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KMID : 0043320140370081032
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Archives of Pharmacal Research
2014 Volume.37 No. 8 p.1032 ~ p.1038
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Down-regulation of oxidative stress and COX-2 and iNOS expressions by dimethyl lithospermate in aged rat kidney
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Choi Yeon-Ja
Kim Hyung-Suk
Lee Ju-Youn
Chung Jin
Lee Jun-Sik
Choi Jae-Sue
Yoon Taek-Rim
Kim Hyung-Keun
Chung Hae-Young
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Abstract
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Oxidative stress has been proposed to be a major cause of aging and many age-related diseases. Peroxynitrite (ONOO?), formed from the reaction of superoxide (?O2?) and nitric oxide (NO), is a cytotoxic species that can oxidize various cellular components, such as proteins, lipids, and DNA. The present study investigated whether dimethyl lithospermate (DML), isolated from Salvia miltiorrhiza, modulates age-related increases of ONOO?, NO, and reactive species (RS) levels and expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). For this study, 20-month-old rats were intraperitoneally injected with 5 or 10 mg/kg/day of DML, and 6-month-old rats were used as young control animals. Our results indicated that DML reduces ONOO? levels in a dose-dependent manner. The data also revealed that DML has significant inhibitory effects on NO metabolites and RS generation in a dose-dependent manner during aging. Furthermore, the results of Western blot analysis revealed that DML treatment reduces age-associated increases in COX-2 and iNOS expressions. Thus, this study found that DML caused the decrease of renal oxidative stress and COX-2 and iNOS expressions in aged rats. The significance of the present study is the finding of DML in its potential application against the aging process.
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KEYWORD
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Aging, COX-2, Dimethyl lithospermate, iNOS, Reactive species, ONOO-
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