Defensive role of silibinin against arsenic induced oxidative stress mediated dyslipidemia and neurotoxicity in rats

  • Authors

    • Muthumani Muthu Annamalai University
    • Sumedha Naroem Chanu Annamalai University
    • Shagirtha Kalist St.Joseph's college
    • Milton Prabu Annamalai University
    2016-05-07
    https://doi.org/10.14419/ijpt.v4i1.5803
  • Arsenic, Oxidative Stress, Brain, Lipid Profile, Silibinin, Rat.
  • Arsenic (As) is an environmental toxic metalloid that is present in everywhere such as air, water and soil. Generally, inorganic arsenic has a tendency to be more toxic than organic arsenic. The present study was designed to determine whether oral administration of silibinin (SB), which has been shown to have substantial antioxidant properties, when pre-administered (75 mg/kg body weight) once daily for 4 weeks along with arsenic (5 mg/kg) would prevent arsenic-induced changes in antioxidant defense system, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX),glutathione-S-transferase (GST),glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), reduced glutathione (GSH), total sulfhydryl groups (TSH) and vitamin C in rat brain regions such as cortex, striatum, cerebellum, hippocampus and brain stem. Our study also examined the effect of SB over arsenic-induced reactive oxygen species (ROS) production and lipid peroxidation level (LPO) and protein carbonyl content (PC) in distinct brain regions of rats. Moreover, As also alters the lipid profiles such as total lipids, phospholipids, cholesterol, cerebrosides and gangliosides in various regions of the brain. Pre-administration of SB restores the altered enzymatic and non-enzymatic antioxidants, lipid profiles and also markedly reduced the ROS, LPO, PC and accumulation of As in various regions of the brain. These results suggested that arsenic-induced deficits in antioxidant enzyme activities and increase in ROS production and lipid peroxidation levels in brain regions can be remarkably prevented by pre-administration of SB. 

    Author Biography

    • Milton Prabu, Annamalai University

      Assistant Professor

      Department of Zooogy

      Annamalai University

      India

  • References

    1. [1] Afzal M, Afzal A, Jones A, Armstrong D (2002), A rapid method for the quantification of GSH and GSSG in biological samples. In: Armstrong D, editor. Oxidative stress biomarkers and antioxidant protocol. Humana Press 117–22.http://dx.doi.org/10.1385/1-59259-173-6:117.

      [2] Ballentine R, Burford DD (1957), Determination of metals. Methods Enzymol 3:1002–1035http://dx.doi.org/10.1016/S0076-6879(57)03493-X.

      [3] Basiglio CL, Sanchez Pozzi EJ, Mottino AD, Roma MG(2009), Differential effects of silymarin and its active component SB on plasma membrane stability and hepatocellular lysis. Chemico-Biol Interact 179:297–303.http://dx.doi.org/10.1016/j.cbi.2008.12.008.

      [4] Beutler E (1983), Active transport of glutathione disulfide from erythrocytes. In: Larson A, Orrenius S, Holmgren A, Mannerwik BEDS., eds. Functions of Glutathione, Biochemical, Physiological, Toxicological and Clinical Aspects. New York, NY:Raven Press, 65.

      [5] Bharti VK, Srivastava RS, Anand AK, Kusum K (2012), Buffalo (Bubalusbubalis) epiphyseal proteins give protection from arsenic and fluoride-induced adverse changes in acetylcholinesterase activity in rats. J Biochem Molecular Toxicology 26: 10-15.http://dx.doi.org/10.1002/jbt.20407.

      [6] Bloor WR, Pelkan KF, Allen DM (1922), Determination of fatty acids and cholesterol in small amount of blood plasma. J BiolChem 52: 191-205.

      [7] Bondy SC (1997),Free radical mediated toxic injury to the nervous system. In: Wallace KB (ed): Free Radical Toxicology, Taylor and Francis, Oxford 221-248.

      [8] Brinkel J, Khan MMH, Kraemer A (2009), A systematic review of arsenic exposure and its social and mental health effects with special reference to Bangladesh. Int J Environ Res Public Health 6: 1609–19.http://dx.doi.org/10.3390/ijerph6051609.

      [9] Chattopadhyay S, Bhaumik S, Nag Chaudhury A, Das Gupta S (2002),Arsenic-induced changes in growth development and apoptosis in neonatal and adult brain cells in vivo and in tissue culture. ToxicolLett 128: 73–84.http://dx.doi.org/10.1016/S0378-4274(01)00535-5.

