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Портал Begell Электронная Бибилиотека e-Книги Журналы Справочники и Сборники статей Коллекции
Journal of Environmental Pathology, Toxicology and Oncology
Импакт фактор: 1.625 5-летний Импакт фактор: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Печать: 0731-8898
ISSN Онлайн: 2162-6537

Том 39, 2020 Том 38, 2019 Том 37, 2018 Том 36, 2017 Том 35, 2016 Том 34, 2015 Том 33, 2014 Том 32, 2013 Том 31, 2012 Том 30, 2011 Том 29, 2010 Том 28, 2009 Том 27, 2008 Том 26, 2007 Том 25, 2006 Том 24, 2005 Том 23, 2004 Том 22, 2003 Том 21, 2002 Том 20, 2001

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2020031953
pages 137-147

Immunomodulatory Effect of Eriocitrin in Experimental Animals with Benzo(a)Pyrene-induced Lung Carcinogenesis

Qing Wang
Department of Oncology, The First People’s Hospital of Qujing, Qujing, Yunan, 655000, P.R. China
Liqiong Zhang
Department of Oncology, The First People’s Hospital of Qujing, Qujing, Yunan, 655000, P.R. China
Meifang Huang
Department of Oncology, The First People’s Hospital of Qujing, Qujing, Yunan, 655000, P.R. China
Yuanyuan Zheng
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, P.R. China
Kai Zheng
Department of Breast Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, P.R. China

Краткое описание

Lung carcinogenesis is one of the main sources of cancer-related mortality globally and it is estimated that nearly 1 million people die from it every year. The 5-year survival rate of lung carcinogenesis is reported at just 15%. The aim of the current research was to investigate the immunomodulatory effect of eriocitrin against benzo(a)pyrene [B(a) P]-induced lung tumorigenesis in Swiss albino mice. The lung sarcoma was provoked through oral gavage of B(a)P (50 mg/kg body weight) two times/week for four weeks. CEA, lung weight, lipid peroxidation (LPO), body weight, immuno-globulin (IgG, IgA, and IgM), tumor incidence, serum marker enzymes (LDH, AHH, λ-GT, and 5'-NTs), hematological counts (leucocytes, lymphocytes, neutrophils, absolute numbers of lymphocytes and neutrophils), antioxidants (SOD and CAT), inflammatory modulators (IL-1β, IL-6, and TNF-α), immune complexes (avidity index, phagocyte index, NBT reduction, and SIC) and histopathological changes were analyzed. Moreover, the status of apoptosis proteins (Bax, caspase-9, and caspase-3) and cell proliferative protein (cyclin D1 and cyclin A) expression was determined by Western blot and PCNA by immunohistochemical analysis. B(a)P-challenged cancer-bearing mice exhibited augmented levels of lipid peroxidation, tumor incidence, lung weight, CEA, serum marker enzymes, IgA, SIC, cell proliferative markers, and inflammatory cytokines with concurrent decrease in body weight, antioxidant levels, hematological counts, immunoglobulins, immune complexes, and apoptotic protein expression. The eriocitrin treatments caused significant reversion of all these marker to previous levels. Overall, the results propose the immunomodulatory prospective of eriocitrin against B(a) P-induced lung carcinogenesis on Swiss albino mice.


  1. Hamishehkar H, Bahadori MB, Vandghanooni S, Eskandani M, Nakhlband A, Eskandani M. Preparation, characterization and anti-proliferative effects of sclare-ol-loaded solid lipid nanoparticles on A549 human lung epithelial cancer cells. J Drug Delivery Sci Technol. 2018;45:272-80.

  2. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175-80.

  3. Sakthivel R, Malar DS, Devi KP. Phytol shows anti-angiogenic activity and induces apoptosis in A549 cells by de-polarizing the mitochondrial membrane potential. Biomed Pharmacother. 2018;105:742-52.

  4. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW. Cancer genome landscapes. Science. 2013;339:1546-58.

