Irinotecan chemotherapy-induced intestinal oxidative stress: Underlying causes of disturbed mucosal water and electrolyte transport.

Irinotecan, a chemotherapy drug, can cause acute diarrhea immediately after administration. Hence, the present study was designed to investigate the gastrointestinal (GI) disturbances after an intraperitoneal (IP) administration of irinotecan in rats.Twenty Wistar rats were separated into two groups of ten. Group A was considered as a control group (NaCl, 0.9%). Group B was treated with irinotecan at a single dose of 200mgkg-1. The rats were observed for defecation. For the enteropooling test, the animals were sacrificed by decapitation 1h post-treatment. The small intestine was excised and the fluid was milked into a graduated tube and the volume was measured. After centrifugation of intraluminal liquid, the electrolyte concentrations in the supernatants were measured by flame photometry. Oxidative stress parameters and intracellular mediators as well as the MPO activity were determined in intestinal mucosa by colorimetric methods Our result indicated that irinotecan produces an intestinal fluid accumulation and electrolyte transport disorders. These effects were associated with augmented intestinal MPO activity and oxidative damage such as an elevation of MDA production and a depletion of enzymatic and non-enzymatic antioxidants. More than that, drug administration provoked intracellular mediator disturbances such as a free iron, H2O2 and calcium levels. In conclusion, the data suggest that irinotecan caused a gastrointestinal stress via oxidative stress-induced disturbances in water and electrolyte transport in the intestinal mucosa in rats.