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Studies on the neuroprotective role of Piper longum in C6 glioma induced rats

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Summary

Many naturally occurring substances of plant origin ingested in human diet, exhibit anticarcinogenic and antimutagenic effects. One of the active phytochemical which shows the active anticarcinogenic role is Piper longum Linn. (Pl). Pl is widely used in ayurvedic industry due to its property in healing some of the bodily ailments. Despite being known for the antioxidant, antimicrobial and anticarcinogenic effects, its relation to brain and its tumour development is still scarce. Hence, the experimental glioma model was developed in rats using C6 glioma cells and the effect of Pl was evaluated in the brain tissue of experimental group of rats. From the study, the glioma induced animals showed an increased level of lipid peroxides (LPO), tissue marker enzymes lactate dehydrogenase (LDH), creatine kinase (CK), 5′nucleotidase (5′ND) and acetylcholine esterase (AChE). But Pl treatment (20 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in glioma induced rats. In addition, the anticarcinogenic effect of Pl was confirmed by microscopic analysis and the restoration of increased lipids and protein bound carbohydrates (PBCs) in the brain tissue of glioma induced rats. Hence our results implicate a major role for Pl in preventing the cancer development in the experimental glioma model.

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References

  1. Mamelak AN, Jacoby DB (2007) Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin Drug Deliv 4:175–186

    Article  PubMed  CAS  Google Scholar 

  2. CBTRUS (2004–2005) Statistical Report: Primary Brain Tumors in the United States, 1997–2001. Published by the Central Brain Tumor Registry of the United States

  3. Devasagayam TP, Sainis KB (2002) Immune system and antioxidants, especially those derived from Indian medicinal plants. Indian J Exp Biol 40:639–655

    PubMed  CAS  Google Scholar 

  4. Willett WC (1994) Diet and health: what should we eat? Science 22:532–537

    Article  Google Scholar 

  5. Reddy L, Odhav B, Bhoola KD (2003) Natural products for cancer prevention: a global perspective. Pharmacol Ther 99:1–13

    Article  PubMed  CAS  Google Scholar 

  6. Block G, Patterson B, Subar A (1992) Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 18:1–29

    Article  PubMed  CAS  Google Scholar 

  7. Reen RK, Singh J (1991) In vitro and in vivo inhibition of pulmonary cytochrome P450 activities by piperine, a major ingredient of piper species. Indian J Exp Biol 29:568–573

    PubMed  CAS  Google Scholar 

  8. Khajuria A, Thusu N, Zutshi U, Bedi KL (1998) Piperine modulation of carcinogen induced oxidative stress in intestinal mucosa. Mol Cell Biochem 189:113–118

    Article  PubMed  CAS  Google Scholar 

  9. Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS (1998) Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 64:353–356

    Article  PubMed  CAS  Google Scholar 

  10. Singh YN (1992) Kava: an overview. J Ethnopharmacol 37:13–45

    Article  PubMed  CAS  Google Scholar 

  11. Virinder SP, Subash CJ, Kirpal SB, Rajani J et al (1997) Phytochemistry of genus Piper. Phytochemistry 46:597–673

    Article  Google Scholar 

  12. Koul IB, Kapil A (1993) Evaluation of the liver protective potential of piperine, an active principle of black and long peppers. Planta Med 59:413–417

    Article  PubMed  CAS  Google Scholar 

  13. Kodera T, Nakagawa T, Kubota T, Kabuto M, Sato K, Kobayashi H (2000) The expression and activation of matrix metalloproteinase-2 in rat brain after implantation of C6 rat glioma cells. J Neurooncol 46:105–114

    Article  PubMed  CAS  Google Scholar 

  14. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  15. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  16. King J (1965) The dehydrogenase of oxido-reductase-Lactate dehydrogenase. In: Van D (ed) Practical Clinical Enzymology 83–93

  17. Okinaka S, Kumogai H, Ebashi S, Sugita H, Momoi H, Toyokura Y, Fujie Y (1961) Serum creatine phosphokinase activity in progressive muscular dystrophy and neuro muscular diseases. Arch Neurol 4:520–525

    PubMed  CAS  Google Scholar 

  18. Fini C, Ipata PL, Palmerini CA, Floridi A (1983) 5′-nucleotidase from bull seminal plasma. Biochim Biophys Acta 14:405–412