  5. Zhu W, Cromie MM, Cai Q, Lv T, Singh K, Gao W. Curcumin and vitamin E protect against adverse effects of benzo[a]pyrene in lung epithelial cells. PLoS One. 2014;9:e92992.

  6. Aldarouish M, Su X, Qiao J, Gao C, Chen Y, Dai A, Zhang T, Shu Y, Wang C. Immunomodulatory effects of chemotherapy on blood lymphocytes and survival of patients with advanced non-small cell lung cancer. Int J Immunopathol Pharmacol. 2019;33:2058738419839592.

  7. Lombardi A, Tsomos E, Hammerstad SS, Tomer Y. Interferon alpha: The key trigger of type 1 diabetes. J Autoimmun. 2018;94:7-15.

  8. Chen DS, Mellman I. Elements of cancer immunity and the cancerimmune set point. Nature. 2017;541:321-30.

  9. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350-5.

  10. Matsushita M, Kawaguchi M. Immunomodulatory effects of drugs for effective cancer immunotherapy. J Oncol. 2018:1-7.

  11. Hu R, Kong AN. Activation of MAP kinases, apoptosis and nutrigenomics of gene expression elicited by dietary cancer-prevention compounds. Nutrition. 2004;20:83-8.

  12. Miyake Y, Yamamoto K, Osawa T. Isolation of eriocitrin (eriodictyol 7-rutinoside) from lemon fruit (Citrus limon BURM. f.) and its antioxidative activity. Food Sci Technol Int. 1997;3:84-9.

  13. Minato K, Miyake Y, Fukumoto S, Yamamoto K, Kato Y, Shimomura Y, Osawa T. Lemon flavonoid, eriocitrin, suppresses exercise-induced oxidative damage in rat liver. Life Sci. 2003;72:1609-16.

  14. Hiramitsu M, Shimada Y, Kuroyanagi J, Inoue T, Katagiri T, Zang L, Nishimura Y, Nishimura N, Tanaka T. Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. Sci Rep. 2014;4:3708.

  15. Wang Y, Yu H, Zhang J, Gao J, Ge X, Lou G. Hesperidin inhibits HeLa cell proliferation through apoptosis mediated by endoplasmic reticulum stress pathways and cell cycle arrest. BMC Cancer. 2015;15:682.

  16. Banjerdpongchai R, Wudtiwai B, Khaw-On P, Rachak- hom W, Duangnil N, Kongtawelert P. Hesperidin from citrus seed induces human hepatocellular carcinoma HepG2 cell apoptosis via both mitochondrial and death receptor pathways. Tumour Biol. 2016;37:227-37.

  17. Kasala ER, Bodduluru LN, Barua CC, Madhana RM, Dahiya V, Budhani MK, Mallugari RR, Maramreddy SR, Gogoi R. Chemopreventive effect of chrysin, a dietary flavone against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice. Pharmacol Rep. 2016;68:310-8.

  18. Kakkar P, Das B, Viswanathan PN. A modified spectro- photometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984;21:130-2.

  19. Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47:389-94.

  20. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351-8.

  21. Orlowski M, Meister A. Isolation of gamma-glutamyltranspeptidase from hog kidney. J Biol Chem. 1965; 240:338-47.

  22. Buening MK, Chang RL, Huang MT, Fortner JG, Wood AW, Conney AH. Activation and inhibition of benzo(a) pyrene and aflatoxin B1 metabolism in human liver microsomes by naturally occurring flavonoids. Cancer Res. 1981;41:67-72.

  23. Hardonk MJ, De Boer HG. 5'-nucleotidase-III. Determinations of 5'-nucleotidase isoenzymes in tissues of rat and mouse. Histochemie. 1968;12:29-41.

  24. King J. The transaminases: Alanine and aspartate transaminases. In: Practical clinical enzymology. London: Van Nostrand Reinhold; 1965. p. 363-95.

