Grape Seed and Physalis Extracts as Anti- Inflammatory Agents in Cetuximab Induced Tongue Mucositis in Rats


Affiliations

  • Cairo University, Master degree in Oral and Maxillofacial Pathology, Faculty of Dentistry, Egypt
  • Cairo University, Oral and Maxillofacial Pathology, Faculty of Dentistry, Egypt
  • Cairo University, Head of Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Egypt

Abstract

Background: Oral mucositis induced by cancer therapy alters cancer patient’s life. Nutraceuticals these days is for their various activities which could neutralize the toxicity induced by cancer treatment. Purpose: Comparision between the effect of grape seed and fruits of Physalis peruviana methanol extract in reduction of mucositis induced by Cetuximab drug. Study Design: Animal study. Methods: 60 male rats divided into 6 groups as 10 in each group. Control group of rats with no intervention given. The other 5 groups were given Cetuximab drug alone or with grape seed extract (simultaneously or 1 week before Cetuximab drug) or Physalis extract (simultanously or 1 week before Cetuximab drug). After sacrifice, tongue was dissected and tissue preparation was done for all samples. Digital counting was done by image analyzer computer system for (a) filliform papillae in H&E stained sections, (b) mast cells in mast cell tryptase stained sections to assess inflammation. The area percent for bax immune-expression in other immune stained sections were also measured done to assess apoptosis. Results: The difference between the groups was assessed for statistical significance (P<0.0001) by ANOVA test. The greatest mean number of filiform papillae was recorded in control group I. Greatest mean number of mast cells and the greatest mean area percent of bax immune expression were recorded in group II. Conclusion: Grape seed extract and Physalis extract could neutralize the harmful effect of cancer therapy. Physalis extract had more potent effect in reducing the inflammation induced by Cetuximab drug.

Keywords

Anti-inflammatory Effect, Cetuximab, Mucositis, Physalis peruviana

Subject Discipline

oral pathology / oral medecine

Full Text:

References

Nguyen A, Hoang V, Laquer V, Kelly KM. Angiogenesis in cutaneous disease: part I. Journal of the American Academy of Dermatology. 2009 Dec 1; 61(6):921–42. https://doi.org/10.1016/j.jaad.2009.05.052. PMid:19925924

Santuray RT, Johnson DE, Grandis JR. New therapies in head and neck cancer. Trends in Cancer. 2018 May 1; 4(5):385–96. https://doi.org/10.1016/j.trecan.2018.03.006. PMid:29709262. PMCid:PMC6226306

Bonner JA, Trummell HQ, Bonner AB, Willey CD, Bredel M, Yang ES. Enhancement of cetuximab-induced radiosensitization by JAK-1 inhibition. BMC Cancer. 2015 Oct 12; 15(1):673–775. https://doi.org/10.1186/s12885015-1679-x. PMid:26458879. PMCid:PMC4603644

Keefe DM, Gibson RJ. Mucosal injury from targeted anticancer therapy. Supportive Care in Cancer. 2007 May 1; 15(5):483–90. https://doi.org/10.1007/s00520-006-0181-z. PMid:17103195

Al-Ansari S, Zecha JA, Barasch A, de Lange J, Rozema FR, Raber-Durlacher JE. Oral mucositis induced by anticancer therapies. Current Oral Health Reports. 2015 Dec 1; 2(4):202–11. https://doi.org/10.1007/s40496-015-0069-4. PMid:26523246. PMCid:PMC4623065

da Cruz Campos MI, Neiva Campos C, Monteiro Aarestrup F, Aarestrup V, Julião B. Oral mucositis in cancer treatment: Natural history, prevention and treatment. Molecular and Clinical Oncology. 2014 May 1; 2(3):337–40. https://doi.org/10.3892/mco.2014.253. PMid:24772297. PMCid:PMC3999143

Al-Dasooqi N, Sonis ST, Bowen JM, Bateman E, Blijlevens N, Gibson RJ, et al. Emerging evidence on the pathobiology of mucositis. Supportive Care in Cancer. 2013 Jul 1; 21(7):2075–83. https://doi.org/10.1007/s00520-013-1810-y. PMid:23604521

Sonis ST. New thoughts on the initiation of mucositis. Oral Diseases. 2010 Oct; 16(7):597–600. https://doi.org/10.1111/ j.1601-0825.2010.01681.x. PMid:20846150

Al-Dasooqi N, Gibson RJ, Bowen JM, Logan RM, Stringer AM, Keefe DM. Matrix metalloproteinases are possible mediators for the development of alimentary tract mucositis in the dark agouti rat. Experimental Biology and Medicine. 2010 Oct; 235(10):1244–56. https://doi.org/10.1258/ebm.2010.010082. PMid:20682600

