Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures: Prevention by superoxide dismutase+catalase and vitamins E and C

Abstract

Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenicity of many xenobiotics. In the present study, we investigated the possible induction of lipid peroxidation by aluminium in human foreskin fibroblast cultures by assaying the malondialde hyde (MDA) produced inside the cells. The MDA–thiobarbituric acid (TBA) adduct was assayed by HPLC using fluorometric quantification after extraction in n-butanol. Lactate dehydrogenase (LDH) release was used as a marker of aluminium toxicity. MDA production was significantly increased after 24 h incubation with aluminium and paralleled LDH release. Superoxide dismutase (SOD)+catalase and vitamins C and E added in the culture medium as oxygen radical and free radical scavengers were efficient in preventing MDA production by aluminium, indicating that oxidative processes are one of the main pathways whereby this metal induces cytotoxicity. The latter is also largely prevented, thus confirming the link between oxidative stress induced by aluminium and its cytotoxicity in human skin fibroblasts. Human & Experimental Toxicology (2001) 20, 477–481.

Keywords

aluminium chloride human foreskin fibroblasts LDH release malondialdehyde prevention of lipid peroxidation super-oxide dismutase catalase vitamin E vitamin C

References

Anane R , Bonini M , Grafeille J-M , Creppy EE . Bioaccumulation of water soluble chloride in the hippocampus after transdermal uptake in mice . Arch Toxicol 1995; 69: 568–571 .

Landsdown ABG . Production of epidermal damage in mammalian skin by some simple compounds . Br J Dermatol 1973; 89: 67-67 .

Landsdown ABG . Interspecies variations in response to topical application of selected zinc compounds . Food Chem Toxicol 1993; 29: 57-57 .

Recknagel RO , Glende JR , Waller RL , Lawrey K . Lipid peroxidation: biochemistry, measurement, and significance in liver cell injury. In: Plaa G , Hewitt W.R. (Eds), Toxicology of the Liver. Raven Press, New York , 1982, pp. 213–235.

Jover R , Ponsada X , Castel JV . In vitro investigation of the molecular mechanisms of toxicity. In: Castell JV , Gomez-Lechon MJ (Eds), In Vitro Alternatives to Animal Pharmaco-Toxicology. Farmaindustria, Madrid , 1992, pp. 292–327.

Yu LW , et al. High-performance liquid chromatographic analysis of the thiobarbituric acid adducts of malonaldehyde and trans,trans-muconaldehyde . Anal Biochem 1986; 156: 326–333 .

Ennamany R , Marzetto S , Saboureau D , Creppy EE . Lipid peroxidation induced by bolésatine, a toxin of Boletus satanas: implication in m5dc variation in Vero cells related to inhibition of cell growth . Cell Biol Toxicol 1995; 11: 347–354 .

Bergmeyer HU , Bernt E . Lactate dehydrogenase UV assay with pyruvate and NADH. In: Bergmeyer HU (Ed), Methods of Enzymatic Analysis II, John Wiley, New York , 1974, pp. 574–579.

God SC , Neil CS . Statistics for toxicologists. In: Hayes AW (Ed), Principles and Methods of Toxicology, Raven Press, New York , 1982, p. 273.

10.

Ames BN . Endogenous DNA damage as related to cancer and ageing . Mutat Res 1989; 214: 41–46 .

11.

Chassard-Bouchaud C , et al. Bioaccumulation of aluminium in the brain of several teleost fish as a consequence of environmental pollution: a structural, ultrastructural and microanalytical study . Metal Ions Biol Med 1992; 2: 119–124 .

12.

Bullough WS , Laurence EB . The control of mitotic activity in mouse skin: dermis and hypodermis . Exp Cell Res 1960; 21: 394–405 .

13.

Wiestner M , et al. Inhibitory effect of procollagen peptides on collagen biosynthesis in fibroblast cultures . J Biol Chem 1979; 254: 7016–7026 .

14.

El Ghissassi F , Barbin A , Nair J , Bartsch H . Formation of 1,N6-ethenoadenine and 3,N4-ethenocytosine by lipid peroxidation products and nucleic acid bases . Chem Res Toxicol 1995; 5: 278–283 .

15.

Park JW , Floyd RA . Lipid peroxidation products mediate the formation of 8-hydroxydeoxyguanosine in DNA . Carcinogenesis 1992; 13: 245–250 .

16.

Agarwal S , Draper HH . Isolation of a malondialdehyde–deoxyguanosine adduct from rat liver DNA . Free Radical Biol Med 1992; 13: 695–699 .

17.

Fraga CG , Tappel Al . Damage to DNA concurrent with lipid peroxidation in rat liver slice . Biochem J 1988; 252: 893–896 .

18.

Serra MA , Barassi V , Canavese C , Sabbioni E . Aluminium effect on the activity of superoxide dismutase and of other antioxygenic enzymes in vitro . Biol Trace Elem Res 1991; 31: 79–96 .

19.

Julka D , Gill KD . Effect of aluminium on regional brain antioxidant defense status in Wistar rats . Res Exp Med 1996; 196: 187–194 .

20.

Swain C , Chainy GB . Effects of aluminium sulphate and citric acid ingestion on lipid peroxidation and on activities of superoxide dismutase and catalase in cerebral hemispere and liver of developing young chicks . Mol Cell Biochem 1998; 187: 163–172 .

21.

Olas B , Wachowics B , Buczynski A . Vitamin C suppresses the cisplatin toxicity on blood platelets . Anticancer Drugs 2000; 11: 487–493 .