  25. John MB. Laboratory medicine hematology, 4th ed. St. Louis, MO: CV Mosby; 1972. p. 194-204.

  26. Wilkinson PC. Phagocytosis of killed Candida albicans. Techniq Clin Immunol. 1977;1:99.

  27. Vray B, Plasman N. Separation of murine peritoneal macrophages using Percoll density gradients. J Immunol Methods. 1994;174:53-9.

  28. Rajendran P, Jayakumar T, Nishigaki I, Ekambaram G, Nishigaki Y, Vetriselvi J, Sakthisekaran D. Immuno-modulatory effect of mangiferin in experimental animals with benzo(a)pyrene-induced lung carcinogenesis. Int J Biomed Sci. 2013;9:68-74.

  29. Seth P, Srinivas RV. Circulating immune complexes in cervical cancer: Simple method for detection and characterization. IJMR. 1981;73:926-9.

  30. Gifford RH, Malawista SE. A simple rapid micromethod for detecting chronic granulomatous disease of childhood. J Lab Clin Med. 1970;75:511-8.

  31. Tennant B, Baldwin BH, Braun RK, Norcross NL, Sandholm M. Use of the glutaraldehyde coagulation test for detection of hypogammaglobulinemia in neonatal calves. J Am Vet Med Assoc. 1979;174:848.

  32. Satpathy PK, Dutta NK, Mishra PR, KAI B. Glutaraldehyde coagulation test: Standard curve and its applications to detect gammaglobulin level in kids. Indian Vet J. 1996;73:257-60.

  33. Arivazhagan L, Sorimuthu Pillai S. Tangeretin, a citrus pentamethoxyflavone, exerts cytostatic effect via p53/p21 up-regulation and suppresses metastasis in 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinoma. J Nutr Biochem. 2014;25:1140-53.

  34. Lowry OH, Rosebrough MJ, Farr AL, Randall RJ. Protein measurement with folin-phenol reagent. J Biol Chem. 1951;193:265-75.

  35. Kasala ER, Bodduluru LN, Barua CC, Madhana RM, Dahiya V, Budhani MK, Mallugari RR, Maramreddy SR, Gogoi R. Chemopreventive effect of chrysin, a dietary flavone against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice. Pharmacol Rep. 2016; 68:310-8.

  36. Attalla E. Anti-angiogenic effectiveness of the pomegranate against benzo(a)pyrene induced lung carcinoma in mice. Int J Cancer Res. 2015;11:164-74.

  37. Magesh V, Singh JP, Selvendiran K, Ekambaram G, Sakthisekaran D. Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies. Mol Cell Biochem. 2006;287:127-35.

  38. Muninathan N, Sampson U, Talikoti P, Maheshwari U. Effect of paclitaxel along with diallyl sulfide on immuno-competent cells, immune complexes and immunoglobulins changes in 7,12 di methyl benz (A) anthracene induced skin cancer in Wistar rats. IJMRHS. 2014;3:155-60.

  39. Perez EE, Orange JS, Bonilla F, Chinen J, Chinn IK, Dorsey M, El-Gamal Y, Harville TO, Hossny E, Mazer B, Nelson R. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017;139:S1-46.

  40. Wolf HM, Thon V, Litzman J, Eibl MM. Detection of impaired IgG antibody formation facilitates the decision on early immunoglobulin replacement in hypogammaglobulinemic patients. Front Immunol. 2015;6:32.

  41. Liu WT, Jing YY, Han ZP, Li XN, Liu Y, Lai FB, Li R, Zhao QD, Wu MC, Wei LX. The injured liver induces hyperimmunoglobulinemia by failing to dispose of antigens and endotoxins in the portal system. PLoS One. 2015;10:e0122739.

  42. Raffa D, Maggio B, Raimondi MV, Plescia F, Daidone G. Recent discoveries of anticancer flavonoids. Eur J Med Chem. 2017;142:213-28.

