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Pharmaceuticals
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Rodent Animal Models for Drug Discovery
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Rodent Animal Models for Drug Discovery

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (30 August 2024) | Viewed by 9995

Special Issue Editors

Dr. Yuebang Yin

E-Mail Website
Guest Editor
Independent Researcher, Hangzhou 310018, China
Interests: rodent; animal model; mouse; rat; drug discovery; organoid; 3D model
Dr. Peng Wang

E-Mail Website
Guest Editor
Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan 750004, China
Interests: neurosciences; animal model; rodent; cell model; drug discovery; medical study

Special Issue Information

Dear Colleagues,

Laboratory rodents, particularly the mouse and rat, are the preferred and most frequently used animal models in biomedical research. These models can provide results that allow us to deduce knowledge to study a particular disease state in humans. Rodents have been regarded as a reliable research species mainly due to their small size, short life cycle, reproductive affluence, known genetic background, as well as relative ease of procurement, handling, and housing. With the development of biotechnologies, genetic manipulations further strengthen the predominant utilization of rodents. These manipulations have allowed the researcher to study rat or mice genetically suited specifically to the human disease model of their interests. Thus, rodent animal models play an essential role in drug discovery and medical studies.

Drug discovery is the process through which potential new medicines are identified. The drug discovery process is invariably a lengthy and expensive process in the pharmaceutical industry, which starts with the identification and validation of the putative molecular/cellular drug target, followed by generally lengthy preclinical and clinical investigations, with the process ending in a series of regulatory approvals. Animal models for drug discovery and development have played an important role in the characterization of the pathophysiology of diseases and associated mechanisms of injury, drug target identification, and evaluation of novel therapeutic agents for toxicity/safety, pharmacokinetics, pharmacodynamics, and efficacy. The use of animal models is vitally important in terms of developing clinical predictions of the expected results in humans.

In this Special Issue, we aim to draw together research from experts in the field that highlight applications of rodent animals in drug discovery, covering the utilization of rodent animals, ex vivo tissue in medical research, and identify future directions that will lead to the perfect utilization of rodent animals in drug discovery.

Dr. Yuebang Yin
Dr. Peng Wang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • animal model
  • rodent
  • mouse
  • rat
  • drug discovery

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Published Papers (4 papers)

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Research

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20 pages, 4032 KiB  
Article
Comparison of the Results of Modeling Pulmonary Fibrosis in Sprague Dawley Rats by Intratracheal Administration of Bleomycin in the Form of Sulfate and Chloride at a Dose of 3 mg/kg
by Elena A. Tukhovskaya, Yulia A. Palikova, Mariya S. Severyukhina, Alina M. Ismailova, Victor A. Palikov, Gulsara A. Slashcheva, Natalya A. Borozdina, Evgeniy S. Mikhaylov, Irina N. Kravchenko, Vitaly A. Kazakov, Ekaterina N. Kazakova, Elena A. Kalabina, Ekaterina A. Rasskazova, Maxim V. Shinelev, Dmitry I. Rzhevsky, Vladimir A. Rykov, Igor A. Dyachenko and Arkady N. Murashev
Pharmaceuticals 2024, 17(10), 1360; https://doi.org/10.3390/ph17101360 - 11 Oct 2024
Viewed by 1237
Abstract
Background/Objectives: Intratracheal administration of bleomycin (BLM) to laboratory rodents is a standard, widely used technique used to model pulmonary fibrosis (PF). BLM, as a modeling agent, is produced mainly in the form of two salts—sulfate and chloride. We compared the results of [...] Read more.
Background/Objectives: Intratracheal administration of bleomycin (BLM) to laboratory rodents is a standard, widely used technique used to model pulmonary fibrosis (PF). BLM, as a modeling agent, is produced mainly in the form of two salts—sulfate and chloride. We compared the results of modeling PF in SD rats by intratracheal administration of BLM sulfate and BLM chloride. Methods: Healthy mature male SD rats were used. PF was modeled by intratracheal administration of BLM sulfate and BLM chloride at a dose of 3 mg/kg. The criteria for the development of PF included body weight gain, changes in respiratory parameters, relative lung weight, cellular composition of broncho-alveolar fluid (BALF), histological assessment of the severity of PF with trichrome Masson staining. Results: Intratracheal administration of both BLM salts led to the development of pronounced PF, which was determined by changes in all of the measured parameters relative to control animals. There were no significant differences between the BLM sulfate and BLM chloride groups in body weight gain, hydroxyproline content, and histological evaluation. However, significant differences were identified in the cellular composition of BALF—a significant increase in alveolar macrophages and neutrophils levels in animals treated with BLM sulfate. Conclusions: Intratracheal administration of both BLM salts led to the development of severe PF; however, the inflammatory process in animals receiving BLM sulfate was more pronounced and prolonged than in animals receiving BLM chloride, which in the former, when observed more than 21 days after modeling, can lead to more severe PF. Full article
(This article belongs to the Special Issue Rodent Animal Models for Drug Discovery)
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14 pages, 3506 KiB  
Article
Metformin Hydrochloride Significantly Inhibits Rotavirus Infection in Caco2 Cell Line, Intestinal Organoids, and Mice
by Rui Zhang, Cui Feng, Dandan Luo, Ruibo Zhao, Perumal Ramesh Kannan, Yuebang Yin, Muhammad Zubair Iqbal, Yeting Hu and Xiangdong Kong
Pharmaceuticals 2023, 16(9), 1279; https://doi.org/10.3390/ph16091279 - 11 Sep 2023
Cited by 5 | Viewed by 2225
Abstract
Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin [...] Read more.
Rotavirus is one of the main pathogens that causes severe diarrhea in children under the age of 5, primarily infecting the enterocytes of the small intestine. Currently, there are no specific drugs available for oral rehydration and antiviral therapy targeting rotavirus. However, metformin hydrochloride, a drug known for its antiviral properties, shows promise as it accumulates in the small intestine and modulates the intestinal microbiota. Therefore, we formulated a hypothesis that metformin hydrochloride could inhibit rotavirus replication in the intestine. To validate the anti-rotavirus effect of metformin hydrochloride, we conducted infection experiments using different models, ranging from in vitro cells and organoids to small intestines in vivo. The findings indicate that a concentration of 0.5 mM metformin hydrochloride significantly inhibits the expression of rotavirus mRNA and protein in Caco-2 cells, small intestinal organoids, and suckling mice models. Rotavirus infections lead to noticeable pathological changes, but treatment with metformin has been observed to mitigate the lesions caused by rotavirus infection in the treated group. Our study establishes that metformin hydrochloride can inhibit rotavirus replication, while also affirming the reliability of organoids as a virus model for in vitro research. Full article
(This article belongs to the Special Issue Rodent Animal Models for Drug Discovery)
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Review

