Oxidative stress contributes to methotrexate-induced small intestinal toxicity in rats

Abstract

These results suggest that oxidative stress plays an important role in the MTX-induced small intestinal damage, especially neutrophil infiltration. Thus, the modulation of oxidative stress would be useful in reducing intestinal damage in MTX treatment.

Grape seed extract protects IEC-6 cells from chemotherapy-induced cytotoxicity and improves parameters of small intestinal mucositis in rats with experimentally-induced mucositis.

“…Miyazano et al 14 have reported that oxidative stress may contribute to the MTX-induced small intestinal damage observed in rats, specifically as a result of ROS induced neutrophil infiltration and pro-inflammatory cytokine production. 12 normal colon weights were maintained in 5-FU damaged groups treated with GSE compared to 5-FU controls.…”

“…5-FU is an anti-metabolite chemotherapy drug which blocks DNA synthesis via inhibition of thymidylate synthase 14 and is widely used for anticancer therapy. This drug often induces an inflammatory disorder known as mucositis, which is accompanied by side-effects such as nausea, bloating, vomiting, diarrhoea and gastroenteritis.…”

“…13 These activities result in overproduction of reactive oxygen species (ROS) and pro-inflammatory cytokine expression. 12,14 This can result in unbearable symptoms which include diarrhea, nausea and vomiting. 13 Currently, there is a deficiency of effective prophylactic or curative treatments for intestinal mucositis.…”

Cytotoxic and antioxidant effects of grape seed oil on the treatment of leukemia with methotrexate

“…Furthermore, low dose MTX administration has been applied to cure some autoimmune diseases such as psoriasis and rheumatoid arthritis [2]. MTX, an antimetabolite and a folic acid antagonist, can cause unpredictable serious side effects [3]. Mechanism of the side effects is not clear, yet.…”

“…Mechanism of the side effects is not clear, yet. However, it's assumed that the main reason is related to the oxidative stress occurring during the biotransformation in liver [2][3][4].…”