Gaje PN, AmaliaCeausu R, Jitariu A, Stratul SI, Rusu LC, Popovici RA, et al. Mast cells: Key players in the shadow in oral inflammation and in squamous cell carcinoma of the oral cavity. BioMed Research International. 2016; 2016. https://doi.org/10.1155/2016/9235080. PMid:27847826. PMCid:PMC5101369

Dražić R, Sopta J, Minić AJ. Mast cells in periapical lesions: potential role in their pathogenesis. Journal of Oral Pathology & Medicine. 2010 Mar; 39(3):257–62. https://doi.org/10.1111/j.1600-0714.2009.00870.x. PMid:20359310

Kabashima K, Nakashima C, Nonomura Y, Otsuka A, Cardamone C, Parente R, et al. Biomarkers for evaluation of mast cell and basophil activation. Immunological Reviews. 2018 Mar; 282(1):114–20. https://doi.org/10.1111/ imr.12639. PMid:29431209

Nogueira LT, Costa DV, Gomes AS, Martins CS, Silva AM, Coelho-Aguiar JM, et al. The involvement of mast cells in the irinotecan-induced enteric neurons loss and reactive gliosis. Journal of Neuroinflammation. 2017 Dec; 14(1):79. https://doi.org/10.1186/s12974-017-0854-1. PMid:28388962. PMCid:PMC5384042

Pfeffer CM, Singh AT. Apoptosis: A target for anticancer therapy. International Journal of Molecular Sciences. 2018 Feb; 19(2):448. https://doi.org/10.3390/ijms19020448. PMid:29393886. PMCid:PMC5855670

Hamad İ, Erol-Dayi Ö, Pekmez M, Önay-Uçar E, Arda N. Antioxidant and cytotoxic activities of Aphanesarvensisextracts. Plant Foods for Human Nutrition. 2010 Mar 1; 65(1):44–9. https://doi.org/10.1007/s11130009-0151-y. PMid:20108047

Çakir Ö, Pekmez M, Çepni E, Candar B, Fidan K. Evaluation of biological activities of Physalis peruviana ethanol extracts and expression of Bcl-2 genes in HeLa cells. Food Science and Technology. 2014 Jun; 34(2):422–30. https://doi.org/10.1590/fst.2014.0060

Talwar S, House R, Sundaramurthy S, Balasubramanian S, Yu H, Palanisamy V. Inhibition of caspases protects mice from radiation-induced oral mucositis and abolishes the cleavage of RNA-binding protein HuR. Journal of Biological Chemistry. 2014 Feb 7; 289(6):3487–500. https://doi.org/10.1074/jbc.M113.504951. PMid:24362034. PMCid:PMC3916550

Dewson G, Kluck RM. Mechanisms by which Bak and Baxpermeabilise mitochondria during apoptosis. Journal of Cell Science. 2009 Aug 15; 122(16):2801–8. https://doi.org/10.1242/jcs.038166. PMid:19795525. PMCid:PMC2736138

Tait SW, Green DR. Mitochondria and cell death: Outer membrane permeabilization and beyond. Nature Reviews Molecular Cell Biology. 2010 Sep; 11(9):621–32. https://doi.org/10.1038/nrm2952. PMid:20683470

Chang LC, Sang-ngern M, Pezzuto JM, Ma C. The Daniel K. Inouye College of Pharmacy Scripts: Poha berry (Physalis peruviana) with potential anti-inflammatory and cancer prevention activities. Hawai’i Journal of Medicine and Public Health. 2016 Nov; 75(11):353.

Yen CY, Hou MF, Yang ZW, Tang JY, Li KT, Huang HW, et al. Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. BMC Complementary and Alternative Medicine. 2015 Dec; 15(1):1–9. https://doi.org/10.1186/ s12906-015-0621-8. PMid:25880412. PMCid:PMC4393634

Georgiev V, Ananga A, Tsolova V. Recent advances and uses of grape flavonoids as nutraceuticals. Nutrients. 2014 Jan; 6(1):391–415. https://doi.org/10.3390/nu6010391. PMid:24451310. PMCid:PMC3916869

Procházková D, Boušová I, Wilhelmová N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia. 2011 Jun 1; 82(4):513–23. https://doi.org/10.1016/j.fitote.2011.01.018. PMid:21277359

Cheah KY, Bastian SE, Acott TM, Abimosleh SM, Lymn KA, Howarth GS. Grape seed extract reduces the severity of selected disease markers in the proximal colon of dextran sulphate sodium-induced colitis in rats. Digestive Diseases and Sciences. 2013 Apr 1; 58(4):970–7. https://doi.org/10.1007/s10620-012-2464-1. PMid:23143736

