Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of hexachlorobenzene feeding on liver delta-aminolaevulinate synthase, uroporphyrinogen decarboxylase and cytochrome P 450 was studied at various time-intervals in siderotic and non-siderotic rats. 2 In the non-siderotic group hexachlorobenzene feeding led to a progress decrease in liver uroporphyrinogen decarboxylase activity, accompanied by a progressive increase in delta-aminolaevulinate synthase activity. Cytochrome P 450 concentrations were above normal throughout but fell toward the end of the experiment. 3. Similar but more marked changes were found in the siderotic animals. The fall in uroporphyrinogen decarboxylase activity occurred earlier and was significantly greater in these animals, whereas the increase in delta-aminolaevulinate synthase activity was consistently larger. Liver cytochrome P 450 concentration also rose but to a lesser extent than that in the non-siderotic rats. 4. Hexachlobenzene-induced porphyria would seem to be attributable to inhibition or inactivation of hepatic uroporphyrinogen decarboxylase. Hepatic siderosis has a synergistic effect with hexachlorobenzene on this enzyme and may exert additional effects by promoting cytochrome P 450 turnover.
Clin Sci Mol Med 1977 Aug
PMID:Effects of hexachlorobenzene feeding and iron overload on enzymes of haem biosynthesis and cytochrome P 450 in rat liver. 89 Nov

A unique organic form of iron (dicyclopentadienyl iron; ferrocene) has been used to further elucidate specific hepatic histopathologic, biochemical, and molecular parameters associated with dietary iron overload. Male C57BL/6Ibg mice fed a diet containing 0.04-0.2% w/w ferrocene for 115 days displayed severe hepatic siderosis of hepatocytes accompanied by a 15-fold induction of nonheme iron content compared to control mice receiving a diet with normal amounts of iron. The ferrocene treatment led to significant increases in hepatocellular necrosis as measured by plasma alanine aminotransferase activity. Histological assessment of hepatic fibrosis revealed mild increases in collagen deposition localized with accumulations of hemosiderin primarily in centrilobular hepatocytes. Hepatic fibrosis was confirmed by measurement of hepatic hydroxyproline content that was increased 4-fold in ferrocene-fed animals compared to control animals not ingesting ferrocene. Hepatic siderosis was accompanied by significant increases in hepatic malondialdehyde content suggesting the ferrocene-induced iron burden initiated lipid peroxidation in vivo. Expression of the heavy-chain isoform of ferritin mRNA and protein measured in liver after ferrocene feeding was increased approximately 8- and 2-fold, respectively, compared to the appropriate controls. These results, using an organic form of iron fed to genetically well-characterized inbred mice, provide new additional insight into the specific molecular and biochemical events that occur in association with histopathologic changes initiated by iron-induced liver injury. These data support the hypothesis that peroxidation of cellular membrane lipids is an important mechanism involved in the toxicity of excess hepatic iron and possibly the initiation of liver fibrogenesis. The results presented here also provide novel in vivo evidence documenting the cellular modulation of ferritin in response to the toxic effects of hepatic iron overloading and iron-mediated oxidative stress.
Exp Mol Pathol 2000 Feb
PMID:Characterization of hepatic iron overload following dietary administration of dicyclopentadienyl iron (Ferrocene) to mice: cellular, biochemical, and molecular aspects. 1064 Apr 49