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Salubrious Therapeutic Efficacy of Myrtenal on Colon Carcinoma induced by 1,2-Dimethylhydrazine studied in Experimental Albino rats


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1 Department of Pharmacology and Environmental Toxicology, Dr. A.L. Mudhaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, Tamilnadu, India
     

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Background: LPO-derived DNA adducts in the mammalian cells induce point mutations, chromosomal aberrations, and recombination which are expressed by inflammatory mediators, such as cyclooxygenase-2 and lipoxygenases that are found to be increased during colon cancer development. Since the risk of being diagnosed with cancer, it increases with age, most cases occur in adults who are middle aged or older. Objective: About 77% of all cancers are diagnosed in persons 55 years of age and older. Cancer researchers use the word "risk" in different ways, most commonly expressing risk as lifetime risk or relative risk. DMH acts as a potent site and organ specific carcinogen by generating various reactive metabolic intermediates leading to oxidative stress. Experimental design: Male Wistar albino rats were divided into four groups and each group consisting of six animals. Group I and group IV were vector and drug control. The group II and group III animals were treated with DMH 20 mg/kg body weight to induce colon carcinoma. Rats received cancer bearing Group III animals were treated with Myrtenal at the concentration of 230 mg/kg bodyweight for 15 weeks . At the end of the experimental period all the rats were sacrificed. DNA adducts where investigated in the experimental animal model with a potent pro-carcinogen DMH, an alkylating agent that targets DNA and induces the formation of methyl adducts with DNA bases, point mutations, micronuclei, and sister chromatid exchanges yielding macroscopically visible neoplasm in a dose-dependent manner. Results: The colon and liver tissues levels of the enzymic and non-enzymic antioxidants were significantly decreased in cancer bearing animals when compared to the control animals. Lipid peroxide levels (LPO) were estimated. Conclusion: From our results, we conclude that Myrtenal is a potent antioxidant and play a protective role against DMH induced colon cancer.

