Implementation of Human Endpoints in a Urinary Bladder Carcinogenesis Study in Rats

Oliveira, Marcelo Fernandes de; Nascimento-Gonçalves, Elisabete; Silva, Jéssica; Oliveira, Paula A.; Ferreira, Rita; Antunes, Luís; Arantes‐Rodrigues, Regina; Faustino-Rocha, Ana I.

doi:10.21873/invivo.11172

Cited by 8 publications

(10 citation statements)

References 24 publications

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“…The mean food consumption for each animal in the cage was measured as the difference between the weight of the food repository at the beginning of the week and that at the end of the week divided by the number of animals in the cage times the number of days. The mean water consumption for each animal was calculated as the difference between the weight of the water bottle at the beginning of the week and that at the end of the week divided by the number of animals in the cage times the number of days [ 5 ].…”

Section: Methodsmentioning

confidence: 99%

“…Experiments with laboratory rodents raise many ethical questions. Several studies cause pain and stress, and it is important to minimize them because these factors directly influence experimental results [ 5 ]. In order to improve animal welfare in experimental trials, in 1959, Russel and Burch introduced the concept of the 3Rs (i.e., reduce, refinement, and replacement), suggesting that studies using animals should only be performed after testing all possible alternative methods, the number of animals should be reduced to a minimum and the procedures should be refined, being as strict as possible [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Specific guidelines for animal models of stress, toxicological studies, infectious diseases, and cancer models were also proposed [ 10 , 11 , 12 ]. Later, HEs for experimental assays on cancer were established by Oliveira et al [ 5 ] and Faustino-Rocha et al [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…In order to address all ethical and animal welfare issues in an animal model of chemically induced colorectal carcinogenesis (CRC), this study aimed to define a clear HE scoring system to identify signs of animal suffering before the onset of severe effects of the disease. We hypothesize that HE scoring systems previously proposed for animal models of cancer [ 5 , 9 ] can be applied for chemically induced CRC after the integration of specific parameters, such as abdominal temperature, priapism, and body weight (BW) gain.…”

Section: Introductionmentioning

confidence: 99%

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Refinement of Animal Model of Colorectal Carcinogenesis through the Definition of Novel Humane Endpoints

Silva-Reis

Faustino-Rocha

Gonçalves

et al. 2021

Animals

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This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid (EDTA)–saline solutions and two induced groups (CRC1 and CRC2) injected with 1,2-dimethylhydrazine (DMH) for seven weeks. A score sheet with 14 biological parameters was used to assess animal welfare. Groups CRC1 and CTRL1 and groups CRC2 and CTRL2 were euthanized 11 and 17 weeks after the first DMH administration, respectively. Five animals from the induced groups died unexpectedly during the protocol (survival rates of 75.0% and 66.7% for groups CRC1 and CRC2, respectively). The final mean body weight (BW) was smaller in the CRC groups when compared with that in the CTRL groups. A uniformity of characteristics preceding the premature animals’ death was observed, namely an increase of 10% in mean BW, swollen abdomen, diarrhea, and priapism. The surface abdominal temperature of group CRC2 was significantly higher, when compared with that of group CTRL2. The parameters already described in other cancer models proved to be insufficient. For the CRC model, we considered assessing the abdominal temperature, priapism, and sudden increase in the BW.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Refinement of Animal Model of Colorectal Carcinogenesis through the Definition of Novel Humane Endpoints

Silva-Reis

Faustino-Rocha

Gonçalves

et al. 2021

Animals

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“…Humane endpoints were assessed weekly by the same researcher, using a previously published scoring sheet [39]. Animals that reached a total score equal or greater than four at any time point were designated for euthanasia.…”

Section: Methodsmentioning

confidence: 99%

The Cyclooxigenase-2 Inhibitor Parecoxib Prevents Epidermal Dysplasia in HPV16-Transgenic Mice: Efficacy and Safety Observations

Ferreira

Campos

Silva

et al. 2019

IJMS

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Carcinogenesis induced by high-risk human papillomavirus (HPV) involves inflammatory phenomena, partially mediated by cyclooxigenase-2. In pre-clinical models of HPV-induced cancer, cyclooxygenase-2 inhibitors have shown significant efficacy, but also considerable toxicity. This study addresses the chemopreventive effect and hepatic toxicity of a specific cyclooxigensase-2 inhibitor, parecoxib, in HPV16-transgenic mice. Forty-three 20 weeks-old female mice were divided into four groups: I (HPV16−/−, n = 10, parecoxib-treated); II (HPV16−/− n = 11, untreated); III (HPV16+/−, n = 11, parecoxib-treated) and IV (HPV16+/−, n = 11, untreated). Parecoxib (5.0 mg/kg once daily) or vehicle was administered intraperitoneally for 22 consecutive days. Skin lesions were classified histologically. Toxicological endpoints included genotoxic parameters, hepatic oxidative stress, transaminases and histology. Parecoxib completely prevented the onset of epidermal dysplasia in HPV16+/− treated animals (0% versus 64% in HPV16+/− untreated, p = 0.027). Parecoxib decreases lipid peroxidation (LPO) and superoxide dismutase (SOD) activity and increases the GSH:GSSG ratio in HPV16+/− treated animals meaning that oxidative stress is lower. Parecoxib increased genotoxic stress parameters in wild-type and HPV16-transgenic mice, but didn’t modify histological or biochemical hepatic parameters. These results indicate that parecoxib has chemopreventive effects against HPV16-induced lesions while maintaining an acceptable toxicological profile in this model.

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Disease Animal Models for Cancer Research

Fuochi

Galligioni

2023

Methods in Molecular Biology

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Implementation of Human Endpoints in a Urinary Bladder Carcinogenesis Study in Rats

Abstract: Abstract. Background

Cited by 8 publications

References 24 publications

Refinement of Animal Model of Colorectal Carcinogenesis through the Definition of Novel Humane Endpoints

Refinement of Animal Model of Colorectal Carcinogenesis through the Definition of Novel Humane Endpoints

The Cyclooxigenase-2 Inhibitor Parecoxib Prevents Epidermal Dysplasia in HPV16-Transgenic Mice: Efficacy and Safety Observations

Disease Animal Models for Cancer Research

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