Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E
Publication: Applied Physiology, Nutrition, and Metabolism
27 March 2009
Abstract
Mitochondria are the crossroads of several crucial cellular activities; they produce considerable quantities of superoxide radical and hydrogen peroxide, which can damage important macromolecules. Nicotine affects a variety of cellular processes, from induction of gene expression to modulation of enzymatic activities. The aim of this study was to elucidate the protective effects of andrographolide (ANDRO) aqueous extract (AE-Ap) of Andrographis paniculata, and vitamin E on nicotine-induced brain mitochondria. In this investigation, nicotine (1 mg·kg body mass–1·day–1) was treated, for the period of 7 days, simultaneously with 2 A. paniculata products, ANDRO and AE-Ap (250 mg·kg body mass–1·day–1); and vitamin E (50 mg·kg body mass–1·day–1) was supplemented in different group of male Wistar rats. The activities of mitochondrial electron transport chain (Mito–ETC) complexes (I, II, III), nitric oxide production, superoxide anion, catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, and concentrations of reduced glutathione and oxidized glutathione were measured in discrete regions of brain (the cerebral hemisphere, cerebellum, diencephalons, and brain stem). The study revealed that nicotine inhibits the Mito–ETC complexes and produces nitric oxide, which suppressed the mitochondrial oxidative stress scavenger system in different brain regions. In these circumstances, lipid peroxidation and protein oxidation were noted in different discrete regions of brain mitochondria. ANDRO, AE-Ap, and vitamin E showed the protective potentiality against nicotine toxicity. The analysis of such alterations is important in determining the basis of normal dysfunction in the brain associated with nicotine toxicity, which could be ameliorated by A. paniculata and vitamin E, and may help to develop therapeutic means against nicotine-induced disorders.
Résumé
Les mitochondries sont le siège de plusieurs activités cellulaires fondamentales et produisent une grande quantité de radical superoxyde et de peroxyde d’hydrogène pouvant ainsi endommager les macromolécules importantes. La nicotine modifie un certain nombre de processus cellulaires depuis l’induction de l’expression des gènes jusqu’à la modulation des activités enzymatiques. Cette étude se propose d’élucider le rôle prophylactique de l’andrographolide (ANDRO), d’un extrait aqueux (AE-Ap) de l’Andrographis paniculata et de la vitamine E sur les mitochondries du cerveau induites par la nicotine. Dans cette étude, les animaux recevant de la nicotine (1 mg·kg–1·jour–1) sont traités durant 7 jours au moyen de deux produits issus de l’A. paniculata, ANDRO et AE-Ap (250 mg·kg–1·jour–1) ; simultanément, on administre de la vitamine E (50 mg·kg–1·jour–1) à un autre groupe de rats mâles Wistar. On mesure les activités des complexes (I, II, III) de la chaîne de transfert d’électrons dans la mitochondrie, la production d’oxyde nitrique (NO), les activités de la superoxyde dismutase (SOD), de la catalase (CAT), de la glutathion réductase (GR), de la glutathion peroxydase (GSH-Px), de la GST et les concentrations de glutathion réduit (GSH) et de glutathion oxydé (GSSG) dans des régions déterminées du cerveau : l’hémisphère cérébral, le cervelet, le diencéphale et le tronc cérébral. D’après cette étude, la nicotine inhibe les complexes de la chaîne de transfert d’électrons et augmente la production d’oxyde nitrique dont le rôle est de diminuer l’activité du système d’épuration en présence de stress oxydatif dans les mitochondries des diverses régions du cerveau. Dans ces conditions, on observe une peroxydation lipidique et une oxydation protidique dans des régions très précises des mitochondries du cerveau. L’ANDRO, l’AE-Ap et la vitamine E démontrent un effet prophylactique contre la toxicité de la nicotine. L’analyse de ces modifications est importante pour la détermination des fondements des dysfonctions du cerveau associées à la toxicité de la nicotine. L’A. paniculata et la vitamine E pourraient contribuer au développement d’interventions thérapeutiques en présence d’anomalies causées par la nicotine.
