scholarly journals Development of Novel Diclofenac Analogs Designed to Avoid Metabolic Activation and Hepatocyte Toxicity

ACS Omega ◽  
2020 ◽  
Vol 5 (50) ◽  
pp. 32608-32616
Author(s):  
Yasuhiro Tateishi ◽  
Tomoyuki Ohe ◽  
Mai Ogawa ◽  
Kyoko Takahashi ◽  
Shigeo Nakamura ◽  
...  
Keyword(s):  
Metabolic Activation ◽  
Hepatocyte Toxicity

scholarly journals Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHP

2021 ◽  
Vol 22 (12) ◽  
pp. 6320
Author(s):  
Monia Lenzi ◽  
Veronica Cocchi ◽  
Sofia Gasperini ◽  
Raffaella Arfè ◽  
Matteo Marti ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Metabolic Activation ◽  
Fold Increase ◽  
Synthetic Cathinones ◽  
The Other ◽  
Oxygen Species ◽  
Genetic Damage ◽  
Mutagenic Potential ◽  
Tk6 Cells ◽  
Mutagenic Effects

Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35–100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure.

Effects of steric hindrance and electron density of ester prodrugs on controlling the metabolic activation by human carboxylesterase

2021 ◽  
pp. 100391
Author(s):  
Masato Takahashi ◽  
Ibuki Hirota ◽  
Tomoyuki Nakano ◽  
Tomoyuki Kotani ◽  
Daisuke Takani ◽  
...  
Keyword(s):  
Electron Density ◽  
Steric Hindrance ◽  
Metabolic Activation ◽  
Ester Prodrugs
Sign in / Sign up

Export Citation Format

Share Document