Effect of Hippophae rhamnoides Extract on Oxidative Oropharyngeal Mucosal Damage Induced in Rats Using Methotrexate
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objectives. The objective of this study is to investigate and evaluate the effect of Hippophae rhamnoides extract (HRE) on oropharyngeal mucositis induced in rats with methotrexate (MTX) through biochemical, gene expression, and histopathological examinations. Methods. Experimental animals were divided into a healthy group (HG), a HRE+MTX (HREM) group, HRE group (HREG), and a control group that received MTX (MTXG). The HREM and HREG groups of rats was administered 50 mg/kg HRE, while the MTXG and HG groups were given an equal volume distilled water with gavage. Then, the HREM and MTXG rat groups were given oral MTX at a dose of 5 mg/kg 1 hour after HRE and distilled water was administered. This procedure was repeated for 1 month. At the end of this period, all of the animals were sacrificed with a high dose of anesthesia. Then, the amounts of malondialdehyde (MDA) and total glutathione (tGSH) were determined in the removed oropharyngeal tissues. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) gene expressions were measured, and all the tissues were studied histopathologically. Results. The amount of MDA was significantly increased in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). MTX significantly decreased the amount of tGSH in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). In this study, there were no visible ulcers in the animal group in which the levels of MDA, IL-1β, and TNF-α were high and the level of tGSH was low. However, histopathologic examination revealed mucin pools in wide areas due to ruptured oropharynx glands, and proliferated, dilated, and congested blood vessels and dilated ductal structures in some areas. Conclusion. HRE protected oropharyngeal oxidative damage induced by MTX. As an inexpensive and natural product, HRE has important advantages in the prevention of oropharyngeal damage induced by MTX.
Abstract
Objectives. The objective of this study is to investigate and evaluate the effect of Hippophae rhamnoides extract (HRE) on oropharyngeal mucositis induced in rats with methotrexate (MTX) through biochemical, gene expression, and histopathological examinations. Methods. Experimental animals were divided into a healthy group (HG), a HRE+MTX (HREM) group, HRE group (HREG), and a control group that received MTX (MTXG). The HREM and HREG groups of rats was administered 50 mg/kg HRE, while the MTXG and HG groups were given an equal volume distilled water with gavage. Then, the HREM and MTXG rat groups were given oral MTX at a dose of 5 mg/kg 1 hour after HRE and distilled water was administered. This procedure was repeated for 1 month. At the end of this period, all of the animals were sacrificed with a high dose of anesthesia. Then, the amounts of malondialdehyde (MDA) and total glutathione (tGSH) were determined in the removed oropharyngeal tissues. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) gene expressions were measured, and all the tissues were studied histopathologically. Results. The amount of MDA was significantly increased in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). MTX significantly decreased the amount of tGSH in the MTXG group compared to the HREM, HREG, and HG groups (P<0.001). In this study, there were no visible ulcers in the animal group in which the levels of MDA, IL-1β, and TNF-α were high and the level of tGSH was low. However, histopathologic examination revealed mucin pools in wide areas due to ruptured oropharynx glands, and proliferated, dilated, and congested blood vessels and dilated ductal structures in some areas. Conclusion. HRE protected oropharyngeal oxidative damage induced by MTX. As an inexpensive and natural product, HRE has important advantages in the prevention of oropharyngeal damage induced by MTX.
