Table of Contents    
Year : 2013  |  Volume : 4  |  Issue : 2  |  Page : 393-395  

Evaluation of protective effect of N-acetyl cysteine on arsenic-induced hepatotoxicity

1 Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science, Rajendranagar, Hyderabad, Andhra Pradesh, India
2 Department of Animal Nutrition, College of Veterinary Science, Rajendranagar, Hyderabad, Andhra Pradesh, India

Date of Web Publication26-Aug-2013

Correspondence Address:
Alla Gopala Reddy
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Science, Rajendranagar, Hyderabad, Andhra Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-9668.116986

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Objective : The present study was aimed to study protective role of N-acetyl cysteine (NAC) was assessed against arsenic (As)-induced hepatotoxicity in rats. Methods : Twenty four male Wistar rats were divided into 4 groups of 6 animals each and treated as follows: Group 1: sham control, 2: arsenic control (sodium arsenite @ 10 mg/kg b. wt orally for 4 wks), 3: Pre-treatment with NAC (@ 300 mg/kg orally for 2 wks) followed by sodium arsenite along with NAC (as per above doses) and 4: Sodium arsenite + NAC (as per above doses for 4 wks). Results : The concentration of thiobarbituric acid reacting substances (TBARS) and protein carbonyls was significantly (P<0.05) increased, while the concentration of reduced glutathione (GSH), and the activity of CYP450, Na+ - K+ ATPase and Mg2+ ATPase in liver were significantly (P<0.05) reduced in group 2 as compared to control. Groups 3 and 4 revealed improvement in the parameters in study. Conclusion : The study revealed that arsenic induces hepatotoxicity by inducing oxidative stress and supplementation of NAC is beneficial in countering the adverse effects.

Keywords: Arsenic, hepatotoxicity, N-acetyl cysteine

How to cite this article:
Hemalatha P, Reddy AG, Reddy YR, Shivakumar P. Evaluation of protective effect of N-acetyl cysteine on arsenic-induced hepatotoxicity. J Nat Sc Biol Med 2013;4:393-5

How to cite this URL:
Hemalatha P, Reddy AG, Reddy YR, Shivakumar P. Evaluation of protective effect of N-acetyl cysteine on arsenic-induced hepatotoxicity. J Nat Sc Biol Med [serial online] 2013 [cited 2020 Aug 14];4:393-5. Available from:

   Introduction Top

Arsenic is a major global health concern due to its wide distribution and adverse health effects on humans, animals, birds, aquatic life and plants through polluted ground water and food chains. It is a known carcinogen that has been associated with cancers of the skin, lung, urinary bladder, and possibly liver, kidney and prostate in humans. Besides the natural sources, arsenic-contaminated herbicides, insecticides and rodenticides are also potential vehicles of arsenic toxicity. [1] Organic arsenicals are generally considered non-toxic, whereas inorganic forms are toxic. Inorganic arsenic exists predominantly in trivalent (As 3+ ) and pentavalent (As 5+ ) forms, where trivalent compounds are more toxic than pentavalent ones. [2] Liver is the target of arsenic-induced carcinogenesis. [3] Arsenic-induced global DNA hypomethylation was also seen in mouse livers chronically exposed to inorganic arsenic. [4],[5],[6],[7] The present work was undertaken in male Wistar Kyoto rats to study the protective effect of NAC on arsenic-induced hepatotoxicity.

   Materials and Methods Top

Male albino rats of Wistar Kyoto strain weighing about 200-220 g were procured from National Institute of Nutrition (NIN), Hyderabad, India. The animals were housed in solid bottom polypropylene cages. Animals were placed on commercial standard mash feed for rats (NIN, Hyderabad) and provided water ad libitum. Experimental protocol was approved by the Institutional Animal Ethics Committee. Rats were divided into four groups of 6 in each. Group 1 was kept as sham control, 2 was arsenic control (sodiumarsenite@10 mg/kg b. wt orally for 4 weeks), 3 was pre-treated with N-Acetyl cysteine (@ 300 mg/kg orally for 2 weeks) followed by sodium arsenite along with N-Acetyl cysteine (as per above doses for 4 weeks) and 4 was given sodium arsenite + N-acetyl cysteine (as per above doses for 4 weeks). The animals were then euthanized on 29 th day and livers were immediately excised, rinsed with ice-cold physiological saline and stored at -20°C for further homogenization to estimate the concentration of thiobarbituric acid reacting substances (TBARS), protein carbonyls and reduced glutathione (GSH), and the activity of CYP 450 , Na + -K + ATPase and Mg 2+ ATPase.