Get full access to this article
View all available purchase options and get full access to this article.
References
Aebi, H. 1983. Catalase. In Methods in Enzymatic Analysis. Vol. 3. Edited by H.U. Bergmeyer. Academic Press, New York. pp. 276–286.
Andreyev, A.Y., Kushnareva, Y.E., and Starkov, A.A. 2005. Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc.), 70: 200–214.
Ashakumary, L., and Vijayammal, P.L. 1996. Effect of nicotine on antioxidant defense mechanisms in rats fed a high-fed diet. Pharmacology, 52: 153–158.
Barja, G. 1999. Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity and relation to aging and longevity. J. Bioenerg. Biomembr. 31: 347–366.
Barja, G., and Herrero, A.J. 1998. Localization at complex I and mechanism of the higher free radical production of brain nonsynaptic mitochondria in the short-lived rat than in the longevous pigeon. J. Bioenerg. Biomembr. 30: 235–243.
Basak, A., Cooper, S., Roberge, A.G., Banik, U.K., Chretien, M., and Seidah, N.G. 1999. Enzymic characterization in vitro of recombinant proprotein convertase PC4. Biochem. J. 338: 107–113.
Batkhuu, J., Hattori, K., Takano, F., Fushiya, S., Oshiman, K., and Fujimiya, Y. 2002. Suppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculata. Biol. Pharm. Bull. 25: 1169–1174.
Betarbet, R., Sherer, T.B., and Greenamyre, J.T. 2002. Animal models of Parkinson’s disease. Bioessays, 24: 308–318.
Braughler, J.M., and Hall, E.D. 1989. Central nervous system trauma and stroke. I. Biochemical considerations for free radical dormation and lipid peroxidation. Free Radic. Biol. Med. 6: 289–301.
Butterfield, D.A., Darke, J., Pocernich, C., and Castegna, A. 2001. Evidence of oxidative damage in Alzheimer’s disease brain: central role of Amyloid beta-peptide. Trends Mol. Med. 7: 548–554.
Calabrese, V., Bates, T.E., and Stella, A.M.G. 2000. NO synthase and NO-dependent signal pathways in brain aging and neurodegenerative disorders; the role of oxidant/antioxidant balance. Neurochem. Res. 25: 1315–1341.
Campain, J.A. 2004. Nicotine: Potentially a multifunctional carcinogen? Toxicol. Sci. 79: 1–3.
Cassina, A., and Radi, R. 1996. Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch. Biochem. Biophys. 328: 309–316.
Chance, B., Sies, H., and Boveris, A. 1979. Hydroperoxide metabolism in mammalian organs. Physiol. Rev. 59: 527–605.
Chandran, K., and Venugopal, P.M. 2004. Modulatory effects of curcumin on lipid peroxidation and antioxidant status during nicotine-induced toxicity. Pol. J. Pharmacol. 56: 581–586.
Chang, H.M., and But, P.P.H. (Editors). 1987. Pharmacology and application of Chinese materia medica. Vol. 1. World Scientific, Singapore. pp. 918–928.
Chattopadhyay, A., and Bandyopadhyay, D. 2006. Vitamine E in the prevention of heart disease. Pharmacol. Rep. 58: 179–187.
Cormier, A., Morin, C., Zini, R., Tillement, J.P., and Lagrue, G. 2001. In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation. Brain Res. 900(1): 72–79.
Cross, C.E., Halliwell, B., Borish, E.T., Pryor, W., Ames, B.N., Saul, R.L., et al. 1987. Oxygen radicals and human disease. Ann. Intern. Med. 107: 526–545.