    Google Scholar 

  19. Ellman GL, Courtney KD, Andres VJ, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  PubMed  CAS  Google Scholar 

  20. Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509

    PubMed  CAS  Google Scholar 

  21. Parekh AC, Jung DH (1970) Cholesterol determination with ferric acetate-uranium acetate and sulfuric acid-ferrous sulfate reagents. Anal Chem 42:1423–1427

    Article  CAS  Google Scholar 

  22. Leffler HH, Mc Dougald CH (1963) Estimation of cholesterol in serum by means of improved technics. Tech Bull Regist Med Technol 33:19–23

    PubMed  CAS  Google Scholar 

  23. Rouser G, Fkeischer S, Yamamoto A (1970) Two dimensional then layer chromatographic separation of polar lipids and determination of phospholipids by phosphorus analysis of spots. Lipids 5:494–496

    Article  PubMed  CAS  Google Scholar 

  24. Rice EW (1970) Triglycerides ("neutral fats") in serum. In Standard Methods of Clinical Chemistry 6: 215-22

  25. Horn WT, Menahan LA (1981) A sensitive method for the determination of free fatty acids in plasma. J Lipid Res 22:377–381

    Google Scholar 

  26. Niebes P (1972) Determination of enzymes and degradation products of glycosaminoglycans metabolism in the serum of healthy and varicose subjects. Clin Chim Acta 42:399–408

    Article  CAS  Google Scholar 

  27. Wagner WD (1979) A more sensitive assay discriminating galactosamine and glucosamine in mixtures. Anal Biochem 15:394–396

    Article  Google Scholar 

  28. Winzler RJ (1955) Determination of Serum Glycoproteins. In: Glick D (ed) Methods of Biochemical Analysis 2:279–311

  29. Warren L (1959) The thiobarbituric acid assay of sialic acids. J Biol Chem 234:1971–1975

    PubMed  CAS  Google Scholar 

  30. Cantuti CI, Shukitt-Hale B, Joseph JA (2000) Neurobehavioural aspects of antioxidants in aging. Int J Dev Neurosci 8:367–381

    Article  Google Scholar 

  31. Maxwell SR (1995) Prospects for the use of antioxidant therapies. Drugs 49:345–361

    Article  PubMed  CAS  Google Scholar 

  32. Pompella A, Romani A, Benditti A, Comporti M (1991) Loss of membrane protein thiols and lipid peroxidation of allyl alcohol hepatotoxicity. Biochem Pharmacol 41:1225–1259

    Article  Google Scholar 

  33. Mikhail F, Denissenko K, Annie P, Moon-shong T, Gerd PP (1996) Preferential formation of benzo(a)pyrene adducts at lung cancer mutational hotspots in P53. Science 274:430–432

    Article  Google Scholar 

  34. Dhully JN, Raman PH, Mujumdar AM, Naik SR (1993) Inhibition of lipid peroxidation by piperine during experimental inflammation in rats. Indian J Exp Biol 31:443–445

    Google Scholar 

  35. Srinivasan K (2007) Black pepper and its pungent principle-piperine: a review of diverse physiological effects. Crit Rev Food Sci Nutr 47:735–748

    Article  PubMed  CAS  Google Scholar 

  36. Selvendiran K, Prince Vijeya Singh J, Baba Krishnan K (2003) Cytoprotectiveeffect of piperine against benzo(a)pyrene induced lung cancer with reference to lipid peroxidation and antioxidant system in Swiss albino mice. Fitoterapia 74:109–115

    Article  PubMed  CAS  Google Scholar 

  37. Plaa GL (1997) The Snider Address. A four-decade adventure in experimental liver injury. Drug Metab Rev 29:1–37

    Article  PubMed  CAS  Google Scholar 

  38. Reznick AZ, Witt E, Matsumoto M, Packer L (1992) Vitamin E inhibits protein oxidation in skeletal muscle of resting and exercised rats. Biochem Biophys Res Commun 15:801–806

    Article  Google Scholar 

  39. Anbarasi K, Sabitha KE, Devi CSS (2005) Lactate dehydrogenase isoenzyme patterns upon chronic exposure to cigarette smoke: protective effect of bacoside A. Environ Toxicol Pharmacol 20:345–350

    Article  CAS  Google Scholar 

  40. Helmes MH, Modia A, Moneim EL, Moustafae MS, Bale EL, Safinoz MEL (1998) Clinical values of serum LDH, ceruloplasmin and lipid bound sialic acid in monitoring patients with malignant lymphomas. Med Sci Res 26:613–617

