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Protective Effect of ubiquinone and Precursors of ItsSynthesis on Mitochondrial Respiratory Chain andActivity of Matrix Metalloproteinases in Animal Tissuesunder Effect of Doxorubicin

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Journal of Pharmacy and Pharmacology 2015年第3期3卷 116-127页

作者： Anatoliy Burlaka Olena Kuchmenko Dmytro Petukhov Iryna Ganusevych Sergiy Lukin Evgeniya Lukyanchuk Evgen Sydoryk Georgiy Donchenko Department of Microenvironment of Tumor Cells Kavetsky Institute of Experimental Pathology Oncology and Radiobiology ofthe National Academy of Sciences of Ukraine Kyiv 03022 Ukraine Laboratory of Molecular Biochemistry Department of Fundamental Research National Scientific Centre "Strazhesko Institute ofCardiology" of the National Academy of Medical Sciences of Ukraine Kyiv 03680 Ukraine Laboratory of Cell Signaling Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine Kyiv 01601Ukraine Department of Vitamin and Coenzyme Biochemistry PaUadin Institute of Biochemistry of the National Academy of Sciences ofUkraine Kyiv 01601 Ukraine

Mitochondrial dysfunction, oxidative stress, and their regulation are important fields of study in modem clinical *** CoQ is an efficient therapeutic agent, yet its application has leads to continued suppression of endogenous CoQ synthesis,which limits CoQ applicability. Our aim was to study the state of mitochondrial electron transport chain components, CoQ contentand redox state, superoxide anion radicals and NO production rates, and active MMP-2 and MMP-9 content in rat liver and heartunder treatment with Doxorubicin, CoQ10, and complex preparation of modulators and precursors of CoQ biosynthesis （EPMcomplex）. The results demonstrate that treatment with EPM complex and CoQ10 in addition to Doxorubicin administration exertsprotective effect on liver and heart mitochondria, evidenced by restoration of electron transport in respiratory chain, which isexpressed as decreased nitrile complexes formation with Fe-S-proteins and increased ubisemiquinone content. The protective effectsof EPM complex on mitochondrial electron transport chain under Doxorubicin administration is on par with those of CoQ10, anddecreased MMP2 and MMP9 activities signify lessened extracellular matrix destruction. These results demonstrate the viability ofapproaches to correct adverse effects of Doxorubicin by treatment with CoQ10 and e complex of precursors and modulators of itsbiosynthesis.

关键词： ubiquinone, mitochondrion, matrix metalloproteinases, doxorubicin.

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