ABSTRACT
OBJECTIVE: Our aim was to investigate the effects of growth hormone (GH), hyperbaric oxygen and combined therapy on normal and ischemic colonic anastomoses in rats. METHODS: Eighty male Wistar rats were divided into eight groups (n = 10). In the first four groups, non-ischemic colonic anastomosis was performed, whereas in the remaining four groups, ischemic colonic anastomosis was performed. In groups 5, 6, 7, and 8, colonic ischemia was established by ligating 2 cm of the mesocolon on either side of the anastomosis. The control groups (1 and 5) received no treatment. Hyperbaric oxygen therapy was initiated immediately after surgery and continued for 4 days in groups 3 and 4. Groups 2 and 6 received recombinant human growth hormone, whereas groups 4 and 8 received GH and hyperbaric oxygen treatment. Relaparotomy was performed on postoperative day 4, and a perianastomotic colon segment 2 cm in length was excised for the detection of biochemical and mechanical parameters of anastomotic healing and histopathological evaluation. RESULTS: Combined treatment with hyperbaric oxygen and GH increased the mean bursting pressure values in all of the groups, and a statistically significant increase was noted in the ischemic groups compared to the controls (p<0.05). This improvement was more evident in the ischemic and normal groups treated with combined therapy. In addition, a histopathological evaluation of anastomotic neovascularization and collagen deposition showed significant differences among the groups. CONCLUSIONS: Combined treatment with recombinant human growth hormone and hyperbaric oxygen resulted in a favorable therapeutic effect on the healing of ischemic colonic anastomoses. .
Subject(s)
Animals , Male , Rats , Colon/surgery , Human Growth Hormone/therapeutic use , Hyperbaric Oxygenation/methods , Ischemia/therapy , Wound Healing/drug effects , Anastomosis, Surgical , Combined Modality Therapy , Collagen/analysis , Colon/blood supply , Colon/pathology , Disease Models, Animal , Necrosis , Neovascularization, Physiologic , Pressure , Rats, Wistar , Reproducibility of Results , Treatment OutcomeABSTRACT
PURPOSE: Temozolomide (TMZ) has anti-tumor activity in patients with malignant glioma. Hyperbaric oxygen (HBO) may enhance the efficacy of certain therapies that are limited because of the hypoxic tumor microenvironment. We examined the combined effects of TMZ-HBO in a rat glioma model. METHODS: After stereotactic injection of C6/LacZ rat glioma cells into the Wistar rats brain, the rats were randomly assigned to three treatment groups [group 1, control treatment; group 2, TMZ alone; group 3, a combination of TMZ and HBO]. Rats were sacrificed 18 days after treatment, and number of intra-/peri-tumoral vessels, microendothelial proliferations, immunohistochemistry and necrotic area were evaluated. RESULTS: Tumoral tissue was stained only sparsely with GFAP. Temozolomide treatment was significantly decreased in tumor tissue intratumoral vessel number / total tumor area level. The level of Ki67 was significantly decreased in the tumor tissue of the group 3. Additionally, the total necrotic area / total tumor volume (%) was decreased significantly in tumor tissue of the group 3 rats compared to group1 and 2. CONCLUSION: The combination of hyperbaric oxygen with temozolomide produced an important reduction in glioma growth and effective approach to the treatment of glioblastoma.
OBJETIVO: A temozolomida (TMZ) tem atividade anti-tumoral em pacientes com glioma maligno. Oxigênio hiperbárico (HBO) pode aumentar a eficácia de terapias que são limitadas devido a um microambiente do tumor hipóxico. Foram examinados os efeitos combinados de TMZ-HBO em um modelo de glioma em rato. MÉTODOS: Após a injeção estereotáxica de células de glioma de rato C6/LacZ no cérebro de ratos Wistar, os ratos foram distribuídos aleatoriamente em três grupos de tratamento: Grupo 1: tratamento de controle. Grupo 2: TMZ sozinho. Grupo 3: uma combinação de TMZ e HBO. Os ratos foram sacrificados 18 dias após o tratamento. Foram avaliados o número de vasos intra-/peri-tumoral, proliferação microendotelial, imunohistoquímica e área necrótica . RESULTADOS: O tecido tumoral foi marcado apenas esparsamente com GFAP. O tratamento com temozolomida diminuiu significativamente o tecido intratumoral e a área total do tumor. O nível de Ki67 foi significativamente diminuído no tecido do tumor do grupo 3. Além disso, a superfície necrótica total / volume total do tumor (%) diminuiu significativamente no tecido do tumor do grupo 3 em comparação com grupo 1 e 2. CONCLUSÃO: A combinação de oxigênio hiperbárico com temozolomida produziu uma redução importante no crescimento do glioma podendo ser abordagem eficaz para o tratamento do glioblastoma.