RESUMO
Mucosite é uma inflamação da mucosa oral e/ou gastrintestinal ocasionada pelo tratamento antineoplásico caracterizada por eritema, úlceras dolorosas e formação de pseudomembrana. As condutas atuais para prevenção e tratamento são paliativas. A unha-de-gato (Uncaria tomentosa) é uma planta cujo extrato tem ação imunomoduladora, antiinflamatória, antioxidante, antiviral e antimutagênica. Este trabalho visou comparar clinicamente o efeito preventivo de três doses sistêmicas de UT nas mucosites bucais induzidas por 5-FU em hamsters Sírios dourados. Foram estudados 10 animais por grupo: GC (controle), G2 (2 mg de alcalóide/kg de animal), G5 (5mg/kg) e G10 (10 mg/kg), que foram sedados e receberam a solução de UT dos dias 1 ao 5 por gavagem. Para a indução da mucosite, nos dias 4 e 6 os animais foram anestesiados e receberam 5- FU via intraperitoneal nas doses de 100mg/kg e 60mg/ kg respectivamente e no dia 6 ranhura com fio ortodôntico em ambas mucosas. Nos dias 1, 8, 10, 12, 15 os animais foram pesados, anestesiados e tiveram suas mucosas evertidas para fotografia. Dois avaliadores calibrados, sem conhecimento dos grupos, avaliaram as fotografias e deram escores para as mucosites. Todos os animais apresentaram algum grau de mucosite, a perda de peso foi significativa no grupo G10 e nas condições deste estudo, a Uncaria tomentosa não preveniu ou tratou a mucosite.
Mucositis is an inflammation of oral and/or gastrointestinal mucosa caused by antineoplasic treatment, characterized by eritema, painful ulcers and pseudo membrane formation. There is no widely accepted protocol to prevent and/or to treat mucositis. Cat's claw (Uncaria Tomentosa - UT) is a plant with immunomoduladory, antinflammatory, antioxidant and antimutagenic properties. The objective of this study was to clinically compare the effects of three systemic doses of UT in Golden Sirius hamsters that had mucositis induced by 5-fluorouracil. The experimental groups were divided according to alkaloid dose present at the aqueous extracts of UT: GC (control group), G2 (2mg of alkaloid/kg of animal), G5 (5mg/kg) and G10 (10mg/kg), being ten animals per group, in a total of forty animals. To perform the experiment, the animals received UT extracts at days 1 to 5 through gavage, and to induce the mucositis, an intraperitoneal injection of 5-FU at days 4 and 6, besides, at day 6 a mechanical trauma with orthodontic wire on both mucosas was performed.At days 1, 8, 10, 12 and 15 the animals were weighted, anesthetized and their mucosas were everted to be photographed. Two calibrated observers, with no previous knowledge of the groups evaluated the images and scored the mucositis. All animals developed mucositis, the weight loss was significant in G10, and under the conditions of this study Uncaria tomentosa did not prevent neither treated mucositis.
RESUMO
Interferon-gamma (IFN-gamma) mediates diverse functions in bone marrow-derived phagocytes, including phagocytosis and microbe destruction. This cytokine has also been detected at implantation sites under both physiological and pathological conditions in many different species. At these particular sites, the outermost embryonic cell layer in close contact with the maternal tissues, the trophoblast exhibits intense phagocytic activity. To determine whether IFN-gamma affects phagocytosis of mouse-trophoblast cells, ectoplacental cone-derived trophoblast was cultured and evaluated for erythrophagocytosis. Phagocytic activity was monitored ultrastructurally and expressed as percentage of phagocytic trophoblast in total trophoblast cells. Conditioned medium from concanavalin-A-stimulated spleen cells significantly enhanced trophoblast phagocytosis. This effect was blocked by pre-incubation with an anti-IFN-gamma neutralizing antibody. Introduction of mouse recombinant IFN-gamma (mrIFN-gamma) to cultures did not increase cell death, but augmented the percentage of phagocytic cells in a dose-dependent manner. Ectoplacental cones from mice deficient for IFN-gamma receptor alpha-chain showed a significant decrease of the phagocytosis, even under mrIFN-gamma stimulation, suggesting that IFN-gamma-induced phagocytosis are receptor-mediated. Reverse transcriptase-PCR analyses confirmed the presence of mRNA for IFN-gamma receptor alpha and beta-chains in trophoblast cells and detected a significant increase in the mRNA levels of IFN-gamma receptor beta-chain, mainly, when cultured cells were exposed to IFN-gamma. Immunohistochemistry and Western blot analyses also revealed protein expression of the IFN-gamma receptor alpha-chain. These results suggest that IFN-gamma may participate in the phagocytic activation of the mouse trophoblast, albeit the exact mechanism was not hereby elucidated. Protective and/or nutritional fetal benefit may result from this physiological response. In addition, our data also shed some light on the understanding of trophoblast tolerance to inflammatory/immune cytokines during normal gestation.
