A long term study to unravel the chemopreventive efficacy of pMethoxycinnamic acid in comparison to sorafenib, a standard drug against NDEA induced hepatocarcinogenesis

Authors

  • Sriragavi Ravi
  • Rajagopal Ayyanar
  • Nalini Namasivayam

DOI:

https://doi.org/10.46243/jst.2021.v6.i05.pp39-63

Keywords:

p-methoxycinnamic acid, N-nitrosodiethylamine, 2-acetylaminofluorene, sorafenib

Abstract

p- Methoxycinnamic acid (p-MCA), an active phenolic compound derived from the rice bran, turmeric and Kaempferia galangal, is known to exhibit numerous pharmacological properties. We investigated that chemopreventive effect of p-MCA against N-nitrosodiethylamine (NDEA) induced hepatocarcinogenesis in male wistar rats. Rats were subjectively divided into five groups. Group 1 served as control and was fed modified pellet diet and water. Group 2 received the reference drug (Sorafenib [11.4 mg/kg b.w]). Group 3, 4 and 5 rats received the hepatocarcinogen (NDEA) intraperitoneally in addition to 2-acetylaminofluorene (AAF) as promotor. In addition group 4 rats received p-MCA at the dose of 80 mg/kg b.w. and group 5 rats received sorafenib at the dose of 11.4 mg/kg b.w throughout the experimental period. Our results established that supplementation with p-MCA and the reference drug (sorafenib) to NDEA induced rats significantly decreased the incidence of cancer in the liver, besides altering the phase I and phase II xenobiotic enzymes. Furthermore the increased expressions of collagen, lipid and glycogen accumulation observed in NDEA alone-induced rats were comparable with those of the control rats, p-MCA and sorafenib alone treated rats. Our results proved that p-MCA was equally effective that of the reference drug sorafenib (which is used currently for the treatment of hepatocellular carcinoma against NDEA induced hepatocarcinogenesis

References

Fazal Khan, Tariq Jamal Khan, Gauthaman Kalamegam, Peter Natesan Pushparaj, Adeel Chaudhary,Adel Abuzenadah, Taha Kumosani, Elie Barbour and Mohammed Al-Qahtani. Anticancer effects of Ajwa dates (Phoenix dactylifera L.) in diethylnitrosamine induced hepatocellular carcinoma in Wistar rats. BMC Complementary and Alternative Medicine. (2017) 17:1926-1936

Vishnu Priya Veeraraghavan, Surapaneni Krishna Mohan, Mallika Jainu and Chandra Sada Gopan Venkipuram Seshadri. Ameliorating effects of Garcinia mangostana Linn pericarp extract on hepatic antioxidants in Diethylnitrosamine (DEN) induced Hepatocellular Carcinoma (HCC). Indian Journal of Pharmaceutical Education and Research. (2015) 49; (4)

Cui-Li Zhang, Tao Zeng, Xiu-Lan Zhao, Li-Hua Yu, Zhen-Ping Zhu, and Ke-Qin Xie. Protective Effects of Garlic Oil on Hepatocarcinoma Induced by N-Nitrosodiethylamine in Rats. Int. J. Biol. Sci. (2012) 8(3): 363-374

Dae-Hun Park, Jae Wook Shin, Seung-Kee Park, Jae-Nam Seo, Lan Li, Ja-June Jang, Min-Jae Lee. Diethylnitrosamine (DEN) induces irreversible hepatocellular carcinogenesis through overexpression of G1/S-phase regulatory proteins in rat. ToxicolLett. (2009) 191(2-3):321-326

Stephen C. Strom, Randy L. Jirtle and George Michalopoulos. Genotoxic Effects of 2 Acetylaminofluorene on Rat and Human Hepatocytes. Environmental Health Perspectives (1983) 49:165-170

J.Mann, Natural products in cancer chemotherapy: past, present and future, Nat, Rev. Cancer 2. (2002) 143-148

Gunasekaran sivagami, venkatchalam karthikumar, thangavel balasubramanian, namasivayam nalini. The modulatory influence of p-methoycinnamic acid, an active rice bran phenolic acid, against 1,2dimethylhydrazine-induced lipid peroxidation, antioxidant status and aberrant crypt foci in rat colon carcinogenesis. Chemico-Biological interactions. (2012) 196: 11-22

Lee SR, Kim KJ, Kim YC. Hepatoprotectivephenylpropanoids from Scrophulariabuergeriana roots against CCl4-induced toxicity: action mechanism and structure–activity relationship. Planta Med. (2002) 68:407–441

Adisakwattana S, Roengsamran S, Hsu WH, Yibchok-anun S. Mechanisms of antihyperglycemic effect of p-methoxycinnamic acid in normal and streptozotocin-induced diabetic rats. Life Sci. (2005) 12:406–412

Kim SR, Sung SH, Jang YP, Markelonis GJ, Oh TH, Kim YC E-pmethoxycinnamic acid protects cultured neuronal cells against neurotoxicity induced by glutamate. Br J Pharmacol. (2002) 35:1281–1291