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57 pages, 3641 KiB  
Review
Advancing Pain Understanding and Drug Discovery: Insights from Preclinical Models and Recent Research Findings
by Yahya I. Asiri, Sivakumar S. Moni, Mohankumar Ramar and Kumarappan Chidambaram
Pharmaceuticals 2024, 17(11), 1439; https://doi.org/10.3390/ph17111439 - 28 Oct 2024
Cited by 1 | Viewed by 2994
Abstract
Despite major advancements in our understanding of its fundamental causes, pain—both acute and chronic—remains a serious health concern. Various preclinical investigations utilizing diverse animal, cellular, and alternative models are required and frequently demanded by regulatory approval bodies to bridge the gap between the [...] Read more.
Despite major advancements in our understanding of its fundamental causes, pain—both acute and chronic—remains a serious health concern. Various preclinical investigations utilizing diverse animal, cellular, and alternative models are required and frequently demanded by regulatory approval bodies to bridge the gap between the lab and the clinic. Investigating naturally occurring painful disorders can speed up medication development at the preclinical and clinical levels by illuminating molecular pathways. A wide range of animal models related to pain have been developed to elucidate pathophysiological mechanisms and aid in identifying novel targets for treatment. Pain sometimes drugs fail clinically, causing high translational costs due to poor selection and the use of preclinical tools and reporting. To improve the study of pain in a clinical context, researchers have been creating innovative models over the past few decades that better represent pathological pain conditions. In this paper, we provide a summary of traditional animal models, including rodents, cellular models, human volunteers, and alternative models, as well as the specific characteristics of pain diseases they model. However, a more rigorous approach to preclinical research and cutting-edge analgesic technologies may be necessary to successfully create novel analgesics. The research highlights from this review emphasize new opportunities to develop research that includes animals and non-animals using proven methods pertinent to comprehending and treating human suffering. This review highlights the value of using a variety of modern pain models in animals before human trials. These models can help us understand the different mechanisms behind various pain types. This will ultimately lead to the development of more effective pain medications. Full article
(This article belongs to the Special Issue Rodent Animal Models for Drug Discovery)
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34 pages, 11241 KiB  
Review
Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents
by Magdalena Jasińska-Stroschein
Pharmaceuticals 2023, 16(10), 1449; https://doi.org/10.3390/ph16101449 - 12 Oct 2023
Cited by 1 | Viewed by 2366
Abstract
Background: While the prevalence of heart failure with preserved ejection fraction (HFpEF) has increased over the last two decades, there still remains a lack of effective treatment. A key therapeutic challenge is posed by the absence of animal models that accurately replicate the [...] Read more.
Background: While the prevalence of heart failure with preserved ejection fraction (HFpEF) has increased over the last two decades, there still remains a lack of effective treatment. A key therapeutic challenge is posed by the absence of animal models that accurately replicate the complexities of HFpEF. The present review summarizes the effects of a wide spectrum of therapeutic agents on HF. Methods: Two online databases were searched for studies; in total, 194 experimental protocols were analyzed following the PRISMA protocol. Results: A diverse range of models has been proposed for studying therapeutic interventions for HFpEF, with most being based on pressure overload and systemic hypertension. They have been used to evaluate more than 150 different substances including ARNIs, ARBs, HMGR inhibitors, SGLT-2 inhibitors and incretins. Existing preclinical studies have primarily focused on LV diastolic performance, and this has been significantly improved by a wide spectrum of candidate therapeutic agents. Few experiments have investigated the normalization of pulmonary congestion, exercise capacity, animal mortality, or certain molecular hallmarks of heart disease. Conclusions: The development of comprehensive preclinical HFpEF models, with multi-organ system phenotyping and physiologic stress-based functional testing, is needed for more successful translation of preclinical research to clinical trials. Full article
(This article belongs to the Special Issue Rodent Animal Models for Drug Discovery)
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