Cell Biology and Toxicology

, 25:425 | Cite as

Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats

  • Panneerselvam Janani
  • Kanakarajan Sivakumari
  • Chandrakesan Parthasarathy
Article

Abstract

N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and γ-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

Keywords

Antioxidants Bacoside A Hepatotoxicity Lipid peroxidation N-Nitrosodiethylamine 

Abbreviations

ALT

alanine transaminase

ALP

alkaline phosphatases

AST

aspartate transaminase

CAT

catalase

DEN

N-nitrosodiethylamine

GGT

γ-glutamyl transpeptidase

GPx

glutathione peroxidase

GR

glutathione reductase

GSH

reduced glutathione

GST

glutathione-S-transferase

LDH

lactate dehydrogenase

LPO

lipid peroxidation

MDA

malondialdehyde

ROS

reactive oxygen species

SOD

superoxide dismutase

Notes

Acknowledgement

The authors wish to acknowledge Nivaran Herbal, Chennai, India, for gifting crude bacoside A and Natural Remedies, Bangalore, India, for gifting standard bacoside A to carry on the research work.

References

  1. Anbarasi K, Kathirvel G, Vani G, Jayaraman G, Shyamala Devi CS. Cigarette smoking induces heat shock protein 70 kDa expression and apoptosis in rat brain: modulation by bacoside A. Neuroscience 2006;138(4):1127–35. doi: 10.1016/j.neuroscience.2005.11.029.PubMedCrossRefGoogle Scholar
  2. Bartch H, Montesano R. Relevance of nitrosamines to human cancer. Carcinogenesis 1984;5:1381–93. doi: 10.1093/carcin/5.11.1381.CrossRefGoogle Scholar
  3. Bartsch H, Hietanen E, Malaveille C. Carcinogenic nitrosamines: free radical aspects of their action. Free Radic Biol Med 1989;7:637–44. doi: 10.1016/0891-5849(89)90144-5.PubMedCrossRefGoogle Scholar
  4. Bergmeyer HV, Gowehn K, Grassel M. Methods of enzymatic analysis. New York: Academic; 1974. p. 438.Google Scholar
  5. Bhattacharya SK, Bhattacharya A, Kumar A, Ghosal S. Antioxidant activity of Bacopa monniera in rat frontal cortex, striatum and hippocampus. Phytother Res 2000;14:174–9. doi: 10.1002/(SICI)1099-1573(200005)14:3<174::AID-PTR624>3.0.CO;2-O.PubMedCrossRefGoogle Scholar
  6. Bulle F, Mavier P, Zafrani ES, Preaux AM, Lescs MC, Siegrist S, et al. Mechanism of g-glutamyl transpeptidase release in serum during intrahepatic and extrahepatic cholestasis in the rat: a histochemical, biochemical and molecular approach. Hepatology 1990;11:545–50. doi: 10.1002/hep.1840110404.PubMedCrossRefGoogle Scholar
  7. Chandel NS, Schumacker PT, Arch RH. Reactive oxygen species are downstream products of TRAF-mediated signal transduction. J Biol Chem 2001;276:42728–36. doi: 10.1074/jbc.M103074200.PubMedCrossRefGoogle Scholar
  8. Channa S, Dar A, Yaqoob M, Anjum S, Sultani Z, Rahman A. Bronchovasodilatory activity of fractions of pure constituents isolated from Bacopa monnieri. J Ethnopharmacol 2003;86:27–35. doi: 10.1016/S0378-8741(03)00013-8.PubMedCrossRefGoogle Scholar
  9. Channa S, Dar A, Anjum S, Yaqoob M, Rahman A. Anti inflammatory activity of Bacopa monniera in rodents. J Ethnopharmacol 2006;104:286–9. doi: 10.1016/j.jep.2005.10.009.PubMedCrossRefGoogle Scholar
  10. Chopra RN, Nayar SL, Chopra IC. Glossary of Indian medicinal plants. New Delhi: CSIR; 1956.Google Scholar
  11. Chowdhuri DK, Parmar D, Kakkar P, Shukla R, Seth PK, Srimal RC. Antistress effects of bacosides of bacopamonnieri:modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. Phytother Res 2002;16:639–45. doi: 10.1002/ptr.1023.PubMedCrossRefGoogle Scholar
  12. Deepak M, Sangli GK, Arun PC, Amit A. Quantitative determination of the major saponin mixture bacoside A in bacopa monnieri by HPLC. Phytochem Anal 2005;16:24–9. doi: 10.1002/pca.805.PubMedCrossRefGoogle Scholar
  13. Elangovan V, Govindasamy S, Ramamoorthy N, Balasubramanian K. In vitro studies on the anticancer activity of bacopa monnieri. Fitoterapia 1995;66:211–5.Google Scholar
  14. Farber JL, Gerson RJ. Mechanisms of cell injury with hepatotoxic chemicals. Pharmacol Rev 1984;36:71S–5S.PubMedGoogle Scholar
