Review
Cell Biology
Esteban Torres-Dimas, Alfredo Cruz-Ramirez, Rosa Maria Bermudez-Cruz
Summary: Compared to other animals, wild amphibians have a relatively low occurrence of tumors, usually limited to specific populations or species. Recent studies suggest that regenerating tissues have a resistance to tumorigenesis compared to nonregenerative tissues in the same amphibian models. The mechanisms behind this resistance are still unclear, but amphibians possess certain characteristics that may contribute to their ability to resist tumor development.
CELL BIOLOGY INTERNATIONAL
(2022)
Review
Pharmacology & Pharmacy
Jose D. Suarez-Torres, Camilo A. Orozco, Carlos E. Ciangherotti
Summary: The 2-year rodent bioassay (RCB) has been widely used as the benchmark method to screen the carcinogenicity of substances to humans, despite controversy. RCB conducted at maximum tolerated doses (MTDs) showed high sensitivity in detecting human carcinogens while avoiding reactions to non-carcinogens. Specific rodent mechanisms contributed to unspecificity in RCBs, but Bayesian forecasting could help resolve the paradox between sensitivity and unspecificity. Additional caution is advised in discontinuing mouse-RCBs to avoid missing potential human carcinogens.
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2021)
Article
Pharmacology & Pharmacy
Monica G. Silva, Maria Manuel Oliveira, Francisco Peixoto
Summary: Mitochondria play a central role in cellular metabolism and signaling cascades. However, little is known about the effects of emerging contaminants, such as microplastics, on mitochondrial metabolism. Animal models are being used to uncover the molecular mechanisms behind the toxicity of micro- and nanoplastics, and their potential impact on mitochondria.
Article
Toxicology
Liesl K. Janssens, Simon Hudson, David M. Wood, Caitlin Wolfe, Paul I. Dargan, Christophe P. Stove
Summary: This study evaluated the clinical features, serum concentrations of 5F-MDMB-PICA, and the relationship with cannabinoid activity in individuals experiencing recreational drug toxicity. The findings suggest that the contribution of 5F-MDMB-PICA metabolites to overall cannabinoid activity in serum is negligible. Additionally, in vitro pharmacological characterization allows for the prediction of an individual's ex vivo CB1 activity, which is related to the level of consciousness.
ARCHIVES OF TOXICOLOGY
(2022)
Book Review
Biochemistry & Molecular Biology
Graziela P. F. Dantas, Fausto S. Ferraz, Lidia M. Andrade, Guilherme M. J. Costa
Summary: The use of nanoscale materials for biomedical applications has raised concerns about their toxic effects on human health. This systematic review focuses on the reproductive toxicity of different types of inorganic nanoparticles in male rodents. The findings indicate that these nanoparticles can cause structural and functional alterations in testicular cells, leading to oxidative stress, apoptosis, and/or necrosis. However, the lack of standardized protocols in the studies results in highly variable outcomes.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Chemistry, Medicinal
Bin Zeng, Ailing Wei, Qiang Zhou, Minghao Yuan, Kelu Lei, Yushi Liu, Jiawen Song, Li Guo, Qiang Ye
Summary: Andrographis paniculata, known as "Chuan Xin Lian" in China, is a widely used herb in traditional Chinese medicine for various ailments. Its main active compound, andrographolide, has multiple therapeutic actions, but there is a lack of systematic summaries on its specific mechanisms, safety issues, and clinical transformation bottlenecks. Further research is needed to fully understand its efficacy and safety.
