Down-regulation of oxidative stress and COX-2 and iNOS expressions by dimethyl lithospermate in aged rat kidney

• Published in: Archives of pharmacal research Vol. 37; no. 8; pp. 1032 - 1038
• Main Authors: Choi, Yeon Ja, Kim, Hyung Suk, Lee, Juyoun, Chung, Jin, Lee, Jun Sik, Choi, Jae Sue, Yoon, Taek Rim, Kim, Hyung Keun, Chung, Hae Young
• Format: Journal Article
• Language: English
• Published: Heidelberg Pharmaceutical Society of Korea 01.08.2014; 대한약학회
• Subjects: Aging - metabolism; Animals; Antioxidants - administration & dosage; Antioxidants - isolation & purification; Antioxidants - therapeutic use; Benzofurans - administration & dosage; Benzofurans - isolation & purification; Benzofurans - therapeutic use; Cyclooxygenase 2 - biosynthesis; cytotoxicity; DNA; dose response; Down-Regulation; inducible nitric oxide synthase; kidneys; lipids; Male; Medicine; metabolites; nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - biosynthesis; oxidative stress; Oxidative Stress - drug effects; Peroxynitrous Acid - metabolism; Pharmacology/Toxicology; Pharmacy; prostaglandin synthase; proteins; rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Research Article; Salvia miltiorrhiza; Salvia miltiorrhiza - chemistry; superoxide anion; Western blotting; 약학; Aging; iNOS; ONOO; COX-2; Reactive species; Dimethyl lithospermate
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-014-0332-6

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 ( • O 2 − ) 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.