      [10] Das AK, Bag S, Sahu R, Dua TK, Sinha MK, Gangopadhyay M, et al (2010), Protective effect of Corchorusolitorius leaves on sodium arsenite-induced toxicity in experimental rats. Food ChemToxicol 48: 326–35.http://dx.doi.org/10.1016/j.fct.2009.10.020.

      [11] Ellman GL, Courtney KD, Andres V, Featherstone RM (1961), A new and rapid colorimetric determination of acetylcholinesterase activity. BiochemPharmacol7: 88–95.http://dx.doi.org/10.1016/0006-2952(61)90145-9.

      [12] EllmanGL (1959), Tissue sulfhydryl groups. Arch BiochemBiophys 82: 70–77.http://dx.doi.org/10.1016/0003-9861(59)90090-6

      [13] Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, Schneider B (1989), Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 9: 105–113.http://dx.doi.org/10.1016/0168-8278(89)90083-4.

      [14] Flora SJ and Gupta R (2007), beneficial effect of Centellaasiatica aqueous extract against arsenic induced oxidative stress and essential metal status in rats. Phytother Res 21: 980–988.http://dx.doi.org/10.1002/ptr.2208.

      [15] Flora SJ, Bhatt K, Mehta A (2009), Arsenic moiety in gallium arsenide is responsible for neuronal apoptosis and behavioral alterations in rats. ToxicolApplPharmacol 240: 236–44.http://dx.doi.org/10.1016/j.taap.2009.05.013.

      [16] Folch J, Ascoli I, Less M, Meath JA et al (1951), Preparation of lipid extracts from brain tissue. J BiolChem 191: 833-41.

      [17] Glowinski J, Iverson IL (1966), Regional studies on catecholamines in the rat brain. I. The disposition of (3H) norepinephrine, (3H) dopamine and (3H) dopa in various regions of the rat brain. J Neurochem 13: 665-9.

      [18] Gutteridge JMC (1995), Lipid peroxidation and antioxidants as biomarkers of tissue damage. ClinChem41: 1819–1828.

      [19] Haider SS,Najar MSA (2008), Arsenic induces oxidative stress, sphingolipidosis, depletes proteins and some antioxidants in various regions of rat brain. Kathmandu University Medical Journal 6 (21): 60-69.

      [20] Halliwell B (2006), Oxidative stress and neurodegeneration: Where are we now? J Neurochem 97:1634-1658.http://dx.doi.org/10.1111/j.1471-4159.2006.03907.x.

      [21] Horn HD, Burns FH (1978), Assay of glutathione reductase activity. In: Bergmeyer HV ed. Methods of Enzymatic Analysis. New York:Academic Press 142–146.

      [22] Hughes MF (2002), Arsenic toxicity and potential mechanisms of action. ToxicolLett 133:1–16.http://dx.doi.org/10.1016/S0378-4274(02)00084-X.

      [23] International Agency for Research on Cancer (1989), Overall evaluations of carcinogenicity: an update of IARC monographs. IARC monographs on the evaluation of Carcinogenic Risks to humans 7: 1–42.

      [24] Jones DP (2002), Redox potential of GSH/GSSG couple: assay and biological significance. Methods Enzymol 348: 93–112.http://dx.doi.org/10.1016/S0076-6879(02)48630-2.

      [25] Kakkar P, Das B, Viswanathan PN (1984), a modified spectrophotometric assay of superoxide dismutase. Indian J BiochemBiophys 21:130–132.

      [26] Kapaj S, Peterson H, Liber K, Bhattacharya P (2006), Human health effects from chronic arsenic poisoning: a review. J Environ Sci Health A41: 2399–428.http://dx.doi.org/10.1080/10934520600873571.

      [27] Khan MMH, Aklimunnessa K, Kabir M, Mori M (2006), Case - control study of arsenicosis in some arsenic contaminated villages of Bangladesh. Sapporo Med J 75: 51–61.

      [28] Kirkman HN and Gaetani GF (1984), Catalase: a tetrameric enzyme with four tightly bound molecules of NADPH. ProcNatlAcadSci USA 81: 4343–4347.http://dx.doi.org/10.1073/pnas.81.14.4343.

      [29] Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn B, ShaltielS,Stadtman ER (1990), Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186: 464–478.http://dx.doi.org/10.1016/0076-6879(90)86141-H.

      [30] Lowry OH, Rosenberg NJ, Farn AL, Randall RJ (1951), Protein measurement with Folin phenol reagent. J BiolChem 193: 265-75.

