Histological and immunohistochemical study on the effect of 5-fluorouracil on the jejunal mucosa of adult albino rat and evaluation of the protective role of L-glutamine

ABSTRACT

5-Fluorouracil [5-FU] is the most frequently used chemotherapeutic agent in colorectal cancer. L-glutamine is the principal circulating amino acid, accounting for around SO% of the total exchangeable amino acid pool. The gut is a major site of glutamine utilization and the small bowel epithelium is considered the principal organ of glutamine uptake. Alimentary tract mucositis is a serious problem complicating cancer treatment and its pathobiology remains incompletely understood. This work was performed to study the effect of 5-EU on the jejunal mucosa of adult male albino rats and to evaluate the possible protective role of L-glutaminc. This study was carried out on 35 adult male albino rats which were divided into; group I [control group], group II [animals received an intrapcritonial injection of 5-FU at 150 mg/kg as a single injection and killed 4 days later] and group Ill [animals received 5-PU as group II and L-glutamine 1 g/kg orally once daily for 5 days, starting I day before 5-PU]. The specimens were prepared for histological and immunohistochemical examination. Morphometric study was also done and statistical results were analyzed. Sections of 5-PU-treated rats [Group II] showed shortening, kinking, broading of the jejunal villi, flattened mucosa. erosion of the lining epithelium. decrease in the number of goblet cells and disrupted crypt area. Immunohistochemical staining of proliferating cell nuclear antigen [PCNA] showed a significant decrease in the number of PCNA - positive nuclei in the crypts. On the other hand. animals which received 5-PU and L-glutaminc [Group Ill] showed improvements in the mucosal architecture and also a significant increase in the number of PCNA positive nuclei in the crypts. Supplementation of L-glutaminc is effective in reducing the morphological derangement of jejunal mucosa caused by 5-FU. It is advisable that patients receiving 5-PU could use L-glutamine to minimize its side effects