Das, K.C., Lewis-Molock, Y., and White, C.W. 1995. Thiol modulation of TNFa and Il-1 induced MnSOD gene expression and activation of NF-kappaB. Mol. Cell. Biochem. 148: 45–57.
Das, S., Neogy, S., Gautam, N., and Roy, S. 2008. In vitro nicotine induced superoxide mediated DNA fragmentation in lymphocytes: protective role of Andrographis paniculata Nees. Toxicol. In Vitro, 23: 90–98.
de Vries, S. 1986. The pathway of electron transfer in the dimeric QH2: cytochrome c oxidoreductase. J. Bioenerg. Biomembr. 18: 195–224.
Fridovich, I. 1995. Superoxide radical and superoxide dismutases. Annu. Rev. Biochem. 64: 97–112.
Fry, M., and Green, D.E. 1980. Cardiolipin requirement by cytochrome c oxidase and the catalytic role of phospholipid. Biochem. Biophys. Res. Commun. 93: 1238–1246.
Gabbita, S.P., Lovell, M.A., and Markesbery, W.R. 1998. Increased nuclear DNA oxidation in the brain of Alzheimer’s disease. J. Neurochem. 71: 2034–2040.
Genova, M.L., Ventura, B., Giuliano, G., Bovina, C., Formiggini, G., Parenti, C.G., and Lenaz, G. 2001. The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2. FEBS Lett. 505: 364–368.
Gozalbes, R., Gálvez, J., Garcia-Domenech, R., and Derouin, F. 1999. Molecular search of new active drugs against Toxoplasma gondii. SAR QSAR Environ. Res. 10: 47–60.
Griffith, O.W. 1980. Determination of glutathione and glutathione sulfide using glutathione reductase and 2-Vinyl pyridine. Anal. Biochem. 106: 207-212.
Grigolava, I.V., Ksenzenko, M., Konstantinob, A.A., Tikhonov, A.N., and Kerimov, T.M. 1980. Tiron as a spin-trap for superoxide radicals produced by the respiratory chain of submitochondrial particles. Biokhimiia, 45: 75–82.
Gupta, A.K. (Editor). 2004. Review on Indian medicinal plants. Vol 1. (Ard-Alli)-ICMR, New Delhi, India.
Habig, W.H., Pabst, M.J., and Jakoby, W.B. 1974. Glutathione S-transferase. The first enzymatic step in mercapyuric acid formation. J. Biol. Chem. 249: 7130–7139.
Halliwell, B., and Gutterridge, J.M.C. 1998. Free radical in biology and medicine. Clarendon Press, Oxford.
Hatefi, Y., and Rieske, J.S. 1967. The preparation and properties of DPNH-cytochrome C reductase (Complex I of respiratory chain). In Methods in Enzymology. Vol. 10. Edited by R.W. Estabrook and M.E. Pullman. Academic Press, New York. pp. 235–239.
Hensley, K., Hall, N., Subramanian, R., Cole, P., Harris, M., Aksenov, M., et al. 1995. Brain regional correspondence between Alzheimer’s disease histopathology and biomarkers of protein oxidation. J. Neurochem. 65: 2146–2156.
Hu, Y., Cardounel, A., Gursoy, E., Anderson, P., and Kalimi, M. 2000. Anti-stress effects of dehydroepiandrosterone. Protection of rats against repeated immobilization stressinduced weight loss, glucocorticoid receptor production, and lipid peroxidation. Biochem. Pharmacol. 59: 753–762.
Jung, B.H., Chung, B.C., Chung, S., and Shim, C. 2001. Different pharmacokinetics of nicotine following intravenous administration of nicotine base and nicotine hydrogen tartarate in rats. J. Control. Release, 77: 183–190.
Kanniappan, M., Mathuram, L.N., and Natrajan, R. 1991. A study of the antipyretic effect of Chiretta (Andrographis paniculata). Indian Vet. J. 68: 314–316.
