Barriers, Nephrotoxicology and Chronic Testing In Vitro

2002 ◽  
Vol 30 (2_suppl) ◽  
pp. 101-105 ◽  
Author(s):  
Pilar Prieto

In many organs of the human body, there are effective physiological barriers which contribute to regulation of the uptake, transport and secretion of endogenous and exogenous materials. ECVAM is involved in the development of several in vitro models for detecting damage to various barriers, including, the renal epithelium, the intestinal barrier, and the blood–brain barrier, after acute and chronic exposure to chemicals and products of various kinds. Long-term toxicity testing is an important issue in toxicology. At present, there are no generally accepted in vitro models available for replacing chronic testing in animals. Under chronic exposure conditions, the cellular response is greater than that which can be predicted in the standard cytotoxicity models. Therefore, the approach to predicting chronic toxicity will need to involve more-complex in vitro models. Several currently available in vitro long-term toxicity systems are under evaluation.

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Patrick D. M. C. Katoto ◽  
Amanda S. Brand ◽  
Buket Bakan ◽  
Paul Musa Obadia ◽  
Carsi Kuhangana ◽  
...  

Abstract Background Air pollution is one of the world’s leading mortality risk factors contributing to seven million deaths annually. COVID-19 pandemic has claimed about one million deaths in less than a year. However, it is unclear whether exposure to acute and chronic air pollution influences the COVID-19 epidemiologic curve. Methods We searched for relevant studies listed in six electronic databases between December 2019 and September 2020. We applied no language or publication status limits. Studies presented as original articles, studies that assessed risk, incidence, prevalence, or lethality of COVID-19 in relation with exposure to either short-term or long-term exposure to ambient air pollution were included. All patients regardless of age, sex and location diagnosed as having COVID-19 of any severity were taken into consideration. We synthesised results using harvest plots based on effect direction. Results Included studies were cross-sectional (n = 10), retrospective cohorts (n = 9), ecological (n = 6 of which two were time-series) and hypothesis (n = 1). Of these studies, 52 and 48% assessed the effect of short-term and long-term pollutant exposure, respectively and one evaluated both. Pollutants mostly studied were PM2.5 (64%), NO2 (50%), PM10 (43%) and O3 (29%) for acute effects and PM2.5 (85%), NO2 (39%) and O3 (23%) then PM10 (15%) for chronic effects. Most assessed COVID-19 outcomes were incidence and mortality rate. Acutely, pollutants independently associated with COVID-19 incidence and mortality were first PM2.5 then PM10, NO2 and O3 (only for incident cases). Chronically, similar relationships were found for PM2.5 and NO2. High overall risk of bias judgments (86 and 39% in short-term and long-term exposure studies, respectively) was predominantly due to a failure to adjust aggregated data for important confounders, and to a lesser extent because of a lack of comparative analysis. Conclusion The body of evidence indicates that both acute and chronic exposure to air pollution can affect COVID-19 epidemiology. The evidence is unclear for acute exposure due to a higher level of bias in existing studies as compared to moderate evidence with chronic exposure. Public health interventions that help minimize anthropogenic pollutant source and socio-economic injustice/disparities may reduce the planetary threat posed by both COVID-19 and air pollution pandemics.


2021 ◽  
Vol 22 (4) ◽  
pp. 1725
Author(s):  
Diego Delgado ◽  
Ane Miren Bilbao ◽  
Maider Beitia ◽  
Ane Garate ◽  
Pello Sánchez ◽  
...  

Platelet-rich plasma (PRP) is a biologic therapy that promotes healing responses across multiple medical fields, including the central nervous system (CNS). The efficacy of this therapy depends on several factors such as the donor’s health status and age. This work aims to prove the effect of PRP on cellular models of the CNS, considering the differences between PRP from young and elderly donors. Two different PRP pools were prepared from donors 65–85 and 20–25 years old. The cellular and molecular composition of both PRPs were analyzed. Subsequently, the cellular response was evaluated in CNS in vitro models, studying proliferation, neurogenesis, synaptogenesis, and inflammation. While no differences in the cellular composition of PRPs were found, the molecular composition of the Young PRP showed lower levels of inflammatory molecules such as CCL-11, as well as the presence of other factors not found in Aged PRP (GDF-11). Although both PRPs had effects in terms of reducing neural progenitor cell apoptosis, stabilizing neuronal synapses, and decreasing inflammation in the microglia, the effect of the Young PRP was more pronounced. In conclusion, the molecular composition of the PRP, conditioned by the age of the donors, affects the magnitude of the biological response.


