Inhibition by blueberries (bilberries) and extract from milk thistle of rat forestomach hyperplasia induced by oral smokeless tobacco (Swedish snus)

Robert Nilsson, Mileva Mićić, Jelena Filipović, Ana Valenta Šobot, Dunja Drakulić, Miloš Stanojlović, Gordana Joksic

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


The aim of this study was to identify palatable additives which have a significant protective action against soft tissue changes in the oral cavity caused by Swedish smokeless tobacco ("snus"), and that satisfy existing legal requirements. Although the cancer risk from snus is extremely low, long term use may result in highly undesirable keratotic lesions and associated epithelial abnormalities in the oral cavity.The rat forestomach, which is vulnerable to the irritative action of non-genotoxic compounds like butylated hydroxyanisole, propionic acid as well as snus, was chosen as an experimental model. Studied toxicological endpoints included histopathology and cellular proliferation based on DNA incorporation of bromodeoxyuridine.After 6 weeks' exposure, blueberries (bilberries) and an extract from the common milk thistle were found to exert a highly significant inhibition of cell proliferation induced by snus in the rat forestomach epithelium, indicating a potential protection with respect soft tissue changes in the human oral cavity.

Original languageEnglish (US)
Pages (from-to)94-101
Number of pages8
JournalRegulatory Toxicology and Pharmacology
StatePublished - Apr 1 2016

Bibliographical note

Funding Information:
The preparation of the BrdU tablets by Dr. Bojan Čalija, Faculty of Pharmacy, University of Belgrade, is gratefully acknowledged. We thank A.T. Natarajan, professor emeritus, Leiden University, for his valuable suggestions. This study was supported by a grant from Swedish Match AB. The sponsor had no role in study design, the collection, analysis and interpretation of data, writing of the report or in the decision to submit the article for publication.


  • Blueberries
  • Bromodeoxyuridine
  • Forestomach
  • Hyperplasia
  • Milk thistle
  • Phytoprotection
  • Silymarin
  • Smokeless tobacco
  • Snus


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