      [31] Manna P, Sinha M, Sil PC (2008), Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid. Arch Toxicol 82:137–49. http://dx.doi.org/10.1007/s00204-007-0272-8.

      [32] Marinetti GV (1962), Chromatographic separation, identification and analysis of phosphatides. J Lipid Res 3:1-12.

      [33] Mates JM (2000), Effects of antioxidant enzymes in the molecular control of reactive oxygen species. Toxicology 153: 83–84.http://dx.doi.org/10.1016/S0300-483X(00)00306-1.

      [34] Mccarty MF (2005), potential utility of natural polyphenols for reversing fat-induced insulin resistance. Med. Hypotheses 64(3): 628-635.http://dx.doi.org/10.1016/j.mehy.2003.11.042.

      [35] McCord JM, Keele BB, Fridovich I (1976), an enzyme based theory of obligate anaerobis: the physiological functions of superoxide dismutase. ProcNatlAcadSci, U.S.A 68: 1024–1031.http://dx.doi.org/10.1073/pnas.68.5.1024.

      [36] Naso LG, Ferrer EG, Butenko N, Cavaco I, Lezama L, Rojo T, Etcheverry SB, Williams PAM (2011), Antioxidant, DNA cleavage, and cellular effects of silibinin and a new oxovanadium(IV) /silibinin complex. J BiolInorgChem 16:653–668.http://dx.doi.org/10.1007/s00775-011-0769-8.

      [37] North DW, Gibb HJ, Abernathy CO (1997), as: past, present and future considerations. In: Abernathy CO, Calderon RL, Chappell WR, Eds. As Exposure and Health Effects. London, UK: Chapman and Hall 407–423.

      [38] Ohkawa H, Ohishi N, Yagi K (1979), Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem 95 (2): 351–358.http://dx.doi.org/10.1016/0003-2697(79)90738-3.

      [39] Omaye ST, Turbull TD, Sauberlich HC (1979), Selected method for the determination of ascorbic acid in animal cells, tissues and fluids. In: McCormic DB, Wright DL, eds. Methods in Enzymology. New York, NY: Academic Press, 3–11.http://dx.doi.org/10.1016/0076-6879(79)62181-x.

      [40] Pietrangelo A, Borella F, Casalgrandi G, Montosi G, Ceccarelli D, Gallesi D, Giovannini F, Gasparetto A, Masini A (1995), Antioxidant activity of silybinin vivo during long-term iron overload in rats. Gastroenterology 109: 1941–1949.http://dx.doi.org/10.1016/0016-5085(95)90762-9.

      [41] Pollet S, Ermidou S, Lesaux F, Monge M, and Baumann N (1979), Microanalysis of brain lipids: Multiple two dimensional thin layer chromatography. J Lipid Res 19: 916-21.

      [42] Pradhan SC and Girish C (2006), Hepatoprotective herbal drug, Silymarin from experimental pharmacology to clinical medicine. Indian J Med Res 124: 491-504.

      [43] Radabaugh TR, Aposhian HV (2000), enzymatic reduction of arsenic compounds in mammalian system: reduction of arsenate to arsenite by human liver arsenate reductase. Chem Res Toxicol 13:26–30.http://dx.doi.org/10.1021/tx990115k.

      [44] Rajnarayana K, Sripalreddy M, Chaluvadi MR, Krishna DR (2001),Bioflavonoids Classification, Pharmacological, Biochemical Effects and Therapeutic Potential. Indian J Pharm 33:2–16.

      [45] Rios R, Zarazua S, Santoyo ME, Sepulveda-Saavedra J, Romero-Dı´az V, Jimenez V, et al (2009), Decreased nitric oxide markers and morphological changes in the brain of arsenic exposed rats. Toxicology 261: 68–75.http://dx.doi.org/10.1016/j.tox.2009.04.055.

      [46] Rosado JL, Ronquillo D, Kordas K, Rojas O, Alatorre J, Lopez P, et al (2007), Arsenic exposure and cognitive performance in Mexican schoolchildren. Environ Health Perspect 115: 1371–5.http://dx.doi.org/10.1289/ehp.9961.

      [47] Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973), Selenium: biochemical role as a component of glutathione peroxidase. Science 179:588–590.http://dx.doi.org/10.1126/science.179.4073.588.

      [48] Roughan PG, Batt RD (1968), Quantitative analysis of sulfolipids and galactolipids in plant tissues. Anal Biochem 22: 74-88. http://dx.doi.org/10.1016/0003-2697(68)90261-3.

