Effects of lycopene, synbiotic and their association on early biomarkers of rat colon carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Amitriptyline aggravates the fibrosis process in a rat model of infravesical obstruction

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The role of the TP53 gene during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Wound healing and colon carcinogenesis. Enhancing effects of skin wounding on development of colon tumors induced by 1,2 Dimethylhydrazine in the rat

Este estudo foi desenvolvido com a finalidade de investigar a possível influência do processo de cicatrização sobre o desenvolvimento neoplásico à distância, em um modelo experimental de carcinogênese do colon induzido pela 1,2 dimetil-hidrazina ( DMH). Ratos Wistar machos receberam injeções semanais de DMH ( 20mg/Kg, via subcutânea) ou solução salina, durante oito semanas. Na nona semana, um grupo tratado com DMH e um controle, foram submetidos à intervenção cirúrgica para retirada de um retalho cutâneo de 4cm no flanco direito, que cicatrizou por segunda intenção. Na 12ª semana, logo após o fechamento da ferida cutânea, os animais foram submetidos à eutanásia. O colon foi dividido em segmentos proximal e distal e examinado a nível macroscópico e histológico. Foram analisadas a incidência, distribuição e morfologia das lesões. O número total de tumores na mucosa do colon e o número de tumores por animal foi significantimente maior no grupo submetido à ferida cutânea do que no grupo tratado somente com DMH. O número de carcinomas pouco diferenciados foi significantimente maior no grupo com ferida cutânea do que em seu respectivo controle. Estes resultados sugerem que o processo de reparação de uma ferida cutânea favorece o desenvolvimento neoplásico em um órgão à distância, tal como o colon e que este efeito parece estar relacionado ao tipo histológico da neoplasia.

Placental glutathione S-transferase correlates with cellular proliferation during rat tonguie carcinogenesis induced by 4-nitroquinoline 1-oxide

Taking into consideration that glutatione S-transferase (GST) and cellular proliferation play a crucial role during carcinogenesis, the goal of this study was to investigate the expression of placental GST, called GST-P, and proliferating cellular nuclear antigen (PCNA) by means of immunohistochemistry during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide (4NQO). This is a useful model for studying oral squamous cell carcinoma phase by phase. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. GST-P positive foci were detected in non-neoplastic oral cells at 4 weeks of 4NQO administration. In the same way, GST-P positive cells were detected in pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks-treatment, respectively. None of the control animals expressed GST-P positive cells. Regarding cellular proliferation, PCNA positive nuclei were higher at 12 and 20 weeks following 4NQO exposure (p < 0.05) when compared to negative control. These results suggest that the expression of GST-P is correlated with cellular proliferation, in which GST-P is associated with risk and progression of oral cancer, whereas PCNA is closely involved during neoplastic conversion. (c) 2007 Published by Elsevier GmbH.

Pressure evaluation of the antireflux ability of the rat ureterovesical junction

The bladder pressure necessary to cause vesicoureteral reflux (VUR) was measured in 16 female rats. Under general anesthesia, the ureters were exposed via an abdominal incission and a pressure catheter was placed near the uterovesical junction. Values of bladder distension and bladder pressure increase to cause VUR were obtained by injecting isotonic saline in one ureter until VUR in the opposite ureter was detected as a sudden pressure increase. After 5 min the same procedure was done on the contralateral side. This procedure was repeated eight times in each rat with a 15-min intermission. The bladder pressure at which VUR occurred was measured through a uretral catheter. Two groups were studied: G1, control, and G2, administration of intravenous metoclopramide (0.007 mg/100 g body weight) four times.

Effects of crude extracts of Agaricus blazei on DNA damage and on rat liver carcinogenesis induced by diethylnitrosamine

The effects of crude extracts of the mushroom Agaricus blazei Murrill (Agaricaceae) on both DNA damage and placental form glutathione S-transferase (GST-P)-positive liver foci induced by diethylnitrosamine (DEN) were investigated. Six groups of adult male Wistar rats were used. For two weeks, animals of groups 3 to 6 were treated with three aqueous solutions of A. blazei (mean dry weight of solids being 1.2, 5.6, 11.5 and 11.5 mg/ml, respectively). After this period, groups 2 to 5 were given a single ip injection 200 mg/kg DEN and groups 1 and 6 were treated with 0.9% NaCl. All animals were subjected to 70% partial hepatectomy at week five and sacrificed 4, 24 and 48 h or 8 weeks after DEN or 0.9% NaCl treatments (10th week after the beginning of the experiment). The alkaline comet assay and GST-P-positive liver foci development were used to evaluate the influence of the mushroom extracts on liver cell DNA damage and on the initiation of liver carcinogenesis, respectively. Previous treatment with the highest concentration of A. blazei (11.5 mg/ml) significantly reduced DNA damage, indicating a protective effect against DEN-induced liver cytotoxicity/genotoxicity. However, the same dose of mushroom extract significantly increased the number of GST-P-positive liver foci.

