Vinblastine, an anticancer drug, causes constipation and oxidative stress as well as others disruptions in intestinal tract in rat

摘要

Abbreviations: CAT, catalase; GPx, glutathione peroxidase; H2O2, hydrogen peroxide; MDA, malondialdehyde; NaCl, sodium chloride; ROS, reactive oxygen species; –SH, sulfhydryl groups; SOD, superoxide dismutaseKeywords: Vinblastine, Gastrointestinal disorders, Constipation, Oxidative stress, Intracellular mediators, Rat

Abstract

The purpose of this study is to examine the gastrointestinal disorders after injection of vinblastine (2 mg kg⁻¹ b.w. i.v.) in rats. Animals were divided into two equal groups: Group 1 was considered as a control group (NaCl, 0.9%). Group 2 was treated with intravenous injection of vinblastine for 7 days. Loperamide (2 mg kg⁻¹) was injected in a saline solution subcutaneously to induce constipation in another group of rats during the same period. Fecal parameters of the different groups have been determined. At the end of the experiment, animals were anaesthetized and sacrificed by decapitation. The intestinal mucosa specimens were examined for lipid peroxidation, sulfhydryl groups (−SH) and protein carbonylation as well as antioxidant enzyme activities and intracellular mediators. Gastrointestinal motility was realized by the test meal (10% charcoal in 5% gum arabic). In result, statistically significant decreases in the fecal number and water content collected during 24 h were detected in the vinblastine group, but less important than loperamide control group. The animals treated with vinblastine, showed also a significant decrease (13%) of GIT, lower than that of loperamide (34%). The intestinal tissues from vinblastine-treated rats were showed a significant increase in lipoperoxydation and H2O2 production as well as a significant depletion of enzymatic and non-enzymatic antioxidants. Added to that, a disruption of intracellular iron and calcium levels was observed. Therefore, the present study provide the first strong evidence that vinblastine induced numerous disruptions in gastrointestinal which are related to oxidative stress and intracellular mediators disorders.