Article

Ex-vivo and in vitro protective effects of kolaviron against oxygen-derived radical-induced DNA damage and oxidative stress in human lymphocytes and rat liver cells.

Institute of Food Safety and Nutrition, Division of Biochemical and Molecular Toxicology, 2860 Søborg, Denmark.
Cell Biology and Toxicology (impact factor: 2.51). 04/2004; 20(2):71-82. DOI:10.1023/B:CBTO.0000027916.61347.bc pp.71-82
Source: PubMed

ABSTRACT The present study reports the protective effects of kolaviron, a Garcinia biflavonoid from the seeds of Garcinia kola widely consumed in some West African countries against oxidative damage to molecular targets ex-vivo and in vitro. Treatment with hydrogen peroxide (H2O2) at a concentration of 100 micromol/L increased the levels of DNA strand breaks and oxidized purine (formamidopyrimidine glycosylase (FPG) and pyrimidine (endonuclease III (ENDO III) sites) bases in both human lymphocytes and rat liver cells using alkaline single cell gel electrophoresis (the comet assay). Kolaviron was protective at concentrations between 30-90 micromol/L and decreased H2O2-induced DNA strand breaks and oxidized bases. Neither alpha-tocopherol nor curcumin decreased H2O2-induced DNA damage in this assay. In lymphocytes incubated with Fe3+/GSH, Fe3+ was reduced to Fe2+ by GSH initiating a free radical generating reaction which induced 11.7, 6.3, and 4.9 fold increase respectively in strand breaks, ENDO III and FPG sensitive sites compared with control levels. Deferoxamine (2 mmol/L), an established iron chelator significantly inhibited GSH/Fe3+-induced strand breaks and oxidized base damage. Similarly, kolaviron at 30 and 90 micromol/L significantly attenuated GSH/Fe3+-induced strand breaks as well as base oxidation. Kolaviron (100 mg/kg bw) administered to rats for one week protected rat liver cells against H2O2-induced formation of strand breaks, ENDO III, and FPG sensitive sites, Fe3+/EDTA/ascorbate-induced malondialdehyde formation and protein oxidation using gamma-glutamyl semialdehyde (GGS) and 2-amino-adipic semialdehyde (AAS) as biomarkers of oxidative damage to proteins. We suggest that kolaviron exhibits protective effects against oxidative damage to molecular targets via scavenging of free radicals and iron binding. Kolaviron may therefore be relevant in the chemoprevention of oxidant-induced genotoxicity and possibly human carcinogenesis.

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    Article: Antioxidative and chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoid.
    Ebenezer O Farombi, Olatunde Owoeye
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Keywords

90 micromol/L
 
DNA strand breaks
 
ENDO III
 
endonuclease III
 
established iron chelator
 
Fe3+/EDTA/ascorbate-induced malondialdehyde formation
 
Garcinia kola
 
H2O2-induced DNA damage
 
H2O2-induced DNA strand breaks
 
human carcinogenesis
 
hydrogen peroxide
 
Kolaviron
 
kolaviron exhibits protective effects
 
molecular targets ex-vivo
 
oxidant-induced genotoxicity
 
oxidative damage
 
oxidized base damage
 
oxidized purine
 
rat liver cells
 
West African countries
 

E Olatunde Farombi