Objective: To investigate the protective and curative effect of silymarin against fluoride-induced hepatotoxity and oxidative degradation in rats. Material and Methods: Of the 45 rats, 9 were given only sodium fluoride (F); 9 were given only silymarin (S), 9 were given only tap water (K), 9 were given sodium fluoride and silymarin together (FS) and 9 were given silymarin after sodium fluoride was completed (T). Results: In Group F, serum AST level was significantly higher than in control group (p<0.001) and in Group FS and group T, serum AST and ALT levels were lower than in Group F, which was evaluated as improved toxic effect of sodium fluoride by silymarin. When compared with the control group; in Group F, a decrease in serum SOD and GSH-Px values and an increase in MDA levels showed oxidative deterioration in liver tissue; high SOD and GSHPx levels and low MDA levels in Group S and Group T showed that silymarin prevents and improves tissue damage.Histopathological significant differences were found between Group F, Group S and Group T in terms of deterioration in remak cords (p<0.01 p=0,007). In addition, there was a significant difference between Group F, Group T and Group FS in terms of degenerative changes (p<0.001). Conclusion: It was concluded that sodium fluoride has toxic and destructive effects on liver tissue and silymarin has a protective and healing effect against these effects.
Keywords: Liver function tests; silymarin; sodium fluoride
Amaç: Silimarinin sıçanlarda florür kaynaklı hepatotoksite ve oksidatif bozunmaya karşı koruyucu ve iyileştirici etkisini araştırmak amaçlandı.Gereç ve Yöntemler: Çalışmada kullanılan 45 ratın, 9'una sadece NaF (F); 9'una sadece silimarin (S), 9'una sadece çeşme suyu (K), 9'una NaF ve silimarin birlikte (FS) ve 9'una, NaF verilmesi tamamlandıktan sonra, silimarin (T) verildi. Bulgular: Grup F'de, serum AST düzeyinin kontrol grubuna göre önemli düzeyde yüksek (p<0,001) ve Grup FS'de ve Grup T'de, serum AST ve ALT düzeylerinin F grubuna göre düşük olması bulguları", sodyum floridin karaciğer dokusuna olan toksik etkisi ve buna karşı silimarinin koruyucu ve iyileştirici etkisi olarak değerlendirildi. Bu sonucun histopatolojik olarakta desteklendiği görüldü. Kontrol grubuyla yapılan karşılaştırmalarda; karaciğer dokusunda Grup F'de, SOD ve GSH-Px değerlerindeki düşüş ve MDA düzeyindeki artış karaciğer dokusundaki oksidatif yıkımı gösterirken; Grup FS'de ve Grup T'de SOD ve GSH-Px düzeylerinin yüksek, MDA düzeylerinin düşük bulunması, silimarinin oksidatif doku yıkımını önlediği ve bunu iyileştirdiğinin göstergesi oldu. Histopatolojik olarak remakerlerde bozulma açısından Grup F, Grup S ve Grup T arasında anlamlı fark bulundu (p<0,01 p=0,007). Ayrıca, Grup F, Grup T ve Grup FS arasında dejeneratif değişiklikler açısından anlamlı fark vardı. Sonuç: Bu çalışmada; sodyum floridin karaciğer dokusuna toksik ve yıkılmayıcı etki yaptığı; bu etkilere karşı silimarin'in koruyucu ve iyileştirici etkisinin olduğu sonucuna varıldı.
Anahtar Kelimeler: Karaciğer fonksiyon testleri; silymarin; sodyum florid
- Barbier O, Arreola-Mendoza L, Del Razo LM. Molecular mechanisms of fluoride toxicity. Chem Biol Interact. 2010;188(2):319-33.[Crossref] [PubMed]
- Ergun HS, Rüssel-Sinn HA, Baysu N, Dündar Y. Studies on the fluoride contents in water and soil, urine, bone and teeth of sleep, and urine of human from eastern and western parts of Turkey. Dtsch Tierarztl Wochenschr. 1987;94(7):416-20.[PubMed]
- Tokatlıoğlu Ş, Kartal Ş, Uğur Ş. Determination of fluoride in various samples and some infusions using a fluoride selective electrode. Türk J Chem. 2004;28(2):203-11.
- Radositits O, Gay C, Hincliff K, Constable P. Disease associated with inorganic and farm chemicals. In: Radostits O, Gay C, Hinchcliff K, Constable P, eds. Vetrinary Medicine, A textbook of the disease of cattle, horse, sheep, gigs and goats. Saunders Ltd; 10th ed. 2006. p.1815-9.
