RESUMO
PURPOSE: The neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP) mediate physiologic activities in the intestine, not least in relation to motility and inflammatory processes. Neuropeptides are up-regulated and play particular importance during tissue stress. This paper aims to quantify mucosal and smooth muscle SP, VIP and total innervation in human colon in short- and long-term perspectives after abdominal irradiation. MATERIALS AND METHODS: Colon specimens from 23 irradiated or non-irradiated patients were investigated with immunohistochemistry and computerized image analysis. Plasma levels of SP and VIP in 15 additional patients receiving radiotherapy were analyzed. RESULTS: At 4-7 days after irradiation (5 x 5 Gy), the overall innervation, and also VIP and SP nerve fiber densities, were increased in both mucosa and circular muscle layer. In contrast, 5-6 weeks as well as several years after irradiation, the VIP and SP nerve fiber densities were decreased. No peptide changes were revealed in plasma. CONCLUSIONS: The degree of VIP and SP intestinal innervation was increased after radiotherapy in the short-term perspective but it decreased in the long-term. In the short-term, SP may have pro-inflammatory and VIP anti-inflammatory effects and the peptides may have trophic effects and be related to the occurrence of motor changes. It cannot be excluded that the decrease in VIP and SP neuronal supply seen in the long-term may contribute to intestinal malfunction.
Assuntos
Colo/inervação , Neoplasias do Colo/radioterapia , Fibras Nervosas/metabolismo , Fibras Nervosas/efeitos da radiação , Neoplasias Retais/radioterapia , Substância P/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Abdome , Idoso , Carcinoma/radioterapia , Contagem de Células , Colo/patologia , Colo/efeitos da radiação , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Mucosa Intestinal/inervação , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Músculo Liso/inervação , Músculo Liso/patologia , Músculo Liso/efeitos da radiação , Fibras Nervosas/patologia , Neurônios/metabolismo , Neurônios/patologia , Neurônios/efeitos da radiação , Pelve , Doses de Radiação , Radioimunoensaio , Substância P/sangue , Tioléster Hidrolases/biossíntese , Tempo , Ubiquitina Tiolesterase , Peptídeo Intestinal Vasoativo/sangueRESUMO
It has previously been shown that high dose of irradiation to the rat abdomen leads to an increased level of substance P (SP) in the duodenum. In the present study the pattern of distribution of NK1 receptors (NK1-R) in rat duodenum after irradiation (5-30 Gy), was examined at the same time-point (7 days) after irradiation, comparisons being made with the distribution of SP-innervation. Immunohistochemical methods were used. In controls, NK1-R-like immunoreactivity (-LI) was detected in epithelial cells, in cells in the region of the intestinal cells of Cajal within the deep muscular plexus (ICC-DMP), in neuronal cells in the myenteric plexus, and variably in granulocytes in the mucosa. Irradiation with 5-10 Gy did not lead to obvious changes in the pattern of NK1-R-LI. After irradiation with the highest doses (25-30 Gy), the mucosa was often gravely damaged, displaying granulation tissue. No epithelial NK1-R-LI was detected in this tissue, but was present in less affected mucosa after these doses. In the region of the ICC-DMP, in the myenteric plexus, and in granulocytes, NK1-R-LI was detected also after high dose irradiation. However, the degree of NK1-R-LI in the region of the ICC-DMP was somewhat lower than seen in controls and after low doses. SP-immunoreactive nerve fibers were present in the regions where NK1-R-LI was detected. These findings support a suggestion that an increased level of SP after irradiation may contribute to the dose-dependent gastrointestinal adverse effects that occur after radiotherapy.
Assuntos
Duodeno/metabolismo , Duodeno/efeitos da radiação , Receptores da Neurocinina-1/metabolismo , Substância P/metabolismo , Animais , Relação Dose-Resposta à Radiação , Duodeno/patologia , Feminino , Raios gama , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos da radiação , Mastócitos/patologia , Mastócitos/efeitos da radiação , Microscopia de Fluorescência , Músculo Liso/metabolismo , Músculo Liso/patologia , Músculo Liso/efeitos da radiação , Plexo Mientérico/metabolismo , Plexo Mientérico/patologia , Plexo Mientérico/efeitos da radiação , Ratos , Ratos Sprague-Dawley , Receptores da Neurocinina-1/imunologia , Plexo Submucoso/metabolismo , Plexo Submucoso/patologia , Plexo Submucoso/efeitos da radiação , Substância P/imunologiaRESUMO
Irradiation was administered to the upper abdomen of rats, whereupon the duodenum was examined. Numerous vasoactive intestinal peptide (VIP)- and substance P (SP)-like immunoreactive nerve fibers were seen in the damaged mucosa, often in close association to each other. The intensity of the SP- and VIP-like immunoreaction was increased in several of the tissue compartments and, as measured with radioimmunoassay, the contents of SP- and VIP-like materials were increased after 30 Gray. The results show that SP and VIP levels increase after irradiation and suggest that SP and VIP are involved in interactive reactions in the reorganization and inflammatory processes in the gut after abdominal irradiation.
