In laboratory experiments, many electrophilic cytotoxic agents induce cell death accompanied by reactive oxygen species (ROS) production and/or by glutathione (GSH) depletion. Not surprisingly, millimolar concentrations of N-acetylcysteine (NAC), which is used as a universal ROS scavenger and precursor of GSH biosynthesis, inhibit ROS production, restore GSH levels, and prevent cell death. The protective effect of NAC is generally used as corroborative evidence that cell death induced by a studied cytotoxic agent is mediated by an oxidative stress-related mechanism. However, any simple interpretation of the results of the protective effects of NAC may be misleading because it is unable to interact with superoxide (O2•-), the most important biologically relevant ROS, and is a very weak scavenger of H2O2. In addition, NAC is used in concentrations that are unnecessarily high to stimulate GSH synthesis. Unfortunately, the possibility that NAC as a nucleophile can directly interact with cytotoxic electrophiles to form non-cytotoxic NAC-electrophile adduct is rarely considered, although it is a well-known protective mechanism that is much more common than expected. Overall, apropos the possible mechanism of the cytoprotective effect of NAC in vitro, it is appropriate to investigate whether there is a direct interaction between NAC and the cytotoxic electrophile to form a non-cytotoxic NAC-electrophilic adduct(s).

• Klíčová slova
• N-acetylcysteine, N-acetylcysteine-electrophile adduct, electrophile, mechanism of protection, nucleophile,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Antiradical and cytoprotective activities of several flavanones isolated from Paulownia tomentosa (Thunb.) Steud. (Scrophulariaceae) have been evaluated using different in vitro and in vivo methods. The capacity of flavanones to scavenge radicals was measured in vitro by means of DPPH and ABTS assays, the inhibition of hydroxyl radicals produced in Fenton reactions, FRAP, scavenging superoxide radicals using enzymatic and nonenzymatic assays and the inhibition of peroxynitrite-induced nitration of tyrosine. The in vivo testing involved measuring the cytoprotective effect of chosen flavanones against alloxan-induced diabetes in mice. The activity of tested compounds was expressed either as a Trolox® equivalent or was compared with rutin or morine as known antioxidant compounds. The highest activity in most tests was observed for diplacone and 3´-O-methyl-5´-hydroxydiplacone, and the structure vs. the antioxidant activity relationship of geranyl or prenyl-substituted flavonoids with different substitutions at the B and C ring was discussed.

• MeSH
• cytoprotekce účinky léků   MeSH
• experimentální diabetes mellitus farmakoterapie   MeSH
• flavanony izolace a purifikace   farmakologie   MeSH
• myši MeSH
• ovoce chemie   MeSH
• scavengery volných radikálů izolace a purifikace   farmakologie   MeSH
• Scrophulariaceae chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• flavanony MeSH
• scavengery volných radikálů MeSH