    Google Scholar 

  41. Yun K (1980) Early effects of ethylnitrosourea on the LDH isozyme of rat fetal central nervous system. Acta Pathol Jpn 30:389–395

    PubMed  CAS  Google Scholar 

  42. Hara M, Yokota H, Ogashiwa M, Takeuchi K (1981) Biochemical monitoring of postoperative glioma. No To Shinkei 33:505–511

    PubMed  CAS  Google Scholar 

  43. Sadej R, Spychala J, Skladanowski AC (2006) Expression of ecto-50-nucleotidase (eN, CD73) in cell lines from various stages of human melanoma. Melanoma Res 16:213–222

    Article  PubMed  CAS  Google Scholar 

  44. Ujhazy P, Berleth ES, Pietkiewicz JM et al (1996) Evidence for the involvement of ecto-50-nucleotidase (CD73) in drug resistance. Int J Cancer 68:493–500

    Article  PubMed  CAS  Google Scholar 

  45. Spychala J (2000) Tumor-promoting functions of adenosine. Pharmacol Ther 87:161–173

    Article  PubMed  CAS  Google Scholar 

  46. Pellegrina CD, Padovani G, Mainente F et al (2005) Anti-tumor potential of a gallic acid containing phenolic fraction from Oenothera biennis. Cancer Lett 226:17–25

    Article  PubMed  CAS  Google Scholar 

  47. Parkinson FE, Ferguson J, Zamzow CR, Xiong W (2006) Gene expression for enzymes and transporters involved in regulating adenosine and inosine levels in rat forebrain neurons, astrocytes and C6 glioma cells. J Neurosci Res 84:801–808

    Article  PubMed  CAS  Google Scholar 

  48. Ramakrishnan G, Augustine TA, Jagan S, Vinodhkumar R, Devaki T (2007) Effect of silymarin on N-nitrosodiethylamine induced hepatocarcinogenesis in rats. Exp Oncol 29:39–44

    PubMed  CAS  Google Scholar 

  49. Vanisree AJ, Shyamaladevi CS (1998) Effect of therapeutic strategy established by N-acetyl cysteine and vitamin C on the activities of tumour marker enzymes in vitro. Indian J Pharmacol 31:275–278

    Google Scholar 

  50. Volker DL (2003) Assisted dying and end-of-life symptom management. Cancer Nurs 26:392–399

    Article  PubMed  Google Scholar 

  51. Ludwig HC, Rausch S, Schallock K, Markakis E (1999) Expression of CD 73 (ecto-5′-nucleotidase) in 165 glioblastomas by immunohistochemistry and electronmicroscopic histochemistry. Anticancer Res 19:1747–1752

    PubMed  CAS  Google Scholar 

  52. Salpeter MM (1967) Electron microscope radioautography as a quantitative tool in enzyme cytochemistry. I. The distribution of acetylcholinesterase at motor end plates of a vertebrate twitch muscle. J Cell Biol 32:379–389

    Article  PubMed  CAS  Google Scholar 

  53. Dietschy JM, Turley SD (2001) Cholesterol metabolism in the brain. Curr Opin Lipidol 12:105–112

    Article  PubMed  CAS  Google Scholar 

  54. Stolar MW (1988) Atherosclerosis in diabetes: the role of hyperin sulinemia. Metabolism 37:1–9

    Article  PubMed  CAS  Google Scholar 

  55. Goldstein JL, Hazzard WR, Schrott HG, Bierman EL, Motulsky AG (1973) Hyperlipidemia in coronary heart disease I. Lipid levels in 500 survivors of myocardial infarction. J Clin Invest 52:1533

    Article  PubMed  CAS  Google Scholar 

  56. Yuvaraj S, Premkumar VG, Vijayasarathy K, Gangadaran SG, Sachdanandam P (2007) Ameliorating effect of coenzyme Q10, riboflavin and niacin in tamoxifen-treated postmenopausal breast cancer patients with special reference to lipids and lipoproteins. Clin Biochem 40:623–628

    Article  PubMed  CAS  Google Scholar 

  57. Ramakrishnan G, Elinos-Baez CM, Jagan S, Augustine TA, Kamaraj S, Anandakumar P, Devaki T (2008) Silymarin downregulates COX-2 expression and attenuates hyperlipidemia during NDEA-induced rat hepatocellular carcinoma. Mol Cell Biochem 313:53–61