Kushnareva, Y., Murphy, A.N., and Andreyev, A. 2002. Complex I mediated reactive oxygen species generation: modulation by cytochrome c and NAD(P)+ oxidation-reduction state. Biochem. J. 368: 545–553.
Liu, J., Wang, X., Shigenaga, M.K., Yeo, H.C., Mori, A., and Ames, B.S. 1996. Immobilization stress causes oxidative damage to lipid, protein and DNA in the brain of rats. FASEB J. 10: 1532–1538.
Lovell, M.A., Gabbita, S.P., and Markesbery, W.R. 1999. Increased DNA oxidation and decreased level of repair product in Alzheimer’s disease ventricular CSF. J. Neurochem. 72: 771–776.
Lowry, O.H., Rosenbrough, N.J., Farr, A.L., and Randall, R.J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265–275.
Machlin, L.J., and Bendich, A. 1987. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1: 441–445.
Madav, H.C., Tripathi, T., and Mishra, S.K. 1995. Analgesic, antipyretic and antiulcerogenic effects of andrographolide. Indian J. Pharm. Sci. 57(3): 121–125.
Marklund, S., and Marklund, M. 1974. Involvement of superoxide anion radical in autoxidation of pyrogallol and a convenient assay of superoxide dismutase. Eur. J. Biochem. 47: 469–474.
Marttila, R.J., Roytta, M., Lorentz, H., and Rinne, U.K. 1988. Oxygen toxicity protecting enzymes in the human brain. J. Neural Transm. 74: 87–95.
Maser, E. 1997. Stress hormonal changes, alcohol food constituents and drugs: Factors that advance the incidence of tobacco smoke related cancers? Trends Pharmacol. Sci. 18: 270–275.
Matsuda, T., Kuroyanagi, M., Sugiyama, S., Umehara, K., Ueno, A., and Nishi, K. 1994. Cell differentiation-inducing diterpenes from Andrographis paniculata Nees. Chem. Pharm. Bull. (Tokyo), 42: 1216–1225.
Miwa, S. 1972. Hematology. In Modern medical techonology. Vol. 3. Edited by N. Kosakai, H. Abe, Y. Hayashi, T. Furukawa. Igaku Shohin Ltd, Tokyo. pp. 306–310.
Morrow, J.D., Frei, B., Longmire, A.W., Gaziano, J.M., Lynch, S.M., Shyr, Y., et al. 1995. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers. Smoking as a case of oxidative damage. N. Engl. J. Med. 332: 1198–1203.
Muller, F.L., Liu, Y., and Van Remmen, H. 2004. Complex III releases superoxide to both sides of the inner mitochondrial membrane. J. Biol. Chem. 279: 49064–49073.
Murley, J.S., Kataoka, Y., Hallahan, D.E., Roberts, J.C., and Grdina, D.J. 2001. Activation of NFkappaB and MnSOD gene expression by free radical scavengers in human microvascular endothelial cells. Free Radic. Biol. Med. 30: 1426–1439.
Neogy, S., Das, S., Kar Mahapatra, S., Mandal, N., and Roy, S. 2008. Amelioratory array of Andrographis paniculata Nees on liver, kidney, heart, lungs and spleen during nicotine induced oxidative stress. Environ. Toxicol. Pharmacol. 25: 321–328.
Nicholls, D.G. 2002. Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease. Int. J. Biochem. Cell Biol. 34: 1372–1381.
Nomura, K., Imai, H., Koumura, T., Kobayashi, T., and Nakagawa, Y. 2000. Mitochondrial phospholipid hydroperoxide glutathione peroxidase inhibits the release of cytochrome c from mitochondria by suppressing the peroxidation of cardiolipin in hypoglycaemia induced apoptosis. Biochem. J. 351: 183–193.
Oberley, L.W., St. Clair, D.K., Autor, A.P., and Oberley, T.D. 1987. Increase in manganese superoxide dismutase activity in the mouse heart after X-irradiation. Arch. Biochem. Biophys. 254: 69–80.
