QUENCHING OF N-NITROSOPYRROLIDINE INDUCED HEPATOCELLULAR CARCINOMA ON POST TREATMENT WITH THE HELICTERES ISORA
Objective: The present study was aimed at probing the protective potential of Helicteres isora hydroethanolic stem bark extract (HIHSBE) against
N-nitrosopyrrolidine (NPYR) induced hepatocellular carcinoma (HCC) in Swiss albino male mice.
Method: Mice were divided into six groups of six mice in each. Hepatocellular carcinoma (HCC) was induced by single intraperitoneal injection of
the carcinogen nitrosopyrrolidine (NPYR). Followed by the subcutaneous injection of carbon tetrachloride (CCl4). Carcinogen treated mice were then
orally administered with Helicteres isora hydroethanolic stem bark extract (HIHSBE) at a dose of 100 and 200 mg/kg once daily for 4 weeks followed
by investigation of liver injury markers like alanine transaminase (ALT), aspartate transaminase (AST), alanine phosphatase (ALP), gamma glutamyl
transferase (GGT), Lactate dehydrogenase (LDH). Tumor markers alpha fetoprotein and carcinoembryonic antigen were determined in serum. Level
of catalase (CAT), reduced glutathione (GSH), glutathione-s- transferase (GST) and lipid peroxidation were also estimated.
Results: The level of liver injury markers and antioxidant enzymes decreased in the liver tissue of NPYR treated mice compared to normal control mice.
However, HIHSBE post treatment increased the level of these enzymes compared to only carcinogen treated mice. HIHSBE also lowered the level of tumor
markers and lipid peroxidation in serum and liver tissue of mice bearing HCC respectively. Histological studies also supported biochemical investigations.
Conclusion: The chemopreventive effect of HIHSBE is well supported in our study as it hinders the development of HCC by interacting with ROS
during carcinogenesis and thus counterbalancing the antioxidant defense system as analyzed.
Keywords: Helicteres isora, Hepatocellular carcinoma, Liver enzymes, N-nitrosopyrrolidine, Oxidative stress.
Masuda M, Mower HF, Pignatelli B, Celan I, Friesen MD, Nishino H, et al. Formation of N-nitrosamines and N-nitramines by the reaction of secondary amines with peroxynitrite and other reactive nitrogen species: Comparison with nitrotyrosine formation. Chem Res Toxicol 2000;13(4):301-8.
Ohsawa K, Nakagawa SY, Kimura M, Shimada C, Tsuda S, Kabasawa K, et al. Detection of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic acid, teas and fruit juices. Mutat Res 2003;539(1-2):65-76.
Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: From genes to environment. Nat Rev Cancer 2006;6(9):674-87.
International Agency for Research and Cancer. Some N-nitroso compounds. IARC Monographs on the Evaluation of Carcinogenic risk of Chemicals to Humans. Lyon, France: IARC; 1978. p. 365.
International Agency for Research on Cancer. IARC monographs on the evaluation of carcinogenic risks to humans. Tobacco Smoke and Involuntary Smoking. Lyon, France: IARC; 2004. p. 53.
Marnett LJ. Oxyradicals and DNA damage. Carcinogenesis 2000;21(3):361-70.
Cooke JP. NO and angiogenesis. Atheroscler Suppl 2003;4(4):53-60.
Klaunig JE, Kamendulis LM. The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol 2004;44:239-67.
Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 2010;38(1):96-109.
Rajeshkumar NV, Kuttan R. Protective effect of Picroliv, the active constituent of Picrorhiza kurroa, against chemical carcinogenesis in mice. Teratog Carcinog Mutagen 2001;21(4):303-13.
Ranneh Y, Ali F, Esa NM. The protective effect of cocoa (Theobroma cacao L.) in colon cancer. J Nutr Food Sci 2013;3:193.
Kitagishi Y, Kobayashi M, Matsuda S. Protection against cancer with medicinal herbs via activation of tumor suppressor. J Oncol 2012;2012:236530.
Li B, Zhao J, Wang CZ, Searle J, He TC, Yuan CS, et al. Ginsenoside Rh2 induces apoptosis and paraptosis-like cell death in colorectal cancer cells through activation of p53. Cancer Lett 2011;301(2):185â€‘92.
Gao J, Morgan WA, Sanchez-Medina A, Corcoran O. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells. Toxicol Appl Pharmacol 2011;254(3):221-8.
Liu H, Zang C, Emde A, Planas-Silva MD, Rosche M, KÃ¼hnl A, et al. Anti-tumor effect of honokiol alone and in combination with other anti-cancer agents in breast cancer. Eur J Pharmacol 2008;591(1-3):43-51.
Zhang L, Arnold L, Hanson JR, Clark AM. Natural products as a resource for new drugs. Pharm Res 1996;13(8):1133-44.
Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nat Rev Drug Discov 2005;4(3):206-20.
Ntie-Kang F, Nwodo JN, Ibezim A, Simoben CV, Karaman B, Ngwa VF, et al. Molecular modeling of potential anticancer agents from African medicinal plants. J Chem Inf Model 2014;54(9):2433-50.
Yoganarasimhan SN. Medicinal Plants of India. Karnataka: Interline Publishing Private Limited; 1996. p. 1-237.