  15. Feng Q, Kumagai T, Torii Y, Nakamura Y, Osawa T, Uchida K. Anticarcinogenic antioxidants as inhibitors against intracellular oxidative stress. Free Radic Res 2001;35:779–88. doi: 10.1080/10715760100301281.PubMedCrossRefGoogle Scholar
  16. Gey KF. Prospects for the prevention of free radical disease, regarding cancer and cardiovascular disease. Br Med Bull 1993;49:679–99.PubMedGoogle Scholar
  17. Goel RK, Sairam K, Babu MD, Tavares IA, Raman A. In vitro evaluation of Bacopa monniera on anti-helicobacter pylori activity and accumulation of prostaglandins. Phytomedicine 2003;10:523–7. doi: 10.1078/094471103322331494.PubMedCrossRefGoogle Scholar
  18. Habig WH, Pabst MJ, Jakoby WB. Glutathione-S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9.PubMedGoogle Scholar
  19. Heath DF, Magee PN. Toxic properties of dialkyl nitrosamines and some related compounds. Br J Ind Med 1962;19:276–82.Google Scholar
  20. Hietnen E, Ahotupa M, Bartsch H. Lipid peroxidation and chemically induced cancer in rats fed lipid, rich diet. In: Lapis K, Kckharst S, editors. Carcinogenesis and tumor progression. Budapest: Akademiaikiado; 1987. p. 9–16.Google Scholar
  21. Hou CC, Lin SJ, Cheng JT, Hsu FL. Bacopaside III, bacopasaponin G and bacopaside A, B and C from Bacopa monnieri. J Nat Prod 2002;65:1759–63. doi: 10.1021/np020238w.PubMedCrossRefGoogle Scholar
  22. Ito N, Imaida K, Hasegawa R, Tsuda H. Rapid bioassay methods for carcinogens and modifiers of hepatocarcinogenesis. Crit Rev Toxicol 1989;19:385–415. doi: 10.3109/10408448909029328.PubMedCrossRefGoogle Scholar
  23. King J. The dehydrogenases or oxidoreductases—lactate dehydrogense. In: Van D, editor. Practical clinical enzymology. London: Nostrand; 1965a. p. 83–93.Google Scholar
  24. King J. In: Van D, editor. Practical clinical enzymology. London: Nostrand; 1965b. p. 363.Google Scholar
  25. Kiritikar KR, Basu BD. Indian medicinal plants, vol I. Dehradun: Bishen Singh Mahendrapal Singh; 1994. p. 1816.Google Scholar
  26. Kono Y, Fridovich I. Superoxide radicals inhibit catalase. J Biol Chem 1982;257:5751–4.PubMedGoogle Scholar
  27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–75.PubMedGoogle Scholar
  28. Meister A. Glutathione metabolism and its selective modification. J Biol Chem 1988;263:17205–8.PubMedGoogle Scholar
  29. Meister A, Anderson ME. Glutathione. Annu Rev Biochem 1983;52:711–60.PubMedCrossRefGoogle Scholar
  30. Misra HP, Fridovich J. The role of superoxide anion in the autooxidation of epinehrine and a simple assay for superoxide dismutase. J Biol Chem 1972;247:3170–5.PubMedGoogle Scholar
  31. Miyao H, Ara OT, Udayma M, Kinji OJ, Mahara T. Kaikosaponin III and soyasaponin I, major triterpene saponins of abrus cantoniensis, act on GOT and GPT influence on transamination elevation of rat liver cells concomitanly expo to eclip for one hour. Planta Med 1998;64:5. doi: 10.1055/s-2006-957355.PubMedCrossRefGoogle Scholar
  32. Nadkarni KM. Indian materia medica. Bombay: Popular Prakashan; 1976. p. 624–5.Google Scholar
  33. Ohkawa H, Ohnishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351–8. doi: 10.1016/0003-2697(79)90738-3.PubMedCrossRefGoogle Scholar
  34. Orlowski K, Meister A. Isolation of gamma glutamyl transpeptidase from hog kidney. J Biol Chem 1965;240:338–47.PubMedGoogle Scholar
  35. Pawar R, Gopalakrishnan C, Bhutani KK. Dammarane triterpene saponin from Bacopa monniera as the superoxide inhibitor in polymorphonuclear cells. Planta Med 2001;67:752–4.PubMedCrossRefGoogle Scholar
  36. Piot HC, Sirica AE. The stage of initiation and promotion in hepato-carcinogenesis. Biochim Biophys Acta 1980;60:191–215.Google Scholar
  37. Plaa GL, Hewitt WR. Detection and evaluation of chemically induced liver injury. In: Wallace Hayes A, editor. Principles and methods of toxicology. New York: Raven; 1989. p. 399–628.Google Scholar
  38. Rohini G, Sabitha KE, Devi CSS. Bacopa monniera Linn. Extract modulates antioxidant and marker enzymes status in fibrosarcoma bearing rats. Indian J Exp Biol 2004;42:776–80.PubMedGoogle Scholar
