The role of nitric oxide in small intestine differs between a single and a consecutive administration of methotrexate to rats.

Abstract:

: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.

journal_name

J Pharmacol Sci

authors

Shiga S,Machida T,Yanada T,Machida M,Hirafuji M,Iizuka K

doi

10.1016/j.jphs.2020.02.006

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

30-38

issue

1

eissn

1347-8613

issn

1347-8648

pii

S1347-8613(20)30018-9

journal_volume

143

pub_type

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