RESUMO
Background and purpose: The discovery of chemical substances with carcinogenic properties has allowed the development of several experimental models of colorectal cancer (CRC). Classically, experimental models of CRC in mice have been evaluated through clinical or serial euthanasia. The present study aims to investigate the role of low endoscopy in the analysis of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods: Thirty C57BL6 mice were divided into two groups: a control group with fifteen animals that underwent rectal instillation of saline solution on day 0 and a carcinogen group with fifteen animals that underwent a 100 mg/kg MNNG rectal instillation on day 0. In both groups, low endoscopies were performed on weeks 4 and 8. We used a validated endoscopic scoring system to evaluate the severity of colitis and colorectal tumor. Euthanasia was carried out at week 12. Results: We observed higher inflammation scores (p <0.001) and a higher number of tumors (p <0.05) in the MNNG group than the control group, both at weeks 4 and 8. A worsening of inflammation scores from the first to the second endoscopy was also noticeable in the MNNG group. There were no bowel perforations related to the procedure, and there was one death in the control group. Conclusion: Low endoscopy in experimental animals allows safe macroscopic evaluation of colorectal carcinogenesis without the need for euthanasia.
Assuntos
Metilnitronitrosoguanidina/toxicidade , Neoplasias Experimentais/induzido quimicamente , Neoplasias Retais/induzido quimicamente , Administração Retal , Animais , Carcinogênese/induzido quimicamente , Carcinogênese/patologia , Colonoscopia/métodos , Feminino , Humanos , Metilnitronitrosoguanidina/administração & dosagem , Camundongos , Neoplasias Experimentais/diagnóstico , Neoplasias Experimentais/patologia , Neoplasias Retais/diagnóstico , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Reto/efeitos dos fármacos , Reto/patologiaRESUMO
Tumor hypoxia may compromise the results of chemotherapy for treating colorectal cancer because it stimulates angiogenesis and the release of tumor growth factors. Hyperbaric oxygen (HBO) supplementation may potentiate the effects of chemotherapy in such cases. This study aimed to assess the effect of HBO therapy combined with chemotherapy on the treatment of colorectal cancer in mice. C57BL6 mice were submitted to the intrarectal instillation of N-methyl-N-nitrosoguanidine (MNNG) and treated with 5-fluorouracil (5FU) and/or HBO therapy. The MNNG group presented the highest dysplastic crypt rate. The 5FU + HBO group presented the highest rate of apoptotic cells per dysplastic crypt. The 5FU group presented the highest expression of hypoxia-inducible factor-1 alpha and CD44. HBO therapy increased the effect of 5FU on the treatment of the experimental colorectal neoplasia in mice.
Assuntos
Neoplasias Colorretais , Fluoruracila , Oxigenoterapia Hiperbárica , Camundongos Endogâmicos C57BL , Animais , Fluoruracila/farmacologia , Camundongos , Neoplasias Colorretais/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Masculino , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Receptores de Hialuronatos/metabolismo , Terapia Combinada , Metilnitronitrosoguanidina/farmacologiaRESUMO
Experimental denervation of organs plays a key role in understanding the functional aspects of the normal innervation as well as the diseases related to them. In 1978 the experimental model of myenteric denervation of the rat gut by serosal application of benzalkonium chloride (BAC) was proposed. BAC is a positively charged surface-active alkylamine and is a powerful cationic detergent, which destroys bacteria after ionic attraction and for this reason is largely used as a surgical antiseptic. Since its initial report, the BAC-induced myenteric denervation model has been used to study many functional and pathological aspects of the enteric nervous system. So far this is the only pure method of myenteric denervation available for research in this area. Promising reports in the literature have shed light on the possibilities for the development of new uses of the BAC-denervation experimental model as a therapeutic tool in some pathological situations. This review aims to shed light on the main historical and recent findings provided by this experimental model.
Assuntos
Compostos de Benzalcônio/administração & dosagem , Denervação/métodos , Sistema Nervoso Entérico/efeitos dos fármacos , Animais , Compostos de Benzalcônio/farmacologia , Humanos , Modelos Animais , RatosRESUMO
PURPOSE: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine. METHODS: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C - control). RESULTS: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. CONCLUSION: This may provide a new promising approach to the surgical treatment of SBS.
Assuntos
Toxinas Botulínicas/farmacologia , Denervação/métodos , Íleo/inervação , Síndrome do Intestino Curto/cirurgia , Animais , Compostos de Benzalcônio/farmacologia , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Íleo/patologia , Jejuno/inervação , Debilidade Muscular/patologia , Ratos , Ratos Wistar , Síndrome do Intestino Curto/patologiaRESUMO
Abstract Purpose: The denervation of the intestine with benzalkonium chloride (BAC) reduces mortality and improves weight gain in rats with short bowel syndrome (SBS). Nevertheless, translating these promising findings from bench to bedside is not feasible because BAC promotes peritonitis and irreversible denervation which may be followed by an uncontrolled dilatation of the viscera. The use of botulinum toxin (BT) instead of BAC to achieve the denervation of the remaining small intestine in SBS could be an interesting option because it leads to a mild and transient denervation of the intestine. Methods: Here we evaluated the effects of the ileal denervation with BT in rats with SBS by verifying the body weight variation and intestinal morphological parameters. Four groups with 6 animals each were submitted to enterectomy with an ileal injection of saline (group E) or BT (group EBT). Control groups were submitted to simulated surgery with an ileal injection of BT (group BT) or saline (group C - control). Results: We observed that the treatment of the remaining ileum with BT completely reversed the weight loss associated to extensive small bowel resection. Conclusion: This may provide a new promising approach to the surgical treatment of SBS.