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Biology
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Animal Models in Toxicology
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Animal Models in Toxicology

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Toxicology".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 12121

Special Issue Editor

Dr. Rob U. Onyenwoke

E-Mail Website
Guest Editor
Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC 27707, USA
Interests: toxicology; pulmonary; calcium signaling; lung physiology; kinases; ion channel biology; high throughput screening; drug discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

For an animal model of toxicology to be relevant to human health, the route of administration/exposure, the exposure dose(s) and the pattern/frequency of doses should all be justified and defined in terms of overall applicability to human physiology and potential physiological disruption and then ideally similar across studies to allow for comparisons between and among studies. This set of statements should be arguably true independent of chemical, drug, etc. being scientifically assessed/studied. However, complexities will, of course, exist and include questions surrounding route of exposure, e.g., dermal, ingestion or inhalation. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: studies aimed at the development and/or use of (novel) animal models to address human health concerns related to chemically defined substances, such as drugs, with regard to well-perceived or as of yet not perceived toxicological effects; using animal models to study or derive new biomarkers of harm; or studies aimed at exploring or defining the numerous routes of exposure of a single chemical. Appropriate and thorough reviews of existing animal models of toxicology would also be especially welcomed.

Dr. Rob U. Onyenwoke
Guest Editor

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Keywords

  • animal model
  • biomarker of harm
  • pharmacokinetics
  • route of exposure
  • toxicology
  • toxin

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Published Papers (7 papers)

