2007, Number 1
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Bioquimia 2007; 32 (1)
Chlorophyllin as modulator and DNA damage protector: in vivo mouse system experience
García-Rodríguez MC, Altamirano-Lozano MA
Language: Spanish
References: 73
Page: 15-24
PDF size: 138.70 Kb.
ABSTRACT
Exposure of human populations to different environmental xenobiotic agents has generated considerable attention in the use of dietary supplements particularly plant products because exists an inverse correlation between the consumption of vegetables and incidence of cancer. These search and study of substances with protective properties or damage modulators to DNA emerge as a complementary option to genotoxicity studies. The analysis of the protection mechanisms generates alternatives to counteract the effects of agents causing the genotoxicity damage. Chlorophyllin (CHL) is a sodium-copper chlorophyll salt with a flat porphyrin ring and a metal ion atom in the center, with sodium or potassium atoms replacing the phytil ester groups. Several authors have demonstrated the antimutagenic and anticarcinogenic effects of CHL in live organisms including humans. Results obtained in our laboratory show that when CHL was administered i.p. to normal mice, and pregnant female mice, it had a protective effects against genotoxic damage induced by metals such CrO3 in all animals, including the fetuses, with out toxicity in the treated animal. The same results were observed using gamma radiation. On the other hand when pregnant females were exposed to high doses of CHL, its induce total litter loss, however when CrO
3 was injected to pregnant mice resulted in significant increase in the external and skeletal malformations. CHL treatment before chromium injection resulted in a decreased in the external alterations. According the previous studies, the probable antimutagenic mechanisms of CHL are scavenging of free radicals and active oxygen species, suppression or interference with metabolic activation by specific cytochrome (P-450) and others metabolizing enzymes, and formation of complexes with promutagens or reactive moieties.
REFERENCES
Phillips RL. Role of life-style and dietary habits in risk of cancer among seventh-day Adventists. Cancer Res. 1975; 35: 3513-3522.
Kada T, Morita K, Inoue T. Anti-mutagenic action of vegetable factor(s) on the mutagenic principle of tryptophan pyrolysate. Mutat Res. 1978; 53: 351-353.
Morita K, Hara M, Kada T. Studies on natural desmutagens screening for vegetables and fruit factors active in inactivation of mutagenic pyrolysis products from amino acids. Agric Biol Chem. 1978; 42: 1235-1238.
Kada T, Kato M, Aikawa K, Kiriyama S. Adsorption of pyrrolisate mutagens by vegetable fibers. Mutat Res. 1984; 141: 149-152.
Terwel L, Van der Hoeven CM. Antimutagenic activity of some naturally occurring compounds towards cigarette-smoke condensate and benzo[a]pyrene in the Salmonella/microsome assay. Mutat Res. 1985; 152: 1-4.
Mendes-Pinto MM, Silva-Ferreira AC, Caris-Veyrat C, Guedes de Pinho P. Carotenoid, chlorophyll, and chlorophyll-derived compounds in grapes and port wines. J Agric Food Chem. 2005; 53: 10034-10041.
Ferguson LR, Philpott M, Karunasinghe N. Dietary cancer and prevention using antimutagens. Toxicology. 2004; 198: 147-159.
Lai CN. Chlorophyll: the active factor in wheat sprout extract inhibiting the metabolic activation of carcinogens in vitro. Nutr Cancer. 1979; 1: 19-21.
Lai CN, Butler MA, Matney TS. Antimutagenic activities of common vegetables and their chlorophyll content. Mutat Res. 1980; 77: 245-250.
Whong W, Stewart J, Brockman HE, Ong T. Comparative antimutagenicity of chlorophyllin and five other agents against aflatoxin B1-induced reversion in Salmonella typhimurium strain TA98. Teratogen Carcinogen Mutagen. 1988; 8: 215-224.
Ong TM, Whong WZ, Stewart J, Brockman HE. Comparative antimutagenicity of five compounds against five mutagenic complex mixtures in Salmonella typhimurium strain TA98. Mutat Res. 1989; 222: 19-25.
Gentile JM, Gentile GJ. The metabolic activation of 4-nitro-O-phenylenediamine by chlorophyll-containing plant extracts: The relationship between mutagenicity and antimutagenicity. Mutat Res. 1991; 250: 79-86.
García-Rodríguez MC, Altamirano-Lozano M. Sales de sodio y cobre de la clorofila: usos, aplicaciones terapéuticas, actividad antimutágena y anticancerígeno. TIP Revista Especializada en Ciencias Químico-Biológicas 2001; 4: 77-86.