- Urbansky ET. Fate of fluorosilicate drinking water additives. Chem Rev. 2002;102(8):2837-54.[Crossref] [PubMed]
- Şentut T, Kırzıoğlu Z, Gökçimen A, Aslan H, Erdoğan Y. Quantitative analysis of odontoblast cells in fl uorotic and nonfl uorotic primary tooth pulp. Turk J Med Sci. 2012; 42,(2):351-7.[Link]
- Grandjean P, Olsen JH. Extended follow-up of cancer incidence in fluoride-exposed workers. J Natl Cancer Inst. 2004;96(10):802-3.[Crossref] [PubMed]
- He L, Chen JG. DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes. World J Gastroenterol. 2006;12(7):1144-8.[Crossref] [PubMed] [PMC]
- Zhang Z, Zhou B, Wang H, Wang F, Song Y, Liu S, et al. Maize purple plant pigment protects against fluoride-induced oxidative damage of liver and kidney in rats. Int J Environ Res Public Health. 2014;11(1):1020-33.[Crossref] [PubMed] [PMC]
- Efe U, Dede S, Yüksek V, Çetin, S. Apoptotic and Oxidative Mechanisms in Liver and Kidney Tissues of Sheep with Fluorosis. Biol Trace Elem Res. 2020.[Crossref] [PubMed]
- Agalakova NI, Gusev GP. Molecular mechanisms of cytotoxicity and apoptosis induced by inorganic fluoride. ISRN Cell Biol. 2012;1-16.[Crossref]
- Song GH, Gao JP, Wang CF, Chen CY, Yan XY, Guo M, et al. Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated pathways and DNA damage. J Physiol Biochem. 2014;70(3):857-68.[Crossref] [PubMed]
- Liu J, Cui H, Peng X, Fang J, Zuo Z, Wang H, et al. Dietary high fluorine induces apoptosis and alters Bcl-2, Bax, and caspase-3 protein expression in the cecal tonsil lymphocytes of broilers. Biol Trace Elem Res. 2013;152(1):25-30.[Crossref] [PubMed]
- Kanagaraj VV, Panneerselvam L, Govindarajan V, Ameeramja J, Perumal E. Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in rats: A possible mechanism. Biofactors. 2015;41(2):90-100.[Crossref] [PubMed]
- Bouasla A, Bouasla I, Boumendjel A, El Feki A, Messarah M. Hepatoprotective role of gallic acid on sodium fluoride-induced liver injury in rats. Int J Pharm Sci Rev Res. 2014;29(2):14-8. Erişim Tarihi: 01.06.2019[Link]
- Thangapandiyan S, Miltonprabu S. Epigallocatechin gallate effectively ameliorates fluoride-induced oxidative stress and DNA damage in the liver of rats. Can J Physiol Pharmacol. 2013;91(7):528-53.[Crossref] [PubMed]
- Ekambaram P, Namitha T, Bhuvaneswari S, Aruljothi S, Vasanth D, Saravanakumar M. Therapeutic efficacy of tamarindus indica (l) to protect against fluoride-induced oxidative stress in the liver of female rats. Fluoride. 2010;43(2):134-40. Erişim Tarihi: 01.06.2019[Link]
- Atmaca N, Atmaca HT, Kanici A, Anteplioglu T. Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity in rats. Food Chem Toxicol. 2014;70:191-7.[Crossref] [PubMed]
- Chouhan S, Flora SJ. Effects of fluoride on the tissue oxidative stress and apoptosis in rats: biochemical assays supported by IR spectroscopy data. Toxicology. 2008;254(1-2):61-7.[Crossref] [PubMed]
- Chouhan S, Lomash V, Flora SJ. Fluoride-induced changes in haem biosynthesis pathway, neurological variables and tissue histopathology of rats. J Appl Toxicol. 2010;30(1):63-73.[Crossref] [PubMed]
- Prabu K, Kanchana N, Sadıq AM. Hepatoprotective effect of Eclipta alba on paracetamol induced liver toxicity in rats. JMBR. 2017;1(3):75-9.[Link]
- Sabiu S, Sunmonu T.O, Ajani E.O, Ajiboye T.O. Combined administration of silimarin and vitamin C stalls acetaminophen-mediated hepatic oxidative insults in Wistar rats. Rev Bras Farmacogn. 2015;25(1):29-34.[Crossref]
- Cecen E, Dost T, Culhaci N, Karul A, Ergur B, Birincioglu M. Protective effects of silymarin against doxorubicin-induced toxicity. Asian Pac J Cancer Prev. 2011;12(10):2697-704.[PubMed]
- Kazemifar AM, Hajaghamohammadi AA, Samimi R, Alavi Z, Abbasi E, Asl MN. Hepatoprotective property of oral silimarin is comparable to n-acetyl cysteine in acetaminophen poisoning. Gastroenterology Research. 2012;(5):190-4.[Crossref] [PubMed] [PMC]
- Yaman D, Atasever A. [The Effects of Rosemary Extract (Rosmarinus officinalis) on Carbon Tetrachloride Induced Acute and Chronic Hepatic Damage]. Erciyes Üniv Vet Fak Derg. 2016;13(2):83-100.
