Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relationships between hepatic antioxidant paraoxonase (PON1) activity, lipid peroxidation, and liver injury were investigated in rats with CCl(4)-induced cirrhosis. The study was performed in 60 CCl(4)-treated rats and 60 control animals receiving a standard diet or one supplemented with zinc. Subsets of 10 animals each were killed at weeks 1, 5, and 7 of the study. Results showed that PON1 significantly decreased in rats given CCl(4) alone compared with control animals. This effect was partially reversed in animals receiving zinc. Conversely, lipid peroxides were significantly increased in rats given CCl(4) alone and returned to approximately normal values in animals receiving zinc supplement. PON1 was inversely correlated with lipid peroxidation in all the animals studied. These alterations coincided with changes in serum alanine aminotransferase activity. In vitro incubation of isolated microsomes with CCl(4) or malondialdehyde did not produce any significant changes in PON1, indicating that the decrease in PON1 in CCl(4)-treated animals was not secondary to a direct inhibitory effect of lipid peroxidation products. These data show a time course and quantitative relationship between PON1 activity and lipid peroxidation in rats with CCl(4)-induced cirrhosis and suggest that this enzyme plays a significant role within the antioxidant systems in liver microsomes.
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PMID:Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis. 1155 27

High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.
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PMID:Liver disease alters high-density lipoprotein composition, metabolism and function. 2710 40