PHYTOTHERAPY RESEARCH
(2022)
Article
Environmental Sciences
Yixuan Zhang, Jianchao Liu, Chenyang Jing, Runren Jiang, Xiqiang Zheng, Chao He, Wenliang Ji
Summary: BPS, as a substitute for BPA, has lower toxicity. However, the ecological impact and toxicology effect of BPS on aquatic organisms with multigenerational exposure are still unclear. This study shows that chronic exposure to low concentrations of BPS can have adverse effects on population health of aquatic organisms with short breeding cycles, highlighting the necessity to assess the ecotoxicology of BPS exposure for public health.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Review
Oncology
Hossein Javid, Alireza Sharbaf Mashhad, Shaghayegh Yazdani, Mahsa Akbari Oryani, Sanaz Akbari, Nastaran Rezagholinejad, Mahboubeh Tajaldini, Mehdi Karimi-Shahri
Summary: Despite the limitations of conventional therapeutic agents, virotherapy has emerged as a promising approach in cancer therapy. It involves the use of oncolytic or genetically engineered viruses to selectively infect and kill tumor cells, while stimulating the host immune response. Virotherapy agents can also be used in combination with conventional cancer treatments, offering enhanced efficacy and reduced side effects.
Article
Environmental Sciences
Katie O'Rourke, Christina Virgiliou, Georgios Theodoridis, Helen Gika, Konstantinos Grintzalis
Summary: Pharmaceuticals are considered emerging contaminants in the aquatic ecosystem due to increased use and improper disposal. These compounds have been detected in surface waters worldwide and have detrimental effects on non-target organisms. Analytical approaches for detecting pharmaceutical pollution are limited by sensitivity and coverage, but effect-based methods provide mechanistic insight. This study evaluated the acute effects of antibiotics, estrogens, and other common pharmaceutical pollutants on daphnids in freshwater ecosystems, finding distinct patterns in biological responses. Enzyme changes and metabolite up-regulation were observed following exposure to certain pharmaceuticals.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Lars Mecklenburg, Sarah Lenz, Georg Hempel
Summary: The safety assessment of human pharmaceuticals often requires animal experiments with concurrent control groups. However, this study suggests that the use of concurrent controls may not be necessary for identifying toxic hazards, as certain measurements can be compared to pre-dosing values or historical reference data. It is suggested that virtual control groups could be implemented in nonclinical safety testing instead.
Article
Medicine, Legal
Ruth Danzeisen, Gerd-Ruediger Jaenig, Arne Burzlaff, Steven Verberckmoes, Janine Adam, Vanessa Viegas
Summary: This study presents a mode of action for cobalt substances based on the International Programme on Chemical Safety Conceptual Framework. The evaluation includes parameters such as solubility, biomarkers for cytotoxicity, reactive oxygen species, hypoxia mimicry, inhalation toxicity, and repeated dose inhalation effects. The cobalt substances can be grouped into two distinct groups based on their effects. One group induces all effects across the mode of action and is associated with lung cancer in rodents, while the other group has no or limited effects.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2022)
Review
Urology & Nephrology
Christopher D. Gaffney, Andrew Katims, Neeta D'Souza, Marc A. Bjurlin, Richard S. Matulewicz
Summary: Bladder cancer at an individual level is likely to be the consequence of repeated, long-term exposure to one or more known bladder carcinogens, some of which are endemic or unavoidable in daily life, in addition to host factors. This Mini-Review highlights exposures that are associated with higher risk of bladder cancer, summarizes the evidence for each association, and suggests strategies to decrease risk at both individual and population levels.
EUROPEAN UROLOGY FOCUS
(2023)
Article
Environmental Sciences
Stephanie A. Maggio, Jeffrey J. Jenkins
Summary: This study evaluated the effects of variable chronic chlorpyrifos exposure using a second-tier, screening-level methodology that employed Daphnia magna multi- and transgenerational bioassays spanning four generations. The results showed that continuous chlorpyrifos exposure to four generations of D. magna at ecologically relevant concentrations led to an apparent tolerance response in the F3 generation. However, chlorpyrifos exposure to the F0 generation did not affect the survival and reproduction of the unexposed F1, F2, and F3 generations. The study highlights the importance of using a suite of acute and chronic bioassays, including chronic exposures spanning multiple generations, to evaluate the potential impact of chlorpyrifos on aquatic receptors.