Keywords

Colon Cancer, Myrtenal, 1,2-Dimethylhydrazine, Antioxidants, Phase I Enzyme.
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  • Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69_90.
  • The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330_7.
  • Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990;61:759_67.
  • Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordinger B, et al. Colorectal cancer. Lancet 2010;375:1030_47.
  • Andre' T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350: 2343_51.
  • DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 9th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2011. p. 084_126.
  • Jemal, R. Siegel, J. Xu, E. Ward, Cancer Statistics, Ca Cancer J. Clin. 60 (2010) 277-300.
  • Abu-Abid S, Szold A, Klausner J. Obesity And Cancer. J Med 2002;33:73e86.
  • Diet And Cancer: Risk Factors And Epidemiological Evidence Raul Baena Ruiz*, Pedro Salinas Hernandez Maturitas 77 (2014) 202-208
  • Valko M, Rhodes Ci, Moncol J, Izakovic M, Mazur M. Free Radicals, Metals And Antioxidants In Oxidative Stress-Induced Cancer. Chem Biol Interact 2006; 160:1-40.
  • Esterbauer, H., Schaur, R.J., Zollner, H., Chemistry And Biochemistry Of 4-Hydroxynonenal, Malonaldehyde And Related Aldehydes. Free Radic. Biol. Med.11, 81e128 (2010) 261e266.
  • Chung F-L, Chen H-Jc, Nath Rg. Lipid Peroxidation As A Potential Endogenous Source For The Formation Of Exocyclic Dna Adducts.Carcinogenesis 1996;17:2105-11.
  • Bartsch, H.; Barbin, A.; Marion, M. J.; Nair, J.; Guichard, Y. Formation, Detection, And Role In Carcinogenesis Of Etheno bases In Dna. Drug Metab. Rev. 26:349-371;1994.
  • Singer, B., Bartsch, H., Exocyclic Dna Adducts In Mutagenesis And Carcinogenesis. Iarc, Lyon, Pp. 1-361 Iarc Sci. Publ. No 150. Toxicology 153 (2000) 105-114. 15. Devasena, T., Menon, V. P., and Rajasekharan, K. N. Prevention Of 1,2-Dimethylhydrazine induced Circulatory Oxidative Stress By Bis-1,7-(2-Hydroxyphenyl)-Hepta-1,6-Diene-3,5-Dione During Colon Carcinogenesis. Pharmacological Reports(2006),58, 229-235.
  • Choudhary, G., Hansen, H.,. Human Health Perspective on Environmental Exposure to Hydrazines: A Review. Chemosphere 1998. 37, 801-843.
  • E.S. Fiala, Investigations Into The Metabolism And Mode Of Action Of The Colon Carcinogen 1,2-Dimethylhydrazine And Azoxymethane, Cancer 40 (1977) 2436-2445.
  • Cotgreave I, Moldens P, Orrenius S. Host Biochemical Defence Mechanisms against Prooxidants. Annu Rev Pharmacol Toxicol 1988; 28:189-212.
  • Natarajan Nandakumar , Ramachandran Jayaprakash , Thamaraiselvan Rengarajan , Venkatachalam Ramesh , Maruthaiveeran Periyasamy Balasubramanian* Hesperidin, A Natural Citrus Flavono glycoside, Normalizes Lipid Peroxidation and Membrane Bound Marker Enzymes in 7, 12-Dimethylbenz (A) Anthracene Induced Experimental Breast Cancer Rats Biomedicine and Preventive Nutrition 1 (2011) 255-262
  • Hayes, J. D., And Mcmahon, M Cancer Lett . (2001). 174, 103- 113.
  • Yoshimasa N, Oshigashi H, Masuda S, Akira M, Yasujiro M, Yoshiyuki K, Toshihiko O, Masayoshi I, Koji U. Redox Regulation Of Glutathione S-Transferase Induction By Benzyl Isothiocyanates: Correlation Of Enzyme Induction With The Formation Of Reactive Oxygen Intermediates. Cancer Res 2000; 60:219-225.
  • Nelson Dr. The Cytochrome P450 Homepage. Hum Genomics. 2009; 4(1):59-65.
  • Wattenberg Lw. Inhibition Of Carcinogenesis By Naturally Occurring And Synthetic Compounds. Basic Life Sci 1990; 52:155-66
  • Chemopreventive Efficacy Of Ginger, A Naturally Occurring Anticarcinogen During The Initiation, Post-Initiation Stages Of 1,2 Dimethylhydrazine-Induced Colon Cancer Vaiyapuri Manju, Namasivayam Nalini Clinica Chimica Acta 358 (2005) 60-67
  • M.N. Gould, Cancer Chemoprevention And Therapy By Monoterpenes. Environ. Health Perspect. 105, 977-979 (1997)
  • Lingaiah Hari Babu, Srinivasan Perumal, Maruthaiveeran Periyasamy Balasubramanian Myrtenal Attenuates Diethylnitrosamine- Induced Hepatocellular Carcinoma In Rats By Stabilizing Intrinsic Antioxidants And Modulating Apoptotic And Anti-Apoptotic Cell Oncol.Doi 10.1007/S13402-012-0086-4
  • H. Marica Lindmark, I. Dan, V. Tomas, V. Irena, H. Hans-Erik, S. Kristina, Transformation Of Terpenes Using A Picea Abies Suspension Culture. J. Biotechnol. 107, 173-184 (2004).
  • J.B. Vibha, K. Choudhary, S. Mangal, M.S. Rathore, N.S. Shekhawat, A Study On Pharmacokinetics And Therapeutic Efficacy Of Glycyrrhiza Glabra. A Miracle Medicinal Herb Botany Research International 2, 157-163 (2009)
  • Myrtenal Attenuates Diethylnitrosamine-Induced Hepatocellular Carcinoma In Rats By Stabilizing Intrinsic Antioxidants And Modulating Apoptotic And Anti-Apoptotic Cascades Lingaiah Hari Babu and Srinivasan Perumal and Maruthaiveeran Periyasamy Balasubramanian Cell Oncol.Doi 10.1007/S13402-012-0086-4.
  • Lowry O H, Rosebrough N J, Farr A L and Randall R J. Protein Measurement With The Folin Phenol Reagent. J. Biol. Chem. 193:265-275.
  • Schneider, Walter C. "99. Determination Of Nucleic Acids In Tissues By Pentose Analysis." Methods In Enzymology 3 (1957): 680-684.
  • A Study Of The Conditions And Mechanism Of The Diphenylamine Reaction For The Colorimetric Estimation Of Deoxyribonucleic Acid By K. Burton J.Biochem 1956;62:315-23
  • Rawal Um, Patel Us, Rao Gn, Desai Rr. Clinical And Biochemical Studies On Cateractous Human Lens Iii. Quantitative Study Of Protein, Rna And Dna. Arogya J Health Sci. 1977; 3: 69-72.
  • Ohkawa H, Ohishi N, Yagi K: Assay For Lipid Peroxides In Animal Tissues By Thiobarbituric Acid Reaction. Anal Biochem 1979, 95:351-8.
  • Short Term Supplementation Of Dietary Antioxidants Selectively Regulates The Inflammatory Responses During Early Cutaneous Wound Healing In Diabetic Mice Na-Young Park And Yunsook Lim Nutrition and Metabolism 2011, 8:80.
  • Hiroshi Ohkawa, Nobuko Ohishi, Kunio Yagi Assay For Lipid Peroxides In Animal Tissues By Thiobarbituric Acid Reaction, Analytical Biochemistry 2008, 471: 24-39.
  • Sinha Ak. Colorimetric Assay Of Catalase. Anal Biochem 1972; 47:389-94.
  • Marklund, S., and Marklund, G. Involvement Of The Superoxide Anion Radical In The Autoxidation Of Pyrogallol And A Convenient Assay For Superoxide Dismutase. European Journal Of Biochemistry (1974), 47(3), 469-474.
  • Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., and Hoekstra, W. G. Selenium: Biochemical Role As A Component Of Glutathione Peroxidase. Science (1973)., 179(4073), 588-590.
  • Moron, M. S., Depierre, J. W., and Mannervik, B. Levels Of Glutathione, Glutathione Reductase And GlutathioneS-Transferase Activities In Rat Lung And Liver. Biochimica Et Biophysica Acta (Bba)-General Subjects (1979), 582(1), 67-78.
  • Habig, W. H., Pabst, M. J., and Jakoby, W. B. Glutathione S Transferases the First Enzymatic Step In Mercapturic Acid Formation. Journal Of Biological Chemistry (1974)., 249(22), 7130-7139.
  • Staal, G. E., Visser, J., and Veeger, C Purification And Properties Of Glutathione Reductase Of Human Erythrocytes. Biochimica Et Biophysica Acta (Bba)-Enzymology . (1969)., 185(1), 39-48.
  • Desai, I. D Vitamin E Analysis Methods For Animal Tissues Alpha Tocopherol. . Methods In Enzymology (Usa) . (1984).
  • Omura, T., and Sato, R. The Carbon Monoxide-Binding Pigment of Liver Microsomes. I. Evidence For Its Hemoprotein Nature. J. Biol. Chem (1964)., 239(7), 2370-2378.
  • D. Ziech, R. Franco, A. Pappa, M.I. Panayiotidis, Reactive Oxygen Species (Ros)-Induced Genetic And Epigenetic Alterations In Human Carcinogenesis, Mutat. Res. 711 (2011) 167-173.
  • Wang, X. R.; Jiang, B. H. Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res. 67:10823-10830; 2007.
  • Sabitha, K. E., and C. S. Shyamaladevi. "Oxidant and Antioxidant Activity Changes In Patients With Oral Cancer And Treated With Radiotherapy." Oral Oncology 35.3 (1999): 273-277.
  • Kolanjiappan K, Manoharan S, Kayalvizhi M, Measurement of erythrocyte lipids, lipid peroxidation antioxidants and osmotic fragility in cervical cancer patients, Clinica Chimica ACTA, 326: 143-149, (2002).
  • Zarkovic, N. 4-Hydroxynonenal as a bioactive marker of pathophysiological processes. Mol. Aspects Med. 24:281-291; 2003.
  • Pories, S.E., Ramchurren, N., Summerhayes, I., Steele, G.,. Animal models for colon carcinogenesis. Arch. Surg 1993. 128, 647-653.