1995 ◽  
Vol 23 (4) ◽  
pp. 491-496
Author(s):  
Hanna Tähti ◽  
Leila Vaalavirta ◽  
Tarja Toimela

— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tasks concerning the use of in vitro models in the evaluation of neurotoxic risks. It is based on our previous studies with various in vitro models and on recent literature. The induction of glial fibrillary acidic protein in astrocyte cultures after treatment with known neurotoxicants (mercury compounds and aluminium) is discussed in more detail as an important response which can be detected in vitro. When used appropriately with in vivo tests and with previous toxicological data, in vitro neurotoxicity testing considerably improves risk assessment. The incorporation of in vitro tests into the early stages of risk evaluation can reduce the number of animals used in routine toxicity testing, by identifying chemicals with high neurotoxic potential.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1334
Author(s):  
Ye Liu ◽  
Zahra Mohri ◽  
Wissal Alsheikh ◽  
Umber Cheema

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.


2013 ◽  
Vol 2 (1) ◽  
pp. 23-39 ◽  
Author(s):  
Valerie Y. Soldatow ◽  
Edward L. LeCluyse ◽  
Linda G. Griffith ◽  
Ivan Rusyn

Author(s):  
Geeta Bhandari Garima Negi

Abstract-Acute and chronic exposure to nonphysiological doses of ultraviolet radiation leads to variety of changes of skin ranging from sun-burn, erythema to skin cancer. For skin protection from deleterious effects of sunlight, sunscreen products are used in various forms having chemical and physical filters. However, synthetic sunscreen formulations are reported to cause adverse effects. Thus the present study was planned to evaluate the sun protection factor (SPF) of leaves extract of Murraya koenigii for their application as herbal sunscreens. The results suggested that the occurrence of active compounds responsible for ultraviolet absorption can be extracted for use in sunscreens preparations as better, cheaper and safe alternative to harmful chemical sunscreens. Keywords: UV radiations, SPF, Murraya koenigii


2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 110-115 ◽  
Author(s):  
Susan Yung ◽  
Chan Tak Mao

♦ Background The introduction of peritoneal dialysis (PD) as a modality of renal replacement therapy has provoked much interest in the biology of the peritoneal mesothelial cell. Mesothelial cells isolated from omental tissue have immunohistochemical markers that are identical to those of mesothelial stem cells, and omental mesothelial cells can be cultivated in vitro to study changes to their biologic functions in the setting of PD. ♦ Method The present article describes the structure and function of mesothelial cells in the normal peritoneum and details the morphologic changes that occur after the introduction of PD. Furthermore, this article reviews the literature of mesothelial cell culture and the limitations of in vitro studies. ♦ Results The mesothelium is now considered to be a dynamic membrane that plays a pivotal role in the homeostasis of the peritoneal cavity, contributing to the control of fluid and solute transport, inflammation, and wound healing. These functional properties of the mesothelium are compromised in the setting of PD. Cultures of peritoneal mesothelial cells from omental tissue provide a relevant in vitro model that allows researchers to assess specific molecular pathways of disease in a distinct population of cells. Structural and functional attributes of mesothelial cells are discussed in relation to long-term culture, proliferation potential, age of tissue donor, use of human or animal in vitro models, and how the foregoing factors may influence in vitro data. ♦ Conclusions The ability to propagate mesothelial cells in culture has resulted, over the past two decades, in an explosion of mesothelial cell research pertaining to PD and peritoneal disorders. Independent researchers have highlighted the potential use of mesothelial cells as targets for gene therapy or transplantation in the search to provide therapeutic strategies for the preservation of the mesothelium during chemical or bacterial injury.


Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2621
Author(s):  
Gerrit Bredeck ◽  
Angela A. M. Kämpfer ◽  
Adriana Sofranko ◽  
Tina Wahle ◽  
Veronika Büttner ◽  
...  

The increasing use of engineered nanomaterials (ENM) in food has fueled the development of intestinal in vitro models for toxicity testing. However, ENM effects on intestinal mucus have barely been addressed, although its crucial role for intestinal health is evident. We investigated the effects of ENM on mucin expression and aimed to evaluate the suitability of four in vitro models of increasing complexity compared to a mouse model exposed through feed pellets. We assessed the gene expression of the mucins MUC1, MUC2, MUC5AC, MUC13 and MUC20 and the chemokine interleukin-8 in pre-confluent and confluent HT29-MTX-E12 cells, in stable and inflamed triple cultures of Caco-2, HT29-MTX-E12 and THP-1 cells, and in the ileum of mice following exposure to TiO2, Ag, CeO2 or SiO2. All ENM had shared and specific effects. CeO2 downregulated MUC1 in confluent E12 cells and in mice. Ag induced downregulation of Muc2 in mice. Overall, the in vivo data were consistent with the findings in the stable triple cultures and the confluent HT29-MTX-E12 cells but not in pre-confluent cells, indicating the higher relevance of advanced models for hazard assessment. The effects on MUC1 and MUC2 suggest that specific ENM may lead to an elevated susceptibility towards intestinal infections and inflammations.


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