 1818840175142240256 |
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| author | Saki Shiga Takuji Machida Takumi Yanada Maiko Machida Masahiko Hirafuji Kenji Iizuka |
| author_facet | Saki Shiga Takuji Machida Takumi Yanada Maiko Machida Masahiko Hirafuji Kenji Iizuka |
| author_sort | Saki Shiga |
| collection | DOAJ |
| description | The role of nitric oxide (NO) on intestinal mucosal injury induced by single or consecutive administration of methotrexate was investigated in a rodent model. Rats received methotrexate intraperitoneally either as a single administration (50 mg/kg) or as a consecutive administration (12.5 mg/kg/day) for 4 days. NG-nitro-l-arginine methyl ester (L-NAME) was given subcutaneously to inhibit NO synthase (NOS). Ninety-six hours after the first administration of methotrexate, ileal tissues were collected for analysis. Consecutive administration of methotrexate led to decreased body weight and reduced intake of food and water, which were further worsened by L-NAME. Although a slight mucosal injury resulted from single administration of methotrexate, L-NAME had almost no effect. Consecutive administration of methotrexate caused a significant mucosal injury, which was further worsened by L-NAME. Consecutive, but not single, administration of methotrexate induced mRNA expression of inflammatory cytokines in ileal tissue. Consecutive administration of methotrexate significantly induced constitutive NOS expression in ileal tissue. These results suggest that consecutive administration, rather than single administration, of methotrexate aggravates mucosal injury. Potentiation of constitutive NOS expression by consecutive administration might be one of the main reason to antagonize the intestinal mucosal injury as well as lead to a reduction in rat quality of life. Keywords: Methotrexate, Chemotherapy-induced mucositis, Nitric oxide, Inflammation |
| first_indexed | 2024-12-19T04:06:00Z |
| format | Article |
| id | doaj.art-a232ca00840b4ef4a72bf0ed7649e92c |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-19T04:06:00Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-a232ca00840b4ef4a72bf0ed7649e92c2022-12-21T20:36:32ZengElsevierJournal of Pharmacological Sciences1347-86132020-05-0114313038The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to ratsSaki Shiga0Takuji Machida1Takumi Yanada2Maiko Machida3Masahiko Hirafuji4Kenji Iizuka5Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan; Corresponding author. Fax: +81 133 23 1379.Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, JapanDivision of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, Sapporo, Hokkaido, 006-8590, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, JapanDepartment of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, 061-0293, JapanThe role of nitric oxide (NO) on intestinal mucosal injury induced by single or consecutive administration of methotrexate was investigated in a rodent model. Rats received methotrexate intraperitoneally either as a single administration (50 mg/kg) or as a consecutive administration (12.5 mg/kg/day) for 4 days. NG-nitro-l-arginine methyl ester (L-NAME) was given subcutaneously to inhibit NO synthase (NOS). Ninety-six hours after the first administration of methotrexate, ileal tissues were collected for analysis. Consecutive administration of methotrexate led to decreased body weight and reduced intake of food and water, which were further worsened by L-NAME. Although a slight mucosal injury resulted from single administration of methotrexate, L-NAME had almost no effect. Consecutive administration of methotrexate caused a significant mucosal injury, which was further worsened by L-NAME. Consecutive, but not single, administration of methotrexate induced mRNA expression of inflammatory cytokines in ileal tissue. Consecutive administration of methotrexate significantly induced constitutive NOS expression in ileal tissue. These results suggest that consecutive administration, rather than single administration, of methotrexate aggravates mucosal injury. Potentiation of constitutive NOS expression by consecutive administration might be one of the main reason to antagonize the intestinal mucosal injury as well as lead to a reduction in rat quality of life. Keywords: Methotrexate, Chemotherapy-induced mucositis, Nitric oxide, Inflammationhttp://www.sciencedirect.com/science/article/pii/S1347861320300189 |
| spellingShingle | Saki Shiga Takuji Machida Takumi Yanada Maiko Machida Masahiko Hirafuji Kenji Iizuka The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats Journal of Pharmacological Sciences |
| title | The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats |
| title_full | The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats |
| title_fullStr | The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats |
| title_full_unstemmed | The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats |
| title_short | The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats |
| title_sort | role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats |
| url | http://www.sciencedirect.com/science/article/pii/S1347861320300189 |
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