Public concern over the safety of food remains high. Consumers most commonly perceive additives and pesticides as the most important issues in food safety . Currently, discussions of large-scale incidents of the risks of chronic exposure to particular chemicals or additives in food is a common issue of debate in the literature . Monosodium glutamate (MSG), elicits a unique taste termed “umam”, and its consumption has increased throughout the world in recent years as flavoring in cooking to increase palatability and food selection in a meal [1]. However, MSG overfeeding has been associated with endothelial dysfunction ,obesity , cancer & cardiovascular disease . Most of the toxic effects due to MSG were related to its unbalancing effect on oxidant/antioxidant system and enhancing oxidative stress [2]. Observational epidemiologic studies indicate that diets high in carotenoid-rich fruits and vegetables , especially increased β-carotene intake ,has been found to be inversely correlated with risk for cardiovascular disease [3]. In fact ,β-carotene supplementation may help to strengthen the immune system [4], increase lung capacity and reduce cholesterol levels [5]. N-acetyl-cysteine (NAC), is another exogenous antioxidant that may protect against oxidative tissue injury. NAC has been shown to have antimutagenic activity towards various genotoxic agents. [6].

The purpose of this study is to evaluate the expected role of NAC& β-carotene and their possible synergistic effect in ameliorating the deteriorative effect of MSG on rat's heart.

Fifty adult male Wistar albino rats were divided into five groups. Group I was normal control (untreated group), group II : MSG-treated group (4 mg/g body wt o.p. Three times/week for 3 weeks) , groups III , IV, and V were treated with NAC, β-carotene and their combination (20 and 10 mg/kg , i.p. Three times/week for three weeks ,respectively) alternatively with MSG treatment. Animals were sacrificed 24 hour following last dose administration. Cardiac marker enzymes ,serum nitric oxide (NO) levels and cardiac ATP-ase activity were measured. Total lipids, total cholesterol, low density lipoprotein (LDL) ,and glucose levels were also estimated. In addition, tissue MDA, GSH, SOD , Catalase , L-ascorbic acid concentrations were determined. Moreover, the biochemical analysis was supported by histopathological examination of heart tissues.

Data are presented as the mean ± S.D. For comparison of multiple data sets one way analysis of variance (ANOVA) followed by Bonferroni multiple comparison test was used. Significance was accepted when p ≤ 0.05 .

N-Acetyl Cysteine and Pro Vitamin A Help in The Reversal of Monosodium Glutamate Oxidative Damage in Rat's Heart

Nayira A. Abdel Baky *, Azza A. Mostafa* * and L. M. Faddah *

*Faculty of Pharmacy, Pharmacology Department, King Saud University , KSA.

* * Therapeutic Chemistry Department, NRC, Egypt.In the present study, heart toxicity induced by MSG was indicated from significant increases in the activities of AST, CPK, LDH , and serum nitrite concentrations. In addition , total lipids, total cholesterol, low density lipoprotein (LDL) ,and glucose levels were also increased. Moreover, tissue malonaldehyde concentration and adenosine triphosphate hydrolyzing enzyme (ATP-ase) activity were significantly increased. Also, heart contents of L-ascorbic acid ,GSH ,SOD and catalase activities as well as high density lipoprotein (HDL) concentration were decreased compared to normal control group. oxidative stress and accumulation of free radicals seems to be responsible for MSG toxicity[2] . NAC and β-carotene either alone or in combination significantly restored the normal antioxidant balance in myocardial cells. Being a precursor of GSH, NAC provides protection from cardiac damage by elevating intracellular GSH levels [7]. As a source of SH groups, NAC can enhance glutathione-S-transferase activity, promote detoxification, and act directly on reactive oxidant radicals [8] . In addition, β-carotene, like other antioxidants, protects the body against free radicals, quench singlet oxygen, and reduce peroxyl radicals [9]. Simultaneous supplementation of NAC or/and β-carotene with MSG significantly decreased NO serum levels. This may be due to that, β-carotene helps to strengthen immune system [4] ,and also NAC enhances inflammatory and immune response [10] . In conclusion, The use of naturally occurring antioxidants like NAC and β-carotene is potentiated with their synergetic combination in ameliorating the hazardous effects of MSG. This combination may have a promising prophylactic or/and therapeutic effects in heart

diseases .

