Synthetic Water-Soluble Phenolic Antioxidant Regulates L-Arginine Metabolism in Macrophages: a Possible Role of Nrf2/ARE

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V. O. Tkachev^1,2*, E. B. Menshchikova¹, N. K. Zenkov¹, N. V. Kandalintseva³, and N. N. Volsky²

¹Research Center of Clinical and Experimental Medicine, Siberian Branch of the Russian Academy of Medical Sciences, ul. Timakova 2, 630117 Novosibirsk, Russia; fax: (383) 333-6456; E-mail: Tkachev_victor@mail.ru

²Research Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, ul. Yadrintsevskaya 14, 630047 Novosibirsk, Russia; fax: (383) 236-0329; E-mail: v_kozlov@online.nsk.su

³Novosibirsk State Pedagogical University, ul. Vilyuiskaya 28, 630126 Novosibirsk, Russia; fax: (383) 244-1856; E-mail: chemistry@ngs.ru

^* To whom correspondence should be addressed.

Received September 13, 2009; Revision received October 30, 2009

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Synthetic water-soluble phenolic antioxidant TS-13 exhibits pronounced anti-inflammatory properties in vivo and induces intracellular signal system Nrf2/ARE. At concentrations 150-1000 µM it inhibits nitric oxide (NO) production in mouse peritoneal macrophages. However, this compound at low concentrations (1-100 µM) paradoxically increases NO production and decreases activity of arginase. These results are indicative of an ambiguous role of NO and its metabolites in the mechanism of development of inflammatory reaction.

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KEY WORDS: nitric oxide, arginase, macrophages, inflammation, antioxidant responsive element, Nrf2, TS-13

DOI: 10.1134/S0006297910050020

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