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Research

16 pages, 3332 KiB  
Article
A Preclinical Model to Assess Intestinal Barrier Integrity Using Canine Enteroids and Colonoids
by Megan P. Corbett, Vojtech Gabriel, Vanessa Livania, David Díaz-Regañón, Abigail Ralston, Christopher Zdyrski, Dongjie Liu, Sarah Minkler, Hannah Wickham, Addison Lincoln, Karel Paukner, Todd Atherly, Maria M. Merodio, Dipak Kumar Sahoo, David K. Meyerholz, Karin Allenspach and Jonathan P. Mochel
Biology 2025, 14(3), 270; https://doi.org/10.3390/biology14030270 - 6 Mar 2025
Viewed by 1408
Abstract
While two-dimensional (2D) cell cultures, such as Caco-2 and Madin–Darby canine kidney (MDCK) cells are widely used in a variety of biological models, these two-dimensional in vitro systems present inherent limitations in replicating the complexities of in vivo biology. Recent progress in three-dimensional [...] Read more.
While two-dimensional (2D) cell cultures, such as Caco-2 and Madin–Darby canine kidney (MDCK) cells are widely used in a variety of biological models, these two-dimensional in vitro systems present inherent limitations in replicating the complexities of in vivo biology. Recent progress in three-dimensional organoid technology has the potential to address these limitations. In this study, the characteristics of conventional 2D cell culture systems were compared to those of canine intestinal organoids (enteroids, ENT, and colonoids, COL). Light microscopy and transmission electron microscopy were employed to evaluate the microanatomy of ENT, COL, Caco-2, and MDCK cell monolayers, while transepithelial electrical resistance (TEER) values were measured to assess monolayer integrity. The TEER values of canine ENT monolayers more closely approximated reported TEER values for human small intestines compared to Caco-2 and MDCK monolayers. Additionally, canine ENT demonstrated greater monolayer stability than Caco-2 and MDCK cells. Notably, while all systems displayed desmosomes, canine ENT and COL exclusively produced mucus. These findings highlight the potential of the canine organoid system as a more biologically relevant model for in vitro studies, addressing the limitations of conventional 2D cell culture systems. Full article
(This article belongs to the Special Issue Animal Models in Toxicology)
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20 pages, 8656 KiB  
Article
Edible Bird’s Nest (EBN) Ameliorates the Effects of Indomethacin (IMC)-Induced Embryo Implantation Dysfunction in Rats
by Maria Amir, Nurhusien Yimer, Mark Hiew, Md Sabri Mohd Yusoff, Sadiq Mohammed Babatunde and Abdul Quddus
Biology 2025, 14(2), 159; https://doi.org/10.3390/biology14020159 - 4 Feb 2025
Viewed by 1057
Abstract
IMC has been reported to influence embryo implantation negatively in animals including rats. While EBN has been known to have a potential protective effect against reproductive toxicity, there is limited study on the effect of EBN on IMC toxicity in reproduction. This study [...] Read more.
IMC has been reported to influence embryo implantation negatively in animals including rats. While EBN has been known to have a potential protective effect against reproductive toxicity, there is limited study on the effect of EBN on IMC toxicity in reproduction. This study aimed to ascertain whether pretreatment with a natural substance, Edible Bird’s Nest (EBN), will reduce IMC-induced toxicity in pregnant rats. Thirty Sprague-Dawley rats divided into five equal groups were treated with EBN and IMC as follows: G1 = Control, G2 = IMC (4.33 mg/kg), G3 = IMC + EBN (4.33 mg/kg + 60 mg/kg), G4 = IMC + EBN (4.33 mg/kg + 90 mg/kg), and G5 = IMC + EBN (4.33 mg/kg +120 mg/kg). EBN was administered once daily for 8 weeks while IMC was injected subcutaneously. On day 8 after mating, all rats were sacrificed for blood sampling and embryo implantation rate (EIR) assessment; the uterine tissues were also subjected to immunohistochemical and histological analyses. G5 recorded significantly higher EIR, fertility index, and expression of epidermal growth factor receptor (EGFR) in the uterine section, across stroma cells, the glandular epithelium, and the luminal epithelium compared to control and other groups. IMC-induced inflammatory alterations, endometrial atrophy, vacuolar degeneration, and atrophy were not detected in uterine tissue sections in G4 and G5, with the latter group demonstrating the highest EIR with protective effects on uterine tissues. Thus, EBN supplementation might be of great benefit in guarding the fertility of individuals who depend on IMC for the treatment of chronic inflammatory illness. Full article
(This article belongs to the Special Issue Animal Models in Toxicology)
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19 pages, 4540 KiB  
Article
Peroxisome Proliferator Activator α Agonist Clofibrate Induces Pexophagy in Coconut Oil-Based High-Fat Diet-Fed Rats
by Kanami Ohshima, Emika Hara, Mio Takimoto, Yidan Bai, Mai Hirata, Wen Zeng, Suzuka Uomoto, Mai Todoroki, Mio Kobayashi, Takuma Kozono, Tetsuhito Kigata, Makoto Shibutani and Toshinori Yoshida
Biology 2024, 13(12), 1027; https://doi.org/10.3390/biology13121027 - 7 Dec 2024
Cited by 1 | Viewed by 1036
Abstract
Peroxisomes are crucial for fatty acid β-oxidation in steatosis, but the role of pexophagy—the selective autophagy of peroxisomes—remains unclear. This study investigated the effects of the peroxisome proliferator-activated receptor-α (PPARα) agonist clofibrate on pexophagy in a coconut oil-based high-fat diet (HFD)-induced hepatocarcinogenesis model. [...] Read more.
