Background and aims: Neuronal oxidative stress has beenstrongly implicated in the pathogenesis of hepatic encephalopathy (HE). Normal liver functioning, by producing “scavengers” proteins like transferrin (Tf) and ceruloplasmin (Cp), prevents metal systemic overload, which is a great contributor to oxidativedamage. We aimed to verify if liver dysfunction determinesan alteration in metals homeostasis in encephalopathicpatients. Methods: Normal controls without liver disease(CON), patients with chronic hepatitis (CH), and cirrhoticpatients without (NENC) or with (ENC) anamnesis and/orongoing clinical signs of overt HE, were studied. All subjects underwent: 1) determination of Cp, Cp activity, iron, and Tf; 2)repeatable battery for the assessment of neuropsychologicalstatus (RBANS); 3) 10-20 system electroencephalography(EEG). Biochemical variables were measured by validatedmethods. The ratios Cp activity/Cp and Cp/Tf were calculated as recognized indices of specific Cp activity and of the Cp-Tfsystem functionality, respectively. Results: Fourteen CON, 7 CHpatients, and 18 cirrhotic patients (8 NENC and 10 ENC),were studied. At RBANS, cirrhotics performed significantly worse with respect to CON and CH patients (p<0.01). EEGalterations suggestive of HE were observed in 3 out the 10ENC patients but in none of the patients from the other 3 subgroups (p<0.01). Biochemical results are reported in Table 1.While demonstrating nonsignificant fluctuations in CH and NENC patients, Cp activity, Tf, and the ratios Cp activity/Cp and Cp/Tf showed significant alterations in ENC cirrhoticscompared with the other 3 subgroups. Moreover, also Cp and Tf Sat were altered in ENC patients with respect to controls, while no differences were observed in iron concentrations. Conclusions: Cirrhotics with HE present strong alterations in metal homeostasis. The decrease in Cp, Cp specific activity and Tf contribute to a reduced capacity to contrast metal tissue accumulation, possibly also in the brain, leading to oxidative stress. The increase of the Cp/Tf ratio represents the activation of an ineffective antioxidant system.
METAL HOMEOSTASIS IN PATIENTS WITH PORTO-SYSTEMIC ENCEPHALOPATHY
Vespasiani Gentilucci U;Galati G;Ursini F;Tombini M;Quintiliani L;Vernieri F;Picardi A.
2011-01-01
Abstract
Background and aims: Neuronal oxidative stress has beenstrongly implicated in the pathogenesis of hepatic encephalopathy (HE). Normal liver functioning, by producing “scavengers” proteins like transferrin (Tf) and ceruloplasmin (Cp), prevents metal systemic overload, which is a great contributor to oxidativedamage. We aimed to verify if liver dysfunction determinesan alteration in metals homeostasis in encephalopathicpatients. Methods: Normal controls without liver disease(CON), patients with chronic hepatitis (CH), and cirrhoticpatients without (NENC) or with (ENC) anamnesis and/orongoing clinical signs of overt HE, were studied. All subjects underwent: 1) determination of Cp, Cp activity, iron, and Tf; 2)repeatable battery for the assessment of neuropsychologicalstatus (RBANS); 3) 10-20 system electroencephalography(EEG). Biochemical variables were measured by validatedmethods. The ratios Cp activity/Cp and Cp/Tf were calculated as recognized indices of specific Cp activity and of the Cp-Tfsystem functionality, respectively. Results: Fourteen CON, 7 CHpatients, and 18 cirrhotic patients (8 NENC and 10 ENC),were studied. At RBANS, cirrhotics performed significantly worse with respect to CON and CH patients (p<0.01). EEGalterations suggestive of HE were observed in 3 out the 10ENC patients but in none of the patients from the other 3 subgroups (p<0.01). Biochemical results are reported in Table 1.While demonstrating nonsignificant fluctuations in CH and NENC patients, Cp activity, Tf, and the ratios Cp activity/Cp and Cp/Tf showed significant alterations in ENC cirrhoticscompared with the other 3 subgroups. Moreover, also Cp and Tf Sat were altered in ENC patients with respect to controls, while no differences were observed in iron concentrations. Conclusions: Cirrhotics with HE present strong alterations in metal homeostasis. The decrease in Cp, Cp specific activity and Tf contribute to a reduced capacity to contrast metal tissue accumulation, possibly also in the brain, leading to oxidative stress. The increase of the Cp/Tf ratio represents the activation of an ineffective antioxidant system.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
