Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C,vitamin E and quercetin

Abstract

Monosodium glutamate (MSG) continues to function as a flavor enhancer in West African and Asian diets. The present study examines the modulatory effects of dietary antioxidant vitamin C (VIT C), vitamin E (VIT E) and quercetin on MSG-induced oxidative damage in the liver, kidney and brain of rats. In addition, the effect of these antioxidants on the possible genotoxicity of MSG was investigated in a rat bone marrow micronuclei model.

MSG administered intraperitoneally at a dose of 4 mg/g body wt markedly increase malondialdehyde (MDA) formation in the liver, the kidney and brain of rats. Simultaneous administration of VIT C, VIT E and quercetin to MSG-treated rats significantly reduced this increase in MDA induced by MSG. VIT E reduced lipid peroxidation most in the liver followed by VIT C and then quercetin, while VIT C and quercetin showed a greater ability to protect the brain from membrane damage than VIT E.

The decreased glutathione (GSH) level elicited by MSG in the three organs corresponded with marked increase in the activity of glutathione-S-transferase (GST). While MSG increased (P B / 0.001) the activities of superoxide dismutase and catalase in the liver, it decreased significantly the activities of these enzymes in the kidney and the brain. The three antioxidants were effective at ameliorating the effects of MSG on GSH levels and the enzymes in the three organs examined. While MSG increased the activity of glucose-6-phosphatase in the liver and kidneys of rats (P B / 0.001), the activity of the enzyme was abysmally low in the brain. There were marked increases in the activities of alanine aminotransferase, aspartate aminotransferase and g-glutamyl transferase in rats treated with MSG. The antioxidants tested protected against MSG-induced liver toxicity significantly.

MSG at a dose of 4 mg/g significantly (P B / 0.01) induced the formation of micronucleated polychromatic erythrocytes (MNPCEs). Co-treatment of rats with VIT C and quercetin inhibited the induction of MNPCEs by MSG (P B / 0.001). VIT E failed to protect against MSG-induced genotoxicity.

The results indicate that dietary antioxidants have protective potential against oxidative stress induced by MSG and, in addition, suggest that active oxygen species may play an important role in its genotoxicity.

Keywords

antioxidants dietary vitamins genotoxicity micronucleus monosodium glutamate oxidative stress

References

1 Obaseiki-Ebor EE , McGhee EM , Shankel DM . Improved detection of the genotoxic and mutagenic potentials of a food condiment A-One (monosodium glutamate) . Presented at the Fourth International Conference of the Pan-African Environmental Mutagen Society (PAEMS) in Dar El Diafa-Ain Shams University, Cairo, Egypt, 2-7.March, 2003: 63-63 .

2 Schaumberg HH , Byck R , Gerst R , Mashman JH . Monosodium l-glutamate; its pharmacology and role in the Chinese restaurant syndrome . Science 1969; 163: 826-828 .

3 Geha RS , Beiser A , Ren C , Patterson R , Grammar LC , Ditto AM , et al. Review of allergic reaction to monosodium glutamate and outcome of a multicenter double blind placebo-controlled study . J Nutr 2000; 130: 1032-1038 .

4 Park CH , Choi SH , Piao Y , Kim S , Lee YJ , Kim HS , et al. Glutamate and aspartate impair memory retention and damage hypothalamic neurons in adult mice . Toxicol Lett 2000; 115: 117-125 .

5 Singh K , Ahluwalia P . Studies on the effects of monosodium glutamate (MSG) administration on some antioxidant enzymes in the arterial tissue of adult male mice . J Nutr Sci Vitaminol [Tokyo] 2003; 49: 145-148 .

6 Bergen HT , Mizuno TM , Taylor J . Hyperphagia and weight gain after gold-thioglucose and monosodium glutamate: relation to hypothalamic neuropeptide Y . Endocrinology 1998; 139: 4483-4488 .

7 Mozes S , Sefcikova Z , Lenhardt L , Racek L . Obesity and changes of alkaline phosphatase activity in the small intestine of 40and 80-day-old rats subjected to early postnatal overfeeding or monosodium glutamate . Physiol Res 2004; 53: 177-186 .

8 Ahluwalia P , Tewari K , Choudhary P . Studies on the effects of monosodium glutamate (MSG) on oxidative stress in erythrocytes of adult male mice . Toxicol Lett 1996; 84: 161-165 .

9 Diniz YS , Fernandes AA , Campos KE , Mani F , Ribas BD , Novelli EL . Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue . Food Chem Toxicol 2004; 42: 319-325 .

10.

10 Hayatsu H , Arimoto S , Negishi T . Dietary inhibitors of mutagenesis and carcinogenesis . Mutat Res 1988; 302: 429-446 .

11.

11 Block G , Langseth L . Antioxidant vitamins and disease prevention . Food Technol 1994; 48: 80-84 .

12.

12 Barber DA , Harris SR . Oxygen free radicals and antioxidants: a review . Am Pharmacol 1994; N534: 26-35 .

13.

13 Chaudiere J , Ferrar-Iiou R . Intracellular antioxidants: from chemical to biochemical mechanisms . Food Chem Toxicol 1999; 37: 949-962 .

14.

14 Khaidakov M , Bishop M , Manjanatha MG , Lyn-Cook LL , Desai VG , Chen JJ , et al. Influence of dietary antioxidants on mutagenicity of 7,12 dimethylbenz[a]anthracene and bleomycin in female rats. Mutat Res 2001; 480-481. 163-170.

15.