Peroxisomes are crucial for fatty acid β-oxidation in steatosis, but the role of pexophagy—the selective autophagy of peroxisomes—remains unclear. This study investigated the effects of the peroxisome proliferator-activated receptor-α (PPARα) agonist clofibrate on pexophagy in a coconut oil-based high-fat diet (HFD)-induced hepatocarcinogenesis model. Rats were divided into four groups: control, clofibrate, HFD, and HFD with clofibrate. The HFD induced steatosis, along with a 2.4-fold increase in pexophagy receptor NBR1-positive granules in hepatocytes. Clofibrate significantly inhibited HFD-induced steatosis, increasing p62-, LAMP2-, and Pex5-positive granules by 7.5-, 7.2-, and 71.4-fold, respectively, while decreasing NBR1 expression. The effects were associated with peroxisome proliferation and pexophagy in ultrastructural observations and increased levels of Lc3, p62, Pex2, Pex14, Acox1, and Scd1 in gene expression analysis. The results suggested that clofibrate effectively reduced steatosis through combined peroxisome proliferation and pexophagy, though it had a marginal impact on hepatocarcinogenesis in coconut oil-based HFD-fed rats. These findings highlight the utility of PPARα agonists in studying mammalian pexophagy. Full article
(This article belongs to the Special Issue Animal Models in Toxicology)
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16 pages, 70002 KiB  
Article
Safety Evaluation for Acute and Chronic Oral Toxicity of Maha Pigut Triphala Contains Three Medicinal Fruits in Sprague-Dawley Rats
by Supaporn Intatham, Weerakit Taychaworaditsakul, Parirat Khonsung, Sunee Chansakaow, Kanjana Jaijoy, Nirush Lertprasertsuke, Noppamas Soonthornchareonnon and Seewaboon Sireeratawong
Biology 2024, 13(12), 1005; https://doi.org/10.3390/biology13121005 - 2 Dec 2024
Viewed by 1206
Abstract
Maha Pigut Triphala is the herbal mixture of three fruits consisting of T. bellirica, T. chebula, and E. officinalis also known as P. emblica. Humans regularly eat the fresh fruits of these plants on a daily basis. Maha Pigut Triphala [...] Read more.
Maha Pigut Triphala is the herbal mixture of three fruits consisting of T. bellirica, T. chebula, and E. officinalis also known as P. emblica. Humans regularly eat the fresh fruits of these plants on a daily basis. Maha Pigut Triphala is one of the widely known herbal medicinal formulas used in traditional Thai medicine. Besides studying pharmacological properties, attention should also be paid to the safety and toxicity studies of herbal medicines. The objective of the present study was to evaluate the acute and chronic oral toxicity of Maha Pigut Triphala (2:1:3) in Sprague-Dawley rats. A single dose of Maha Pigut Triphala at a concentration of 5000 mg/kg body weight was administered orally to female rats in the acute oral toxicity study. In the chronic oral toxicity study, male and female rats were treated with various concentrations of Maha Pigut Triphala (600, 1200, and 2400 mg/kg body weight) once daily for 270 consecutive days. The presence of abnormalities in the symptoms and behavior of the rats were observed and recorded throughout the experiment. Additionally, body weight, organ weight, and mortality were recorded. At the end of the study, blood samples were collected for hematological and blood chemistry analysis, while the internal organs were evaluated for gross pathological and histopathological changes. The acute oral toxicity study revealed no mortality and abnormal symptoms or behavior in Maha Pigut Triphala-treated rats. Moreover, gross pathological and histopathological findings did not reveal any abnormalities in the internal organs. In the chronic oral toxicity evaluation, although there were negligible changes in body weight, organ weight, and hematological and blood chemistry parameters in rats treated with Maha Pigut Triphala for 270 days, no behavioral or gross pathological and histopathological abnormalities were observed. Overall, the results of this study demonstrate that Maha Pigut Triphala (2:1:3) neither causes acute nor chronic oral toxicity in rats, proposing the safety of this herbal formula in animals prior to human trials and use. Full article
(This article belongs to the Special Issue Animal Models in Toxicology)
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10 pages, 1594 KiB  
Article
Copaiba Oleoresin Improves Weight Gain and IL-10 Concentration, with No Impact on Hepatic Histology, in Liver Cirrhosis
by Maiara Taffarel, Bianca Sulzbacher da Silva, Angélica Macedo Borgês Paulino, Luciana Ortega Telles, Sabrina Trigueiro Mendonça, Cintia Vieira dos Santos, Morenna Alana Giordani, André Ferreira Nascimento, Danilo Henrique Aguiar, Valéria Dornelles Gindri Sinhorin, Carla Regina Andrighetti, Renata de Azevedo Melo Luvizotto and Gisele Facholi Bomfim
Biology 2024, 13(11), 853; https://doi.org/10.3390/biology13110853 - 23 Oct 2024
Viewed by 1435
Abstract
Copaifera sp. is a native tree in the Amazon region. Copaiba oleoresin has components such as sesquiterpenes, which have anti-inflammatory and antioxidant potential. Liver cirrhosis is the end stage of liver disease with limited therapeutic options. We aimed to evaluate the effect of [...] Read more.
