Title: The impact of vitamins A,C,E, and selenium compound on
   prevention of liver cancer in rats.
   
   Author(s): Nyandieka HS; Wakhisi J
   
   Address: Department of Biochemistry, College of Health Sciences,
   University of Nairobi.
   
   Source: East Afr Med J 1993 Mar;70(3):151-3
   
   Abstract: A study was initiated to determine the impact of vitamins A,
   C, E, and selenium compound (Se) on the prevention of liver cancer.
   Sixty animals were fed a diet with or without these vitamins followed
   by aflatoxin B treatment for a period of 24 months. Most of the
   animals fed a diet devoid of vitamins developed liver cancer, while
   none or only a few of the animals given vitamins suffered during this
   period. We suggest that vitamins can inhibit liver cancer by inducing
   hepatic microsomal enzymes that metabolise aflatoxins to
   noncarcinogenic products
   
   Major Indexes:
     * Ascorbic Acid [therapeutic use]
     * Liver Neoplasms, Experimental [drug therapy]
     * Selenium [therapeutic use]
     * Vitamin A [therapeutic use]
     * Vitamin E [therapeutic use]
       
   Minor Indexes:
     * Aflatoxin B1
     * Aminopyrine N-Demethylase [drug effects]
     * Ascorbic Acid [pharmacology]
     * Cytochrome P-450 [drug effects]
     * Dimethyl Sulfoxide
     * Disease Models, Animal
     * Drug Screening
     * Liver Neoplasms, Experimental [chemically induced] [enzymology]
       [pathology] [prevention & control]
     * Rats, Wistar
     * Rats
     * Selenium [pharmacology]
     * Vitamin A [pharmacology]
     * Vitamin E [pharmacology]
       
   Reagent Names:
     * EC 1.5.3.- (Aminopyrine N-Demethylase)
     * 11103-57-4 (Vitamin A)
     * 1162-65-8 (Aflatoxin B1)
     * 1406-18-4 (Vitamin E)
     * 50-81-7 (Ascorbic Acid)
     * 67-68-5 (Dimethyl Sulfoxide)
     * 7782-49-2 (Selenium)
     * 9035-51-2 (Cytochrome P-450)
       
   Language: English
   Periodical Type: JOURNAL ARTICLE


   ILTS ELTA LICAGE Berlin 2001
   
   # 349
   High transferrin saturation and non.transferrin bound iron in acute
   fulminant liver failure compared to choronic liver failure
   Helena M Isoniemi1 , Leni von Bonsdorff2 , Jaakko Parkkinen2 , Krister
   Höckerstedt1
   1Helsinki University Hospital, Transplantation and Liver Surgery Unit,
   00130 Helsinki, Finland
   Iron has ability to catalyse reactions leading to the production of
   highly toxic oxygen radicals. Normally serum iron is trasferrin bound
   and the remaining non-transferrin-bound iron (NTBI) fraction is
   extremely small. It is not known whether iron-induced hepatotoxicity
   may be directly involved in hepatitis and cirrhosis. Hepatocytes,
   unlike many other cells, have clearance mechanism of NTBI in iron
   overload. Our aim was to study the occurrence of NTBI in acute
   fulminant and end-stage chronic liver failure immediately prior to the
   liver transplantation (LTx) and at discharge after LTx Blood samples
   were investigated in 12 patients with acute fulminant hepatitis (AHF)
   and 16 patients with primary biliary cirrhosis (PBC) before LTx anf
   after LTx with good graft function. NTBI was measured by the
   bleomycin-detectable iron (BDI) method and considered as positive if
   >0.1µmol/L. In AHF, 9/12 (75%) of the patients were positive for NTBI
   before LTx, whereas in PBC only 2/16 (12.5%) were positive. After LTx,
   all AHF patients were negative for NTBI. In AHF, the mean transferrin
   saturation was 84% before LTx and decreased to 35% after LTx. This was
   mainly due to a decrease of the mean serum total iron level to less
   than half after LTx. Serum transferrin level was clearly below the
   reference level both before and after LTx in AHF. In PBC transferrin
   saturation was at normal range and total iron was low before LTx.Table
   1.Median of BDI and mean levels of S-Fe and Transferrin and % of
   transferrin saturationAHF n =12 positive NTBI BDI µmol/L s-Fe µmol/L
   Transferrin g/l Saturation %beforeLTx 9 (75%) 0.48 32.4 1.44 84%after
   LTx 0 (0%) 0.02 12.9 1.61 35% p<.05 p<.0001 ns p<.0001PBC n=16
   beforeLTx 2 (12.5%) 0.03 16.24 1.84 40%after LTx 2 (12.5%) 0.04 14.86
   1.82 35% ns ns ns nsOur results indicate that the majority of patients
   with AHF have high transferrin saturation and NTB in serum before
   transplantaion. Theoretically, this could worsen acute liver cell
   damage.
   