  39. Rotruck JT, Pope AL, Ganther HE. Selenium: biochemical role as a component of glutathione peroxidase, purification and assay. Science 1973;179:588–90. doi: 10.1126/science.179.4073.588.PubMedCrossRefGoogle Scholar
  40. RRL, IDMA. Indian herbel pharmacopoeia, vol I. Mumbai: IDMA; 1998. p. 30–7.Google Scholar
  41. Russo A, Borrelli F. Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine 2005;12:305–17. doi: 10.1016/j.phymed.2003.12.008.PubMedCrossRefGoogle Scholar
  42. Russo A, Izzo AA, Borrelli F, Renis M, Vanella A. Free radical scavenging capacity and protective effect on DNA damage of Bacopa monniera Linn. Phytother Res 2003a;17:870–5. doi: 10.1002/ptr.1061.PubMedCrossRefGoogle Scholar
  43. Russo A, Borrelli F, Campisi A, Acquaviva R, Raciti G, Vanella A. Nitric oxide related toxicity in cultured astrocytes: effect of Bacopa monniera. Life Sci 2003b;73:1517–26. doi: 10.1016/S0024-3205(03)00476-4.PubMedCrossRefGoogle Scholar
  44. Sairam K, Rao CV, Babu MD, Goel RK. Prophylactic and curative effects of Bacopa monniera in gastric ulcer models. Phytomedicine 2001;8:423–30. doi: 10.1078/S0944-7113(04)70060-4.PubMedCrossRefGoogle Scholar
  45. Shank RC. Toxicology of N-nitroso compounds. Toxicol Appl Pharmacol 1975;31:729–32. doi: 10.1016/0041-008X(75)90257-4.CrossRefGoogle Scholar
  46. Simonsen R, Uirji MA. Interpreting the profile of liver function tests in pediatric liver transplants. Clin Chem 1984;30:1607–10.PubMedGoogle Scholar
  47. Singh HK, Dhawn BN. Neuropsychopharmacological effects of the ayurvedic nootropic Bacopa monnieri Linn. J Ethnopharmacol 1982;5:205–14. doi: 10.1016/0378-8741(82)90044-7.PubMedCrossRefGoogle Scholar
  48. Sing HK, Rastogi RP, Srimal RC, Dhawan BN. Effect of bacosides A and B on avoidance responses in rats. Phytother Res 1988;2:70–5. doi: 10.1002/ptr.2650020205.CrossRefGoogle Scholar
  49. Spiteller G. Enzymic lipid peroxidation—a consequence of cell injury? Free Radic Biol Med 1996;21:1003–9. doi: 10.1016/S0891-5849(96)00268-7.PubMedCrossRefGoogle Scholar
  50. Staal GEJ, Visser J, Veger C. Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta 1969;185:39–48.PubMedGoogle Scholar
  51. Sumathy T, Subramanian S, Govindasamy S, Balakrishna K, Veluchamy G. Protective role of Bacopa monniera on morphine induced hepatotoxicity in rats. Phytother Res 2001;15:643–5. doi: 10.1002/ptr.1007.PubMedCrossRefGoogle Scholar
  52. Tricker AR, Pfundstein B, Theobald E, Preussman R, Spiegenhalder B. Mean daily intake of volatile N-nitrosamines from foods and beverages in west Germany in 1989–90. Food Chem Toxicol 1991;29:729–32. doi: 10.1016/0278-6915(91)90180-F.PubMedCrossRefGoogle Scholar
  53. Tripathi YB, Chaurasia S, Tripathi E, Upadhyay A, Dubey GP. Bacopa monniera Linn. As an antioxidant: mechanism of action. Indian J Exp Biol 1996;34:523–6.PubMedGoogle Scholar
  54. Voellmy R. In: Feige U, Morimoto RI, Yahura I, Polla B, editors. Stress inducible cellular response. Basel: Birkhauser; 1996. p. 121–37.Google Scholar
  55. Waris G, Ahsan H. Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 2006;5:14. doi: 10.1186/1477-3163-5-14.PubMedCrossRefGoogle Scholar
  56. Yoshiki Y, Okubo K. Active oxygen scavenging activity of DDMP (2,3-dihydro-2, 5-dihydroxy-6-methyl-4H-pyran-4-one) saponin in soybean seed. Biosci Biotechnol Biochem 1995;59:1556–7.CrossRefGoogle Scholar
  57. Yoshiki K, Kudou S, Okubo K. Relationship between chemical structures and biological activities of triterpinoid saponins from soyabean. Biosci Biotechnol Biochem 1998;62:2291–9. doi: 10.1271/bbb.62.2291.PubMedCrossRefGoogle Scholar
  58. Yu BP. Cellular defense against damage from reactive oxygen species. Physiol Rev 1994;74:136–62.Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Panneerselvam Janani
    • 1
  • Kanakarajan Sivakumari
    • 1
  • Chandrakesan Parthasarathy
    • 2
  1. 1.Department of ZoologyPresidency CollegeChennaiIndia
  2. 2.Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical SciencesUniversity of MadrasChennaiIndia

Personalised recommendations