The data were subjected to statistical analysis by applying one way ANOVA using SPSS (version 15.0) and the means were compared by Duncan's multiple comparison test. Significance was set at P < 0.05.

   Results and Discussion Top

The concentration of TBARS (n mol MDA/mg protein) and protein carbonyls (n mol/mg protein) in liver showed a significant (P < 0.05) rise in Group 2 (3.06 ± 0.16 and 4.07 ± 0.25, respectively) as compared to group 1 (1.47 ± 0.09 and 1.19 ± 0.03, respectively). Groups 3 and 4 showed a significant (P < 0.05) decrease as compared to Group 2. The concentration of GSH in liver revealed a significant (P < 0.05) reduction in Group 2 (14.12 ± 1.47 μ mol/mg protein) as compared to the remaining groups [Table 1].
Table 1: Results of oxidative stress and enzymes in liver tissue

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Oxidative stress mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is the cause for arsenic toxicity. [8] In the present study, concentration of TBARS and protein carbonyls were increased in the liver of arsenic toxic group suggesting an ongoing oxidative stress. Similar results were obtained by Demerdash et al., [9] Flora et al.,[10] and Sharma et al. [11] Arsenic produces oxidative damage by disturbing the prooxidant-antioxidant balance, because it has very high affinity for sulfhydryl groups in GSH (non-enzymatic antioxidant), which might have implications in the maintenance of thiol-disulfide balance. [12] Arsenic also induces oxidative tissue damage through interference with GSH utilization. [13] N-Acetylcysteine (NAC) is a thiol-containing antioxidant that has been used to reduce various conditions of oxidative stress. Its antioxidant action is attributed to GSH synthesis; therefore maintaining intracellular GSH levels [14],[15] and scavenging reactive oxygen species (ROS). [16] It is also known as potent metal chelator. [17] NAC has a strong ability to restore the impaired pro-oxidant/antioxidant balance in metal poisoning.

The activity of CYP 450 (n mol/mg microsomal protein), Na + -K + ATPase (μ mol Pi liberated/mg microsomal protein/30 min) and Mg 2+ ATPase (μ mol Pi liberated/mg microsomal protein/30 min) in liver revealed a significant (P < 0.05) reduction in Group 2 (1.16 ± 0.19, 5.16 ± 0.28 and 4.94 ± 0.42, respectively) as compared to Group 1 (3.55 ± 0.39, 16.64 ± 1.25 and 13.96 ± 1.11, respectively) [Table 1]. Groups 3 and 4 showed a significant (P < 0.05) increase in the activity of CYP 450 and ATPases as compared to Group 2. The altered activity of ATPases may be attributed to the membrane lipid peroxidation resulting in structural derangement. Earlier reports confirm that low levels of ATP in hepatic cells with arsenic and treatment with NAC improved the activity of Na + /K + ATPases. [10] The activity of CYP 450 was significantly reduced in Group 2 as compared to control in this study, which is in agreement with the findings of Noreault et al. [18]

   Conclusion Top

The study revealed that arsenic induces toxic effects in liver due to generation of reactive oxygen species with eventual oxidative damage. Supplementation of NAC is beneficial in preventing these toxic effects to certain extent. Pre-treatment with NAC was found more protective as compared to NAC co-treatment against arsenic-induced toxicity.