Kapiotis S, Hermann M, Exner M, Laggner H, Gmeiner BM. Cooper- and magnesium protoporphyrin complex inhibit oxidative modification of LDL induced by hemin, transition metal ions and tyrosyl radicals. Free Radic Res. 2005; 39: 1193-1202.
Pietrzak M, Wieczorek Z, Wieczorek J, Darzynkiewicz Z. The "interceptor" properties of chlorophyllin measured within the three-components system: intercalator-DNA-chlorophyllin. Biophys Chem. 2006; 123: 11-19.
Ferguson LR. Antimutagens as cancer chemopreventive agents in the diet. Mutat Res. 1994; 307: 395-410.
Lee BM, Park KK. Beneficial and adverse effects of chemopreventive agents. Mutat Res. 2003; 523-524: 265-278.
Kephart JC. Chlorophyll derivates their chemistry commercial preparation and uses. Econ Bot 1955; 9: 3-38.
Sarkar D, Sharma A, Talukder G. Comparison of the effects of crude extract of spinach-beet leaves and equivalent amounts of chlorophyll and chlorophyllin in modifying the clastogenic activity of chromium (VI) oxide in mice. Phytother Res. 1994; 9: 99-202.
Arimoto S, Negishi T, Hayatsu H. Inhibitory effect of hemin the mutagenic activities of carcinogens. Cancer Lett. 1980; 11: 29-33.
Kimm S, Tchai B, Park S, Kang S. Antimutagenic activity of chlorophyll to direct-acting and indirect-acting mutagens and its contents in vegetables. Korean J Biochem. 1982; 14: 1-8.
Katoh Y, Nemoto N, Tanaka M, Takayama S. Inhibition of benzo [a] pyrene-induced mutagenesis in Chinese hamster V79 cells by hemin and related compounds. Mutat Res. 1983; 121: 153-157.
Ong TM, Whong WZ, Stewart J, Brockman HE. Clorophyllin: a potent antimutagen against environmental and dietary complex mixtures. Mutat Res. 1986; 173: 111-115.
Negishi T, Arimoto S, Nishizake C, Hayatsu H. Inhibitory effect of chlorophyll on the genotoxicity of 3 – amino – 1 – methyl - 5H – pyrido [4,3 – b-indole (Trp - P2). Carcinogenesis 1989; 10: 145-149.
Renner HW. In vivo effects of single or combined dietary antimutagens on mutagen-induced chromosomal aberrations. Mutat Res. 1990; 244: 185-188.
Zimmmering S, Olvera O, Hernandez ME, Cruces MP, Arceo C, Pimental E. Evidence for a radioprotective effect of chlorophyllin in Drosophila. Mutat Res. 1990; 245: 47-49.
Warner JR, Joginder N, Ong T. Antimutagenicity studies of chlorophyllin using the Salmonella arabinose resistant assay system. Mutat Res. 1991; 262: 25-30.
Dashwood RH, Breinholt V, Bailey GS. Chemo-preventive properties of chlorophyllin: inhibition of aflatoxin B1 (AFB1)-DNA binding in vivo and antimutagenic activity against AFB1 and two heterocyclic amines in the Salmonella mutagenicity assay. Carcinogenesis 1991; 12: 939-942.
Sen S, Sharma A, Talukder G. Inhibition of clastogenic effects of nicotine by chlorophyllin in mice bone marrow cells in vivo. Phytother Res. 1991; 5: 130-133.
Palit S, Sen S, Sharma A, Talukder G. Protection by chlorophyllin against induction of chromosomal aberrations by cobalt in bone marrow cells of mice in vivo. Fitoterapia 1991; 42: 425-428.
Ghosh A, Sen A, Sharma A, Talukder G. Inhibition of clastogenic effects of cesium chloride in mice in vivo by chlorophyllin. Toxicol Lett. 1991; 57: 11-18.
Ghosh A, Sen S, Sharma A, Talukder G. Modification of clastogenic effects of mercuric chloride by chlorophyllin in bone marrow cells in vivo. Food Chem Toxicol. 1991; 29: 777-779.
Sarkar D, Sharma A, Talukder G. Differential protection of chlorophyllin against clastogenic effects of chromium and chlordane in mouse bone marrow in vivo. Mutat Res. 1993; 301: 33-38.
Morales-Ramírez P, García-Rodríguez MC. In vivo effect of chlorophyllin on g-ray-induced sister chromatid exchange in murine bone marrow cells. Mutat Res. 1994; 320: 329-334.
Morales-Ramírez P, Mendiola-Cruz MT. In vivo radioprotective effect of chlorophyllin on sister chromatid exchange induction in murine spermatogonial cell. Mutat Res. 1995; 344: 73-78.