  43. Masihi KN. Immunomodulatory agents for prophylaxis and therapy of infections. Int J Antimicrob Agents. 2000;14:181-91.

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

  45. Kamaraj S, Vinodhkumar R, Anandakumar P, Jagan S, Ramakrishnan G, Devaki T. The effects of quercetin on antioxidant status and tumor markers in the lung and serum of mice treated with benzo(a)pyrene. Biol Pharm Bull. 2007;30:2268-73.

  46. Kamaraj S, Ramakrishnan G, Anandakumar P, Jagan S, Devaki T. Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice. Invest New Drugs. 2009;27:214-22.

  47. Moustafa S, Swilam NF, Ghanem OB, Hashim AN, Naw- war MA, Lindequist U, Linscheid MW. A coumarin with an unusual structure from Cuphea ignea, its cytotoxicity and antioxidant activities. Pharmazie. 2018;73:241-3.

  48. Salam S, Velli SK, Krishnan P, Selvanathan I, Murugan M, Subramaniam N, Thiruvengadam D. Anti-cancer efficacy of umbelliferone against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice. MJB. 2018;5:79-89.

  49. Turgut F, Bayrak O, Catal F, Bayrak R, Atmaca AF, Koc A, Akbas A, Akcay A, Unal D. Antioxidant and protective effects of silymarin on ischemia and reperfusion injury in the kidney tissues of rats. Int Urol Nephrol. 2008;40:453-60.

  50. Yoshikawa M, Arashidani K, Kawamoto T, Kodama Y. Aryl hydrocarbon hydroxylase activity in human lung tissue: In relation to cigarette smoking and lung cancer. Environ Res. 1994;65:1-11.

  51. Simon HU, Haj-Yehia A, Levi-Schaffer F. Role of reactive oxygen species (ROS) in apoptosis induction. Apoptosis. 2000;5:415-8.

  52. Erdemli HK, Adam B, Bavbek N. Pyrimidine 5'nucleotidase I and II activities in acute leukaemias. Acta Medica (Hradec Kralove). 2004;47:129-31.

  53. Sakao Y, Tomimitsu S, Takeda Y, Natsuaki M, Itoh T. Carcinoembryonic antigen as a predictive factor for postoperative tumor relapse in early-stage lung adenocarcinoma. Eur J Cardiothorac Surg. 2004;25:520-2.

  54. Al-Radahe S, Ahmed KA, Salama S, Abdulla MA, Amin ZA, Al-Jassabi S, Hashim H. Antiulcer activity of Swietenia mahagoni leaf extract in ethanol-induced gastric mucosal damage in rats. J Med Plants Res. 2012; 6:2266-75.

  55. Al-Jasabi S, Abdullah MS. The role of antioxidant hesperidin in the attenuation of lung cancer caused by benzo [a] pyrene in Balb/c mice. WorldAppl Sci J. 2013;22:1106-10.

  56. Arumugam K, Arunkumar L, Sivakumar M, Murugan K. Anticancer effect of fucoidan on cell proliferation, cell cycle progression, genetic damage and apoptotic cell death in HepG2 cancer cells. Toxicol Rep. 2019;6:556-63.

  57. Pucci B, Kasten M, Giordano A. Cell cycle and apoptosis. Neoplasia. 2000;2:291-9.

  58. Bravo R, Frank R, Blundell PA, Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987;326:515-7.

  59. Rajendran P, Rengarajan T, Nishigaki I, Ekambaram G, Sakthisekaran D. Potent chemopreventive effect of mangiferin on lung carcinogenesis in experimental Swiss albino mice. J Cancer Res Ther. 2014;10:1033-9.

  60. Wang Z, Zhang H, Zhou J, Zhang X, Chen L, Chen K, Huang Z. Eriocitrin from lemon suppresses the proliferation of human hepatocellular carcinoma cells through inducing apoptosis and arresting cell cycle. Cancer Chemother Pharmacol. 2016;78:1143-50.

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