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Drug Res (Stuttg) 2016; 66(09): 489-494
DOI: 10.1055/s-0042-110932
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Phenozan, a Synthetic Phenolic Antioxidant, Inhibits the Development of Spontaneous Tumors in Rats and Mice

V. G. Bespalov
1   Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia
3   International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, St. Petersburg, Russia
,
V. A. Alexandrov
1   Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia
3   International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, St. Petersburg, Russia
,
D. B. Korman
2   Laboratory of Oncology, N.M. Emanuel Institute of Biochemical Physics of the Russian Academy of Sciences, Moscow, Russia
,
D. A. Baranenko
3   International Research Centre “Biotechnologies of the Third Millennium”, ITMO University, St. Petersburg, Russia
› Institutsangaben
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Publikationsverlauf

received 30. März 2016

accepted 18. Juni 2016

Publikationsdatum:
19. Juli 2016 (online)

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Abstract

Synthetic phenolic antioxidant β-(4-hydroxy-3,5-di-tert-butylphenyl) propionic acid, named phenozan, is a potential antiepileptic drug. In pre-clinical trials this substance did not manifest any toxicity, and also inhibited the development of some spontaneous tumors in animals. The purpose of this study was to evaluate inhibiting effect of phenozan on spontaneous carcinogenesis in rats and mice. In experiments with rats LIO and mice SHR of local breeding, with high spontaneous tumor incidence, phenozan was dissolved in sunflower oil and administered by gavage in therapeutic dose 5 mg/kg 3 times per week for 18 months. There were no any signs of toxicity and differences in weight of animals during the phenozan treatment compared with the control (sunflower oil). Phenozan significantly reduced the overall incidence and multiplicity of all tumors but only multiplicity of malignant tumors, compared with the control. Moreover a significant decrease of overall incidence and multiplicity was observed in pituitary and breast tumors in females and only overall multiplicity of tumors of pituitary and lymphoid tissue in males. In mice phenozan reduced overall incidence and multiplicity of lung tumors (in females) and also overall multiplicity of all tumors (in females) and only malignant tumors (in males). These findings allow us to classify phenozan as anticarcinogenic agent. Anticarcinogenic activity of phenozan is important because clinical study of this drug as the possible antiepileptic drug goes along and it is known that such drugs are designed for long-term use.

Key words

synthetic phenolic antioxidant phenozan - spontaneous tumors - chemoprevention
 

  • References

  • 1 Fedotova IB, Semiokhina AE, Archipova GV et al. The possibilities of correcting some complex behavior reactions in KM rats by using an antioxidant. Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova 1990; 40: 318-325 (in Russian)
    PubMedGoogle Scholar
  • 2 Archipov VI, Archipova GV, Fedotova IB. The influence of the synthetic antioxidant fenozan-K on the effects of pentobarbital during dissociative learning. Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova 1990; 40: 1140-1144 (in Russian)
    PubMedGoogle Scholar
  • 3 Archipov VI, Archipova GV, Fedotova IB. The effect of the synthetic antioxidant fenozan-K on the reproduction of dissociated conditioned reactions and on the phospholipids composition on Wistar and KM strain rats. Zhurnal Vysshei Nervnoi Deyatelnosti Imeni I.P. Pavlova 1994; 44: 569-574 (in Russian)
    PubMedGoogle Scholar
  • 4 Burlakova EB. Bioantioxidants: yesterday, today, tomorrow. In: Burlakova EB, Varfolomeev SD. (eds.). Chemical and biological kinetics. New horizons. Leiden: Publ Koninklijke Brill NV; 2005: 1-33
    Google Scholar
  • 5 Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxidants and Redox Signaling 2008; 10: 475-510
    CrossrefPubMedGoogle Scholar
  • 6 Kahl R. Synthetic antioxidants: biochemical actions and interference with radiation, toxic compounds, chemical mutagens and chemical carcinogens. Toxicology 1984; 33: 185-228
    CrossrefPubMedGoogle Scholar
  • 7 Carocho M. Ferreira ICFR. A review on antioxidants, prooxidants and related controversy: Natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food and Chemical Toxicology 2013; 51: 15-25
    CrossrefPubMedGoogle Scholar
  • 8 Williams GM, Iatropoulos MJ, Jeffrey AM. Anticarcinogenicity of monocyclic phenolic compounds. European Journal of Cancer Prevention 2002; 11: 101-107
    CrossrefPubMedGoogle Scholar
  • 9 Hocman G. Chemoprevention of cancer: phenolic antioxidants (BHT, BHA). International Journal of Biochemistry 1988; 20: 639-651
    CrossrefPubMedGoogle Scholar
  • 10 Botterweck AA, Verhagen H, Goldbohm RA et al. Intake of butylated hydroxyanisole, and butylated hydroxytoluene and stomach cancer risk: results from analyses in the Netherlands Cohort Study. Food and Chemical Toxicology 2000; 38: 599-605
    CrossrefPubMedGoogle Scholar
  • 11 Kirillov VN. Effect of phenozan on kidney carcinogenesis induced in rats by nitrosodimethylamine. Eksperimentalnaya Onkologiya 1988; 10: 23-26 (in Russian)
    PubMedGoogle Scholar
  • 12 Kirso UE, YuV Pashin, Bahitova LM et al. Effects of antioxidants on the carcinogenic and mutagenic activity of benzo(a)pyrene. Voprosy onkologii 1985; 21: 70-75 (in Russian)
    PubMedGoogle Scholar
  • 13 Erokhin VN, Krementsova AV, Semenov VA et al. Effect of antioxidant β-(4-hydroxy-3,5-ditertbutylphenyl)propionic acid (phenozan) on the development of malignant neoplasms. Biology Bulletin 2007; 34: 485-491
    CrossrefPubMedGoogle Scholar