Mohan VR, Rajesh A, Athiperumalsamia T, Sutha S. Ethnomedicinal plants of the Tirunelveli district, Tamil Nadu, India. Ethnobot Leafl 2008;12(3):79-95.
Arjariya A, Chaurasia K. Some medicinal plants among the tribes of Chhatarpur district (M.P) India. Ecoprint 2009;16:43-50.
Meena R, Santhana GK, Selin RA. Ethnomedicinal shrubs of Marunduvalmalai, Western Ghats, Tamil Nadu, India. J Basic Appl Biol 2009;3(1,2):67-70.
Babu NC, Naidu MT, Venkaiah M. Ethnomedicinal plants of Kotia hills of Vizianagaram district, Andhra Pradesh, India. J Phytol 2010;2:76-82.
Dhare DK, Jain A. Ethnobotanical studies on plant resources of Tahsil Multai, district Betul, Madhya Pradesh, India. Ethnobot Leafl 2010;14:694-705.
Sankaranarayanan S, Bama P, Ramachandran J, Kalaichelvan PT, Deccaraman M, Vijayalakshimi M, et al. Ethnobotanical study of medicinal plants used by traditional users in Villupuram district of Tamil Nadu, India. J Med Plants Res 2010;4(12):1089-101.
Basha SK, Sudarsanam G, Mohammad MS, Parveen N. Investigations on anti-diabetic medicinal plants used by Sugali Tribal inhabitants of Yerramalais of Kurnool district, Andhra Pradesh, India. Stamford J Pharm Sci 2011;4(2):19-24.
Kumar G, Murugesan AG. Hypolipidaemic activity of Helicteres isora L. bark extracts in streptozotocin induced diabetic rats. J Ethnopharmacol 2008;116(1):161-6.
Sundaresan S, Subramanian P. S-allylcysteine inhibits circulatory lipid peroxidation and promotes antioxidants in N-nitrosodiethylamine-induced carcinogenesis. Pol J Pharmacol 2003;55(1):37-42.
Singh BN, Singh BR, Sarma BK, Singh HB. Potential chemoprevention of N-nitrosodiethylamine-induced hepatocarcinogenesis by polyphenolics from Acacia nilotica bark. Chem Biol Interact 2009;181(1):20-8.
Ramakrishnan G, Raghavendran HR, Vinodhkumar R, Devaki T. Suppression of N-nitrosodiethylamine induced hepatocarcinogenesis by silymarin in rats. Chem Biol Interact 2006;161(2):104-14.
Rao GM, Rao CV, Pushpangadan P, Shirwaikar A. Hepatoprotective effects of rubiadin, a major constituent of Rubia cordifolia Linn. J Ethnopharmacol 2006;103(3):484-90.
Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28(1):3856-63.
Orlowski M, Meister A. Isolation of gamma-glutamyl transpeptidase from hog kidney. J Biol Chem 1965;240:338-47.
Rosalki SB, Rau D. Serum - glutamyl transpeptidase activity in alcoholism. Clin Chim Acta 1972;39(1):41-7.
King J. In: Practical Clinical Enzymology. London: Von Nostrand D, Company Ltd.; 1965. p. 106.
Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47(2):389-94.
Ellman GI. Tissue sulphhydryl groups. Arch Biochem Biophys 1959;82:70-7.
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249(22):7130-9.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351â€‘8.
Montesano R. Alkylation of DNA and tissue specificity in nitrosamine carcinogenesis. J Supramol Struct Cell Biochem 1981;17(3):259-73.
Feo F, Pascale RM, Simile MM, De Miglio MR, Muroni MR, Calvisi D. Genetic alterations in liver carcinogenesis: Implications for new preventive and therapeutic strategies. Crit Rev Oncog 2000;11(1):19â€‘62.
Wang M, Hecht SS. A cyclic N7, C-8 guanine adduct of N-nitrosopyrrolidine (NPYR): Formation in nucleic acids and excretion in the urine of NPYR-treated rats. Chem Res Toxicol 1997;10(7):772-8.
Hecht SS, Upadhyaya P, Wang M. Evolution of research on the DNA adduct chemistry of N-nitrosopyrrolidine and related aldehydes. Chem Res Toxicol 2011 20;24:781-90.
Wong FW, Chan WY, Lee SS. Resistance to carbon tetrachloride-induced hepatotoxicity in mice which lack CYP2E1 expression. Toxicol Appl Pharmacol 1998;153(1):109-18.
Maestranzi S, Przemioslo R, Mitchell H, Sherwood RA. The effect of benign and malignant liver disease on the tumour markers CA19-9 and CEA. Ann Clin Biochem 1998;35:99-103.
Mittal G, Vadhera S, Brar AP, Soni G. Protective role of dietary fibre on N-nitrosopyrrolidine-induced toxicity in hypercholesterolemic rats. Hum Exp Toxicol 2007;26(2):91-8.
Shori A, Paliwal SK, Sharma V. Quantitative determination of polyphenols and study of antioxidant activity of a traditionally important medicinal plant: Helicteres isora Linn. J Plant Dev Sci 2013;5(4):489â€‘94.
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