Methotrexate Produces Gastrointestinal Stress via Oxidative Stress-caused Acute Physiological Disruptions in Water and Electrolytes Transport in the Mucosal Intestine

Abstract

Methotrexate (MTX), a chemotherapeutic agent, is used to treat various types of cancers. MTX was known for its toxic effects, particularly in the gastrointestinal (GI) tract. Consequently, the objective of this present research was to investigate the GI disorders during oxidative stress in rats subjected to oral dose of MTX (100 mg kg−1). Thirty male Wistar rats were equally divided at random into three groups (10 animals in each group): the unexposed group and two groups treated with a single dose of MTX. Acute diarrhea was assessed in rats using the defecation and enteropooling methods. Electrolyte levels in intraluminal fluid were analyzed by flame photometry. Oxidative stress indicators and intracellular mediators were determined in mucosal intestine by colorimetric methods. The MTX treatment of rats caused critical changes in the gastrointestinal functions. Mainly, intensification of the liquid stools and intestinal fluid accumulation as well as perturbation in the electrolyte transport was observed. In addition, MTX has a prooxidant effect, which was indicated by an augmentation of malondialdehyde (MDA) and H2O2 generation and a decrease of the enzymatic antioxidants such as SOD, CAT, and GPx. These effects were accompanied with hispathological injury and alteration of lipid metabolism and intracellular mediators such as free iron and calcium. In summary, we found a close association between the gastrointestinal disruptions and the oxidative stress intensity induced by MTX in rats.