Ohkawa, H., Ohishi, N., and Yagi, K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 95: 351–358.
Paglia, D.E., and Valentine, W.N. 1967. Studies on quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med. 70: 158–169.
Phung, C.D., Ezieme, J.A., and Turrens, J.F. 1994. Hydrogen peroxide metabolism in skeletal muscle mitochondria. Arch. Biochem. Biophys. 315: 479–482.
Poderoso, J.J., Carreras, M.C., Lisdero, C., Riobó, N., Schöpfer, F., and Boveris, A. 1996. Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch. Biochem. Biophys. 328: 85–92.
Puri, A., Saxena, R., Saxena, R.P., Saxena, K.C., Srivastava, V., and Tandon, J.S. 1993. Immunostimulant agents from Andrographis paniculata. J. Nat. Prod. 56: 995–999.
Radi, R., Beckman, J.S., Bush, K.M., and Freeman, B.A. 1991a. Peroxynitrite oxidation of sulfhydryls: the citotoxic potential of superoxide and nitric oxide. J. Biol. Chem. 266: 4244–4250.
Radi, R., Turrens, J.F., Chang, L.Y., Bush, K.M., Crapo, J.D., and Freeman, B.A. 1991b. Detection of catalase in rat heart mitochondria. J. Biol. Chem. 266: 22028–22034.
Radi, R., Cassina, A., and Hodara, R. 2002. Nitric oxide and peroxynitrite interactions with mitochondria. Biol. Chem. 383: 401–409.
Ray, G., and Husain, S.A. 2002. Oxidants, antioxidants and carcinogenesis. Indian J. Exp. Biol. 40: 1213–1232.
Reznick, A.Z., and Packer, L. 1994. Oxidative damage to proteins: spectrophotometric methods for carbonyl assay. Methods Enzymol. 233: 357-363.
Ribiere, C., Hininger, I., Saffar-Boccara, C., Sabourault, D., and Nordmann, R. 1994. Mitochondrial respiratory activity and superoxide radical generation in the liver, brain and heart after chronic ethanol intake. Biochem. Pharmacol. 47(10): 1827–1833.
Rich, P.R., and Bonner, W.D. 1978. The sites of superoxide anion generation in higher plant mitochondria. Arch. Biochem. Biophys. 188: 206–213.
Rieske, J.S. 1967. Preparation and properties of reduced coenzyme Q cytochrome C reductase (complex III of the respiratory brain). In Methods Enzymology. Vol. 10. Edited by R.W. Estabrook and M.E. Pullman. Academic Press, New York. pp. 239–245.
Sanai, S., Tomisato, M., Shinsuka, N., Mayoko, Y., Mayoko, H., and Akio, N. 1998. Protective role of nitric oxide in S. aurues infection in mice. Infect. Immun. 66: 1017–1028.
Sen, T., Sen, N., Tripathy, G., Chatterjee, U., and Chakraborty, S. 2006. Lipid peroxidation associated cardiolipin loss and membrane depolarization in rat brain mitochondria. Neurochem. Int. 49: 20–27.
Shen, Y.C., Chen, C.F., and Chiou, W.F. 2002. Andrographolide prevents oxygen radical production by human neutrophils: possible mechanism(s) involved in its anti-inflammatory effect. Br. J. Pharmacol. 135: 399–406.
Singh, S.N., Vats, P., Kumria, M.M., Ranganthan, S., Shyam, R., Arora, M.P., et al. 2001. Effect of high altitude (7,620 m) exposure on glutathione and related metabolism in rats. Eur. J. Appl. Physiol. 84: 233–237.
Singha, P.K., Roy, S., and Dey, S. 2007. Protective activity of andrographolide and arabinogalactan proteins from Andrographis paniculata Nees. against ethanol-induced toxicity in mice. J. Ethnopharmacol. 111(1): 13–21.