     _________________________________________________________________
   

     _________________________________________________________________
     _________________________________________________________________


Subject: fattyliver

Could oxidative stress and lipid peroxidaton be critical factors in the
genesis and progression of NAFL?
Sem Liver Disease 21(1):81-88, 2001
http://www.medscape.com/38460.rhtml?srcmp=ms-060101
Read it
Here

     _________________________________________________________________


Subject: chelator/liver/iron

[Why are we not surprised?]

Deferoxamine prevents lipid peroxidation-related liver injury in rats 

WESTPORT, Mar 30 (Reuters Health) - Administration of the iron 
chelator deferoxamine reduces preneoplastic hepatic lesions in a rat 
model of lipid peroxidation, indicating that iron control may be 
important in preventing liver cirrhosis and neoplasia. 

Dr. Isao Sakaida and colleagues at Yamaguchi University in Japan 
examined the effects of deferoxamine in rats maintained on a 
choline-deficient L-amino acid-defined diet. The diet induces liver 
fibrosis and neoplasm development via lipid peroxidation, according to 
a report in the March issue of Digestive Diseases and Sciences. 

After only 2 weeks, rats fed the diet demonstrated an increase in 
serum ALT levels, which was inhibited by administration of
deferoxamine. And after 12 weeks on the diet, "...[deferoxamine] 
reduced the liver hydroxyproline content...in a dose-dependent manner 
up to a dose of 400 mg/kg with a reduction of iron content in the  
liver and an increase of the serum iron concentration." 

Untreated rats developed preneoplastic lesions that "...mainly 
consisted of nodules surrounded by fibrous septa, resulting in the
formation of pseudolobuli..." after 12 weeks, Dr. Sakaida and his team 
report. Administration of the iron chelator prevented these events as 
well. 

The findings support a key role for lipid peroxidation-catalyzed iron 
in liver injury, the Japanese team concludes. 

Dig Dis Sci 1999;44:560-569. 

     _________________________________________________________________


Subject: siderosis/lung/kidney

   
   Semin Hematol 1998 Jan;35(1):77-86
   
Secondary iron overload disorders.

    Bottomley SS
    
   Department of Medicine, University of Oklahoma College of Medicine,
   Oklahoma City, USA.
   
   Diverse clinical disorders distinct from hereditary hemochromatosis
   are associated with accumulation of excess body iron in heterogeneous
   patterns and through various mechanisms. A deranged iron turnover
   somehow relates to the altered physiological barrier for iron
   absorption in several defined chronic anemias with ineffective
   erythropoiesis. Unexcretable excess iron acquired from transfusions
   provides a therapeutic challenge. Genetic defects of proteins
   essential for transport of iron into and out of cells (transferrin and
   ceruloplasmin) deprive the erythron of the metal and cause its
   accumulation in other vital organs. The hemochromatosis alleles
   predictably contribute to an iron burden from other causes, commonly
   facilitate the expression of porphyria cutanea tarda, and their
   clinical expression may be accelerated by hereditary hemolytic
   anemias. Even minimal iron excess in liver disease may contribute to
   the hepatocellular injury from factors such as alcohol and viruses.
   Uniquely localized siderosis occurs in the lung and kidney where iron
   cannot turn over and causes variable tissue damage. The most
   devastating iron overload disorder, neonatal hemochromatosis, is
   understood least of all.
   
   Publication Types:
     * Review
     * Review, tutorial
       
   PMID: 9(HOME) 460811, UI: 98122143
     _________________________________________________________________


Subject: iron and liver

   
   Can J Gastroenterol 2000 Nov;14(Suppl D):89D-92D
   
Iron and liver diseases.

    Fargion S, Mattioli M, Fracanzani AL, Fiorelli G
    
   Universita di Milano, Milano, Italy.
   
