Cytochrome P-450 heme and the regulation of hepatic heme oxygenase activity

Drug interaction of antitumor drugs. III. Antitumor activity of tegafur in lipopolysaccharide-treated mice.

“…LPS markedly reduced the activities of aminopyrine N demethylase and aniline hydroxylase in the 9,000xg supernatant of the liver homogenate and reduced cytochrome P-450 or cyto chrome b5 contents in the microsomes of the liver 24 hr after the injection. Decrease of enzyme activity induced by LPS is probably a consequence of damage to some compo nent of the electron-transport system such as cytochrome P-450 (18,19). A dose of 2.5 mg/kg, i.v., of LPS corresponds to about one twelfth the LD50 in mice.…”

Elucidating the Role of Biliverdin Reductase in the Expression of Heme Oxygenase-1 as a Cytoprotective Response to Stress

“…Several studies, including a few that were cited above (Nakahira et al, 2003;Odaka et al, 2000), have postulated that HO-1 induction following a stress event coincides with a rapid accumulation of free heme which presumably originates from damaged P450 enzymes. Evidence also was derived by observing a dramatic increase in the rate of degradation of labeled heme from P450 enzymes after HO-1 was induced by either hemin or endotoxin treatment (Bissell and Hammaker, 1976). More specifically, the data suggested that HO-1 increased the degradation of the P450 and not just the catabolism of the heme released from the P450.…”

Degradation of endogenous hepatic heme by pathways not yielding carbon monoxide. Studies in normal rat liver and in primary hepatocyte culture.

“…Similarly, catabolism of endogenous hepatic heme is known to give rise to biliruibin and CO (2, 7) and appears to be related to microsomal heme oxygenase in the liver (8). Because the latter is the only mechanism for heme breakdown of demonstrated physiological relevance, it has been assumed that endogenous hepatic heme, like exogenous heme, is degraded quantitatively to bile pigment and CO.…”