Histological and Ultra Structural Study of 5-fluorouracil-indueed Small Intestinal Mucosal Damage in Rats

摘要

The fluoropyrimidine 5-fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents. It is particularly mucotoxic and causes many gastrointestinal manifestations. The aim of this study was to assess the light and electron microscopic aspects of 5-fluorouracil induced cytotoxicity on the small intestinal mucosa. Sixteen adult male albino rats divided into two groups; control and FU groups were used in this study. Control group rats received a single intraperitoneal saline injection, equivalent to the 5-fluorouracil dose. FU group rats were given a single intraperitoneal dose of 5-fluorouracil (5-FU) (150 mg kg~(-1)) and were subdivided into 2 subgroups (FU3 and FU9). Four rats from each subgroup were sacrificed 3 and 9 days after 5-FUinjection. Specimens from the jejunum were obtained and processed for transmission electron microscopic study. Paraffin sections were prepared and stained with Haematoxylin and Eosin and Periodic acid-Schiffs stains. In FU3 group, 5-fluorouracil administration resulted in detachment and loss of surface epithelium, shortening and marked exfoliation and denudation of the villi. The cell architecture of both villi and crypts was disturbed, with marked widening of the intercellular spaces. Ultrastructuraldegenerative changes in the form of loss of microvilli, cytoplasmic vacuolations, many lysosomes, dilated and vesiculated rER, swollen mitochondria with disintegrated cristae and degranulated goblet cells were also demonstrated. Recovery of these changesand restore of the normal structure were observed in FU9 group with only some residual ultrastructural changes. It could be concluded that 5-FU induces marked histological and ultrastructural degenerative changes in the small intestinal mucosa.