Abstract
Microcystin LR (MC-LR), a liver-specific toxin synthesized by Microcystis aeruginosa, was investigated. MC-LR initiated reactive oxygen species formation followed by damaging DNA and some other cellular components. We investigated the ability of MC-LR to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) using HPLC with electrochemical detection. Melatonin, vitamin C (ascorbate), and vitamin E (as Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% (IC50) was 0.55, 31.4, and 36.8 μM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60-and 70-fold more effective than vitamin C or vitamin E, respectively, in reducing oxidative DNA damage. These findings are consistent with the conclusion that melatonin’s highly protective effect against microcystin toxicity relates, at least in part, to its direct hydroxyl radical scavenging ability.
Similar content being viewed by others
Abbreviations
- ALT:
-
alanine transaminase
- 8-OH-dG:
-
8-hydroxydeoxyguanosine
References
Pinho, G. L., Rosa, C., Yunes, J. S., Luquet, C. M., Bianchini, A., and Monserrat, J. M. (2003) Comp. Biochem. Physiol. Part C, 135, 459–468.
Ding, W. X., Shen, H. M., and Ong, C. N. (2000) Environ. Health Perspect., 108, 605–609.
Carmichael, W. W. (1994) Sci. Am., 270, 64–72.
Gehringer, M. M., Shephard, E. G., Downing, T. G., and Neilan, B. A. (2004) Int. J. Biochem. Cell Biol. 36, 931–941.
Ding, W. X., Shen, H. M., and Ong, C. N. (2001) J. Toxicol. Environ. Health. Part A, 64, 507–519.
Aust, A. E., and Eveligh, J. (1999) Exp. Biol. Med., 43, 246–252.
Qi, W., Reiter, R. J., Tan, D., Garcia, J. J., Manchester, L. C., Karbownik, M., and Calvo, J. R. (2000) Environ. Health Perspect., 108, 398–402.
Cheng, K. C., Cahill, D. S., Kasai, H., Nishimura, S., and Loeb, L. A. (1992) J. Biol. Chem., 267, 166–172.
Asami, S., Manabe, H., Miyake, J., Tsurudome, Y., Hirano, T., Yamaguchi, R., Itoh, H., and Kasai, H. (1997) Carcinogenesis, 18, 1763–1766.
Lloyd, D. R., Carmichael, P. L., and Phillips, D. H. (1998) Chem. Res. Toxicol., 11, 420–427.
Ding, W. X., and Ong, C. N. (2003) FEMS Microbiol. Lett., 220, 1–7.
Kuo, H. W., Cheng, S. F., Wu, K. Y., and Wu, F. Y. (2003) Occup. Environ. Med., 60, 590–594.
Reiter, R. J., Melchorri, D., Chuang, J. I., and Oritz, G. G. (1995) J. Pineal Res., 18, 1–11.
Karbownik, M., and Reiter, R. J. (2000) Exp. Biol. Med., 47, 9–22.
Ferry, G., Ubeaud, C., Mozo, J., Pean, C., Galizzi, P., Philippe, D., Renard, P., Yons, S., Lesieur, D., and Boutin, J. (2004) Eur. J. Biochem., 271, 418–428.
Fischer, C. P., Hiscock, N. J., Penkowa, M., Basu, S., Vessby, B., and Pedersen, B. (2004) J. Physiol., 558, 633–645.
Costa, E. J. X., Lopes, R. H., and Lamy, F. (1994) J. Pineal Res., 16, 123–126.
Shida, C. S., Castrucci, A. M., and Lamy, M. T. (1994) J. Pineal Res., 16, 198–201.
Black, H. S. (1974) Res. Commun. Chem. Pathol. Pharmacol., 7, 783–786.
Ames, B. N. (1989) Free Rad. Res. Commun., 7, 121–128.
Wu, T., Hashimoto, N., Wu, J., Carey, D., Li, R., Mickle, D., and Weisel, R. (1990) Biochem. Cell Biol., 68, 1189–1194.
Cerutti, C. A. (1985) Science, 227, 375–380.
Reiter, R. J., Guerrero, J. M., Garcia, J. J., and Acuna, D. (1998) Ann. N. Y. Acad. Sci., 854, 410–424.
Sies, H., and Stahl, W. (1995) Am. J. Clin. Nutr., 62, 1315–1321.
Floyd, R. A., West, M. S., Eneff, K. L., Hogsett, W. E., and Tingey, D. T. (1988) Arch. Biochem. Biophys., 262, 266–272.
Gehringer, M. M., Downs, K. S., Downing, T. G., Naude, R. J., and Shephard, E. G. (2003) Toxicon, 41, 451–458.
Gehringer, M. M., Govender, S., Shah, M., and Downing, T. G. (2003) Exp. Toxicol., 18, 142–148.
Yoshida, T., Makita, Y., Nagata, S., Tsutsumi, T., Yoshida, F., Tamaru, S., and Ucno, Y. (1997) Nat. Toxins, 5, 91–95.
Tsou, T. C., Chen, C. L., Liu, T. Y., and Yang, J. L. (1996) Carcinogenesis, 17, 102–108.
Ding, W. X., Shen, H. M., Zhu, H. G., and Ong, C. N. (1998) Environ. Res., 78, 12–18.
Rao, P. V. L., Gupta, N., and Jayaraj, R. (2004) Indian J. Pharmacol., 36, 87–92.
Stewart, M. S., Cameron, G. S., and Pence, B. C. (1996) J. Invest. Dermatol., 106, 1086–1089.
Toyokuni, S., and Sagripanti, J.-L. (1996) Free Rad. Biol. Med., 20, 859–864.
Halliwell, B., and Aruoma, O. I. (1991) FEBS Lett., 281, 9–19.
Bissett, D. L., Chatterjee, R., and Hannon, D. P. (1990) Photodermatol. Photomed., 7, 56–92.
Shen, C. L., Song, W., and Pence, B. C. (2001) Epidemiol. Biomarkers Prev., 10, 385–390.
Fang, Y. Z., Yang, S., and Wu, G. (2002) Nutr., 18, 872–879.
Mayo, J. C., Tan, D. X., Sainz, R. M., Burillo, S. L., and Reiter, R. J. (2003) Free Rad. Res., 37, 543–553.
Tan, D., Chen, L. D., Manchester, L. C., and Retier, R. J. (1993) Endocrinol. J., 1, 57–60.
Pahkla, R., Zilmer, M., and Rago, L. (1998) J. Pineal Res., 24, 96–101.
Stasica, P., Ulanskis, P., and Roseak, J. M. (1998) J. Pineal Res., 25, 65–66.
Tan, D., Manchester, L. C., Reiter, R. J., Plummer, B. F., Hardies, L. J., and Weintraub, S. F. (1998) Biochem. Biophys. Res. Commun., 253, 614–620.
Limson, J., Nykong, T., and Daya, S. (1998) J. Pineal Res., 24, 15–21.
Reiter, R. J. (1997) Adv. Pharmacol., 38, 103–117.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published in Russian in Biokhimiya, 2006, Vol. 71, No. 10, pp. 1377–1382.
Rights and permissions
About this article
Cite this article
Al-Jassabi, S., Khalil, A.M. Microcystin-induced 8-hydroxydeoxyguanosine in DNA and its reduction by melatonin, vitamin C, and vitamin E in mice. Biochemistry (Moscow) 71, 1115–1119 (2006). https://doi.org/10.1134/S0006297906100099
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1134/S0006297906100099