Prooxidant activity and toxicity of nordihydroguaiaretic acid in clone-9 rat hepatocyte cultures.
Nordihydroguaiaretic acid (NDGA) is a polyphenol. It is present at high concentrations in the leaves of the evergreen desert shrub, Larrea tridentate (Creosote bush), which has a long history of medicinal use traditionally by the native Americans and Mexicans. It is generally believed that the antioxidant properties of NDGA are responsible for the medicinal value of this desert shrub. The clone-9 rat hepatocyte cultures were used as an in vitro model to assess the hepatotoxic potential of NDGA and to determine whether it exhibits any prooxidant activity. The hepatocyte cultures were treated with NDGA for 2 h at 37 degrees C at concentrations of 0-100 microM. After the treatment period the cells, the culture supernatants and cell lysates were assayed for evaluation of prooxidant activity and toxicity of NDGA. Oxidative stress level and oxidative cell injury as measured by the peroxidation of membrane lipids and DNA double-strand breaks were used to index prooxidant activity. Cytotoxicity as measured by the leakage of the liver enzyme lactate dehydrogenase (LDH) into the culture medium, mitochondrial function and extent of cell proliferation were used as the endpoints of toxicity. Significant concentration-dependent differences were observed in these biomarkers over the concentration range examined demonstrating the prooxidant activity and toxicity of NDGA in clone-9 rat hepatocyte cultures.
Sahu
Saura C
SC
Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, 8301 Muirkirk Road, Laurel, MD 20708, USA. saura.sahu@fda.hhs.gov
Ruggles
Dennis I
DI
O'Donnell
Michael W
MW
D000818:Animals; D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009637:Masoprocol / Q000494:pharmacology / Q000633:toxicity*; D008930:Mitochondria, Liver / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000494:pharmacology / Q000633:toxicity*
D017382:Reactive Oxygen Species; D009637:Masoprocol