Abstract
Carnosic acid, a primary phenolic compound found in the leaves of rosemary (Rosmarinus officinalis), has diverse pharmacological and biological activities. The aim of the present study was to investigate the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. The frequency of bone marrow micronucleated polychromatic erythrocytes (MnPCEs), chromosomal aberrations (cytogenetic end points), the status of Phase I and II detoxification enzymes, lipid peroxidation by-products and antioxidants (biochemical endpoints) were analyzed to assess the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. Oral pretreatment of carnosic acid for five days to DMBA-treated hamsters significantly protected DMBA-induced clastogenesis as well as biochemical abnormalities. Although the exact mechanism of anti-clastogenic effects of carnosic acid is unclear, the antioxidant potential and effect on modulation of Phase I and II detoxification enzymes could play a possible role.
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Abbreviations
- CAT:
-
catalase
- DMBA:
-
7,12-dimethylbenz(a)anthracene
- GPx:
-
glutathione peroxidase
- GR:
-
glutathione reductase
- GSH:
-
reduced glutathione
- GST:
-
glutathione-Stransferase
- MnPCEs:
-
micronucleated polychromatic erythrocytes
- NCEs:
-
normochromatic erythrocytes
- PCEs:
-
polychromatic erythrocytes
- SOD:
-
superoxide dismutase
- TBARS:
-
thiobarbituric acid reactive substances
References
Aruma OI, Halliwell B, Aeschbach R, Lolingers J: Anti-oxidant and pro-antioxidant properties of active rosemary constituents: carnosol and carnosic acid. Xenobiotica, 1992, 22, 257–268.
Beutler E, Kelley BM: The effect of sodium nitrate on RBC glutathione. Experientia, 1963, 19, 96–97.
Carlberg I, Mannervik B: Gluathione reductase. Methods Enzymol, Academic Press, New York, 1985, 113–190.
Chandramohan KVP, Bhuvaneswari V, Abraham SK, Nagini S: Dose-dependent protection of tomato against 7, 12-dimethylbenz(a)anthracene induced genotoxicity and oxidative stress in mice. J Med Food, 2003, 6, 169–173.
Guerin MR: Energy sources of polycyclic aromatic hydrocarbons. In: Polycyclic Hydrocarbons and Cancer, Chemistry, Molecular Biology and Environment. Eds. Gelboin HV, Ts’o POP, Academic Press, New York, 1978, 142.
Habig WH, Pabst MJ, Jakoby WB: Glutathione-S-transferase, the first enzymatic step in mercapturic acid formation. J Biol Chem, 1974, 249, 7130–7139.
Cheung KC, Loeb LA: Genomic stability and instability: a working paradigm. Curr Top Microbiol Immunol, 1997, 221, 5–18.
Kakkar P, Das B, Visvanathan PN: A modified spectro-photometric assay of superoxide dismutase. Indian J Biophys, 1984, 21, 130–132.
Kilian DJ, Moreland FM, Benge MC, Legator MS, Whorton EB: A collaborative study to measure interlaboratory variation with the in vivo bone narrow metaphase procedure. In: Handbook of Mutagenicity Test Procedures. Eds. Kilbey BJ, Legator M, Nichols W, Romel C, Elsevier/North-Holland, Amsterdam, 1977, 243–260.
Kriskins E, Suter W, Hartmann A: High-throughput comet assay using 96-well plates. Mutagenesis, 2002, 17, 37–43.
Kussmaul AR, Bogacheva MA, Shkurat TP, Pavlov NB: Inhibitory effect of apigenin on benzo(a)pyrene-mediated genotoxicity in Swiss albino mice. J Pharm Pharmacol, 2006, 58, 1655–1660.
Kwong YY, Husain Z, Biswas DK: c-Haras gene mutation and activation precede pathological changes in DMBA-induced in vivo carcinogenesis. Oncogene, 1992, 7, 1481–1489.
Li RH: Aneuploidy Vs gene mutation hypothesis of cancer: Recent study claims mutation but is found to support aneuploidy. Proc Natl Acad Sci USA, 2000, 97, 3236–3079.
Manoharan S, Panjamurthy K, Balakrishnan S, Vasudevan K, Vellaichamy L: Circadian time-dependent chemo-preventive potential of withaferin-A in 7, 12-dimethylbenz[a]anthracene-induced oral carcinogenesis. Pharmacol Rep, 2009, 61, 719–726.
