Advertisement

Molecular Biology Reports

, Volume 38, Issue 1, pp 309–317 | Cite as

Protective effect of Spirulina against 4-nitroquinoline-1-oxide induced toxicity

  • Vijaya Padma Viswanadha
  • Siddharth Sivan
  • Roopesh Rajendra Shenoi
Article

Abstract

In the present study, we focused on the protective effect of Spirulina against 4-nitroquinoline-1-oxide (4NQO) induced hepato and nephrotoxicity in the experimental rats. The 4NQO administration resulted in increased levels of hepatic and renal markers [Alanine Transaminase (ALT), Aspartate Transaminase (AST), Lactate Dehydrogenase (LDH), urea, creatinine and uric acid] in the serum of experimental animals. It also increased the oxidative stress resulting in increased levels of the lipid peroxidation with a concomitant decline in the levels of non enzymic [reduced glutathione (GSH)] and enzymic antioxidants [(Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), and Glutathione-S-transferase (GST)] in both liver and kidney. Oral pretreatment with aqueous extract of Spirulina prevented 4NQO induced changes in the levels of hepatic and kidney diagnostic marker enzymes in the serum of experimental rats. It counteracted the 4NQO induced lipid peroxidation and maintained the hepatic and kidney antioxidant defense system at near normal in both liver and kidney. The antioxidant responsiveness mediated by Spirulina may be anticipated to have biological significance in eliminating reactive free radicals that may otherwise affect normal cell functioning and provide a scientific rationale for the use of Spirulina.

Keywords

4NQO Spirulina Lipid peroxidation Antioxidants Hepatic markers Renal markers 

Abbreviations

ALT

Alanine transaminase

AST

Aspartate transaminase

CAT

Catalase

CD

Conjugated dienes

GPx

Glutathione peroxidase

GST

Glutathione-S-transferase

4HAQO

4-Hydroxyaminoquinoline 1-oxide

8OHdG

8-Hydroxydeoxyguanosine

LDH

Lactate dehydrogenase

4NQO

4-Nitroquinoline-1-oxide

PenCB

3,4,5,3′,4′-Pentachlorobiphenyl

PCDF

Polychlorinated dibenzo-furans

GSH

Reduced glutathione

SOD

Superoxide dismutase

TBARS

Thio barbituric acid reactive substances

Notes

Acknowledgments

Disclosure statement

No competing financial interests exist.

