Mucosite e disfunção da barreira intestinal : modelo de estudo experimental em ratos com o uso de metotrexate e em pacientes portadores de câncer submetidos a tratamento quimioterápico

Abstract

Mucositis is a feared complication of cancer treatment. It may harm the treatment as a whole or not doing its in the ideal form. The objectives were: a) to investigate the function of barrier of small intestine with a model of mucositis induced by methotrexate (MTX) m rats, associating alterations with morphologic damage; b) determination of the prevalence of oral mucositis in patients treated with chemotherapic agents; c) determination of alterations in permeability and possible mechanisms of intestinal lesion; d) establishing correlations between mucositis' level and the intensity of permeability alterations. Wistar adults, males, rats, distributed randomly in 4 grups of 6 animals, were treated with 3 differents doses of MTX or saline during 3 consecutive days. In the MTX-group it was detected a notable reduction of mannitol absorption (p < 0,05), suggesting lesion of the absortive area, not observed in the control-group. The groups not were differents about lactulose captation, indicating the integrity of permeation zones ofmembreane. Moreover, the treated rats exhibited important redution of weigh and of food ingestion (p < 0,05), t Student. 28 cancer's patients, submitted to treatment with various antineoplasic agents, were compared with 20 healthy individuals, in a prospective case-control study, taking in consideration sex, age, type of neoplasia, antineoplasics used, diagnosis of clinical mucositis and detection of alterations in the intestinal permeability through urinary fathoming of lactulose and mannitol by the HPLC-PAD. There was no difference in the groups regarding the demographic characters. The clinical mucositis was registered in 19 patients (67.9%), altering the diet in 09 cases (32.1%).The mannitol captation did not differ in the tests realized, being, however, a considerable increase in the urinary recuperation of lactulose, identifying a broad passage of this sugar through the junction nexuses damaged (p < 0.05). The reason lactulose-mannitol was eleven times higher in the patients ( p < 0.01). Comparing patients with mucositis (19), and those without (09), once again it did not verify any difference in the fathoming of mannitol, but a increase of the urinary excretion oflactulose (p < 0.05). Also, the difference of excretion lactulose/mannitol was very meaningful (p < 0.01). Such data confirm an increase in the permeation of lactulose indicating a disfuction in the intestinal barrier by toxic effects of the chemotherapic agents in the junction nexuses, with minimal effects in the absorption zone, considering the small repercussion of the mannitol absorption, contrasting with findings ofMTX-rats. The HPLC-PAD was too confrimed as a structural lesion marker in the the small intestine, establishing clinical correlations with the mucositis level developed, creating a perspective of the method's use in new lines of research, searching for alternatives of prophylaxis and therapeutics of the oral and intestinal mucositis.