   References Top

1.Gupta R, Flora SJ. Protective role of Aloe vera againstarsenic toxicity in rats. Phytother Res 2005;19:23-8.  Back to cited text no. 1
2.Duker AA, Carranza EJ, Hale M. Arsenic geo chemistry and health. Environ Int 2005;31:631-41.  Back to cited text no. 2
3.Liu J, Waalkes MP. Liver is a target of arsenic carcinogenesis. Toxicol Sci 2008;105:24-32.  Back to cited text no. 3
4.Okoji RS, Yu RC, Maronpot RR, Froines JR. Sodium arsenite administration via drinking water increases genome-wide and Ha-ras DNA hypomethylation in methyl-deficient C57BL/6J mice. Carcinogenesis 2002;23:777-85.  Back to cited text no. 4
5.Chen H, Li S, Liu J, Diwan BA, Barrett JC, Waalkes MP. Chronic inorganic arsenic exposure induces hepatic global and individual gene hypomethylation: Implications for arsenic hepatocarcinogenesis. Carcinogenesis 2004;25:1779-86.  Back to cited text no. 5
6.Xie Y, Trouba KJ, Liu J, Waalkes MP, Germolec DR. Biokinetics and subchronic toxic effects of oral arsenite, arsenate monomethylarsonic acid, and dimethylarsinic acid in v-Ha-ras transgenic (Tg.AC) mice. Environ Health Perspect 2004;112:1255-63.  Back to cited text no. 6
7.Xie Y, Liu J, Benbrahim-Tallaa L, Ward JM, Logsdon D, Diwan BA, et al. Aberrant DNA methylation and gene expression in livers of newborn mice transplacentally exposed to a hepatocarcinogenic dose of inorganic arsenic. Toxicology 2007;236:7-15.  Back to cited text no. 7
8.Von Ehrenstein OS, Poddar S, Yuan Y, Mazumder DG, Eskenazi B, Basu A, et al. Children's intellectual function in relation to arsenic exposure. Epidemiology 2007;18:44-51.  Back to cited text no. 8
9.El-Demerdash FM, Yousef MI, Radwan FM. Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs. Food Chem Toxicol 2009;47:249-54.  Back to cited text no. 9
10.Flora SJ, Mehta A, Gupta R. Prevention of arsenic-induced hepatic apoptosis by concomitant administration of garlic extracts in mice. Chem Biol Interact 2009;177:227-33.  Back to cited text no. 10
11.Sharma A, Sharma MK, Kumar M. Modulatory role of Emblica officinalis fruit extract against arsenic induced oxidative stress in Swiss albino mice. Chem Biol Interact 2009;180:20-30.  Back to cited text no. 11
12.Yamanaka K, Hesegwa A, Sawamuna R, Okada S. Cellular response to oxidative damage in lung induced by the administration of dimethylarsinic acid, a major metabolite of inorganic arsenics, in mice. Toxicol Appl Pharmacol 1991;108:205-13.  Back to cited text no. 12
13.Bhadauria S, Flora SJ. Response of arsenic-induced oxidative stress, DNA damage, and metal imbalance to combined administration of DMSA and monoisoamyl-DMSA during chronic arsenic poisoning in rats. Cell Biol Toxicol 2007;23:91-104.  Back to cited text no. 13
14.Moldeus P, Cotgreave IA. N-acetylcysteine. Methods Enzymol 1994;234:482-92.  Back to cited text no. 14
15.Gurer H, Ozunes H, Neal R, Spitz DR, Ercal N. Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead exposed rats. Toxicology 1998;120:181-9.  Back to cited text no. 15
16.Arouma OL, Halliwell B, Hoey BM, Butler J. The antioxidant action of N-acetyl cysteine in reaction with hydrogen peroxide, hydroxyl radical, superoxide and hypochlorous acid. Free Radical Biol Med 1989;6:593-7.  Back to cited text no. 16
17.Banner W, Koch M, Capin DM, Hopf SB, Chang S, Tong TG. Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds. Toxicol Appl Pharmacol 1986;83:142-7.  Back to cited text no. 17
18.Noreault LT, Kostrubsky VE, Wood SG, Nichols RC, Strom SC, Trask HW, et al. Arsenite decreases CYP3A4 and RXR in primary human hepatocytes. Drug Metab Dispos 2005;33:993-1003.  Back to cited text no. 18


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