Verma A, Brockman HE, Mayer VW. Utility of a test for chromosomal malsegregation in Saccharomyces cerevisiae strain D61.M for the detection of antianeugens: test of the model combination of chlorophyllin and nocodazole. Mutat Res. 1996; 358: 73-80.
Okai Y, Higashi-Okai K, Yano Y, Otani S. Suppressive effects of chlorophyllin on mutagen-induced umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002) and tumor promoter-dependent ornithine decarboxylaxe induction in BALB/c 3T3 fibroblast cells. Mutat Res. 1996; 370: 11-17.
Blum AC, Xu M, Orner AG, Fong TA, Bailey, SG, Stoner DG, et al. b-catenin mutation in rat colon tumors initiated by 1,2-dimethylhydrazine and 2-amino-3-methylimidazo[4,5-f]quinoline, and the effect of post-initiation treatment with chlorophyllin and indole-3-carbinol. Carcinogenesis 2001; 22: 315-320.
García-Rodríguez MC, López-Santiago V, Altamirano-Lozano M. Effect of chlorophyllin on chromium trioxide-induced micronuclei in polychromatic erythrocytes in mouse peripheral blood. Mutat Res. 2001; 496: 145-151.
Chernomorsky S, Segelman A, Poretz RD. Effect of dietary chlorophyll derivatives on mutagenesis and tumor cell growth. Teratogen Carcinogen Mutagen. 1999; 19: 313-322.
Sato M, Iguchi N, Murata T. Effect of sodium cooper chlorophyllin on lipid peroxidation: I. Effect on lipid peroxidation in rat liver homogenates in the presence of both Fe2+ and L-ascorbic acid. Yakugaku Zasshi 1977; 97: 268-273.
Sato M, Fujimoto I, Sakai T, Aimoto T, Kimura R, Murata T. Effect of sodium cooper chlorophyllin on lipid peroxidation: IX On the antioxidative components in commercial preparations on sodium coopeer chlorophyllin. Chem Pharm Bull. (Tokyo) 1986; 34: 2428-2434.
Cho KJ, Han SH, Kim BY, Hwang SG, Park KK, Yang KH, et al. Chlorophyllin suppression of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. Toxicol Appl Pharmacol. 2000; 166: 120-127.
Hayashi, Schimerlik M, Bailey G. Mechanism of chlorophyllin anticarcinogenesis: dose-responsive inhibition of aflatoxin uptake and biodistribution following oral co-administration in rainbow trout. Toxicol Appl Pharmacol. 1999; 158: 132-140.
Breinholt V, Arbogast D, Loveland P, Pereira C, Dashwood R, Heendricks J, et al. Chlorophyllin chemoprevention in trout initiated by aflatoxin B1 bath treatment: an evaluation of reduced bioavailability vs. target organ protective mechanisms. Toxicol Appl Pharmacol 1999; 158: 141-151.
Sato M, Imai K, Kimura R, Murata T. Effect of sodium cooper chlorophyllin on lipid peroxidation. VI. Effect of its administration on mitochondrial and microsomal lipid peroxidation in rat liver. Chem Pharm Bull. 1984; 32: 3513-3522.
Dashwood R, Guo D. Inhibition of 2-amino-3-methylimidazol[4,5-f]quinoline (IQ)-DNA binding by chlorophyllin: studies of enzyme inhibition and molecular complex formation. Carcinogenesis 1992; 13: 1121-1126.
Tajmir-Riahi HA, Neault JF, Diamantoglou S. DNA adducts with chlorophyllin as antimutagenic agents: synthesis, stability, and structural features. Methods Mol Biol. 2004; 274:159-171.
Marty R, Ouameur AA, Neault JF, Tajmir-Riahi HA. RNA adducts with chlorophyllin: stability and structural features. J Biomol Struc Dyn. 2004; 22: 45-50.
Dashwood R, Guo D. Antimutagenic potency of chlorophyllin in the Salmonella assay and its correlation with binding constants of mutagen-inhibitor complexes. Environ Mol Mutagen. 1993; 22: 164-171.
Dashwood R, Liew C. Chlorophyllin-enhanced excretion of urinary and fecal mutagens in rats given 2-amino-3-methylimidazol [4,5-f] quinoline. Environ Mol Mutagen. 1992; 20: 199-205.
Imai K, Aimoto T, Sato M, Watanabe K, Kimura R, Murata T. Effects of sodium metalochlorophyllin on the activity and components of the microsomal drug-metabolizing enzyme system in rat liver. Chem Pharm Bull. 1986; 34: 4287-4293.
Ait Amara-Mokrane, Lehucher-Michel MP, Balansard G, Duménil G, Botta A. Protective effects of alfa-hederin, chlorophyllin and ascorbic acid towards the induction of micronuclei by doxorubicin in cultured human lymphocytes. Mutagenesis 1996; 11: 161-167.