Assuntos
Duodeno/efeitos da radiação , Substância P/metabolismo , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Duodeno/patologia , Feminino , Imunofluorescência , Histocitoquímica , Inflamação/patologia , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos da radiação , Músculo Liso Vascular/patologia , Músculo Liso Vascular/efeitos da radiação , Radioimunoensaio , Ratos , Ratos Sprague-DawleyRESUMO
The immunohistochemical expression of various neuropeptides, including substance P (SP), and the substance P receptor (SPR), was examined in irradiation-induced enteropathy in man. Samples from irradiated and non-irradiated patients operated on for rectal carcinoma were examined. The samples were from the sigmoid and corresponded macroscopically to non-cancerous sigmoid colon. There was a marked atrophy, ulcerations and inflammatory reactions in the irradiation-influenced mucosa. In this mucosa, there was a very pronounced innervation of varicose nerve fibers showing SP-like immunoreactivity (LI). The degree of SP-LI in the ganglionic cells of the submucous plexus was increased as compared to non-irradiated patients. There were only few or no nerve fibers showing immunoreaction for other neuropeptides examined (CGRP, enkephalin, NPY) in the irradiation-influenced mucosa. A marked SPR immunoreaction was detected in cells in the lamina propria which were interpreted as representing polymorphonuclear leukocytes. The marked expression of SP in the irradiation-damaged mucosa and the presence of SPR immunoreactive leukocytes suggest that SP is highly involved in the inflammatory reactions that occur in response to radiotherapy. The observations also suggest that SP, but not NPY, CGRP and enkephalin, has an important role in the reorganisation processes that take place in the mucosa in irradiation-induced enteropathy.
Assuntos
Colo/metabolismo , Neoplasias Retais/metabolismo , Substância P/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Colo/patologia , Colo/efeitos da radiação , Encefalinas/metabolismo , Feminino , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos da radiação , Masculino , Neuropeptídeo Y/metabolismo , Neoplasias Retais/patologia , Neoplasias Retais/radioterapiaRESUMO
Vasoactive intestinal peptide (VIP) is known to modulate inflammatory reactions, to have trophic effects, and to contribute to diarrhea and has been implicated as an important factor in several inflammatory conditions in the human gut. The aim of the present study was to investigate the effects of irradiation on the expression of VIP in the colon of patients operated on for adenocarcinoma. Some of the patients had received preoperative irradiation (25 Gy) within one week before the operation. Specimens of sigmoideum, 10 cm cranial to the margin of the cancer, were examined, by using antiserum against VIP and immunohistochemistry. There were numerous nerve fibers showing VIP-like immunoreactivity in the damaged mucosa, including the regions showing ulcerations. There was a higher degree of expression of VIP in the ganglion cells in the submucous plexuses in irradiated than nonirradiated patients. The study shows that there is a marked immunohistochemical expression of VIP concomitant with the occurrence of inflammatory and repair processes in the irradiation-damaged human colonic mucosa.
Assuntos
Colo/metabolismo , Colo/efeitos da radiação , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos da radiação , Peptídeo Intestinal Vasoativo/biossíntese , Adenocarcinoma/radioterapia , Colo/patologia , Neoplasias do Colo/radioterapia , Feminino , Humanos , Imuno-Histoquímica , Mucosa Intestinal/patologia , MasculinoRESUMO
Rats were given radiotherapy (total dose 30 Gy) over the abdomen. Seven days later specimens of the duodenum were prepared for in vitro receptor autoradiography using the radioligand [125I]VIP. The autoradiograms were quantitatively analyzed using a computer system. Histological examination revealed that a very marked reorganization of the mucosa had occurred in response to irradiation. Using receptor autoradiography, we found [125I]VIP-specific binding sites in the reorganizing mucosa, except where denudation had occurred. Such binding sites also occurred in the smooth muscle layer of the duodenal wall. The observations suggest that VIP has profound effects in radiation-induced enteropathy.
Assuntos
Duodeno/efeitos da radiação , Mucosa Intestinal/efeitos da radiação , Receptores de Peptídeo Intestinal Vasoativo/efeitos da radiação , Peptídeo Intestinal Vasoativo/metabolismo , Animais , Autorradiografia , Sítios de Ligação , Duodeno/metabolismo , Feminino , Mucosa Intestinal/metabolismo , Radioisótopos do Iodo , Músculo Liso/metabolismo , Músculo Liso/efeitos da radiação , Aceleradores de Partículas , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Valores de ReferênciaRESUMO
In the present study, the immunohistochemical expression of vasoactive intestinal polypeptide (VIP) in the parotid gland of rats exposed to fractionated irradiation was examined. VIP concentration was analyzed by radioimmunoassay (RIA). Irradiation lead to a marked increase in the immunohistochemical expression of VIP in the innervation of the gland parenchyme. VIP-like immunoreactivity (LI) frequently coexisted with SP (substance P)-LI in these nerve fibers. The pattern of VIP-innervation in association with large ducts and blood vessel walls was unchanged. RIA analysis revealed a more than three-fold elevation in VIP content in the gland in response to irradiation. The increase in VIP immunoreaction and VIP content was seen at examination ten days after cessation of a five-day treatment with a total dose of 30-40 Gray. The upregulation of VIP may be related to changes in the production of neurotrophic factors and to an increased demand for a potentiation of secretagogue effects of SP.