Mahajan R, Kaur DJ, Bajaj KL. Nematical activity of phenolic compounds against meloidodyne incognita. NematolMedit. (1992) 20:217–219

Othman R, Ibrahim H, Mohd MA, Mustafa MR, Awang K. Bioassay-guided isolation of a vasorelaxant active compound from Kaempferia galangal L. Phytomed. (2006) 13:61–66

Sivagami, G., KarthikKumar, V., and Nalini, N. “p-Methoxycinnamic acid, an active phenylpropanoid induces mitochondrial mediated apoptosis in HCT-116 human colon adenocarcinoma cell line.” Environmental Toxicology and Pharmacology. (2012) S1382-6689 (15), 30091-30100

Schladt L, Worner W, Setiabudi F, Oesch F. Distribution and inducibility of cytosolic epoxide hydrolase in male Sprague-Dawley rats. Biochem. Pharmacol. (1986) 35; 3309-3316

Niehaus, W.G., and Samuelsson, J.R.B. “Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation.” Eur J Biochem. (1968) 6: 126–30

Jiang, Z.Y., Hunt, J.V., and Wolff, S.P. “Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxides in low density lipoprotein.” Anal Biochem. (1992) 202: 384–389

Kakkar, P., and Das, B. “Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase.” Ind J BiochemBiophys. (1984) 21: 131-132

Ellman GL. Tissue sulphydryl groups. Arch Biochem Biophys. (1959) 82; 70-77

Habig. W.H., Pabst, M.J., and Jakoby, W.B. “Glutathione-S-transferase.” J. Biol. Chem. (1974) 249: 7130–7139

Omura, T., and Sato, R. “The carbon monoxide-binding pigment of liver micro-somes.” J. Biol. Chem. (1964) 239: 2370–2378

Strittmatter, P., and Velick, S.F. “The isolation and properties of microsomal cytochrome” J. Biol. Chem. (1956) 221: 253–264

Mehmet Kanter, Omer Coskun, Mustafa Budancamanak. Hepatoprotective effects of Nigella sativa L and Urtica dioic aL on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol. (2005) 11(42): 6684-6688

Isselbacher, K.J., Charabas, M.F., and Quinn, R.C. “The solublisation and partial purification of a Glucuronyltransferase from rabbit liver microsomes.” J. Biol. Chem. (1962) 237: 3033

Akshatha, G.M., Raval, S.K., Arpitha, G.M., Raval S.H., and Ghodasara, D.J. “Immunohistochemical, histopathological study and chemoprotective effect of Solanumnigrum in Nnitrosodiethylamine-induced hepatocellular carcinoma in Wistar rats.” Veterinary World. (2018) 11(4): 402-409

Benjamin Vogel, Hanna Siebert, Ulrich Hofmann, Stefan Frantz. Determination of collagen content within picrosirius red stained paraffin-embedded tissue sections using fluorescence microscopy. Methods X 2 (2015) 124–134

Nisha, S.T., Kiran, G., Sivaranjani, A., Vijay, M., Aktarul, I. S., and Nalini, N. “The in vivo antineoplastic and therapeutic efficacy of troxerutin on rat preneoplastic liver: biochemical, histological and cellular aspects.” Eur J Nutr. (2016) 1275-1280

Chengyu Liu, Zhen Chen, Yuejie Chen, Jia Lu,Yuan Li, Shujing Wang, Guoliang Wu,and Feng Qian. Improving Oral Bioavailability of Sorafenib by Optimizing the “Spring” and “Parachute” Based on Molecular Interaction Mechanisms. (2015) December 28

Fahad Ali, Rahul, Smita Jyoti, Ambreen Fatima, Saba Khanam, Falaq Naz, and Yasir Hasan Siddique. Protective Role of Curcumin against N-Nitrosodiethylamine (NDEA)-Induced Toxicity in Rats. Sci Pharm. (2016) 84(2): 361–377

Saraswati S, Alhaider AA, Agarwal SS. Anticarcinogenic effect of brucine in diethylnitrosamine initiated and phenobarbital-promoted hepatocarcino-genesis in rats. Chem Biol Interact. (2013) 206: 214-221

Edoardo G. Giannini, Roberto Testa, Vincenzo Savarino. Liver enzyme alteration: a guide for clinicians. CMAJ. (2005) 172(3):367-79

Janani P, Sivakumar K, Geetha A, Ravisankar B, Parthasarathy C. Chemopreventive effect of bacoside A on Ns-nitrosodiethylamine-induced hepatocarcin-ogenesis in rats. J Cancer Res Clin Oncol. (2010) 136: 759-770

Samar Rajendra Kumar, Jain Suman, Sogani Sonal. Clinical studies to evaluate peroxidative stress and antioxidant complement in liver cancer in Indian and Hungarian subjects. Asian J Pharm Clin Res. (2020) 13(3): 95-97