Manoharan S, Panjamurthy K, Vasudevan K, Sasikumar D, Kolanjiappan K: Protective effect of Jasminum grandiflorum Linn. on DMBA-induced chromosomal aberrations in bone marrow of Wistar rats. Int J Pharmacol, 2006, 2, 406–410.
Maurin M, Delbano JN, Mackaya L, Colomb H, Guier C, Mandjee A, Recule C, Croize J: Human infection with Schineriaiarvae. Emerg Infect Dis, 2007, 13, 657–659.
Offord EA, Guillot F, Aeschbach R, Liliger J, Pfeifer AMA: Antioxidant and biological properties of rosmary compounds: implications for food and health. In: Natural Antioxidants: Chemistry, Health Effects, and Applications. iEd. Shahidi F, AOCS Press, Champaign, IL, 1997, 88–96.
Offord EA, Mace K, Avant O, Pfeifer A: Mechanisms involved in the chemoprotective effects of rosemary extracts studied in human liver and bronchial cells. Cancer Lett, 1997, 114, 275–281.
Offord EA, Mark K, Ruffieux C, Malone A, Pfeifer AMA: Rosemary components inhibit benzo(a)pyrene- induced genotoxicity in human bronchial cells. Carcinogenesis, 1995, 16, 2057–2062.
Ohkawa H, Ohisi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 1979, 95, 351–358.
Omura T, Sato R: The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem, 1964, 239, 2370–2378.
Panjamurthy K, Manoharan S, Venugopal P, Menon, Madhavan, R Nirmal, Senthil N: Protectective role of withaferin-A on 7, 12-dimethylbenz(a)anthracene induced genotoxicity in bone marrow of Syrian golden hamsters. J Biochem Mol Toxicol, 2008, 22, 251–258.
Pérez-Fons L, Aranda FJ, Guillén J, Villalaín J, Micol V: Rosemary (Rosmarinus officinalis) diterpenes affect lipid polymorphism and fluidity in phospholipid membranes. Arch Biochem Biophys, 2006, 453, 224–236.
Premkumar K, Abraham SK, Santhiya ST, Ramesh A: Protective effect of Spirulina fusiformis on chemical-induced genotoxicity in mice. Fitoterapia, 2004, 75, 24–31.
Pugalendhi P, Manoharan S, Panjamurthy K, Balakrishnan S, Nirmal MR: Antigenotoxic effect of genistein against 7, 12-dimethylbenz(a)anthracene induced genotoxicity in bone marrow of female wistar rats. Pharmacol Rep, 2009, 61, 296–303.
Rotruck JT, Pope AL, Ganther HT, Swanson AB, Hafeman DG, Hockstra WG: Selenium: Biochemical role as a component of glutathione peroxidase. Science, 1973, 179, 588–590.
Schmid W: The micronucleus test. Mutat Res, 1975, 31, 9–15.
Singletary KW: Rosemary extract and carnosol stimulate rat liver glutathione-S-transferase and quinone reductase activities. Cancer Lett, 1996, 100, 139–144.
Sinha KA: Colorimetric assay of catalase. Anal Biochem, 1972, 17, 389–394.
Steiner MI, Priel J, Giant J, Levy, Sharoni Y, Danilenko M: Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1, 25-dihydroxy vitamin D3 and retenoic acid. Nutr Cancer, 2001, 41, 135–144.
Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H: Single cell gel/comet assay. Environ Mol Mutagen, 2000, 35, 206–221.
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M: Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact, 2006, 160, 1–40.
Vogelstein B, Kinzler KW: The Genetic Basis of Human Cancer. Eds. Kinzler KW, Vogelstein B, McGraw-Hill, New York, 1988, xv–xvi.
Wijeratne SS, Cuppett SL: Potential of rosemary (Rose-marinus officinalis L.) diterpenes in preventing lipid hydroperoxide-mediated oxidative stress in Caco-2 cells. J Agric Food Chem, 2007, 55, 1193–1199.
Yagi K: Lipid peroxides and human diseases. Chem Phys Lipids, 1987, 45, 337–351.
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Manoharan, S., Balakrishnan, S., Vinothkumar, V. et al. Anti-clastogenic potential of carnosic acid against 7,12-dimethylbenz(a) anthracene (DMBA)-induced clastogenesis. Pharmacol. Rep 62, 1170–1177 (2010). https://doi.org/10.1016/S1734-1140(10)70379-0
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DOI: https://doi.org/10.1016/S1734-1140(10)70379-0