β-Carotene Degradation Products - Formation, Toxicity and Prevention of Toxicity

被引:24
作者
Siems, Werner [1 ]
Salerno, Costantino [4 ]
Crifo, Carlo [5 ]
Sommerburg, Olaf [2 ]
Wiswedel, Ingrid [3 ]
机构
[1] KortexMed Inst Med Educ, Res Inst Physiotherapy & Gerontol, DE-38667 Bad Harzburg, Germany
[2] Univ Heidelberg, Univ Childrens Hosp, Dept 3, D-6900 Heidelberg, Germany
[3] Otto VonGuericke Univ Magdegurg, Inst Clin Chem & Pathol Biochem, Dept Pathol Biochem, Magdeburg, Germany
[4] Univ Roma La Sapienza, Lab Clin Biochem, Rome, Italy
[5] Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy
来源
FOOD FACTORS FOR HEALTH PROMOTION | 2009年 / 61卷
关键词
LUNG-CANCER; OXIDATIVE STRESS; VITAMIN-A; RECEPTOR RESPONSES; CLEAVAGE PRODUCTS; HYPOCHLOROUS ACID; MITOCHONDRIA; ANTIOXIDANT; SUPPLEMENTATION; INHIBITION;
D O I
10.1159/000212740
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Carotenoids are widely used as important micronutrients in food. Furthermore, carotenoid supplementation has been used in the treatment of diseases associated with oxidative stress such as various types of cancer, inflammatory diseases or cystic fibrosis. However, in some clinical studies harmful effects have been observed, e.g. a higher incidence of lung cancer in individuals exposed to extraordinary oxidative stress. The causal mechanisms of harmful effects are still unclear. Carotenoid breakdown products (CBPs) including highly reactive aldehydes and epoxides are formed during oxidative attacks in the course of antioxidative action. We investigated the formation of CBPs by stimulated neutrophils (and at further conditions), tested the hypothesis that CBPs may exert mitochondriotoxicity and tried to prevent toxicity in the presence of members of the antioxidative network. Stimulated neutrophils are able to degrade beta-carotene and to generate a number of CBPs. Concerning mitochondriotoxicity, we found that CBPs strongly inhibit state 3 respiration of rat liver mitochondria at concentrations between 0.5 and 20 mu M. This was true for retinal, beta-ionone, and for mixtures of cleavage/breakdown products. The inhibition of mitochondrial respiration was accompanied by a reduction in protein sulfhydryl content, decreasing GSH levels and redox state, and elevated accumulation of malondialdehyde. Changes in mitochondrial membrane potential favor functional deterioration in the adenine nucleotide translocator as a sensitive target. The presence of additional antioxidants such as alpha-tocopherol, ascorbic acid, N-acetyl-cysteine or others could mitigate mitochondriotoxicity. The findings reflect a basic mechanism of increasing the risk of cancer induced by carotenoid degradation products. Copyright (C) 2009 S. Karger AG, Basel
引用
收藏
页码:75 / 86
页数:12
相关论文
共 38 条
[1]   alpha-tocopherol and beta-carotene supplements and lung cancer incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: Effects of base-line characteristics and study compliance [J].
Albanes, D ;
Heinonen, OP ;
Taylor, PR ;
Virtamo, J ;
Edwards, BK ;
Rautalahti, M ;
Hartman, AM ;
Palmgren, J ;
Freedman, LS ;
Haapakoski, J ;
Barrett, MJ ;
Pietinen, P ;
Malila, N ;
Tala, E ;
Liippo, K ;
Salomaa, ER ;
Tangrea, JA ;
Teppo, L ;
Askin, FB ;
Taskinen, E ;
Erozan, Y ;
Greenwald, P ;
Huttunen, JK .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1996, 88 (21) :1560-1570
[2]   MICROTITER PLATE ASSAY FOR THE MEASUREMENT OF GLUTATHIONE AND GLUTATHIONE DISULFIDE IN LARGE NUMBERS OF BIOLOGICAL SAMPLES [J].
BAKER, MA ;
CERNIGLIA, GJ ;
ZAMAN, A .
ANALYTICAL BIOCHEMISTRY, 1990, 190 (02) :360-365
[3]   Hepatic subcellular storage of beta-carotene in rats following diet supplementation [J].
Bianchi-Santamaria, A ;
Stefanelli, C ;
Cembran, M ;
Gobbi, M ;
Peschiera, N ;
Vannini, V ;
Santamaria, L .
INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH, 1999, 69 (01) :3-7
[4]   BETA-CAROTENE - AN UNUSUAL TYPE OF LIPID ANTIOXIDANT [J].
BURTON, GW ;
INGOLD, KU .
SCIENCE, 1984, 224 (4649) :569-573
[5]   Mitochondrial free radical generation, oxidative stress, and aging [J].
Cadenas, E ;
Davies, KJA .
FREE RADICAL BIOLOGY AND MEDICINE, 2000, 29 (3-4) :222-230
[6]   INHIBITION OF ADENINE-NUCLEOTIDE TRANSLOCATOR BY LIPID-PEROXIDATION PRODUCTS [J].
CHEN, JJ ;
BERTRAND, H ;
YU, BP .
FREE RADICAL BIOLOGY AND MEDICINE, 1995, 19 (05) :583-590
[7]  
CHIRICO S, 1994, METHOD ENZYMOL, V233, P314
[8]   POTENTIAL ROLES OF HYPOCHLOROUS ACID AND N-CHLOROAMINES IN COLLAGEN BREAKDOWN BY PHAGOCYTIC-CELLS IN SYNOVITIS [J].
DAVIES, JMS ;
HORWITZ, DA ;
DAVIES, KJA .
FREE RADICAL BIOLOGY AND MEDICINE, 1993, 15 (06) :637-643
[9]   TISSUE SULFHYDRYL GROUPS [J].
ELLMAN, GL .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1959, 82 (01) :70-77
[10]   RAPID ONE-STEP PROCEDURE FOR PURIFICATION OF MONONUCLEAR AND POLYMORPHONUCLEAR LEUKOCYTES FROM HUMAN-BLOOD USING A MODIFICATION OF HYPAQUE-FICOLL TECHNIQUE [J].
FERRANTE, A ;
THONG, YH .
JOURNAL OF IMMUNOLOGICAL METHODS, 1978, 24 (3-4) :389-393