Down-regulation of oxidative stress and COX-2 and iNOS expressions by dimethyl lithospermate in aged rat kidney.
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.
Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, 609-735, South Korea.
Yeon Ja
YJ
Choi
Hyung Suk
HS
Kim
Juyoun
J
Lee
Jin
J
Chung
Jun Sik
JS
Lee
Jae Sue
JS
Choi
Taek Rim
TR
Yoon
Hyung Keun
HK
Kim
Hae Young
HY
Chung
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D001572:Benzofurans / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D015536:Down-Regulation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry
D000975:Antioxidants; D001572:Benzofurans; D017382:Reactive Oxygen Species; C530488:dimethyl lithospermate; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat