An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Author(s):  
Talita Miguel Marin ◽  
Nathalia de Carvalho Indolfo ◽  
Silvana Aparecida Rocco ◽  
Murilo de Carvalho ◽  
Marilia Meira Dias ◽  
...  
2020 ◽  
pp. 31-32
Author(s):  
Mikhail A. Levchenko ◽  
◽  
Natalia A. Sennikova ◽  

Toxicological assessment is a mandatory research step in the development of new insecticidal drugs. At the All-Russian Research Institute of Veterinary Entomology and Arachnology, a prototype of the insecticidal bait Mukhnet IF was obtained with an active ingredient content of 0.06% ivermectin and 0.015% fipronil, which showed a highly effective effect against houseflies. This work presents the results of the study of acute oral toxicity of the above agent. For this, male white mice with a live weight of 16-26 g were selected. They were kept on a starvation diet for one day in individual houses with water. The drug was given in mg/kg body weight the next day. A total of 33 doses have been tested, ranging from 100 mg/kg to 40,000 mg/kg. The animals were observed for 14 days. According to the research results, it was revealed that at doses up to 20,000 mg/kg there were no signs of intoxication, but when tested at 25,000 mg/kg in some mice, these signs were noted, and at 30,000, 35,000 and 40,000 mg/kg deaths were recorded 20±10, 45±30 and 60±20%, respectively. It was not possible to test the drug over the last above dose due to incomplete eaten by mice. According to the degree of danger for warm-blooded animals, the drug belongs to the 4th class of low-hazard drugs (average lethal dose of 5000 mg/kg or more) in accordance with the classification of GOST 12.1.007-76. When analyzing the literature data on the toxicological characteristics of preparations containing ivermectin and chlorfenapyr, it was revealed that the insecticidal agent in its acute toxicity for warm-blooded animals is comparable to known analogues.


2019 ◽  
Vol 3 (3) ◽  
pp. 64-70 ◽  
Author(s):  
Rashydah Ahmed ◽  
◽  
Hadiza Nuhu ◽  
Hajara Ibrahim ◽  
Aliyu Nuhu ◽  
...  

Author(s):  
A. A. Maslennikov ◽  
S. A. Demidova ◽  
A. V. Ryabova

Water containing polyvinyl nitrate was experimentally assessed on the basis of organoleptic, general sanitary and toxicological indicators of harmfulness. It was established that that the compound did not change water organoleptic properties but produced a negative impact on viability of saprophytic microflora , nitrification processes and biochemical oxygen demand. Besides, in tests on animals. the substance caused acute, sub-acute and chronic toxicity. Based on those signs of harmfulness, threshold levels of exposure were established. Data obtained were taken into account for substantiation of MAC (Maximum allowable concentration) of polyvinyl nitrate in water bodies.


2020 ◽  
Author(s):  
Katharine Horzmann ◽  
◽  
Chloe de Perre ◽  
Linda S. Lee ◽  
Andrew J. Whelton ◽  
...  

2020 ◽  
Vol 10 (4) ◽  
pp. 242
Author(s):  
Giulia Di Prima ◽  
Giuseppina Campisi ◽  
Viviana De Caro

Nowadays the therapeutic strategies to manage Parkinson’s Disease are merely symptomatic and consist of administering L-DOPA and/or dopamine receptor agonists. Among these, Ropinirole (ROP) is a widely orally-administered molecule, although it is extensively susceptible to hepatic metabolism. Since literature reports the buccal mucosa as a potentially useful route to ROP administration, the development of novel, effective, and comfortable oromucosal formulations should prove desirable in order to both enhance the therapeutic efficacy of the drug and allow a personalized therapeutic strategy able to meet the patient’s needs. The results of the proposed ROP film as a new dosage form show that it is flexible; uniform; and characterized by suitable surface pH; good mucoadhesiveness; low swelling degree; and fast, complete drug release. Moreover, after ex vivo evaluation on a film having an area of 0.282 cm2 and dose of 2.29 mg, the results of drug flux through the buccal mucosa are closely comparable to the amount of ROP that reaches the bloodstream at the steady-state condition after ROP-PR 4 mg oral administration, calculated according to the literature (0.237 mg/cm2·h−1 vs. 0.243 mg/h, respectively). Moreover, drug flux and ROP dose could be accurately modulated time-by-time depending on the patient’s need, by varying the administered disk area. In addition, the proposed ROP film displays no lag time, producing an immediate drug input in the bloodstream, which could result in a prompt therapeutic response. These findings make ROP film a potentially comfortable and patient-friendly formulation, and a promising candidate for further clinical trials.


2011 ◽  
Vol 45 (3) ◽  
pp. 1394-1402 ◽  
Author(s):  
Alam G. Trovó ◽  
Raquel F. Pupo Nogueira ◽  
Ana Agüera ◽  
Amadeo R. Fernandez-Alba ◽  
Sixto Malato

2021 ◽  
pp. 096032712110227
Author(s):  
S Kara-Ertekin ◽  
S Yazar ◽  
M Erkan

Pyrethroid pesticides are frequently used for household insect control of insects and in agriculture and livestock. Flumethrin is a pyrethroid that is used against ectoparasites in many animals. The goal of this study was to evaluate the cytotoxic, apoptotic, genotoxic, and estrogenic effects of flumethrin on the mammalian breast cancer cell line (MCF-7). Compared with control groups, a dose-dependent decrease was observed in cell viability at concentrations of 100 µM and higher. The cytotoxic and apoptotic effects detected by LDH assay and AO/EtBr staining increased significantly at a concentration of 1000 µM. The expression of BCL2, which is an anti-apoptotic gene, significantly decreased, whereas BAX, TP53, and P21 expression significantly increased. The results of a comet assay indicated that flumethrin significantly changed tail length, tail % DNA, tail moment, and Olive tail moment in concentrations above 1 and 10 µM. In addition, a 0.1 µM concentration of flumethrin affected ERα receptor mediated cell proliferation and increased transcription of estrogen-responsive pS2 (TFF1) and progesterone receptor (PGR) genes. As a result, flumethrin-induced apoptosis and cytotoxicity at a high concentration, while induced genotoxicity even at lower concentrations. Flumethrin is an endocrine disrupting insecticide with estrogenic effects at very low concentrations.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 508
Author(s):  
Sara Silva ◽  
António J. Almeida ◽  
Nuno Vale

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.


2019 ◽  
Vol 679 ◽  
pp. 209-220 ◽  
Author(s):  
Nazrul Islam ◽  
Anjum Dihingia ◽  
Prasenjit Manna ◽  
Tonkeswar Das ◽  
Jatin Kalita ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document