Medium-term tongue carcinogenesis assays: A comparative study between 4-nitroquinoline 1-oxide (4NQO)-induced rat and dimethylbenzanthracene (DMBA)-induced hamster carcinogenesis

The most used animal models in oral cancer research are the hamster treated by dimethylbenzanthracene (DMBA), and the rat treated by 4-nitroquinoline 1-oxide (4NQO). The purpose of this study was to compare the DMBA-induced hamster tongue carcinogenesis and 4NQO-induced rat tongue carcinogenesis by means of morphological analysis. Male Wistar rats were distributed into three groups of ten animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. A total of 18 Syrian golden hamsters were submitted to 0.5% DMBA (dissolved in acetone) topical application three times/week for 4, 12 and 20 weeks. The primary histopathological change i.e., hyperplasia and hyperkeratosis, was evidenced after 4 weeks treatment with DMBA. Regarding 12 weeks treatment, 4NQO and DMBA were able to induce morphological changes as depicted by hyperplasia and dysplasia. At 20 weeks, squamous cell carcinoma was found in the majority of animals for both carcinogens used. Taken together, our results suggest that the hamster experimental model disclosed aspects related with tongue carcinogenesis in lesser time than rats. Probably, such discrepancies depend strongly on route of administration and the susceptibility with respect to animal species. © 2006 Elsevier GmbH. All rights reserved.

Lack of protective effects of zinc gluconate against rat colon carcinogenesis

Zinc has been proposed as a promising chemopreventive candidate against colon cancer. However, few studies on the potential beneficial effects of this trace element on cancer chemoprevention are available. The present study was designed to investigate the potential modifying influence of zinc gluconate (ZnGly) on the initiation step of colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH). Male Wistar rats received orally ZnGly (15 mg elemental zinc/kg, 3 times per wk) 2 wk before and during DMH treatment (3 × 40 mg/kg, once a wk). The animals were euthanized at the end of 4th and 16th wk. Colons were analyzed for aberrant crypt foci (ACF) and tumor development. Blood and colon zinc levels, cell proliferation, and apoptosis indexes in colonic crypts were analyzed 24 h after the last DMH administration. Oral treatment with ZnGly did neither alter the number of ACF nor the indexes of cell proliferation and apoptosis in the colonic mucosa. The incidence and multiplicity of colon tumors induced by DMH and their histopathological patterns were not modified by previous treatment with ZnGly. These findings indicate a lack of chemopreventive action of zinc gluconate supplementation on the initiation step of rat colon carcinogenesis induced by DMH. © 2013 Copyright Taylor and Francis Group, LLC.

Açai (Euterpe oleracea Mart.) feeding attenuates dimethylhydrazine-induced rat colon carcinogenesis

This study investigated the protective effect of spray-dried açaí powder (AP) intake on colon carcinogenesis induced by 1,2-dimethylhydrazine (DMH) in male Wistar rats. After 4. weeks of DMH administrations, the groups were fed with standard diet, a diet containing 2.5% or 5.0% AP or a diet containing 0.2% N-acetylcysteine (NAC) for 10. weeks, using aberrant crypt foci (ACF) as the endpoint. Additionally, two groups were fed with standard diet or a diet containing 5.0% AP for 20. weeks, using colon tumors as the endpoint. In ACF assay, a reduction in the number of aberrant crypts (ACs) and ACF (1-3 AC) were observed in the groups fed with 5.0% AP (37% AC and 47% ACF inhibition, p=. 0.036) and 0.2% NAC (39% AC and 41% ACF inhibition, p=. 0.042). In tumor assay, a reduction in the number of invasive tumors (p<. 0.005) and tumor multiplicity (p=. 0.001) was observed in the group fed with 5.0% AP. Also, a reduction in tumor Ki-67 cell proliferation (p=. 0.003) and net growth index (p=. 0.001) was observed in the group fed with 5.0% AP. Therefore the findings of this study indicate that AP feeding may reduce the development of chemically-induced rat colon carcinogenesis. © 2013 Elsevier Ltd.

Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antioxidant activity of apple extract protects against rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

Several studies have shown that apple (Malus sp.) has many components able to exert chemopreventive activity. The aim of this study was to evaluate the chemopreventive potential of apple extract following medium-term oral carcinogenesis assay induced by 4-nitroquinoline 1-oxide (4NQO) by means of histopathological analysis and gene expression of antioxidant enzymes, such as CuZnSOD, MnSOD and catalase. A total of 30 male Wistar rats were distributed into five groups, as follows (n = 6 per group): Group 1 - negative control group (non-treated group); Group 2 - received 4NQO during 8 weeks in drinking water and treated with apple extract by gavage between the 1st and 4th weeks daily (initiation phase); Group 3 - received 4NQO for 8 weeks in drinking water and treated with apple extract by gavage between the 5th and 8th weeks daily (promotion phase); Group 4 - received apple extract by gavage for eight consecutive weeks only; and Group 5 - received 4NQO for 8 weeks in drinking water daily. Histopathological analysis revealed that apple extract protect oral lesions induced by 4NQO at initiation or promotion phase. Higher gene expression of CuZnSOD and MnSOD enzymes were noticed in groups treated with apple extract as well. Taken together, our results demonstrate that the apple extract is able to modulate medium-term oral carcinogenesis assay as a result of antioxidant activity.