참고문헌 (31)
- Kwong KK, "Prevention and treatment of oropharyngeal mucositis following cancer therapy: are there new approaches?", Cancer Nurs, 27(3), pp.183~205 (2004)
- Weisdorf DJ, "Oropharyngeal mucositis complicating bone marrow transplantation: prognostic factors and the effect of chlorhexidine mouth rinse", Bone Marrow Transplant, 4(1), pp.89~95 (1989)
- Sonis ST., "Mucositis: the impact, biology and therapeutic opportunities of oral mucositis", Oral Oncol, 45(12), pp.1015~1020 (2009)
- Scully C, "Oral mucositis: a challenging complication of radiotherapy, chemotherapy, and radiochemotherapy: part 1, pathogenesis and prophylaxis of mucositis", Head Neck, 25(12), pp.1057~1070 (2003)
- Ahmed KM., "The effect of olive leaf extract in decreasing the expression of two pro-inflammatory cytokines in patients receiving chemotherapy for cancer: a randomized clinical trial", Saudi Dent J, 25(4), pp.141~147 (2013)
- Mardani M, "Hydroalcoholic extract of Carum carvi L. in oral mucositis: a clinical trial in male golden hamsters", Oral Dis, 22(1), pp.39~45 (2016)
- de Araujo RF Jr, "Olmesartan decreased levels of IL-1β and TNF-α, down-regulated MMP-2, MMP-9, COX-2, RANK", RANKL and up-regulated SOCs-1 in an intestinal mucositis model, 2014, pp.9(12), e114923~
- Vokurka S., "Oropharyngeal mucositis: pain management", Klin Onkol, 24(4), pp.278~280 (2011)
- Epstein JB, "The role of salivary function in modulating chemotherapy-induced oropharyngeal mucositis: a review of the literature", Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 94(1), pp.39~44 (2002)
- Brown CG, "Stomatitis: an overview: protecting the oral cavity during cancer treatment", Am J Nurs, 102(Suppl 4), pp.20~23 (2002)
- Altindag O, "Intoxication due to high dose methotrexate in a patient with rheumatoid arthritis: a case report", Turk J Rheumatol, 26(1), pp.58~60 (2011)
- Vanhoecke B, "Dark Agouti rat model of chemotherapy-induced mucositis: establishment and current state of the art", Exp Biol Med (Maywood), 240(6), pp.725~741 (2015)
- Ilgenli T, "The acute effects of chemotherapy upon the oral cavity: prevention and management", Turk J Cancer, 31(3), pp.93~105 (2001)
- Jahovic N, "Amelioration of methotrexate-induced enteritis by melatonin in rats", Cell Biochem Funct, 22(3), pp.169~178 (2004)
- Alamir I, "Beneficial effects of cathepsin inhibition to prevent chemotherapy-induced intestinal mucositis", Clin Exp Immunol, 162(2), pp.298~305 (2010)
- Suleyman H, "Antiulcerogenic effect of Hippophae rhamnoides L", Phytother Res, 15(7), pp.625~627 (2001)
- Andersson SC, "Tocopherols and tocotrienols in sea buckthorn (Hippophae rhamnoides L.) berries during ripening", J Agric Food Chem, 56(15), pp.6701~6706 (2008)
- Kwon DJ, "Casuarinin suppresses TNF-α-induced ICAM-1 expression via blockade of NF-κB activation in HaCaT cells", Biochem Biophys Res Commun, 409(4), pp.780~785 (2011)
- Ohkawa H, "Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction", Anal Biochem, 95(2), pp.351~358 (1979)
- Sedlak J, "Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent", Anal Biochem, 25(1), pp.192~205 (1968)
- Kisaoglu A, "Tissue damage and oxidant", antioxidant balance, 2013, pp.45(1), 47~49
- Clarkson PM, "Antioxidants: what role do they play in physical activity and health?", Am J Clin Nutr, 72(2 Suppl), pp.637~646 (2000)
- Yeum KJ, "Biomarkers of antioxidant capacity in the hydrophilic and lipophilic compartments of human plasma", Arch Biochem Biophys, 430(1), pp.97~103 (2004)
- Aguilar A, "Antioxidant patterns (superoxide dismutase, glutathione reductase, and glutathione peroxidase) in kidneys from non-heart-beating-donors: experimental study", Transplant Proc, 39(1), pp.249~252 (2007)
- Cetinkaya A, "N-acetylcysteine ameliorates methotrexate-induced oxidative liver damage in rats", Med Sci Monit, 12(8), pp.BR274~BR278 (2006)
- Arslan A, "Protective effect of resveratrol against methotrexate-induced oxidative stress in the small intestinal tissues of rats", Int J Clin Exp Med, 8(7), pp.10491~10500 (2015)
- Logan RM, "Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered?", Cancer Chemother Pharmacol, 63(2), pp.239~251 (2009)
- de Araujo AA, "In a methotrexate-induced model of intestinal mucositis, olmesartan reduced inflammation and induced enteropathy characterized by severe diarrhea, weight loss, and reduced sucrose activity", Biol Pharm Bull, 38(5), pp.746~752 (2015)
- Mills EE., "The modifying effect of beta-carotene on radiation and chemotherapy induced oral mucositis", Br J Cancer, 57(4), pp.416~417 (1988)
- Yilmaz I, "The effect of hippophae rhamnoides extract on oxidative damage on rat’s gastric tissue depending on co-implementation of methotrexate and indomethacin", Lat Am J Pharm, 33(3), pp.453~458 (2014)
- Suryakumar G, "Medicinal and therapeutic potential of Sea buckthorn (Hippophae rhamnoides L.)", J Ethnopharmacol, 138(2), pp.268~278 (2011)