References

  1. 1.
    Endo H, Ono T, Sugimura T (1971) Chemistry and biological action of 4-nitroquinoline-1-oxide. Recent Results Cancer Res 34:17–30Google Scholar
  2. 2.
    McCann J, Spingarn NE, Kobori J, Ames BN (1975) Detection of carcinogen as mutagens: bacterial tester strains with R factor plasmids. Proc Natl Acad Sci USA 72:979–983CrossRefPubMedGoogle Scholar
  3. 3.
    Kitano M (2000) Host genes controlling the susceptibility and resistance to squamous cell carcinoma of the tongue in a rat model. Pathol Int 50:353–362CrossRefPubMedGoogle Scholar
  4. 4.
    Nagao M, Sugimura T (1976) Molecular biology of the carcinogen, 4-nitroquinoline 1-oxide. Adv Cancer Res 23:131–169CrossRefPubMedGoogle Scholar
  5. 5.
    Tada M (1975) Seryl-tRNA synthetase and activation of the carcinogen 4-nitroquinoline-1-oxide. Nature 255:510–512CrossRefPubMedGoogle Scholar
  6. 6.
    Kohdab K, Kawazoe Y, Minoura Y, Tada M (1991) Separation and identification of N4-(guanosine-7-yl)-4-aminoquinoline-1-oxide, a novel nucleic acid adduct of carcinogen 4-nitroquinoline 1-oxide. Carcinogenesis 12:1523–1525CrossRefGoogle Scholar
  7. 7.
    Arima Y, Nishigori C, Takeuchi T, Oka S, Morimoto K, Utani A, Miyachi Y (2006) 4-Nitroquinoline-1-oxide forms 8-hydroxydeoxyguanosine in human fibroblasts through reactive oxygen species. Toxicol Sci 91(2):382–392CrossRefPubMedGoogle Scholar
  8. 8.
    Collin G, Höke H (2005) “Quinoline and isoquinoline” Ullmann’s encyclopedia of chemical technology. Wiley-VCH, Weinheim. doi: 10.1002/14356007.a22_465
  9. 9.
    Tanaka T (1995) Chemoprevention of oral carcinogenesis. Eur J Cancer 31:3–15Google Scholar
  10. 10.
    Sugimura T, Nagao M, Okada Y (1966) Carcinogenic action of N-methyl-N-nitro-N-nitrosoguanidine. Nature 210:962–963CrossRefPubMedGoogle Scholar
  11. 11.
    Yoshimura H, Yoshihara S, Koga N, Nagata K, Wada I, Kuroki J, Hokama Y (1985) Inductive effect on hepatic enzymes and toxicity of congeners of PCBs and PCDFs. Environ Health Perspect 59:113–119CrossRefPubMedGoogle Scholar
  12. 12.
    Doll R (1992) The lessons of life: keynote address to the nutrition and cancer conference. Cancer Res 52:2024s–2029sPubMedGoogle Scholar
  13. 13.
    Rogers AE, Zeisel SH, Groopman J (1993) Diet and carcinogenesis. Carcinogenesis 14:2205–2217CrossRefPubMedGoogle Scholar
  14. 14.
    Verma N, Vinayak M (2008) Antioxidant action of Andrographis paniculata on lymphoma. Mol Biol Rep 35:535–540CrossRefPubMedGoogle Scholar
  15. 15.
    Ganesan B, Buddhan S, Anandan R, Sivakumar R, AnbinEzhilan R (2010) Antioxidant defense of betaine against isoprenaline-induced myocardial infarction in rats. Mol Biol Rep 37:1319–1327CrossRefPubMedGoogle Scholar
  16. 16.
    Verma N, Vinayak M (2009) Effect of Terminalia arjuna on antioxidant defense system in cancer. Mol Biol Rep 36:159–164CrossRefPubMedGoogle Scholar
  17. 17.
    Oh SH, Lima SC (2006) A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine mediated catalase upregulation. Toxicol Appl Pharmacol 212:212–223CrossRefPubMedGoogle Scholar
  18. 18.
    Carageorgiou H, Tzotzes V, Pantos C, Mourouzis C, Zarros A, Tsakiris S (2004) In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+, K+)-ATPase and Mg2+-ATPase activities: protection by l-cysteine. Basic Clin Pharmacol Toxicol 94:112–118CrossRefPubMedGoogle Scholar
  19. 19.
    Liu B, Li W, Li Y, Wang Z, Li H, Liu P, Fu J (2009) Protective effects of N-acetylcysteine in isoproterenol-induced myocardium injury in rats. Mol Biol Rep 36:761–765CrossRefPubMedGoogle Scholar
  20. 20.
    Seshadri CV, Umesh BV, Manoharan R (1991) B-carotene studies in Spirulina. Bioresour Technol 38:111–113CrossRefGoogle Scholar
  21. 21.
    Miranda MS, Cintra RG, Barros SB, Mancini Filho J (1998) Antioxidant activity of the microalga Spirulina maxima. Braz J Med Biol Res 31:1075–1079CrossRefPubMedGoogle Scholar
  22. 22.
    Mittal A, Kumar PV, Banerjee S, Rao AR, Kumar A (1999) Modulatory potential of Spirulina fusiforms on carcinogen metabolizing enzymes in Swiss albino mice. Phytother Res 13:111–114CrossRefPubMedGoogle Scholar
  23. 23.