Peluso M, Airoldi L, Magagnotti C, Fiorini L, Munnia A, Hautefeuille A, et al. White blood cell DNA adducts and fruit and vegetable consumption in bladder cancer. Carcinogenesis 2000; 21: 183-187.
Simic MG. Mechanism of inhibition of free-radical processes in mutagenesis and carcinogenesis. Mutat Res. 1988; 202: 377-386.
Arimoto S, Fukuoka S, Itome C, Nakano H, Rai H, Hayatsu H. Banding of polycyclic planar mutagens to chlorophyllin resulting in inhibition of the mutagenic activity. Mutat Res. 1993; 287: 293-305.
Hadnagy W, Seemayer NH. Antimutagenicity of chlorophyllin against airborne pollutants. Mutat Res. 1988; 203: 205-206.
Robins EW, Nelson RL. Inhibition of 1,2-dimethylhydrazine-induced nuclear damage in rat colonic epithelium by chlorophyllin. Anticancer Res. 1989; 9: 981-986.
Bronzetti G, Galli A, Della Croce DM. Antimutagenic effects of chlorophyllin. In: Kuroda Y, Sankel DM, Waters MD. [Eds] Antimutagenesis and anticarcinogenesis: mechanisms II. Ed. New York: Plenum Press. 1990. p. 463-468.
Morales-Ramírez P, Vallarino-Kelly T, Rodríguez-Reyes R. Effect of chlorophyllin on gamma ray induced micronuclei in polychromatic erythrocytes of murine peripheral blood determined by the ABC strategy. Mutat Res. 1996; 367: 51-56.
Bailey GS. Chlorophylls: can these green food pigments prevent some cancers? Available from: URL http://www.orst.edu/dept/lpi/f-w97/chrphyl.html. 30 abril 1998, (fecha de acceso 07 de septiembre del 2001).
Egner PA, Wang JB, Zhu YR, Zhang BC, Wu Y, Zhang QN, et al. Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. Med Sci. 2001; 98: 14601-14606.
Egner PA, Muñoz O, Kensler TW. Chemoprevention with chlorophyllin in individuals exposed to dietary aflatoxin. Mutat Res. 2003; 523-524: 209-211.
Díaz GD, Qingjie L, Daswood RH. Caspase-8 apoptosis-inducing factor mediate a cytochrome c-independent pathway of apoptosis in human colon cancer cells induced by the dietary phytochemical chlorophyllin. Cancer Res. 2003; 63: 1254-1261.
Gao F, Hu XF. Analysis of the therapeutic effect of sodium cooper chlorophyllin tablet in treating 60 cases of leucopenia. Chin J Integr Med. 2005; 11: 279-282.
Kensler TW, Egner PA, Wang JB, Zhu YR, Zhang BC, Lu PX, et al. Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas. Gastroenterology 2004; 127: S210-S218.
García-Rodríguez MC, Pérez-Flores G. Nevares JC, Sánchez-Ruiz JF, Altamirano-Lozano M. Comparison of effects of chlorophyllin administered by differents routs on genotoxicity of hexavalent chromium in cd-1 mice. In: Bronzetti G, Ferguson LR, De Flora S. [Eds] Proceedings of ICMAA-VIII Eighth International Conference on mechanisms of antimutagenesis and anticarcinogenesis. Pisa, Italia, STAR 2003. p. 50-51.
Surh Y-J, Ferguson RF. Dietary and medicinal antimutagens and anticarcinogens: molecular mechanisms and chemopreventive potential highlights of a symposium. Mutat Res. 2003; 523-524: 1-8.
Eriksson UJ, Borg LAH. Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro. Diabetologia 1991; 34: 325-331.
Nosel GP, Klein NW. Methionine decreases the embryotoxicity of sodium valproate in the rat: in vivo and in vitro observations. Teratology 1992; 46: 499-507.
Desesso J M, Scialli RA, Goeringer GC. D-mannitol, a specific hydroxyl free radical scavenger, reduces the developmental toxicity of hydroxyurea in rabbits. Teratology 1994; 49: 248-259.
Pillans PI, Ponzi SF, Parker MI. Effects of ascorbic acid on the mouse embryo and on cyclophosphamide-induced cephalic DNA strand breaks in vivo. Arch Toxicol. 1990; 64: 423-425.
García-Rodríguez MC, Morales-Ramírez P, Altamirano-Lozano M. Effects of chlorophyllin on mouse embryonic and fetal development in vivo. Teratogen Carcinogen Mutagen. 2002; 22: 461-471.