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  • Salubrious Therapeutic Efficacy of Myrtenal on Colon Carcinoma induced by 1,2-Dimethylhydrazine studied in Experimental Albino rats

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Authors

Sathishkumar Venkatachalam
Department of Pharmacology and Environmental Toxicology, Dr. A.L. Mudhaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, Tamilnadu, India
Lokeshkumar Boobathi
Department of Pharmacology and Environmental Toxicology, Dr. A.L. Mudhaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, Tamilnadu, India
Maruthaiveeran Periyasamy Balasubramanian
Department of Pharmacology and Environmental Toxicology, Dr. A.L. Mudhaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, Tamilnadu, India

Abstract


Background: LPO-derived DNA adducts in the mammalian cells induce point mutations, chromosomal aberrations, and recombination which are expressed by inflammatory mediators, such as cyclooxygenase-2 and lipoxygenases that are found to be increased during colon cancer development. Since the risk of being diagnosed with cancer, it increases with age, most cases occur in adults who are middle aged or older. Objective: About 77% of all cancers are diagnosed in persons 55 years of age and older. Cancer researchers use the word "risk" in different ways, most commonly expressing risk as lifetime risk or relative risk. DMH acts as a potent site and organ specific carcinogen by generating various reactive metabolic intermediates leading to oxidative stress. Experimental design: Male Wistar albino rats were divided into four groups and each group consisting of six animals. Group I and group IV were vector and drug control. The group II and group III animals were treated with DMH 20 mg/kg body weight to induce colon carcinoma. Rats received cancer bearing Group III animals were treated with Myrtenal at the concentration of 230 mg/kg bodyweight for 15 weeks . At the end of the experimental period all the rats were sacrificed. DNA adducts where investigated in the experimental animal model with a potent pro-carcinogen DMH, an alkylating agent that targets DNA and induces the formation of methyl adducts with DNA bases, point mutations, micronuclei, and sister chromatid exchanges yielding macroscopically visible neoplasm in a dose-dependent manner. Results: The colon and liver tissues levels of the enzymic and non-enzymic antioxidants were significantly decreased in cancer bearing animals when compared to the control animals. Lipid peroxide levels (LPO) were estimated. Conclusion: From our results, we conclude that Myrtenal is a potent antioxidant and play a protective role against DMH induced colon cancer.

Keywords


Colon Cancer, Myrtenal, 1,2-Dimethylhydrazine, Antioxidants, Phase I Enzyme.

References