Copaifera sp. is a native tree in the Amazon region. Copaiba oleoresin has components such as sesquiterpenes, which have anti-inflammatory and antioxidant potential. Liver cirrhosis is the end stage of liver disease with limited therapeutic options. We aimed to evaluate the effect of copaiba oleoresin supplementation on the liver of animals with thioacetamide (TAA)-induced cirrhosis. For the induction of liver cirrhosis, 100 mg/kg of TAA was administered intraperitoneally twice a week for 8 weeks. A total of 200 mg/kg/day of copaiba oleoresin was administered via gavage for the same period. Copaiba oleoresin supplementation improved cirrhosis-associated cachexia by increasing weight gain and body fat. In addition, copaiba oleoresin attenuated systemic inflammation, as shown by the decrease in the circulating C-reactive protein. In the liver, the copaiba oleoresin decreased carbonyl proteins and increased IL-10 compared with TAA-treated rats. TAA groups demonstrated increased SOD, catalase, GST, and GSH activity in the liver. In conclusion, the supplementation of copaiba oleoresin demonstrated a beneficial systemic effect in alleviating cirrhotic cachexia and antioxidant and anti-inflammatory action in the liver. However, it failed to improve the serological and histological markers of liver damage, which could be associated with the advanced stage of the disease. Full article
(This article belongs to the Special Issue Animal Models in Toxicology)
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14 pages, 2223 KiB  
Article
Dapagliflozin: A Promising Strategy to Combat Cisplatin-Induced Hepatotoxicity in Wistar Rats
by Shakta Mani Satyam, Laxminarayana Kurady Bairy, Abdul Rehman, Mohamed Farook, Sofiya Khan, Anuradha Asokan Nair, Nirmal Nachiketh Binu, Mohamed Yehya and Mohammed Moin Khan
Biology 2024, 13(9), 672; https://doi.org/10.3390/biology13090672 - 29 Aug 2024
Cited by 3 | Viewed by 2183
Abstract
Recognizing the challenges posed by chemotherapy, specifically the hepatotoxic effects of drugs like cisplatin, this study aimed to examine the hepatoprotective potential of dapagliflozin to mitigate cisplatin-induced hepatotoxicity in a rat model. This study focused on repurposing drugs such as dapagliflozin and natural [...] Read more.
Recognizing the challenges posed by chemotherapy, specifically the hepatotoxic effects of drugs like cisplatin, this study aimed to examine the hepatoprotective potential of dapagliflozin to mitigate cisplatin-induced hepatotoxicity in a rat model. This study focused on repurposing drugs such as dapagliflozin and natural agents like silymarin as potential interventions to address cisplatin-induced hepatotoxicity. Thirty adult female Wistar rats were distributed into five groups and treated with cisplatin alone, silymarin, dapagliflozin, or a combination of dapagliflozin and silymarin accordingly for 45 days. Body weight, fasting blood glucose levels, liver function tests, and histopathological analysis were conducted to evaluate the hepatoprotective effects. Cisplatin-induced hepatotoxicity significantly (p < 0.05) increased the serum levels of ALT, AST, TB, and reduced the TP and albumin levels. Dapagliflozin administration led to significant reductions in ALT, AST, TB, and increased albumin levels. Silymarin demonstrated comparable effects. Combining dapagliflozin and silymarin showed synergistic effects, further reducing the liver enzymes and improving albumin levels. Histopathological examination supported these findings, revealing the restoration of liver structure with dapagliflozin and silymarin treatment. Dapagliflozin and silymarin exhibited substantial hepatoprotective benefits against cisplatin-induced hepatotoxicity in rats. The combination therapy demonstrated synergistic effects, highlighting a potential therapeutic approach for mitigating chemotherapy-induced liver damage. Further research into molecular mechanisms and clinical translation is warranted, offering hope for improved clinical outcomes in cancer patients undergoing cisplatin-based chemotherapy. Full article
(This article belongs to the Special Issue Animal Models in Toxicology)
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16 pages, 3773 KiB  
Article
Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats
by Shakta Mani Satyam, Laxminarayana Kurady Bairy, Abdul Rehman, Mohamed Attia, Layth Ahmed, Karam Emad, Yusuf Jaafer and Abdelrehman Bahaaeldin
Biology 2024, 13(7), 473; https://doi.org/10.3390/biology13070473 - 26 Jun 2024
Cited by 6 | Viewed by 2663
Abstract
This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl4)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental [...] Read more.
This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl4)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental animals except the normal control (Group I) were administered CCl4. Additionally, Groups II, III, IV, and V were treated with gum acacia, silymarin, dapagliflozin, and a combination of dapagliflozin and silymarin, respectively, for 14 days. Dapagliflozin, silymarin alone, and in combination, significantly reduced (p < 0.05) serum levels of ALT, AST, AST:ALT ratio, and total bilirubin compared to CCl4-intoxicated control rats. There was a notable reduction (p < 0.05) observed in the levels of IL-1beta, IL-6, TNF-alpha, nitrites, and 4-hydroxynonenal, accompanied by an elevation in catalase, superoxide dismutase, glutathione peroxidase, nuclear erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver homogenates of the groups treated with dapagliflozin, silymarin alone, and in combination, as compared to the CCl4-intoxicated control group. Dapagliflozin in combination with silymarin showed a synergistic hepatoprotective effect. Our study reveals the profound hepatoprotective potential of dapagliflozin alone and in combination with silymarin in CCl4-intoxicated Wistar rats by modulating the Nrf2 and HO-1 signaling pathways. Full article
(This article belongs to the Special Issue Animal Models in Toxicology)
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