    Article  PubMed  CAS  Google Scholar 

  58. Tosi MR, Trinchero A, Poerio A, Tugnoli V (2003) Fast NMR evaluation of lipids in human tissues. Ital J Biochem 52:141–144

    PubMed  CAS  Google Scholar 

  59. Holleran AL, Lindenthal B, Aldaghlas TA, Kelleher JK (1998) Effect of tamoxifen on cholesterol synthesis in HepG2 cells and cultured rat hepatocytes. Metabolism 47:1504–1513

    Article  PubMed  CAS  Google Scholar 

  60. Hirayama T, Honda A, Matsuzaki Y, Miyazaki T, Ikegami T, Doy M, Xu G, Lea M, Salen G (2006) Hypercholesterolemia in rats with hepatomas: increased oxysterols accelerate efflux but do not inhibit biosynthesis of cholesterol. Hepatology 44:602–611

    Article  PubMed  CAS  Google Scholar 

  61. Nalini N, Manju V, Menon VP (2006) Effect of spices on lipid metabolism in 1, 2-dimethylhydrazine-induced rat colon carcinogenesis. J Med Food 9:237–245

    Article  PubMed  CAS  Google Scholar 

  62. Liu CL, Yang TL (2003) Sequential changes in serum triglyceride levels during adjuvant tamoxifen therapy in breast cancer patients and the effect of dose reduction. Breast Cancer Res Treat 79:11–16

    Article  PubMed  CAS  Google Scholar 

  63. Lanza-Jacoby S (1984) Sequential changes in the activities of lipoprotein lipase and lipogenic enzymes during tumor growth in rats. Cancer Res 44:5062–5067

    PubMed  CAS  Google Scholar 

  64. Krämer SD, Schütz YB, Wunderli-Allenspach H, Abbott NJ, Begley DJ (2002) Lipids in blood-brain barrier models in vitro II: Influence of glial cells on lipid classes and lipid fatty acids. In Vitro Cell Dev Biol Anim 38:566–71

    Article  PubMed  Google Scholar 

  65. Tugnoli V, Tosi MR, Tinti A, Trinchero A, Bottura G, Fini G (2001) Characterization of lipids from human brain tissues by multinuclear magnetic resonance spectroscopy. Biopolymers 62:297–306

    Article  PubMed  CAS  Google Scholar 

  66. Kolanjiappan K, Ramachandran CR, Manoharan S (2003) Biochemical changes in tumor tissues of oral cancer patients. Clin Biochem 36:61–65

    Article  PubMed  CAS  Google Scholar 

  67. Selvam S, Nagini S (1995) Administration of the plasticizer di(engl hexyl)phthalate alters glycoconjugate profile. Ind J Physiol Pharmacol 39:252–254

    CAS  Google Scholar 

  68. Ebrahim AS, Gobalakrishnan R, Murugesan A, Sakthisekaran D (1995) In vivo effect of vitamin E on serum and tissue glycoprotein levels in perchloroethylene induced cytotoxicity. Mol Cell Biochem 144:13–18

    Article  PubMed  CAS  Google Scholar 

  69. Lipton A, Harvey HA, Delong S, Allegra J, White D, Allegra M, Davidson EA (1979) Glycoproteins and human cancer, circulating levels in cancer serum. Cancer 43:1766–1771

    Article  PubMed  CAS  Google Scholar 

  70. Kennedy RO, Berns G, Moran E, Smyth H, Caroll K, Thomes RD, Brien AO, Fennelly J, Butler M (1991) A critical analysis of the use of sialic acid determination in the diagnosis of malignancy. Cancer Lett 58:91–100

    Article  Google Scholar 

  71. Hynes RO (1978) Cell surface proteins and malignant transformation. Biochem Biophys Acta 458:73–107

    Google Scholar 

  72. Jagetia GC, Nayak V, Vidyasagar MS (1998) Evaluation of the anti-neoplastic activity of Tinospora cordifolia in cultured He La cells. Cancer Lett 127:71–82

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600 025, India

    Umadevi Subramanian, Sharmila Poongavanam & A. J. Vanisree

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  1. Umadevi Subramanian
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  2. Sharmila Poongavanam
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  3. A. J. Vanisree
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Correspondence to A. J. Vanisree.

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Subramanian, U., Poongavanam, S. & Vanisree, A.J. Studies on the neuroprotective role of Piper longum in C6 glioma induced rats. Invest New Drugs 28, 615–623 (2010). https://doi.org/10.1007/s10637-009-9301-1

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