      [49] Saller R, Meier R, Brignoli R (2001), the use of silymarin in the treatment of liver diseases. Drugs 61: 2035–2063.http://dx.doi.org/10.2165/00003495-200161140-00003.

      [50] Shila S, Kathirvel R, Jayavelu T, Chinnakkannu P (2005a), Protein oxidative damage in arsenic induced rat brain: influence of DL-a-lipoic acid. ToxicolLett155: 27–34.http://dx.doi.org/10.1016/j.toxlet.2004.08.001.

      [51] Shila S, Kokilavani V, Subathra M, Panneerselvam C (2005), Brain regional responses in antioxidant system to alpha-lipoic acid in arsenic intoxicated rat. Toxicology 210: 25–36.http://dx.doi.org/10.1016/j.tox.2005.01.003.

      [52] Shila S, Subathra M, Devi MA, Panneerselvam C (2005b), Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-a-lipoic acid. Arch Toxicol 79: 140–146.http://dx.doi.org/10.1007/s00204-004-0614-8.

      [53] Shinomol G, Muralidhara (2007), Differential induction of oxidative impairments in brain regions of male mice following subchronic consumption of Khesaridhal (Lathyrussativus) and detoxified khesaridhal. Neurotoxicology28:798–806.http://dx.doi.org/10.1016/j.neuro.2007.03.002.

      [54] Sinha AK (1972), Colorimetric assay of catalase. Anal Biochem 47:389–394.http://dx.doi.org/10.1016/0003-2697(72)90132-7.

      [55] Sinha H, Manna P, Sil PC (2008b), Arjunolic acid attenuates arsenic-induced nephrotoxicity. Pathophysiology 15: 147–156.http://dx.doi.org/10.1016/j.pathophys.2008.03.001.

      [56] Travacio M, Polo JM, Liesuy S (2000), Chromium (VI) induces oxidative stress in the mouse brain. Toxicology 150: 137–146.http://dx.doi.org/10.1016/S0300-483X(00)00254-7.

      [57] Vahidnia A, van der Voet GB, de Wolff FA (2007), Arsenic neurotoxicity: a review. Hum ExpToxicol 26: 823–32.http://dx.doi.org/10.1177/0960327107084539.

      [58] Wang MJ, Lin WW, Chen HL, Chang YH,Ou HC, Kuo JS, Hong JS, Jeng KC (2002),Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation. Eur J NeuroSci 16: 2103-2112.http://dx.doi.org/10.1046/j.1460-9568.2002.02290.x.

      [59] Winterbourn CC (2008), Reconciling the chemistry and biology of reactive oxygen species. Nat ChemBiolWinterbourn, C. C. Reconciling the chemistry and biology of reactive oxygen species. Nat ChemBiol 4: 278-286.http://dx.doi.org/10.1038/nchembio.85.

      [60] Woodman DD, Price CP Estimation of serum total lipids (1972), ClinChemActa 38: 39-43. http://dx.doi.org/10.1016/0009-8981(72)90205-7.

      [61] Yadav RS, Sankhwar ML, Shukla RK, Chandra R, Pant AB, Islam F, Khanna VK (2009), Attenuation of arsenic neurotoxicity by curcumin in rats. ToxicolApplPharmacol 240: 367–376.http://dx.doi.org/10.1016/j.taap.2009.07.017.

      [62] Yamanaka K, Hasegawa A, Sawamura R, Okada S (1991), Cellular response to oxidative damage in lung induced by administration of dimethyl arsenic acid, a major metabolite of inorganic arsenic in mice. ToxicolApplPharmacol 108: 205–213.http://dx.doi.org/10.1016/0041-008X(91)90111-Q.

      [63] Yoshida T, Yamauchi H, Sun G (2004) chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review. ToxicolApplPharmacol 198: 243–252.http://dx.doi.org/10.1016/j.taap.2003.10.022.

      [64] Zarazua S, Perez-Severiano F, Delgado JM, Martinez LM, Ortiz-Perez D, Jimenez-Capdeville ME (2006), Decreased nitric oxide production in the rat brain after chronic exposure arsenic exposure. Neurochem Res31: 1069–77.http://dx.doi.org/10.1007/s11064-006-9118-7.

  • Downloads

  • How to Cite

    Muthu, M., Naroem Chanu, S., Kalist, S., & Prabu, M. (2016). Defensive role of silibinin against arsenic induced oxidative stress mediated dyslipidemia and neurotoxicity in rats. International Journal of Pharmacology and Toxicology, 4(1), 78-88. https://doi.org/10.14419/ijpt.v4i1.5803