Cilla A, González-Sarrías A, Tomás-Barberán FA, Espín JC, Barberá R. Availability of polyphenols in fruit beverages subjected to in vitro gastrointestinal digestion and their effects on proliferation, cell-cycle and apoptosis in human colon cancer Caco-2 cells. Food Chemistry. 2009 Jun 1; 114(3):813–20. https://doi.org/10.1016/j.foodchem.2008.10.019

Nawirska-Olszańska A, Stępień B, Biesiada A, KolniakOstek J, Oziembłowski M. Rheological, chemical and physical characteristics of golden berry (Physalis peruviana L.) after convective and microwave drying. Foods. 2017 Aug; 6(8):60. https://doi.org/10.3390/foods6080060. PMid:28758918. PMCid:PMC5575635

Puente LA, Pinto-Muñoz CA, Castro ES, Cortés M. Physalis peruviana Linnaeus, the multiple properties of a highly functional fruit: A review. Food Research International. 2011 Aug 1; 44(7):1733–40. https://doi.org/10.1016/j.foodres.2010.09.034

Zhang YJ, Gan RY, Li S, Zhou Y, Li AN, Xu DP, Li HB. Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules. 2015 Dec; 20(12):21138– 56. https://doi.org/10.3390/molecules201219753. PMid:26633317. PMCid:PMC6331972

Mohammed ZH, Ibraheem RM. Anti-oxidant activity of methanol extracts of Arum maculatum L. and Physalis peruviana L. Plants. Ibn AL-Haitham Journal For Pure and Applied Science. 2017 Mar 13; 28(2):1–7.

Ahmed LA. Renoprotective effect of Egyptian cape gooseberry fruit (Physalis peruviana L.) against acute renal injury in rats. The Scientific World Journal. 2014; 2014. https://doi.org/10.1155/2014/273870.PMid:24757415. PMCid:PMC3976858

Kasali FM, Kadima JN, Mpiana PT, Tshibangu DS. Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guineapig. Asian Pacific Journal of Tropical Biomedicine. 2013 Nov 1; 3(11):841–6. https://doi.org/10.1016/S22211691(13)60166-5

Sasidharan S, Chen Y, Saravanan D, Sundram KM, Latha LY. Extraction, isolation and characterization of bioactive compounds from plants’ extracts. African Journal of Traditional, Complementary and Alternative Medicines. 2011; 8(1). https://doi.org/10.4314/ajtcam.v8i1.60483

Underwood W, Anthony R, Cartner S, Corey D, Grandin T, Greenacre C, et al. AVMA guidelines for the euthanasia of animals: 2013 edition. Schaumburg, IL: American Veterinary Medical Association. (Schaumburg, IL: JAVMA-J AM VET MED A, 2013 accessed on 20 September 2019)

Dai W, Li Y, Zhou Q, Xu Z, Sun C, Tan X, Lu L. Cetuximab inhibits oral squamous cell carcinoma invasion and metastasis via degradation of epidermal growth factor receptor. Journal of Oral Pathology and Medicine. 2014 Apr; 43(4):250–7. https://doi.org/10.1111/jop.12116. PMid:24020947

Valdenegro M, Fuentes L, Herrera R, Moya-León MA. Changes in antioxidant capacity during development and ripening of goldenberry (Physalis peruviana L.) fruit and in response to 1-methylcyclopropene treatment. Postharvest Biology and Technology. 2012 May 1; 67:110–7.

Sengupta P. A scientific review of age determination for a laboratory rat: How old is it in comparison with human age. BioMed Research International. 2011; 2(2):81–9. https:// doi.org/10.1016/j.postharvbio.2011.12.021

Poulopoulos A, Papadopoulos P, Andreadis D. Chemotherapy: Oral side effects and dental interventions. A review of the literature. Stomatological Disease and Science. 2017: 2573-0002. https://doi.org/10.20517/25730002.2017.03

Wu X, Chen P, Sonis ST, Lingen MW, Berger A, Toback FG. A novel peptide to treat oral mucositis blocks endothelial and epithelial cell apoptosis. International Journal of Radiation Oncology* Biology* Physics. 2012 Jul 1; 83(3):e409– 15. https://doi.org/10.1016/j.ijrobp.2012.01.006. PMid:22420966. PMCid:PMC3361587

Porcelli L, Iacobazzi RM, Quatrale AE, Bergamini C, Denora N, Crupi P, et al. Grape seed extracts modify the outcome of oxaliplatin in colon cancer cells by interfering with cellular mechanisms of drug cytotoxicity. Oncotarget. 2017 Aug 1; 8(31):50845. https://doi.org/10.18632/oncotarget.15139. PMid:28881609. PMCid:PMC5584210


Refbacks

  • There are currently no refbacks.