    Hayashi K, Hayashi T, Kojima I (1996) A natural sulphated polysaccharide, calcium Spirulin isolated from Spirulina plantensis: in vitro and ex vivo evaluation of antiherpes simplex virus and antihuman immunodeficiency virus activities. AIDS Res Hum Retroviruses 12(15):1463–1471CrossRefPubMedGoogle Scholar
  24. 24.
    Ayehunie S, Belay A, Baba TW, Ruprecht RM (1998) Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis). J AIDS Hum Retrovirol 18:7–12Google Scholar
  25. 25.
    Qureshi MA, Garlich JD, Kidd MT (1996) Dietary Spirulina platensis enhances humoral and cell-mediated immune functions in chickens. Immunopharmacol Immunotoxicol 18:465–476CrossRefPubMedGoogle Scholar
  26. 26.
    Sharma MK, Sharma A, Kumar A, Kumar M (2007) Spirulina fusiformis provides protection against mercury chloride induced oxidative stress in Swiss albino mice. Food Chem Toxicol 45:2412–2419CrossRefPubMedGoogle Scholar
  27. 27.
    Rasool M, Sabina EP, Lavanya B (2006) Anti-inflammatory effect of Spirulina fusiforms on adjuvant-induced arthritis in mice. Biol Pharm Bull 29(1):2483–2487CrossRefPubMedGoogle Scholar
  28. 28.
    Takai Y, Hossayamada Y, Kato T (1991) Effect of water soluble and water insoluble fractions of Spirulina over serum lipids and glucose resistance of rats. J Jpn Soc Nutr Food Sci 44:273–277Google Scholar
  29. 29.
    Ramamoorthy A, Premakumari S (1996) Effect of supplementation of Spirulina on hypercholesterolemic patients. J Food Sci Technol 33:124–128Google Scholar
  30. 30.
    Mathew B, Sankaranarayanan R, Nair P, Varghese C, Somanathan T, Amma P (1995) Evaluation of chemo prevention of oral cancer with Spirulina fusiformis. Nutr Cancer 24:197–202CrossRefPubMedGoogle Scholar
  31. 31.
    Schwartz J, Troxler RF, Saffer BG (1987) Algae-derived phycocyanin is both cytostatic and cytotoxic to oral squamous cell carcinoma (human or hamster). J Dent Res 66:160–164Google Scholar
  32. 32.
    Fukino H, Takagi Y, Yamane Y (1990) Effect of Spirulina (S. platensis) on the renal toxicity induced by inorganic mercury and cisplatin. Eisei Kagaku 36:5–9Google Scholar
  33. 33.
    Zhi-gang Z, Zhi-li L, Xue-xian L (1997) Study on the isolation, purification and antioxidation properties of polysaccharides from Spirulina maxima. Acta Bot Sin 39:77–81Google Scholar
  34. 34.
    Sabina EP, Samuel J, RajappaRamya S, Patel S, Mandal N, Pranatharthiiharan P, Mishra PP, Rasool MK (2009) Hepatoprotective and antioxidant potential of Spirulina fusiformis on acetaminophen-induced hepatotoxicity in mice. IJIB 6(1):1–5Google Scholar
  35. 35.
    Reitman S, Frankel SA (1959) Colorimetric method for determination of serum glutamate oxalo acetate and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63Google Scholar
  36. 36.
    Nieland A (1955) Lactic acid dehydrogenase of heart muscle. In: Methods in Enzymology, vol 1. Academic Press, New York, pp 394Google Scholar
  37. 37.
    Nichans WG, Samuelson D (1968) Formation of malondialdehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 6:26–30Google Scholar
  38. 38.
    Moore K, Roberts LJ (1998) Measurement of lipid peroxidation. Free Radic Res 28(6):659–671CrossRefPubMedGoogle Scholar
  39. 39.
    Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Ind J Biochem Biophys 21:130–132Google Scholar
  40. 40.
    Sinha KA (1972) Colorimetric assay of catalase. Ann Biochem 47:389–394CrossRefGoogle Scholar
  41. 41.
    Rotruck JT, Pope AL, Ganther HE, Swanson AB (1984) Selenium biochemical roles as a component of glutathione peroxidase. Science 179:588–590CrossRefGoogle Scholar
  42. 42.
    Habig WR, Pbst MJ, Jakpoly WB (1974) Glutathione transferase A first enzymatic step in mercaturic acid formation. J Biol Chem 249:7130–7139PubMedGoogle Scholar
  43. 43.
    Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:7077CrossRefGoogle Scholar
  44. 44.
    Natelson S, Scott ML, Vessac N (1951) Rapid method for the estimation of urea in biological fluid by means of reaction between diacetyl and urea. Am J Clin Pathol 21:275–278PubMedGoogle Scholar
  45. 45.
    Broad J, Sirota JH (1948) Clearance of endogenous creatine in man. J Clin Investig 27:645–654CrossRefGoogle Scholar
  46. 46.
