Preventive effect of polyphenols from geranium sanguineum l on hepatic drug metabolism in influenza infected mice.
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1
Institute of Neurobiology, Bulgaria
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2
Medical University-Sofia, Bulgaria
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3
Bulgarian Academy of Sciences, Institute of Microbiology, Bulgaria
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4
St Kliment Ohridsky Sofia University, Bulgaria
Introduction: Inhibited first phase of drug metabolism is a main reason for numerous side effects and increased drug toxicity, observed in the course of influenza virus infection (IVI). Medical plant Geranium Sanguineum L. (GSL), spread in the Balkans, demonstrated significant antioxidant and antiviral activity. The aim of the study is to evaluate the preventive effect of polyphenol complex (PPC) from GSL on the oxidative drug metabolism in IVI.
Methods: The experimental model of IVI (A/Aichi/2/68/(H3N2)(4.5 lg LD50) is developed in male albino ICR mice. PPC is applied nasally (10 mg/kg). In liver 9 000 g supernatant thiobarbituric acid reactive substances (TBARS) and antioxidant total activity (ATA) as well as monooxygenase N-demethylase activity (ethylmorphyne, amidopyrine and analgin) and hydroxylase activity (aniline and p-nitrophenol), NADPH- cytochrtome P-450 reductase and cytochrome P-450 content are determined. Student-Fisher t-test and correlation coefficients are used for statistics.
Results: High correlation between increased TBARS and decreased monooxygenase activity (p< 0.001) is found in infected animals. It suggests that activation of free radicals can be one of the main reasons for unspecific monooxygenase inhibition, because all components of cytochrome P-450 system are inhibited (mostly the on the 6th and 9th days). PPC pretreatment demonstrates significant preventive effect against increased levels of TBRS and decreased ATA. Drug metabolism in IVI mice is restored by PPC near to healthy controls.
Conclusion: TBARS probably play important role not only in the pathogenesis of IVI, but also in modulation of hepatic monooxygenase activity. All inhibited P-450 monooxygenase activities are significantly restored by PPC pretreatment. The complex mechanism of PPC-protective effect obviously combines several biological activities- antioxidant activity, selective antiviral and protein-bounding effect. In contrast to infected animals, PPC has medium pro-oxidant and weak inhibiting effect on monooxygenases in healthy animals, probably related to its protein–binding effect on membrane proteins and enzymes.
Keywords:
influenza infection,
drug metabolism,
cyt P-450 monooxygenases,
Polyphenols,
Geranium Sanguineum L.
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Poster
Topic:
Xenobiotic metabolism
Citation:
Tantcheva
L,
Encheva
E,
Abarova
S,
Serkedjieva
J,
Dimova
I and
Pavlova
E
(2010). Preventive effect of polyphenols from geranium sanguineum l on hepatic drug metabolism in influenza infected mice..
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00203
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Received:
28 Oct 2010;
Published Online:
04 Nov 2010.
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Correspondence:
Dr. Eleonora Encheva, Medical University-Sofia, Sofia, Bulgaria, eleonora.encheva@medfac.acad.bg