Antonio Ayala, Mario F. Muñoz, and Sandro Argüelles. Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal. Oxidative Medicine and Cellular Longevity. (2014)

Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med. (2000) 342(17): 1266-71

Bansal, AK., Trivedi, R., Soni, GL., Bhatnagar, D.,.Hepatic and renal oxidative stress in acute toxicity of N-nitrosodiethylamine in rats. Indian J Exp Biol. (2000) 38:916-920

Eboh Abraham Sisein1, Ere Diepreye2, Robert Faith Owabhel3, Arhoghro Ejowoke Marcellinous. Garcinia Kola Extract (Kolaviron) Prevents DMH Induced Liver Damage in Wistar Rats by Restoring Antioxidants. Galore International Journal of Health Sciences and Research. (2016) 1(1)

Sudhanshu Jambhulkar, Swathi Deshireddy, Dinesh Babu Jestadi and Latha Periyasamy. Quercetin Attenuating Doxorubicin Induced Hepatic, Cardiac and Renal Toxicity in Male Albino Wistar Rats. AJPCT. (2014) 2(8): 985-1004

Henry Jay Forman, Hongqiao Zhang, and Alessandra Rinna. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med. (2009) 30(1-2): 1–12

Ferruzzi, E, Franceschini, R, Cazzolato, G, Geroni, C, Fowst, C, Pastorino, U, Tradati, N, Tursi, J, Dittadi, R, Gion, M.. Blood glutathione as a surrogate marker of cancer tissue glutathione-Stransferase activity in non-small cell lung cancer and squamous cell carcinoma of the head and neck. Eur J Cancer. (2003) 39: 1019-1029

J-P Villeneuve 1, V Pichette. Cytochrome P450 and liver diseases. Curr Drug Metab. (2004) 5(3):273-82

Raed Lattouf, Ronald Younes, Didier Lutomski, Nada Naaman, Gaston Godeau, Karim Senni, and Sylvie Changotade. Picrosirius Red Staining: A Useful Tool to Appraise Collagen Networks in Normal and Pathological Tissues. Journal of Histochemistry & Cytochemistry. (2014) Vol. 62(10) 751–758

Alexandros Arjmand, Markos G. Tsipouras, Alexandros T. Tzallas, Roberta Forlano, Pinelopi Manousou 3 and Nikolaos Giannakeas. Quantification of Liver Fibrosis—A Comparative Study. Appl. Sci. (2020) 10; 447

Mcgee JOD. Collagen deposition in liver disease. Ann. rheum.Dis. (2000) 29-37

Aatur D Singhi, Dhanpat Jain, Sanjay Kakar, Tsung-Teh Wu, Matthew M Yeh, Michael Torbenson. Reticulin loss in benign fatty liver: an important diagnostic pitfall when considering a diagnosis of hepatocellular carcinoma. Am J Surg Pathol. (2012) 36(5):710-5

R W Horobin, L B Murgatroyd. The staining of glycogen with Best's Carmine and similar hydrogen bonding dyes. A mechanistic study. Histochem J. (1971) 3(1):1-9

Sally Martin and Robert G. Parton. Lipid droplets: a unified view of a dynamic organelle. Nature Reviews Molecular Cell Biology. June (2006) 7;373-378

ZeZheng, ChunbinZhang, KezhongZhang. Chapter Nineteen-Measurement of ER Stress Response and Inflammation in the Mouse Model of Nonalcoholic Fatty Liver Disease. Methods in Enzymology. (2011) 489; 329-348

Ana I. Porcell L, M.D, Barry R. De Young, M.D, Daniela M. Proca, M.D, Wendy L. Frankel, M.D. Immunohistochemical Analysis of Hepatocellular and Adenocarcinoma in the Liver: MOC31 Compares Favorably with Other Putative Markers. Mod Pathol. (2000) 13(7);773–778

Hamdy, Shaheen, Awad, Barakat, Shalaby, Gupta & Gupta. Vascular endothelial growth factor (VEGF) as a biochemical marker for the diagnosis of hepatocellular carcinoma (HCC). Clin. Pract. (2020) 17(1);1441-1453

Zirong P, Jianmin Z, Chenghong J, Zhezhen C, Weijia L and Zhengjie H. Curcumin inhibits hepatocellular carcinoma growth by targeting VEGF expression. Oncology letters (2018) 15: 4821- 4826

Rinku D and Ram I. Mahato. Recent advances in hepatocellular carcinoma therapy. Pharmacol Ther. (2017) 173: 106–117

Published

2021-10-05

How to Cite

Sriragavi Ravi, Rajagopal Ayyanar, & Nalini Namasivayam. (2021). A long term study to unravel the chemopreventive efficacy of pMethoxycinnamic acid in comparison to sorafenib, a standard drug against NDEA induced hepatocarcinogenesis. Journal of Science & Technology , 6(5), 39–63. https://doi.org/10.46243/jst.2021.v6.i05.pp39-63