Affiliation:
1. UCD Centre for Toxicology, School of Biomedical and Biomolecular Sciences, Conway Institute, University College Dublin, Dublin, Ireland
2. International Institute of Nutritional Sciences and Applied Food Safety Studies, University of Central Lancashire, Preston, PR1 2HE, United Kingdom
Abstract
Background:
Potassium bromate (KBrO3), a food additive, has been used in many bakery products as
an oxidizing agent. It has been shown to induce renal cancer in many in-vitro and in-vivo experimental models.
Objectives:
This study evaluated the carcinogenic potential of potassium bromate (KBrO3) and the chemopreventive
mechanisms of the anti-oxidant and anti-inflammatory phytochemical, curcumin against KBrO3-induced
carcinogenicity.
Method:
Lactate dehydrogenase (LDH) cytotoxicity assay and morphological characteristics were used to assess
curcumin's cytoprotective potential against KBrO3 toxicity. To assess the chemopreventive potential of curcumin
against KBrO3-induced oxidative insult, intracellular H2O2 and the nuclear concentration of the DNA adduct 8-
OHdG were measured. PCR array, qRT-PCR, and western blot analysis were used to identify dysregulated genes
by KBrO3 exposure. Furthermore, immunofluorescence was used to evaluate the ciliary loss and the disturbance
of cellular tight junction induced by KBrO3.
Results:
Oxidative stress assays showed that KBrO3 increased the levels of intracellular H2O2 and the DNA adduct
8-OHdG. Combination of curcumin with KBrO3 efficiently reduced the level of H2O2 and 8-OHdG while upregulating
the expression of catalase. PCR array, qRT-PCR, and western blot analysis revealed that KBrO3 dysregulated
multiple genes involved in inflammation, proliferation, and apoptosis, namely CTGF, IL-1, and
TRAF3. Moreover, qRT-PCR and immunofluorescence studies showed that KBrO3 negatively affected the tight
junctional protein (ZO-1) and induced a degeneration of primary ciliary proteins. The negative impact of KBrO3
on cilia was markedly repressed by curcumin.
Conclusion:
Curcumin could potentially be used as a protective agent against carcinogenicity of KBrO3.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Pharmacology
Cited by
16 articles.
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