Activity of NADPH-cytochrome P-450 reductase of the human heart, liver and lungs in the presence of (-)-epigallocatechin gallate, quercetin and resveratrol: an in vitro study.
NADPH-cytochrome P-450 reductase (P-450 reductase) plays a crucial role in the metabolism of many endogenic compounds and xenobiotics detoxication. The enzyme is also involved in the toxicity of some clinically important antitumour drugs (doxorubicin) and pesticides (paraquat). P-450 reductase activates them to their more toxic metabolites via one electron reduction which triggers free radical cascade. In some cases however, such transformation is essential to produce therapeutic effect in anticancer drugs. The main purpose of the paper was to evaluate the effect of three natural compounds found in human diet: (-)-epigallocatechin gallate (EGCG), quercetin and resveratrol on P-450 reductase activity. The activity of the enzyme was determined spectrophotometrically by measurement of the rate of cytochrome c reduction at 550 nm, in vitro, using human heart, liver and lung microsomes. It was found that quercetin increased the P-450 reductase activity in human organs at all tested doses. The activity of microcosms in all organs was enhanced according to the concentrations of quercetin, which increased the activity in the order lung>heart>liver. Addition of EGCG to the reaction mixture enhanced the P-450 reductase activity in the following order: liver>heart>lung. However, no significant effect of resveratrol on P-450 reductase activity was observed. It seems that the presence of quercetin and EGCG in the diet may increase P-450 reductase activity during doxorubicin therapy with subsequent increased risk of toxicity. A beneficial effect may be obtained in anticancer therapy with bioreductive agents like tirapazamine.
Dudka
Jaroslaw
J
Department of Clinical Pathomorphology, Medical University of Lublin, 8 Jaczewskiego Str., PL-20093 Lublin, Poland. ave123@wp.pl
Jodynis-Liebert
Jadwiga
J
Korobowicz
Elzbieta
E
Burdan
Franciszek
F
Korobowicz
Agnieszka
A
Szumilo
Justyna
J
Tokarska
Edyta
E
Klepacz
Robert
R
Murias
Marek
M
D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004032:Diet; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006540:Herbicides / Q000037:antagonists & inhibitors / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity; D011794:Quercetin / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D006540:Herbicides; D013267:Stilbenes; D004317:Doxorubicin; D002392:Catechin; D011794:Quercetin; C045651:epigallocatechin gallate; D009251:NADPH-Ferrihemoprotein Reductase; D010269:Paraquat; D000077185:Resveratrol