|
|
Effect of food supplement mixtures on selected biotransformation enzymes
Kurshakova, Evgeniia ; Dračínská, Helena (advisor) ; Koblihová, Jitka (referee)
Dietary supplements are globally used products designed to complement nutrition with additional nutrients. They contain a wide range of biologically active compounds: amino acids, vitamins, minerals, herbal extracts, etc. Due to the popularity and excessive consumption of food supplements, there is a growing need to research their potential interactions and impact on human health. Certain dietary supplements are metabolized by enzymes from the cytochrome P450 group, which play a key role in the biotransformation of exogenous substrates. Some biologically active compounds may also affect their activity. The presented thesis was focused on studying the influence of several popular components of dietary supplements on cytochromes P450 3A4 and 1A1 expressed in the gastrointestinal tract. The influence of metal ions Zn2+ and Mg2+ , ascorbate from the vitamin group, and curcumin from the polyphenol group was examined. A strong inhibitory effect of curcumin on the activity of both investigated isoforms was confirmed. The reaction of 6β-hydroxylation of testosterone catalyzed by CYP3A4 was significantly suppressed by the addition of curcumin, with the determined IC50 value being 4,7 M. A significant decrease in the rate of resorufin O-deethylation by rat and human CYP1A1 isoforms was also observed (IC50 =...
|
|
|
Effects of heme arginate in HIV-1 acute infection and in latency reversal
Prakash, Shankaran ; Mělková, Zora (advisor) ; Hirsch, Ivan (referee) ; Hejnar, Jiří (referee)
The available antiretroviral compounds can effectively suppress the replication of HIV-1 and block the disease progression. However it is impossible to eradicate the virus from the organism as the HIV-1 integrated in the genome is not affected by the existing anti-HIV-1 drugs. Therefore, new latency reversing agents are being actively developed as part of "shock and kill" therapy to reactivate the provirus and clear the reservoir. Normosang (heme arginate; HA) is a human hemin- containing compound used to treat acute porphyria. Heme is physiologically catabolised by heme oxygenases to form iron (Fe2+ ), carbon monoxide (CO) and biliverdin that is further converted to bilirubin by biliverdin reductase. In this study, we have demonstrated that HA inhibited HIV-1 replication during the acute infection, which was accompanied by the inhibition of reverse transcription. On the other hand, HA synergised with phorbol myristyl acetate (PMA) and reactivated the HIV-1 provirus in ACH-2 cells and the HIV-1 "mini-virus" in Jurkat cell clones A2 and H12. HIV-1 ''mini-virus'' was reactivated also by HA-alone. Further, we have studied the effects of heme degradation products on latent HIV-1 reactivation when added individually. We employed addition of ascorbate to generate Fe2+ , resulting in an increased...
|
|
|
Effects of heme arginate in HIV-1 acute infection and in latency reversal
Prakash, Shankaran ; Mělková, Zora (advisor) ; Hirsch, Ivan (referee) ; Hejnar, Jiří (referee)
The available antiretroviral compounds can effectively suppress the replication of HIV-1 and block the disease progression. However it is impossible to eradicate the virus from the organism as the HIV-1 integrated in the genome is not affected by the existing anti-HIV-1 drugs. Therefore, new latency reversing agents are being actively developed as part of "shock and kill" therapy to reactivate the provirus and clear the reservoir. Normosang (heme arginate; HA) is a human hemin- containing compound used to treat acute porphyria. Heme is physiologically catabolised by heme oxygenases to form iron (Fe2+ ), carbon monoxide (CO) and biliverdin that is further converted to bilirubin by biliverdin reductase. In this study, we have demonstrated that HA inhibited HIV-1 replication during the acute infection, which was accompanied by the inhibition of reverse transcription. On the other hand, HA synergised with phorbol myristyl acetate (PMA) and reactivated the HIV-1 provirus in ACH-2 cells and the HIV-1 "mini-virus" in Jurkat cell clones A2 and H12. HIV-1 ''mini-virus'' was reactivated also by HA-alone. Further, we have studied the effects of heme degradation products on latent HIV-1 reactivation when added individually. We employed addition of ascorbate to generate Fe2+ , resulting in an increased...
|
guest ::