[1] Morrissey PA, O'Brien NM. Dietary antioxidants in health and disease. Int Dairy J 1998;8:463-72. [2] Yeda Sant’ Diniz, Luciane A. Faine, Cristiano M. Galhardi ,Hosana G. Rodrigues, Geovana X. Ebaid, Regina C. Burneiko, Antonio C. Cicogna, Ethel L.B. Novelli. Monosodium glutamate in standard and high-fiber diets: metabolic syndrome and oxidative stress in rats. Nutrition 21 (2005) : 749[3] Tavani A, La Vechia C. Beta-carotene and risk of coronary heart disease. A review of observational and intervention studies. Biomed Pharmacother 1999;53:409-416. [4] Chew BP, Park JS. Carotenoid action on the immune response. J Nutr. 2004; 134(1): 257S-261S.[5] Wang HX, Ng TB. Natural products with hypoglycemic, hypotensive, hypocholesterolemic, antiatherosclerotic and antithrombotic activities.Life Sci. 1999;65(25): 2663[6] Wilpart M, Speder A, Roberfroid M: Anti-initiation activity of N-acetylcysteine in experimental colonic carcinogenesis.Cancer Lett. 1986 ;31:31[7] Singh P, et al., Mol Cell Biochem. 2003; 243(1-2):139. [8] -De Vries N. and De Flora S. , J. Cell Biochem. 1993; 17F:S270.[9] Wang X.D., and Russell R.M. , Nutr. Rev. 1999; 57:263.[10] Chew B.P. and Park J.S., J. Nutr. 2004; 134(1):257S.

Materials and Methods

Aim of the work

0

25

50

75

100

a

b

bcb

ControlMSGMSG+ CARMSG+ NACMSG+COMB

Seru

m N

itrite

Con

cent

ratio

n(

mol

/Lite

re)

0

100

200

300

aac abc

b

Hea

rt L

ipid

Per

oxid

es

(nm

ol/g

m ti

ssue

)

0.0

2.5

5.0

7.5

a

ac ac

b

Car

dia

c V

itam

ine

C C

on

cen

trat

ion

(g

/gm

tis

sue)

0

1

2

aac

bcb

Hea

rt N

PS

H C

on

ten

t

(m

ol/g

m ti

ssu

e)

Statistical Analysis

Introduction

CPK LDH AST Glucose Heart ATP-ase

Control 105.6±6 .4 68.85±7.55 21.12±3.4 83.96±5.4 2.5±0 .39

MSG 488.1±58.9a 118.5±11.37 120.48±19.9a 232.02±7.9a 0.72±0.14a

MSG+

β- caro198.4±12.8bc 100.13±0.91a 25.5±3.9b 91.29±4.1ab 2.6±0.19b

MSG+

NAC207.8±9 .7bc 99.8±1.49a 24.66±2.4b 89.63±5.5b 2.73±0.13b

MSG+

COMB119.6±8 .2 b 88.34±1.49 22.59±2.2b 82.85±6.6b 2.66±0.15b

Results

Total Lipids(mg/dL)

TG(mg/dL)

Total Cholesterol

)mg/dL(

HDL(mg/dL)

LDL(mg/dL)

Control 0.423±0 .05 78.88±9.9 168.06±5.4 51.95±2.6 100.5±4 .9

MSG 2.16±0.23a 257.83±8.3a 261.65±9.6a 22.59±3.5a 183.98±5.2a

MSG+

β- caro0.48±0.09b 84.97±4.9 b 161.45±9.8b 45.3±3.7ab 105.02±2.2b

MSG+

NAC0.37±0.07b 83.04±6.3b 167.54±6.5b 50.23±3.4b 100.75±1.35b

MSG+

COMB0.44±0.02 b 86.22±6.9 b 163.45±3.9b 42.83±2.6b 108.15±2.8ab

0

5

10

15

a

b

ac

b

Hear

t SOD

Act

ivity

(U/m

g pr

otien

)

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10

20

30

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abc

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Hear

t Cat

alas

e Ac

tivity

(U/m

g pr

otie

n)

abc

(a) Normal (b) SMG (c) SMG + COMB

Values are means of 7 experiments SD.a : Significantly different from CONT group at P < 0.05.b : Significantly different from MSG-treated group at P < 0.05.c : Significantly different from MSG+COMB -treated group at P < 0.05.

Fig. 2 : Histopathological changes in rat cardiac tissues (H&E 400)

Table (2) : Effect of Effect of β carotene, N-acetyl-cysteine and their combination on on lipid profile of MSG-treated rats

Fig.(1): Effect of β carotene and/or N-acetyl-cysteine on heart malonaldehyde , glutathion , L-ascorbic acid content and superoxide dismutase and catalase activities Fig 1 (a, b ,c ,d , and e respectively) ,as well as serum nitrite levels Fig. 1 (f) in MSG-treated rats.

(a) (b) (c)

(d) (e) (f)

Table (1): Activities of serum CPK (U/L) , AST(U/L) ,LDH (μmol/ml/min) and glucose level (mg/dL) as well as ATP-ase activity (µ mol/min/mg protein) in normal and MSG-treated groups.

References

Discussion