毒理学相关资料,第五章内容参考文献13.pdfVIP

The labile iron pool in hepatocytes: prooxidant-induced increase in free iron precedes oxidative cell injury ¨ ANNA STAUBLI AND URS A. BOELSTERLI Institute of Toxicology, Swiss Federal Institute of Technology and University of Zurich, CH-8603 Schwerzenbach, Switzerland Sta¨ubli, Anna, and Urs A. Boelsterli. The labile iron equilibrium between free and bound iron, as well as its pool in hepatocytes: prooxidant-induced increase in free iron oxidation state, may be altered (16). With the advent of precedes oxidative cell injury. Am. J. Physiol. 274 (Gastro- the use of calcein (CA) as an iron-sensitive fluorescent intest. Liver Physiol. 37): G1031–G1037, 1998.—The labile probe, it has become possible to quantitate the basal iron pool (LIP) represents the nonferritin-bound, redox-active content, as well as to assess relative changes, of LIP- iron that has been implicated in oxidative stress and cell associated iron in intact cells. With this method, a injury. Here we examined whether alterations in LIP can be detected in cultured murine hepatocytes and whether in- series of elegant studies has characterized the dynam- creases in LIP are related to the oxidative damage inflicted by ics of the LIP in human cell lines (6–8, 10, 12, 44). As the redox cycling drug nitrofurantoin (NFT). Early changes in yet this technique has not been applied to primary LIP were monitored with the metal-sensitive fluorescent cultures of hepatocytes, although hepatic parenchymal probe calcein (CA), the fluorescence of which is quenched on cells play an important role both in the uptake and binding to iron. Short-term exposure ( 1 h) to NFT reduced storage of iron (1, 3), as well as in the metabolic the CA fluorescence signal by 30%, indicating tha