   [Record supplied by publisher]
   
   A mild to moderate iron excess is found in patients with liver
   diseases apparently unrelated to genetic hemochromatosis. Iron appears
   to affect the natural history of hepatitis C virus-related chronic
   liver diseases, alcoholic liver disease and nonalcoholic
   steatohepatitis by leading to a more severe fibrosis and thus aiding
   the evolution to cirrhosis. A higher frequency of mutations of the HFE
   gene, the gene responsible for hereditary hemochromatosis, is found in
   patients with liver diseases and increased liver iron than in normal
   patients. Patients with excess iron are potentially at a higher risk
   of developing hepatocellular carcinoma. Iron depletion therapy could
   interfere with fibrosis development and possibly reduce the risk of
   liver cancer occurrence.
   
   PMID: 11110619
     _________________________________________________________________
   
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Subject: low iron diet/liver

   
   Br J Nutr 2000 Mar;83(3):235-9
   
Beneficial influence of an indigenous low-iron diet on serum indicators of iron
status in patients with chronic liver disease.

    Tandon N, Thakur V, Guptan RK, Sarin SK
    
   Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India.
   
   The main Fe storage organ in the body is the liver. In patients with
   chronic liver disease, secondary Fe overload is common. Phlebotomy,
   often used in the West to reduce Fe overload to improve the efficacy
   of interferon therapy, is not socially acceptable in India. We
   assessed the efficacy of a low-Fe diet in reducing serum Fe levels.
   Nineteen patients with hepatitis B- and C-related chronic liver
   disease, ten with normal (< 25 mumol/l) baseline serum Fe levels
   (group A) and nine with high (> 25 mumol/l) serum Fe levels (group B)
   were included. All the subjects were advised to eat a low-Fe diet. The
   daily Fe intake was reduced approximately 50% by consumption of the
   rice-based diet. Haemoglobin, serum Fe, transferrin saturation index
   (TSI), ferritin and alanine transaminase (EC 2.6.1.2) levels were
   studied at 1 and 4 months. Dietary Fe intake and body weight were
   closely monitored. All patients complied with the dietary regimen and
   at 4 months significant (P < 0.001) reductions from baseline were seen
   in serum Fe (20 (SD 3) v. 12 (SD 4) mumol/l group A; 30 (SD 3) v. 19
   (SD 7) mumol/l group B) and TSI (38 (SD 8) v. 23 (SD 9)% group A; 53
   (SD 15) v. 34 (SD 13)%, group B) in both the groups, albeit earlier in
   group B subjects. Serum ferritin levels, however, reduced only in
   group A (112 (SD 62) v. 43 (SD 25) ng/ml, P < 0.05) and not in group
   B. Non-significant reductions in haemoglobin levels were seen in both
   groups. Alanine transaminase levels reduced significantly (P < 0.05)
   in both the groups (95 (SD 49) v. 44 (SD 25) IU/l, group A; 82 (SD 16)
   v. 51 (SD 14) IU/l group B). Thus, a low-Fe diet results in
   significant reductions in serum Fe and TSI levels, irrespective of
   baseline Fe levels. This diet should be evaluated to improve the
   efficacy of interferon therapy in patients with hepatitis B- and
   C-related chronic liver disease.
   
   PMID: 10884711, UI: 20343090
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Subject: iron and liver

   
   Can J Gastroenterol 2000 Nov;14(Suppl D):89D-92D
   
Iron and liver diseases.

    Fargion S, Mattioli M, Fracanzani AL, Fiorelli G
    
   Universita di Milano, Milano, Italy.
   
   [Record supplied by publisher]
   
   A mild to moderate iron excess is found in patients with liver
   diseases apparently unrelated to genetic hemochromatosis. Iron appears
   to affect the natural history of hepatitis C virus-related chronic
   liver diseases, alcoholic liver disease and nonalcoholic
   steatohepatitis by leading to a more severe fibrosis and thus aiding
   the evolution to cirrhosis. A higher frequency of mutations of the HFE
   gene, the gene responsible for hereditary hemochromatosis, is found in
   patients with liver diseases and increased liver iron than in normal
   patients. Patients with excess iron are potentially at a higher risk
   of developing hepatocellular carcinoma. Iron depletion therapy could
   interfere with fibrosis development and possibly reduce the risk of
   liver cancer occurrence.
   
   PMID: 11110619
     _________________________________________________________________
   
   Save the above report in [Macintosh] [Text] format
   Order documents on this page through Loansome Doc
     _________________________________________________________________



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