Experiments for a systematic comparison between stable-isotope-(deuterium) labeling and radio-(14C) labeling for the elucidation of the in vitro metabolic pattern of pharmaceutical drugs

2013 ◽  
Vol 85 ◽  
pp. 138-144 ◽  
Author(s):  
Helge Grunwald ◽  
Patrick Hargreaves ◽  
Klaus Gebhardt ◽  
Dominique Klauer ◽  
Arnaud Serafyn ◽  
...  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Celinda M. Kofron ◽  
Tae Yun Kim ◽  
Fabiola Munarin ◽  
Arvin H. Soepriatna ◽  
Rajeev J. Kant ◽  
...  

AbstractCardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.


Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 614
Author(s):  
Manoj Kumar ◽  
Sushil Changan ◽  
Maharishi Tomar ◽  
Uma Prajapati ◽  
Vivek Saurabh ◽  
...  

Annona squamosa L. (custard apple) belongs to the family Annonaceae and is an important tropical fruit cultivated in the West Indies, South and Central America, Ecuador, Peru, Brazil, India, Mexico, the Bahamas, Bermuda, and Egypt. Leaves of custard apple plants have been studied for their health benefits, which are attributed to a considerable diversity of phytochemicals. These compounds include phenol-based compounds, e.g., proanthocyanidins, comprising 18 different phenolic compounds, mainly alkaloids and flavonoids. Extracts from Annona squamosa leaves (ASLs) have been studied for their biological activities, including anticancer, antidiabetic, antioxidant, antimicrobial, antiobesity, lipid-lowering, and hepatoprotective functions. In the current article, we discussed the nutritional and phytochemical diversity of ASLs. Additionally, ASL extracts were discussed with respect to their biological activities, which were established by in vivo and in vitro experiments. A survey of the literature based on the phytochemical profile and health-promoting effects of ASLs showed that they can be used as potential ingredients for the development of pharmaceutical drugs and functional foods. Although there are sufficient findings available from in vitro and in vivo investigations, clinical trials are still needed to determine the exact effects of ASL extracts on human health.


Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4287 ◽  
Author(s):  
Taobin Chen ◽  
Hao Wu ◽  
Yan He ◽  
Wenjun Pan ◽  
Zenghao Yan ◽  
...  

Widespread in citrus fruits, naringin, a natural 2,3-dihydroflavonoid, is of particular interest to scientists and has a broad range of beneficial bioactivities to health. Orally administered naringin remains in the gut tract for a relatively long time because of its low bioavailability. Under the metabolism mediated by human gut microbiota, naringin could be an active precursor for derived metabolites to play important physiological roles. However, naringin and its metabolites are hard to accurately quantify due to severe endogenic interference. In this study, an analytical rapid resolution liquid chromatography tandem mass spectrometry (RRLC-MS/MS) method coupled with stable isotope deuterium-labeling is developed and validated to simultaneously quantify naringin as well as its major human gut microbial metabolites naringenin and 3-(4′-hydroxyphenyl) propanoic acid. By eliminating the matrix interferences, this strategy not only confirms naringenin and 3-(4′-hydroxyphenyl) propanoic acid as the predominant metabolites which contribute to the pharmacological effects of naringin but also provides a suitable choice for other flavonoid pharmacokinetics study.


Author(s):  
Vidyavathi M ◽  
Koteswaramma L ◽  
Krishnaveni A ◽  
Madhuri T ◽  
Sarada B

Objective: Pharmacoeconomics refers to the scientific discipline that compares the value of pharmaceutical drugs or drug therapies. The pharmacoeconomic analysis includes the research methods related to cost minimization, cost-effectiveness, and cost-benefit analysis. The present study concerned with the pharmacoeconomic analysis of statin tablets (simvastatin [S1-S5], atorvastatin [A1-A5], and rosuvastatin [R1-R5]) of different brands which are varying in their prices using in vitro evaluation methods of tablets.Methods: Weight variation, friability, hardness, disintegration, and dissolution tests of all selected statin tablets were performed as per official procedure for the pharmacoeconomic comparative analysis.Results: It was found the least T90% with S5 and high T90% with S1 tablets among simvastatin tablets, the least T90% was observed with A1 and A5 and high T90% with A2 tablets among atorvastatin tablets, and least T 90% was observed with R5 and high T90% with R2 was found among rosuvastatin tablets without any relation with their order of prices. Hence, the study concluded that there is no significant correlation between cost and in vitro performance as there is no excellent in vitro performance found from the costliest tablets and vice versa.Conclusion: The range of the cost of different marketed statin tablets is from Rs.17.5 to Rs.127.0 per a strip of 10 tablets. All brands of three drugs have equal strength which are assumed to produce the same outcomes. As there is no significant correlation between cost and results of some of in vitro parameters of the tablets, the cost minimization analysis can be ruled out for these brands of S1 to


2012 ◽  
Vol 50 (6) ◽  
pp. 1866-1873 ◽  
Author(s):  
Maria Inês Dias ◽  
Lillian Barros ◽  
Maria João Sousa ◽  
Isabel C.F.R. Ferreira

2016 ◽  
Vol 133 ◽  
pp. 100-112 ◽  
Author(s):  
Victor Llombart ◽  
Teresa García-Berrocoso ◽  
Joan Josep Bech-Serra ◽  
Alba Simats ◽  
Alejandro Bustamante ◽  
...  

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 228 ◽  
Author(s):  
Ana Margarida Araújo ◽  
Maria Enea ◽  
Félix Carvalho ◽  
Maria de Lourdes Bastos ◽  
Márcia Carvalho ◽  
...  

Background and aims: Liver toxicity is a well-documented and potentially fatal adverse complication of hyperthermia. However, the impact of hyperthermia on the hepatic metabolome has hitherto not been investigated. Methods: In this study, gas chromatography-mass spectrometry (GC-MS)-based metabolomics was applied to assess the in vitro metabolic response of primary mouse hepatocytes (PMH, n = 10) to a heat stress stimulus, i.e., after 24 h exposure to 40.5 °C. Metabolomic profiling of both intracellular metabolites and volatile metabolites in the extracellular medium of PMH was performed. Results: Multivariate analysis showed alterations in levels of 22 intra- and 59 extracellular metabolites, unveiling the capability of the metabolic pattern to discriminate cells exposed to heat stress from cells incubated at normothermic conditions (37 °C). Hyperthermia caused a considerable loss of cell viability that was accompanied by significant alterations in the tricarboxylic acid cycle, amino acids metabolism, urea cycle, glutamate metabolism, pentose phosphate pathway, and in the volatile signature associated with the lipid peroxidation process. Conclusion: These results provide novel insights into the mechanisms underlying hyperthermia-induced hepatocellular damage.


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