Role of Nitric Oxide in the Change of 5-Hydroxytryptamine Synthesis in the Intestine by a Consecutive Administration of Methotrexate to Rats

Abstract

This study aimed to investigate whether the consecutive administration of methotrexate affects 5-hydroxytryptamine (5-HT) synthesis in the rat small intestine. Rats received methotrexate at a dose of 12.5 mg/kg intraperitoneally on 4 consecutive days. N G-nitro-L-arginine methyl ester (L-NAME) was given subcutaneously to inhibit nitric oxide (NO) synthase. Methotrexate moderately altered 5-HT synthesis, whereas the combined administration of methotrexate and L-NAME significantly changed 5-HT synthesis in the rat ileal tissue. These results suggest that endogenous NO has an antagonistic role in the induction of 5-HT synthesis in rats following the consecutive administration of methotrexate.

Ferric Citrate Hydrate Has Little Impact on Hyperplasia of Enterochromaffin Cells in the Rat Small Intestine Compared to Sodium Ferrous Citrate

“…Substance P also plays an important role in the elicitation of delayed emesis stimulated by anticancer drugs; it is also contained in enterochromaffin cells [15- 17]. We previously reported that administration of anticancer drugs such as cisplatin, methotrexate, and cyclophosphamide to rats causes hyperplasia of enterochromaffin cells [17][18][19][20][21][22]. Therefore, as with the administration of anticancer drugs, oral iron preparations, especially oral ferrous preparations, may lead to hyperplasia of enterochromaffin cells as one of the mechanisms that causes nausea and vomiting.…”