Naslov
ACACETIN, APIGENIN, CHRYSIN AND PINOCEMBRIN CAUSE IRREVERSIBLE CYP3A4 INHIBITION BY HEME DESTRUCTION

Autori
Bojić, Mirza ; Kondža, Martin ; Maleš, Željan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
27HSKIKI Book of Abstracts / - , 2021

Skup
27. hrvatski skup kemičara i kemijskih inženjera (27HSKIKI)

Mjesto i datum
Veli Lošinj, Hrvatska, 05.10.2021. - 08.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
flavonoids, inhibition, CYP3A4

Sažetak
Flavonoids are ubiquitous plant compounds consumed in everyday diet through fruits and vegetables. Cytochrome P450 enzymes are hemoproteins, involved in the metabolism of drugs and lipophilic xenobiotics. Most registered active pharmaceutical ingredients are substrates of CYP3A4 enzyme. It has previously been reported that acacetin, apigenin, chrysin and pinocembrin irreversibly inhibit CYP3A4 enzyme. The objective of this study was to determine if inhibition is achieved through heme destruction. For this purpose, hemochromopyridine test was used. Hemochromopyridine test is based on the formation of heme iron complex with pyridine. Complex is yellow colored and can be measured spectrophotometrically. Heme concentration was measured after incubation of flavonoids with CYP3A4 baculosomes containing NADP reductase and cytochrome b5. Reaction was initiated with the addition of coenzyme NADPH. Heme concentration was determined after 30 minutes of incubation and was expressed as percentage to the control that did not contain an inhibitor. The residual heme concentration after incubation with acacetin, apigenin, chrysin, and pinocembrin was 49%, 45%, 5%, 25%, respectively. Heme destruction can also be caused by the reactive oxygen species that are generated in the nonproductive cytochrome P450 cycle. To eliminate this possibility flavonoids incubations were repeated with the addition of superoxide dismutase and catalase. No significant change was observed in residual heme concentration when compared to incubation without superoxide dismutase and catalase. It can be concluded that inhibition of cytochrome P450 by the analyzed flavonoids is mediated by heme destruction. Further analysis is needed to determine possible heme adducts and reactive flavonoid intermediaries responsible for the destruction.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA