1. Table (1): Activities of ALT, AST & ALP (U/L) and LDH (μmol/ml/min) as well as albumin level (gm/dl) in serum of different normal and MSG- treated groups. 1. 1. Hepatoprotective Effect of N-acetyl Cysteine and/or β-Carotene on Monosodium Glutamate-Induced Toxicity in Rats Hazar Yaqub, Naira A. Abdel Baky, Hala A. Attia and Lila M. Faddah Faculty of Pharmacy, Pharmacology department, King Saud University, Riyadh, KSA. Introduction Fig.(1): Effect of β carotene, NAC and their combination on hepatic malondialdehyde (MDA), GSH and L-ascorbic acid levels. Fig 1 (a, b and c, respectively) as well as serum nitrite levels Fig. 1 (d) in normal and MSG-treated groups. Discussion &Conclusions Monosodium glutamate (MSG), is commonly used as a flavor enhancer especially in Chinese, Thainese and Japanese foods (1).However, MSG produce many symptoms such as numbness, flushing, sweating, dizziness and headaches. In addition, ingestion of MSG has been alleged to cause or exacerbate numerous conditions, including asthma, urticaria, atopic dermatitis, ventricular arrhythmia, neuropathy and abdominal discomfort (2). Liver as the most metabolic organ in the body; is higly liable to toxicity due to various agents. Actually, MSG has been reported to increase the activities of serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT) enzymes (3). Moreover, MSG causes membrane damage by initiating free radical and increasing lipid hydroperoxide concentration. It also increases hepatic calcium and ascorbic acid and decreases both superoxid dismutase (SOD) activity and reduced glutathione (GSH) level in hepatic tissue (4). N-acetyl-cysteine (NAC), is one of a large group of exogenous antioxidant drugs that may protect against oxidative tissue injury. It is considered as the drug of choice in ameliorating hepatotoxicity due to acetaminophen intoxication (5).NAC has been shown to have antimutagenic activity towards various genotoxic agents. (6). Another natural antioxidant, β-carotene protects the body against free radicals, quench singlet oxygen, and reduce peroxyl radicals (7). β-carotene also induces hepatic enzymes that detoxify carcinogens (8). Data are expressed as M ± SD a: Significance from control, b: Significance from MSG group c: Significance from MSG +COMP group Results Material & Methods MSG - treated groups Normal groups CON β-caroNAC β-caro + NAC CON β-caroNAC β-caro + NAC ALT 65 ± 4.83 77.83 b ± 4.47 76.62 b ± 2.92 71.6 b ± 4.21 120.5 a ± 13.17 85.13 abc ± 4.40 75.5 b ± 3.5 65 b ± 3.14 AST 103.18 ± 5.75 101.7 b ± 6.78 100.1 b ± 8.27 98.52 b ± 7.69 153.8 a ± 18.34 116.9 b ± 5.26 112.3 b ± 9.89 107.4 b ± 5.18 LDH 68.85 ± 7.55 54.34 bc ± 8.78 51.96 abc ± 5.21 40.5 abc ± 2.54 118.5 a ± 11.37 100.1 abd ± 0.909 99.8 abd ± 1.49 88.34 abd ± 1.49 ALP 90.96 ± 3.12 70.53 bc ± 4.03 77.03 bc ± 11.35 77.36 bc ± 3.96 158.1 a ± 24.4 96.45 b ± 9.36 133.2 abc ± 3.96 112.37 bd ± 17.25 Albu- min 5.62 ± 0.23 5.95 b ± 0.28 5.1 bc ± 0.39 5.13 b ± 0.59 2.8 a ± 0.34 5.93 b ± 0.23 5.97 b ± 0.44 6.4 b ± 0.58 the body against free radicals, quench singlet oxygen, and reduce peroxyl radicals (7).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 (11), and also NAC enhances inflammatory and immune response (12). 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 inflammatory liver diseases. In the present study, liver damage induced by MSG was indicated from significant increases in the activities of ALT, AST, ALP LDH, and serum nitrite concentrations as well as hepatic malonaldehyde level and decreased serum albumin level and hepatic contents of L-ascorbic acid and GSH levels as compared to normal control group. oxidative stress and accumulation of free radicals seems to be responsible for MSG toxicity. NAC and β-carotene either alone or in combination significantly restored the normal antioxidant balance in liver cells. Being a precursor of GSH, NAC provides protection from toxic liver damage by elevating intracellular GSH levels ( 9). As a source of SH groups, NAC can enhance glutathione-S-transferase activity, promote detoxification, and act directly on reactive oxidant radicals (10). In addition, β- carotene, like other antioxidants, protects References Aim of the work The purpose of this study is to evaluate the expected role of NAC &β-carotene and the possible synergistic effect of their co-administration to counteract the hazardous effects of intraperitoneal injection of MSG. This will be achieved through monitoring liver function tests, oxidative status; malondialdehyde (MDA), GSH, Vit. Cand nitric oxide (NO) levels. Eighty adult male Wistar albino rats were divided into two major groups. Group I was consisted of four healthy normal subgroups; normal control, NAC, β-carotene (20 and 10 mg/kg, i.p. Three times/week for three weeks,respectively) and combination of NAC and β-carotene-treated group (Gs1, 2, 3 and 4, respectively). On the other hand, group II comprised of four MSG (4 mg/g body wt i.p. Three times/week for 3 weeks )-treated groups; MSG control, NAC, β-carotene (20 and 10 mg/kg i.p. one hour before MSG injection,respectively) and combination of NAC and β-carotene-treated groups (Gs 5, 6,7 and 8, respectively). Animals were sacrificed 24 hour following last dose adminstration. Liver function tests, MDA, GSH, Vit. C and nitric oxide (NO) levels were determined. Statistical Analysis 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 swas used. Significance was accepted when p ≤ 0.05. 1-Ikeda, K. 1912; 38: 147. 2-Geha R.S., J. Nutr., 2000; 130, 1032S. 3-Onyema O.O., Indian J. Biochem. Biophys. 2006; 43(1):20. 4-Farombi E.O.,et al., Hum. Exp. Toxicol. 2006 ;25 (5):251. 5-Prescott L.F., et al., Br. Med. J. 1979; 2: 1097. 6-Wilpart M, et al., Cancer Lett. 1986 ; 31(3):319. 7-Wang X.D., and Russell R.M., Nutr. Rev. 1999; 57:263. 8-Edes T.E., et al., J. Nutr. 1989; 119:796. 9-Singh P, et al., Mol Cell Biochem. 2003; 243(1-2):139. 10-De Vries N. and De Flora S., J. Cell Biochem. 1993; 17F:S270. 11-Chew B.P. and Park J.S., J. Nutr. 2004; 134(1):257S. 12-Aihara M, et al., J. pathology, 2000; 67(6): 662.