Abstract
Methylguanidine (MG) is known as not only a nephrotoxin but also as a neurotoxine. We have previously showed that MG itself generates hydroxyl radicals (•OH) in an in vitro study. In this study, we examined the inhibitory effects of ascorbate, EPC-K1 (α-tocopheryl-l-ascorbate-2-O-phosphate diester), Trolox (water-soluble vitamin E analogue), and glutathione (GSH) on •OH generation from MG using an electron spin resonance (ESR) spectrometry with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). It was found that these compounds have potent inhibitory effect on •OH generation from MG in the order of ascorbate > GSH > EPC-K1 > Trolox.
Similar content being viewed by others
Abbreviations
- DMPO:
-
5,5-Dimethyl-1-pyrroline-N-oxide
- DMSO:
-
Dimethylsulfoxide
- DMPO-OH:
-
DMPO-spin adducts of hydroxyl radicals
- EPC-K1 :
-
α-Tocopheryl-l-ascorbate-2-O-phosphate diester
- ESR:
-
Electron spin resonance
- GSH:
-
Reduced glutathione
- •OH:
-
Hydroxyl radicals
- MnO:
-
Manganese oxide
- MG:
-
Methylguanidine
- ROS:
-
Reactive oxygen species
- R.P.H.:
-
Relative peak height
- O2 •− :
-
Superoxide anion radicals
- SOD:
-
Superoxide dismutase
References
Giovannetti S, Biagini M, Cioni L (1968) Evidence that methylguanidine is related in chronic renal failure. Experientia 24:341–343. doi:10.1007/BF02140809
Giovannetti S, Biagini M, Balestri PL, Navalesi R, Giagnoni P, De Matteis S et al (1969) Uremia-like syndrome in dogs chronically intoxicated with methylguanidine and creatinine. Clin Sci 36:445–452
Giovannetti S, Balestri PL, Barsotti G (1973) Methylguanidine in uremia. Arch Intern Med 131:709–713. doi:10.1001/archinte.131.5.709
Yokozawa T, Mo ZL, Oura H (1989) Comparison of toxic effects of methylguanidine, guanidinosuccinic acid and creatinine in rats with adenine-induced chronic renal failure. Nephron 51:388–392
Yokozawa T, Fujitsuka N, Oura H (1989) Variations in the distribution of methylguanidine with the progression of renal failure after methylguanidine loading. Nephron 52:347–351
Jinnnai D, Sawai A, Mori A (1966) γ-Guanidinobutyric acid as a convulsive substance. Nature 212:617. doi:10.1038/212617a0
Matsumoto M, Kobayashi K, Kishikawa H, Mori A (1976) Convulsive activity of methylguanidine in cats and rabbits. IRCS Med Sci 4:65
Mori A, Watanabe Y, Akagi M (1982) Guanidino compound anomalies in epilepsy. In: Akimoto H, Kazamatsuri H, Seino M, Ward M (eds) Advances in epileptology: XIIIth epilepsy international symposium. Raven Press, New York, pp 347–351
Mori A (1987) Biochemistry and neurotoxicology of guanidino compounds: history and recent advances. Pavlov J Biol Sci 22:85–94
Mori A (1996) Reactive oxygen species and mechanism of induction of seizure by guanidino compounds. In: Packer L, Hiramatsu M, Yoshikawa T (eds) Free radicals in brain physiology and disorders. Academic Press, San Diego, pp 3–14
Hirayasu Y, Morimoto K, Otsuki S (1991) Increase of methylguanidine and guanidinoacetic acid in the brain of amygdala-kindled rats. Epilepsia 32:761–766. doi:10.1111/j.1528-1157.1991.tb05531.x
Shimizu Y, Morimoto K, Kuroda S, Mori A (1995) Sustained increase of methylguanidine in the rats after amygdala and hippocampal kindling. Epilepsy Res 21:11–17. doi:10.1016/0920-1211(94)00004-G
Mori A, Kohno M, Masumizu T, Packer L (1995) α-Guanidinoglutaric acid as a free radical generater. Biochem Mol Biol Int 37:371–374
Mori A, Kohno M, Masumizu T, Noda Y, Packer L (1996) Guanidino compounds generate reactive oxygen species. Biochem Mol Biol Int 40:135–143
Mori A, Edamatsu R, Kohno M, Ohmori S (1989) A new hydroxyl radical scavenger: EPC-K1. Neurosciences 15:371–376
Ando A, Oriat K, Nakata K, Tsukakihara Y, Takamitsu Y, Ueda N et al (1979) Effect of low protein diet and surpus of essential amino acids on the serum concentration and the urinary excretion of methylguanidine and guanidinosuccinic acid in chronic renal failure. Nephron 24:161–169
Koide H, Azushima C (1985) Metabolic profiles of guanidine compounds in various tissue of uremia rats. In: Mori A, Cohen BD, Lowenthal A (eds) Guanidines. Prenum Press, New York, pp 365–372
Mori A, Yokoi I, Noda Y, Willomore LJ (2004) Natural antioxidants may prevent posttraumatic epilepsy: a proposal based on experimental animal studies. Acta Med Okayama 58:111–118
Aoyagi K, Nagase S, Koyama A, Narita M, Tojo S (1998) Products of creatinine with hydroxyl radical as a useful marker of oxidative stress in vivo. Methods Mol Biol 108:157–164
Nakamura K, Ienaga K, Yokozawa T, Fujitsuka N, Oura H (1991) Production of methylguanidine from creatinine via creatol by active oxygen species: analyses of the catabolism in vitro. Nephron 58:42–46
Author information
Authors and Affiliations
Corresponding author
Additional information
Special issue article in honor of Dr. Akitane Mori.
Rights and permissions
About this article
Cite this article
Noda, Y., Mankura, M. Inhibitory Effect of Antioxidants on Hydroxyl Radical Generation from Methylguanidine: An ESR Study. Neurochem Res 34, 734–738 (2009). https://doi.org/10.1007/s11064-008-9811-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-008-9811-9