Stadtman, E.R., and Berlett, B.S. 1997. Reactive oxygen mediated protein oxidation in aging and disease. Chem. Res. Toxicol. 10: 485–494.
Suleyman, H., Gumustekin, K., Taysi, S., Keles, S., Oztasan, N., Aktas, O., et al. 2002. Beneficial effects of Hippophae rhamnoides L, on nicotine induced oxidative stress in rat blood compared with vitamin E. Biol. Pharm. Bull. 25: 1133–1136.
Trivedi, N., and Rawal, U.M. 2000. Hepatoprotective and toxicological evaluation of Andrographis paniculata on severe liver damage. Indian J. Pharmacol. 32: 288–293.
Trojanowski, J.Q. 2003. Rotenone neurotoxicity: a new window on environmental causes of Parkinson’s disease and related brain amyloidoses. Exp. Neurol. 179: 6–8.
Tsan, M.F., Clark, R.N., Goyert, S.M., and White, J.E. 2001. Induction of TNF-a and MnSOD by endotoxin: role of membrane CD14 and Toll-like receptor-4. Am. J. Physiol. Cell Physiol. 280: C1422–C1430.
Turrens, J.F., and Boveris, A. 1980. Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem. J. 191: 421–427.
Turrens, J.F., Freeman, B.A., Levitt, J.G., and Crapo, J.D. 1982. The effect of hyperoxia on superoxide production by lung submitochondrial particles. Arch. Biochem. Biophys. 217: 401–410.
Ursini, F., Heim, S., Kiess, M., Maiorino, M., Roveri, A., Wissing, J., and Flohe, L. 1999. Dual function of the selenoprotein PHGPx during sperm maturation. Science, 285: 1393–1396.
Visen, P.K., Shukla, B., Patnaik, G.K., and Dhawan, B.N. 1993. Andrographolide protects rat hepatocytes against paracetamol-induced damage. J. Ethnopharmacol. 40: 131–136.
Warner, B.B., Stuart, L., Gebb, S., and Wispé, J.R. 1996. Redox regulation of manganese superoxide dismutase. Am. J. Physiol. 271: L150–L158.
Yildiz, D., Liu, Y.S., Ercal, N., and Armstrong, D.W. 1999. Comparison of pure nicotine and smokeless tobacco extract induced toxicities and oxidative stress. Arch. Environ. Contam. Toxicol. 37: 434–439.
Zhang, C.Y., and Tan, B.K. 1996. Hypotensive activity of aqueous extract of Andrographis paniculata in rats. Clin. Exp. Pharmacol. Physiol. 23(8): 675–678.
Zhang, X.F., and Tan, B.K. 2000. Anti-diabetic property of ethanolic extract of Andrographis paniculata in streptozotocin-diabetic rats. Acta Pharmacol. Sin. 21: 1157–1164.
Ziegler, D., and Rieske, J.S. 1967. Preparation and properties of succinate dehydrogenase coenzyme Q reductase (complex II). In Methods in enzymology. Vol. 10. Edited by R.W. Estabrook and M.E. Pullman. Academic Press, New York. pp. 231–235.
Pagination changed. This paper now begins on page 124.
Information & Authors
Information
Published In
Applied Physiology, Nutrition, and Metabolism
Volume 34 • Number 2 • April 2009
Pages: 124 - 135
History
Received: 3 June 2008
Accepted: 4 December 2008
Version of record online: 27 March 2009
Key Words
Mots-clés
Authors
Metrics & Citations
Metrics
Other Metrics
Citations
Cite As
SubhasisDasS. Das, N.GautamN. Gautam, Sankar KumarDeyS.K. Dey, TarasankarMaitiT. Maiti, and SomenathRoyS. Roy. 2009. Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E. Applied Physiology, Nutrition, and Metabolism. 34(2): 124-135. https://doi.org/10.1139/H08-147