EFFECTS OF PHENTOLAMINE ON THE DAMAGE CAUSED BY ANTINEOPLASTIC DRUG 5-FLUOROURACIL IN THE EPITHELIUM OF THE SMALL INTESTINE OF RAT

Toxicity of antineoplastic agents to the gastrointestinal epithelium is one of the major factors that limit dose and duration of administration of these drugs in cancer chemotherapy. This toxicity is probably due to the rapid rate of epithelial cell proliferation in the gastrointestinal tract. We proposed that selective reduction of the rate of cell proliferation in this tissue, at the time of chemotherapy, may protect it from chemotherapy-induced damage. Several agents are known to reduce the rate of cell proliferation in the epithelium of small intestine. In this study, one of these agents - phentolamine - was investigated. Phentolamine is an adrenoceptor blocking agent.
Twenty four female Wistar rats weighing between 150 to 200 grams were randomly divided into four groups, six each. Rats in two of these groups received an intraperitoneal injection of phentolamine (20 mg/kg) at 10:30, a single intraperitoneal injection of 5-f1uorouracil (350 mg/kg, and 500 mg/kg respectively) at 12:00, and another injection of phentolamine (20 mg/kg) at 13:00. Rats in the remaining two groups received injections of distilled water at 10:30 and 13:00 and a single injection of 5-f1uorouracil (350 mg/kg, and 500 mg/kg respectively) at 12:00. Half of the rats in each group were sacrificed in midday in the third day after injection and the other half in the fifth day. Samples were obtained from small intestine, 7 to 13 centimeters distal to pyloric sphincter and eight hematoxylin-eosin stained microscopic sections were prepard from each rat. Only those villi which were sectioned in their entire longitudinal axes were studied. Individual villus columns were selected randomly and their cells counted under light microscope. Results show that phentolamine significantly prevents villus shortening in the epithelium of small intestine.