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Haris Niksic, Fahir Becic, Emina Koric, Irma Gusic, Elma Omeragic, Samija Muratovic, Bojana Miladinovic, Kemal Duric
Summary: The study showed that Thymus vulgaris L. essential oil exhibits significant cytotoxic effects on tumor cell lines, inhibiting their proliferation. Both in vivo and in vitro experiments confirmed its toxicity on tumor cells.
SCIENTIFIC REPORTS
(2021)
Review
Plant Sciences
Qiang Sun, Ting Gong, Maolun Liu, Shan Ren, Han Yang, Sha Zeng, Hui Zhao, Li Chen, Tianqi Ming, Xianli Meng, Haibo Xu
Summary: Shikonin, a major phytochemical component of Lithospermum erythrorhizon, shows promising therapeutic effects on various diseases by regulating multiple signaling pathways. However, its pharmacokinetics reveal low oral bioavailability and potential toxicological effects, such as nephrotoxicity and skin allergies. Clinical trials validating its pharmacodynamics and pharmacokinetics are limited, with potential for pharmaceutical innovation to develop shikonin-based drugs for clinical use.
Article
Medicine, Legal
Carole L. Yauk, Alison H. Harrill, Heidrun Ellinger-Ziegelbauer, Jan Willem van der Laan, Jonathan Moggs, Roland Froetschl, Frank Sistare, Syril Pettit
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2020)
Article
Toxicology
Alexei A. Podtelezhnikov, James J. Monroe, Amy G. Aslamkhan, Kara Pearson, Chunhua Qin, Alex M. Tamburino, Andrey P. Loboda, Warren E. Glaab, Frank D. Sistare, Keith Q. Tanis
TOXICOLOGICAL SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Matthew S. Bogdanffy, Jacob Lesniak, Raja Mangipudy, Frank D. Sistare, Karyn Colman, David Garcia-Tapia, Thomas Monticello, Diann Blanset
INTERNATIONAL JOURNAL OF TOXICOLOGY
(2020)
Article
Pathology
Katerina Vlasakova, Sean P. Troth, Frank D. Sistare, Warren E. Glaab
TOXICOLOGIC PATHOLOGY
(2020)
Article
Toxicology
Wen Kang, Alexei A. Podtelezhnikov, Keith Q. Tanis, Stephen Pacchione, Ming Su, Kimberly B. Bleicher, Zhibin Wang, George M. Laws, Thomas G. Griffiths, Matthew C. Kuhls, Qing Chen, Ian Knemeyer, Donald J. Marsh, Kaushik Mitra, Jose Lebron, Frank D. Sistare
TOXICOLOGICAL SCIENCES
(2020)
Article
Toxicology
Brenda Smith, Josh Rowe, Paul B. Watkins, Messoud Ashina, Jeffrey L. Woodhead, Frank D. Sistare, Peter J. Goadsby
TOXICOLOGICAL SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Yi-Zhong Gu, Katerina Vlasakova, Jarig Darbes, Erjia Wang, Jude Ferraro, Warren E. Glaab, Frank D. Sistare
Article
Pharmacology & Pharmacy
Michael J. Hafey, Robert Houle, Keith Q. Tanis, Ian Knemeyer, Jackie Shang, Qing Chen, Andreas Baudy, James Monroe, Frank D. Sistare, Raymond Evers
DRUG METABOLISM AND DISPOSITION
(2020)
Article
Toxicology
Warren E. Glaab, Daniel Holder, Yudong D. He, Wendy J. Bailey, David L. Gerhold, Carolann Beare, Zoltan Erdos, Pamela Lane, Laura Michna, Nagaraja Muniappa, Jeffrey W. Lawrence, Keith Q. Tanis, Joseph F. Sina, Thomas R. Skopek, Frank D. Sistare
Summary: A new safety testing paradigm utilizing gene expression biomarkers has been developed to identify drug-induced injuries in rats quickly and easily, aiding in drug candidate selection. By identifying differentially expressed genes in targeted tissues following injuries induced by known toxicants, a set of 22 genes was selected and incorporated into a rapid assessment method for tissue degeneration/necrosis in rats. This approach showed high sensitivity and specificity in detecting tissue injuries across various organs, providing a practical tool for early safety evaluation.
