ABSTRACT
Ethanol increases iron absorption. Therefore, increased amount of iron reaches the liver, and exerts pro-oxidant effects and stimulates ferritin synthesis and hepatic stellate cell activation, promoting fibrosis and inflammation. These mechanisms would theoretically support a role of ferritin as a marker of the transition to liver cirrhosis, and, consequently, as a prognostic factor, but there is controversy regarding its behavior in alcoholics. We analyzed among 238 severe alcoholics the prognostic value of iron, ferritin, transferrin, transferrin saturation index (TSI) and total iron binding capacity (TIBC), and the relationships of these variables with liver function, proinflammatory markers (C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor α), and the presence of cirrhosis. Patients showed higher serum ferritin (Z = 2.50, p = 0.031) but lower transferrin (t(264) = 4.81, p < 0.001), TIBC (t(262) = 4.44, p < 0.001), and iron (Z = 3.19, p = 0.001) values compared with 32 age- and sex-matched controls. Ferritin was related to inflammatory cytokines such as IL-8 (ρ = 0.18, p = 0.012) and to IL-6 (ρ = 0.16, p = 0.016), but not to liver function. On the contrary, cirrhotics showed lower transferrin (t(234) = 4.77, p < 0.001) and TIBC (t(232) = 4.67, p < 0.001), but higher TSI (Z = 3.35, p < 0.001) than non-cirrhotics. Transferrin, TSI, and TIBC were related to liver function impairment (marked differences among the Child's groups regarding transferrin (KW (2) = 22.83, p < 0.001), TSI (KW (2) = 15.81, p < 0.001), and TIBC (KW (2) = 21.38, p < 0.001) but only weakly to inflammation (inverse relationships between IL-6 and total iron (ρ = - 0.16, p = 0.017), TIBC (ρ = - 0.20, p = 0.002), and transferrin (ρ = - 0.20, p = 0.003). In accordance, albumin, IL-6, alcohol quitting, and TSI, in this order, were independently related to mortality, but not ferritin or iron.
Subject(s)
Ferritins/blood , Iron/blood , Liver Diseases, Alcoholic/blood , Transferrin/metabolism , Female , Humans , Liver Diseases, Alcoholic/diagnosis , Male , Middle AgedABSTRACT
Both manganese and copper may affect bone synthesis. Bone content of both metals can be altered in alcoholics, although controversy exists regarding this matter. To analyse the relative and combined effects of ethanol and a low protein diet on bone copper and manganese, and their relationships with bone structure and metabolism, including trabecular bone mass (TBM), osteoid area (OA), osteocalcin (OCN), insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), urinary hydroxyproline (uHP) and vitamin D. Adult male Sprague-Dawley rats were divided into four groups. The control rats received a 18% protein-containing diet; a second group, an isocaloric, 2% protein-containing diet; a third one, an isocaloric, 36% ethanol-containing diet and a fourth, an isocaloric diet containing 2% protein and 36% ethanol. After sacrifice, TBM and OA were histomorphometrically assessed; bone and serum manganese and copper were determined by atomic absorption spectrophotometry, and serum OCN, IGF-1, PTH, uHP and vitamin D by radioimmunoassay. Ethanol-fed rats showed decreased TBM and bone manganese. Significant relationships existed between bone manganese and TBM, serum IGF-1 and OCN. Ethanol leads to a decrease in bone manganese, related to decreased bone mass and bone synthesis. No alterations were found in bone copper.
Subject(s)
Bone and Bones/drug effects , Copper/metabolism , Ethanol/pharmacology , Manganese/metabolism , Protein Deficiency/metabolism , Animals , Bone Density/drug effects , Bone and Bones/metabolism , Central Nervous System Depressants/administration & dosage , Central Nervous System Depressants/pharmacology , Copper/blood , Diet, Protein-Restricted/adverse effects , Ethanol/administration & dosage , Hydroxyproline/urine , Insulin-Like Growth Factor I/metabolism , Male , Manganese/blood , Osteocalcin/blood , Parathyroid Hormone/blood , Protein Deficiency/blood , Protein Deficiency/physiopathology , Radioimmunoassay , Rats , Rats, Sprague-Dawley , Spectrophotometry, Atomic , Vitamin D/bloodABSTRACT
UNLABELLED: Some observations suggest that oxidative damage may affect both osteoblastic function and osteoclastic activity in alcohol-mediated bone alterations. Selenium, a potent antioxidant, is decreased in alcoholics. OBJECTIVE: To analyse if the supplementation with selenium may alter bone changes observed in a murine model fed ethanol and/or a 2% protein-containing diet, following the Lieber-deCarli design. MATERIAL AND METHOD: Adult male Sprague-Dawley rats were divided into 8 groups, which received the Lieber-DeCarli control diet, an isocaloric, 36% ethanol-containing diet, an isocaloric, 2% protein-containing diet; and an isocaloric diet containing 2% protein and 36% ethanol diet, and another similar four groups to which selenomethionine (1mg/kg body weight). After sacrifice (5 weeks later), trabecular bone mass was histomorphometrically assessed, bone and serum selenium were determined by flame atomic absorption spectrophotometry, and serum osteocalcin, insulin growth factor 1 (IGF-1), PTH and telopeptide, by radioimmunoanalysis. Liver glutathione peroxidase (GPX) activity was also determined. RESULTS: Ethanol-fed rats showed decreased TBM, IGF-1 and osteocalcin, especially when ethanol was added to a 2%-protein diet. Selenium did not modify at all bone parameters, despite a marked increase in serum selenium and a less pronounced one in bone selenium, and an increase in liver GPX. CONCLUSION: Our results do not support the existence of a beneficial effect of selenium addition on bone changes observed in this murine model treated following the Lieber-deCarli experimental design.