15 US Department of Health and Human Service . National toxicology program technical report on the toxicology and carcinogenesis. Studies of quercetin in F344/N rats. NIH publication No. 91-3140, 1992.

16.

16 Terao J , Piskula Q , Yao Q . Protective effect of epicatechin, epicatechin gallate, and quercetin on lipid peroxidation in phospholipid bilayers . Arch Biochem Biophys 1994; 308: 1991s-1993s .

17.

17 Karekar V , Joshi S , Shinde SL . Antimutagenic profile of three antioxidants in the Ames assay and the Drosophila wing spot test . Mutat Res 2000; 468: 183-194 .

18.

18 Farombi EO , Adepoju BF , Ola-Davies OE , Emerole GO . Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by Kolaviron, a natural biflavonoid of Garcinia kola seeds . Eur J Cancer Prev 2005; 14: 207-214 .

19.

19 Lowry OH , Rosenbrough NJ , Farr AL , Randall RJ . Protein measurement with Folin phenol reagent . J Biol Chem 1951; 193: 265-265 .

20.

20 Mohun AF , Cook LJ . Simple method for measuring serum level of glutamate-oxaloacetate and glutamatepyruvate transaminases in laboratories . J Clin Chem 1957; 10: 394-399 .

21.

21 Reitman S , Frankel S . A colorimetric method for the determination of serum glutamate-oxaloacetate and pyruvate transaminases . Am J Clin Pathol 1957; 28: 56-63 .

22.

22 Szasz G . A kinetic photometric method for serum glutamyl transpeptidase . Clin Chem 1969; 15: 124-124 .

23.

23 Habig WH , Pabst UJ , Jakoby WB . Glutathione-S-transferase . J Biol Chem 1974; 249: 7130-7139 .

24.

24 Koide H , Oda T . Pathological occurrence of glucose 6phosphatase in serum in liver diseases . Clin Chim Acta 1959; 4: 554-561 .

25.

25 Misra HP , Fridovich I . The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase . J Biol Chem 1972; 247: 3170-3175 .

26.

26 Magwere T , Naik YS , Hasler JA . Effect of chloroquine treatment on antioxidant enzymes in rat liver and kidney . Free Rad Biol Med 1997; 22: 321-327 .

27.

27 Clairborne A . Catalase activity. In Greewald AR ed. Handbook of methods for oxygen radical research. CRC Press , 1995: 237-242.

28.

28 Farombi EO , Tahnteng JG , Agbooola O , Nwankwo JO , Emerole GO . Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by Kolaviron . A Garcinia kola seed extract. Food Chem Toxicol 2000; 38: 535-541 .

29.

29 Buege JA , Aust SD . Microsomal lipid peroxidation . Methods Enzymol 1978; 52: 302-310 .

30.

30 Jollow DJ , Mitchell JR , Zampaglione N , Gillette JR . Bromobenzene induced liver necrosis: protective role of glutathione and evidence for 3,4 bromobenzene oxide as the hepatotoxic metabolite . Pharmacology 1974; 11: 151-169 .

31.

31 Asanami S , Shimono K . Effects of chemicallyand environmentally-induced hypothermia on micronucleus induction in rats . Mutat Res 2000; 471: 81-86 .

32.

32 Choudhary P , Malik VBT , Puri S , Ahluwalia P . Studies on the effects of monosodium glutamate on hepatic microsomal lipid peroxidation, calcium, ascorbic acid and glutathione and its dependent enzymes in adult male mice . Toxicol Lett 1996; 89: 71-76 .

33.

33 Halliwell B . Oxidant and the central nervous system: some fundamental questions. Is oxidant damage relevant to Parkinson’s disease, traumatic injury or stroke? Acta Neurol Scand 2000; Suppl 126: 23-33 .

34.

34 Coyle JT , Puttfarcken P . Oxidative stress, glutamate, and neurodegenerative disorders . Science 1993; 262: 689-695 .

35.

35 Babu GN , Bawari M , Ali MM . Lipid peroxidation potential and antioxidant status of circumventricular organs of rat brain following neonatal monosodium glutamate . Neurotoxicology 1994; 15: 773-777 .

36.

36 Bawari M , Babu GN , Misra UK . Effect of neonatal monosodium glutamate on lipid peroxidation in adult rat brain . Neurosci Rep 1995; 6: 650-652 .

37.

37 Singh RP , Sharad S , Kapur S . Free radicals and oxidative stress in neurodegenerative diseases: relevance of dietary antioxidants . JIACM 2004; 5: 218-225 .

38.

38 Kono Y , Fridovich I . Superoxide radical inhibits catalase . J Biol Chem 1982; 257: 5751-5754 .

39.

39 Baynes JW . Role of oxidative stress in development of complication of diabetes . Diabetes 1991; 40: 405-412 .

40.

40 Kakkar R , Mantha SV , Radhi J , Prasad K , Kalra R . Antioxidant defense system in diabetic kidney: a time course study . Life Sci 1997; 60: 667-679 .

41.

41 Zubay GL , Parson WW , Vance DE . Principles of biochemistry. WCB Publishers , 1995: 270-270.

42.

42 Bain PJ . In Latimer KS, Mahaffey EA, Prasse KW eds. Duncan and Prasse’s veterinary laboratory medicine: clinical pathology, fourth edition. Lowa State Press , 2003: 193-214.

43.

43 Sai K , Hayachi M , Takagi A , Hasegawa R , Sofuni T , Kurokawa Y . Effects of antioxidants on induction of micronuclei in rat peripheral blood reticulocytes by potassium bromate . Mutat Res 1992; 269: 113-118 .