TOXICOLOGICAL SCIENCES
(2021)
Article
Pathology
Yi-Zhong Gu, Larry Handt, Katerina Vlasakova, Vasudevan Bakthavatchalu, Roger Smith, Guillermo E. Fernandez, Stephanie L. Born, Warren E. Glaab, Frank D. Sistare
Summary: This study compared the monitoring performance of serum and urine safety biomarkers, gene expression alterations, and conventional serum biomarkers in diagnosing low-grade kidney injury in rhesus monkeys. Gene expression profiling on kidney biopsy specimens and urinary kidney safety biomarkers showed promising results in monitoring kidney injury, highlighting the potential for future definitive studies.
TOXICOLOGIC PATHOLOGY
(2022)
Article
Pathology
Shigeru Hisada, Kenjiro Tsubota, Kenji Inoue, Hisaharu Yamada, Takanori Ikeda, Frank D. Sistare
Summary: Exceeding a high dose level of 50-fold AM in rasH2-Tg mouse carcinogenicity studies does not appear to be of value according to the survey results.
JOURNAL OF TOXICOLOGIC PATHOLOGY
(2022)
Article
Toxicology
Katerina Vlasakova, Jennifer Bourque, Wendy J. Bailey, Shetal Patel, Elizabeth G. Besteman, Raymond J. Gonzalez, Frank D. Sistare, Warren E. Glaab
Summary: This study evaluated 4 biomarkers of tissue remodeling and inflammation, as well as the traditional serum parameter albumin, as potential blood-based biomarkers for monitoring drug-induced tissue injury and systemic inflammatory response. The results showed that these biomarkers performed well in detecting tissue injury and inflammation, with high sensitivity.
TOXICOLOGICAL SCIENCES
(2022)
Article
Toxicology
J. Christopher Corton, Constance A. Mitchell, Scott Auerbach, J. Pierre Bushel, Heidrun Ellinger-Ziegelbauer, Patricia A. Escobar, Roland Froetschl, Alison H. Harrill, Kamin Johnson, James E. Klaunig, Arun R. Pandiri, Alexei A. Podtelezhnikov, Julia E. Rager, Keith Q. Tanis, Jan Willem van der Laan, Alisa Vespa, Carole L. Yauk, Syril D. Pettit, Frank D. Sistare
Summary: There is growing recognition in the scientific community of the potential for using genomic biomarkers to reduce the need for conventional rodent carcinogenicity studies. These biomarkers can predict tumorigenic doses of chemicals by measuring gene transcripts and cancer driver gene mutations.
TOXICOLOGICAL SCIENCES
(2022)
Review
Biotechnology & Applied Microbiology
Keren J. Carss, Aimee M. Deaton, Alberto Del Rio-Espinola, Dorothee Diogo, Mark Fielden, Diptee A. Kulkarni, Jonathan Moggs, Peter Newham, Matthew R. Nelson, Frank D. Sistare, Lucas D. Ward, Jing Yuan
Summary: Studies of human genetics have provided important insights for drug discovery, including predicting potential effects and assessing safety. Human genetic data can be used as a model to anticipate the long-term effects and potential risks of therapeutic targets. This approach is particularly useful for evaluating the safety of drugs without suitable animal models.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Urology & Nephrology
Brian R. Lane, Stephen K. Babitz, Katerina Vlasakova, Allen Wong, Sabrina L. Noyes, William Boshoven, Pam Grady, Cindy Zimmerman, Susan Engerman, Maureen Gebben, Michael Tanen, Warren E. Glaab, Frank D. Sistare
EUROPEAN UROLOGY FOCUS
(2020)