Search results for "P450 content"
showing 3 items of 3 documents
Peroxynitrite generated from constitutive nitric oxide synthase mediates the early biochemical injury in short-term cultured hepatocytes
2000
AbstractEarly loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study provides experimental evidence for the induction – shortly after isolation through the classical procedure – of strong oxidative stress that involves both oxygen-derived and NO-derived species. NO formation at this stage is due to the early activation of liver constitutive NO synthase (cNOS). Immunodetection of nitrated proteins provides direct evidence of endogenous peroxynitrite (PN) formation upon hepatocyte isolation. On the basis of the combined use of dihydrorhodamine 123 and NOS inhibitors, the analysis of the amount, time course and nature of the species inv…
Endogenous nitric oxide is responsible for the early loss of P450 in cultured rat hepatocytes
1998
AbstractLoss of P450 during the early hours of monolayer formation is known to be the more serious limitation of primary cultured hepatocytes as an adequate model for the study of drug metabolism, toxicity and P450 induction. This study reports that endogenous nitric oxide (NO) formation is activated shortly after isolation by the classical collagenase-based liver perfusion methods. Both rapid P450 loss and aerobic mitochondrial energy metabolism impairment – with subsequent changes on glucose metabolism – are directly related to the high local generation of the radical at this stage. These effects can be reverted by the sole addition of NO biosynthesis inhibitors during liver perfusion and…
Differential sensitivity of rat hepatocyte CYP isoforms to self-generated nitric oxide.
2001
AbstractEarly loss of P450 in rat hepatocyte cultures appears directly related to nitric oxide (NO) overproduction. This study investigates the influence of endogenously generated NO (or NO-derived species) on the relative expression of cytochrome P450 (CYP) isoforms in rat hepatocytes. Our results support the view that loss of P450 holoenzyme in culture is the ultimate consequence of a NO driven process, activated during the common hepatocyte isolation procedure, that leads to an accelerated and selective degradation of specific CYP apoproteins. Under conditions in which NO and peroxynitrite formation is operative, changes in the level of specific CYP isoforms result in a significant alter…