- Surai PF. Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives. Antioxidants (Basel). 2015;4(1):204-47.[Crossref] [PubMed] [PMC]
- Abascal K, Yarnell E. The many faces of silibum marianum (milk thistle): Part 2-Clinical Uses, Safety, and Types of Preparations. Alt Comp Ther. 2003;9(5):251-6.[Crossref]
- Vargas-Mendoza N, Madrigal-Santillán E, Morales-González A, Esquivel-Soto J, Esquivel-Chirino C, García-Luna Y, et al. Hepatoprotective effect of silymarin. World J Hepatol. 2014;6(3):144-9.[Crossref] [PubMed] [PMC]
- Cetinkunar S, Tokgoz S, Bilgin BC, Erdem H, Aktimur R, Can S, et al. The effect of silymarin on hepatic regeneration after partial hepatectomy: is silymarin effective in hepatic regeneration? Int J Clin Exp Med. 2015;8(2):2578-85.[PubMed] [PMC]
- Fantozzi R, Brunelleschi S, Rubino A, Tarli S, Masini E, Mannaioni PF. FMLP-activated neutrophils evoke histamine release from mast cells. Agents Actions. 1986;18(1-2):155-8.[Crossref] [PubMed]
- Alaca N, Özbeyli D, Uslu S, Şahin HH, Yiğittürk G, Kurtel H, et al. Treatment with milk thistle extract (Silybum marianum), ursodeoxycholic acid, or their combination attenuates cholestatic liver injury in rats: Role of the hepatic stem cells. Turk J Gastroenterol. 2017;28(6):476-484.[Crossref] [PubMed]
- Esmaeil N, Anaraki SB, Gharagozloo M, Moayedi B. Silymarin impacts on immune system as an immunomodulator: One key for many locks. Int Immunopharmacol. 2017;50:194-201.[Crossref] [PubMed]
- Jeong DH, Lee GP, Jeong WI, Do SH, Yang HJ, Yuan DW, et al. Alterations of mast cells and TGF-beta1 on the silymarin treatment for CCl(4)-induced hepatic fibrosis. World J Gastroenterol. 2005;11(8):1141-8.[Crossref] [PubMed] [PMC]
- Perera T, Ranasinghe S, Alles N, Waduge R. Effect of fluoride on major organs with the different time of exposure in rats. Environ Health Prev Med. 2018;23(1):17.[Crossref] [PubMed] [PMC]
- Iheka CU, Onyegeme-Okerenta BM, Anacletus FC. Impact of fluoride Toxicity and Ameliorative Effects of Some Antioxidants on Selected Biochemical Indices of Male Rats. AASCIT Journal of Health. 2015;2(6):87-92. Erişim Tarihi: 01.06.2019[Link]
- Emejulu AA, Alisi CS, Asiwe ES, Igwe CU, Nwogu LA, Onwuliri VA. Renal and hepato-protective effects of ırvingia gabonensis juice on sodium fluoride-ınduced toxicity in wistar rats. J Clin Toxicol. 2016;6(2):1-6.[Crossref]
- Iano FG, Ferreira MC, Quaggio GB, Fernandes MS, Oliveira RC, Ximenes VF, et. al. Effects of chronic fluoride intake on the antioxidant systems of the liver and kidney in rats. J Fluor Chem. 2014;168:212-17. Erişim Tarihi: 01.06.2019[Crossref]
- Vasant .A, Narasimhacharya A. Amelioration of fluoride induced oxidative stress by Mangifera indica L. fruit. Spatula DD. 2011;4:181-88.[Crossref]
- Afolabi OK, Oyewo EB, Adekunle AS, Adedosu OT, Adedeji AL. Oxidative indices correlate with dyslipidemia and pro-inflammatory cytokine levels in fluoride-exposed rats. Arh Hig Rada Toksikol. 2013;64(4):521-9.[Crossref] [PubMed]
- Edwards AA, Lloyd DC, Purrott RJ. Dicentric chromosome aberration yield in human lymphocytes and radiation quality: a resume including recent results using alpha-particles. In: Booz J, Ebert HG, Hartfield HD, eds. Seventh Symposium on Microdosimetry. Chur: Harwood Academic Publishers; 1980. vol. 2. p.1263-73.
- Samanta A, Bandyopadhyay B, Das N. Fluoride intoxication and possible changes in mitochondrial membrane microviscosity and organ histology in rats. IJSR. 2016;5(6):42-5.[Link]
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