    Caraway WT (1963) In: Seligson D (ed) Standard methods of clinical chemistry. Academic Press, New York, pp 239–247Google Scholar
  47. 47.
    Lowry OH, Roesborough MJ, Farr AL, Randall RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  48. 48.
    Devasagayam TP, Tilak JC, Boloor KK, Sane KS, Ghaskadbi SS, Lele RD (2004) Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India 52:794–804PubMedGoogle Scholar
  49. 49.
    Collins AR (2005) Antioxidant intervention as a route to cancer prevention. Eur J Cancer 41(13):1923–1930CrossRefPubMedGoogle Scholar
  50. 50.
    Nakahara W (1961) Critique of carcinogenic mechanism. Prog Exp Tumor Res 2:158–202PubMedGoogle Scholar
  51. 51.
    Nakahara W, Fukuoka F, Sugimura T (1957) Carcinogenic action of 4-nitroquinoline A oxide. Gann 48:129–137Google Scholar
  52. 52.
    Tada M, Tada M (1976) Main binding sites of the carcinogen, 4-nitroquinoline-1-oxide in nucleic acids. Biochem Biophys Acta 454:558–566PubMedGoogle Scholar
  53. 53.
    Tada M, Kohda K, Kawazoe Y (1984) Biomimetic preparation and structure determination of QGI, one of the quinoline-DNA base adducts formed in cells treated with 4-nitroquinoline-1-oxide. Gann 75:976–985PubMedGoogle Scholar
  54. 54.
    Ishizawa M, Endo H (1967) On the mode of action of a potent carcinogen. 4-Hydroxylamino quinoline-1-oxide on bacteriophage T4. Biochem Pharmacol 16:637–646CrossRefPubMedGoogle Scholar
  55. 55.
    Sugimura T, Otake H, Matsushima T (1968) Single strand scissions of DNA caused by a carcinogen, 4-hydroxylamino-quinoline-l-oxide. Nature (Lond) 218:392–393CrossRefGoogle Scholar
  56. 56.
    Hozumi M (1969) Production of hydrogen peroxide by 4-hydroxylaminoquinoline-l-oxide. Gann 60:83–90PubMedGoogle Scholar
  57. 57.
    Nunoshiba T, Demple B (1993) Potent intracellular oxidative stress exerted by the carcinogen 4-nitroquinoline-N-oxide. Cancer Res 53:3250–3252PubMedGoogle Scholar
  58. 58.
    Balasenthil S, Ramachandran CR, Nagini S (2001) Prevention of 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis by garlic. Fitoterapia 72(5):524–531CrossRefPubMedGoogle Scholar
  59. 59.
    Henrikson R (1989) Earth food Spirulina. Cited from Recolina Ltd. Renore Enterprises Inc, Launa Beach, California, pp 27–65Google Scholar
  60. 60.
    Bhat VB, Madyastha KM (2000) C-phycocyanin: a potent peroxyl radical scavenger in vivo and in vitro. Biochem Biophys Res Commun 275:20–25CrossRefPubMedGoogle Scholar
  61. 61.
    Viitala P, Newhouse IJ (2004) Vitamin E supplementation, exercise and lipid peroxidation in human participants. Eur J Appl Physiol 93(1–2):108–115CrossRefPubMedGoogle Scholar
  62. 62.
    Qureshi MA, Ali RA (1996) Spirulina platensis exposure enhances macrophage phagocytic function in cats. Immunopharmacol Immunotoxicol 18:457–463CrossRefPubMedGoogle Scholar
  63. 63.
    Karthikeyan S (2004) Hepatotoxicity of isoniazid: a study on the activity of marker enzymes of liver toxicity in serum and liver tissue of rabbits. Indian J Pharmacol 36(4):247–249Google Scholar
  64. 64.
    Seeff LB, Cuccherini BA, Zimmerman HJ (1986) Acetaminophen hepatotoxicity in alcoholics: a therapeutic misadventure. Ann Intern Med 104(3):399–404PubMedGoogle Scholar
  65. 65.
    Vadiraja BB, Gaikwad NW, Madyastha KM (1998) Hepatoprotective effect of C-phycocyanin: protection for carbon tetrachloride and R-(+)-pulegone-mediated hepatotoxicity in rats. Biochem Biophys Res Commun 249:428–431CrossRefPubMedGoogle Scholar
  66. 66.
    Amin A, Hamza AA, Daoud S, Hamza W (2006) Spirulina protects against cadmium-induced hepatotoxicity in rats. Am J Pharmacol Toxicol 1(2):21–25CrossRefGoogle Scholar
  67. 67.
    Farooq SM, Asokan D, Sakthivel R, Kalaiselvi P, Varalakshmi P (2004) Salubrious effect of C-phycocyanin against oxalate mediated renal cell injury. Clin Chim Acta 348:199–205CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Vijaya Padma Viswanadha
    • 1
  • Siddharth Sivan
    • 2
  • Roopesh Rajendra Shenoi
    • 1
  1. 1.Department of BiotechnologyBharathiar UniversityCoimbatoreIndia
  2. 2.Department of BiotechnologyKongunadu Arts and Science CollegeCoimbatoreIndia

Personalised recommendations