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第十五届国际药理学大会

作者： Rumaks Juris Helves Zsuzsanna Dzirkale Zane Dilendorfa Jelena Pupure Jolanta kalvinsh ivars Klusa Vija Department of Pharmacology Faculty of MedicineUniversity of LatviaLatvia. Department of Pharmacology and Pharmacotherapy Faculty of MedicineUniversity of PecsHungary. Department of Pharmacology Faculty of MedicineUniversity of LatviaLatvia. Department of Pharmacology Faculty of MedicineUniversity of LatviaLatvia. Department of Pharmacology Faculty of MedicineUniversity of LatviaLatvia. Latvian Institute of Organic Synthesis. Department of Pharmacology Faculty of MedicineUniversity of LatviaLatvia.

＜正＞ Sensory neuropathy due to mitochondrial impairment is recognized as a common side effect of the anti - HIV drag azidothymidine （AZT）. The aim of the present study was to investigate the effect of mildronate. amitochondria - targeted drug,on hyperalgesia caused by AZT and peripheral nerve injury. Continuous treatment with mildronate （100 mg/kg/day i.p.） reduced hyperalgesia （tail flick test） in Balb/c mice caused by 2 - week administration of AZT （50 mg/kg/day i.p.）. In Wistar rats,traumatic mononeuropathy was induced by partial ligation of the sciatic nerve,mechanonociceptive threshold of the paws was measured by *** of mechanical hyperalgesia was observed from postoperative day 3 （PD3） up to PD12. In control group,hyperalgesia developed on PD7 and lasted throughout the whole observation period. Mildronate （100 and 200 mg/kg/day i. p. for 12 days） prevented the development of hyperalgesia. These data suggest mildronate as a promising drag for the treatment of AZT - induced toxic polyneuropathy, as well as traumatic mononeuropathy after nerve injury.

关键词： mildronate AZT mechanical hyperalgesia rodents

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Effects of Indole-3-Carbinol and Flavonoids Administered Separately and in Combination on Nitric Oxide Production and iNOS Expression in Rats

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Chinese Medicine 2010年第1期1卷 5-17页

作者： Evita Rostoka Larisa Baumane Sergejs Isajevs Aija Line Karina Silina Maija Dzintare Darja Svirina Jelena Sharipova ivars kalvinsh Nikolajs Sjakste 不详

Beneficial effects of natural compounds are often attributed to modulation of NO production;however effects produced by plant extracts do not correlate with effects of purified components. The goal of our work was to study ability of flavonoids and indole-3-carbinol, as well as their combinations to modify NO production, iNOS gene and protein expression in rat tissues. Baicalein and luteolin decreased NO concentration in both intact and LPS-treated animals. Baicalein decreased iNOS gene expression. Luteolin decreased NO production in the liver and heart and number of iNOS-positive cells in the liver of LPS-treated animals. Combination of the two substances did not decrease the NO synthesis triggered by LPS, although it decreased iNOS gene expression. Quercetin decreased NO production in the heart, kidneys and blood of intact rats, but enhanced the LPS effect in testes, spleen and blood on NO production and iNOS protein expression in the liver. Indole-3-carbinol decreased NO concentration in the cerebellum, blood, lungs and skeletal muscles. The drug enhanced the LPS-triggered increase of NO production in all rat organs. It increased iNOS protein expression in intact liver;however it decreased the LPS-triggered outburst of the enzyme biosynthesis. Combination of indole3-carbinol with quercetin decreased NO production in LPS-treated animals however it slightly increased iNOS gene expression. Taken together our results suggest that modifications of NO level in tissues by a natural compound cannot be predicted from data about its effects on NOS expression or activity. Combination of substances can produce an effect differing from that of individual substances. This stresses importance of direct measurements of NO in the tissues.

关键词： Nitric Oxide Baicalein Luteolin Indole-3-Carbinol Quercetin Inducible Nitric Oxide Synthase

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