Sıçanlarda Akciğer Doku Yağ Asit Düzeyleri Üzerinde Kobalt Ve Silibinin Etkileri

Year 2024, Volume: 11 Issue: 3, 807 - 814, 24.07.2024

H. Turan Akkoyun

https://doi.org/10.30910/turkjans.1483278

Abstract

Çalışmada kobalt ve önemli bir flavonoid olan silibin uygulanan sıçanlarda akciğer dokusunun yağ asit içeriğindeki değişimlerin belirlenmesi amaçlandı. 250±300 gr ağırlığında Wistar Albino cinsi 24 sıçan Control(0.5 mL,i.pizotonik), Kobalt(150 mg/kg/gün/oral), Silibinin(100 mg/kg/gün/oral), Kobalt+Silibinin(150 mg/kg/gün+100 mg/kg/gün/oral) olarak 4 gruba ayrıldı. Doku yağ asit analizleri GC kullanılarak gerçekleştirildi. Yağ asitleri analiz sonuçları incelendiğinde, Kontrole kıyasla genel olarak bütün gruplarda doymuş yağ asit düzeylerinde azalma gözlenirken (p>0,05, p<0,01), 16:1 n-7,18:1 n-7,18:1 n-9,18:2 n-6c,18:3 n-3, gibi doymamış yağ asitlerinde kontrole oranla kobalt uygulanan grupta artış, 15:1, 17:1, 22:5 n3, 22:6 n3 ise azalmalar tespit edildi. Silibin uygulanan grupta ise kontrole kıyasla 15:1, 17:1, 18:1 n-9, 20:4 n:6, 22:5 n3, 22:6 n:3, 20:4 n:6 yağ asitlerinde azalmalar belirlenirken bu azalmalardan bazılarının istatistiksel olarak anlamlı olduğu görüldü(p<0.01, p<0.05). Kobalt uygulanan gruba kıyasla; Kobalt+Silibinin uygulanan grupta, 24:0 yağ asit'i hariç diğer tüm doymuş yağ asitlerine (14:0, 15:0, 16:0, 17:0, 17:1, 18:0) kısmi artışlar, bütün tekli doymamış yağ asitlerinde(15:1, 16:1 n-7, 18:1 n-7, 18:1, n-9) değişen oranlarda belirgin artışlar (p<0,01, p<0,05, p<0,001) tespit edildi. Çoklu doymamış yağ asitleri kobalta kıyasla yine Kobalt +Silibinin grubunda; 18:2 n-6c yağ asidi dışındaki tüm çoklu doymamış yağ asitlerinde (18:3 n-3, 20:4 n6, 22:5 n3, 22:6 n3) belirgin artışlar tesbit edildi(p<0.05, p<0.001). Sonuç olarak; Kobalt toksisitesine karşı Silibinin uygulanan sıçan akciğer yağ asit profilini belirlemek üzere yapılan çalışmada; doymuş yağ asidi miktarlarının kontrole oranla, kobalt grubunda azalma göstermesinin bir hasar göstergesi olabileceği düşünülmektedir. Yine kobalt grubunda bazı doymamış yağ asitlerinin artış göstermesinin nedeni olduğunu düşündüğümüz yağ asidi sentezi-enzim aktivitesinin, ileri düzeyde çalışmalarla aydınlatılması gerekmektedir.

Keywords

Kobalt, silibinin, sıçan, yağ asidi

Effects Of Cobalt And Silibin On Lung Tissue Fatty Acid Levels In Rats

Abstract

The study aimed to determine the changes in the fatty acid content of lung tissue in rats administered cobalt and silybin, an important flavonoid. 24 Wistar Albino rats weighing 250±300 g, Control (0.5 mL, i.pisotonic), Cobalt(150mg/kg/day/oral), Silibinin(100mg/kg/day/oral), Cobalt+Silibinin(150mg/kg/day+100 mg/kg/day/oral) were divided into 4 groups. Tissue fatty acid analyzes were performed using GC. When the fatty acid analysis results were examined, a decrease in saturated fatty acid levels was observed in all groups compared to the control (p>0.05, p<0.01). There was an increase in unsaturated fatty acids such as 16:1 n-7,18:1 n-7,18:1 n-9,18:2 n-6c,18:3 n-3, in the cobalt applied group compared to the control. Decreases were detected in 15:1, 17:1, 22:5 n3, 22:6 n3. In the silybin applied group, decreases were determined in 15:1, 17:1, 18:1 n-9, 20:4 n:6, 22:5 n3, 22:6 n:3, 20:4 n:6 fatty acids compared to the control. Some of these decreases were found to be statistically significant (p<0.01, p<0.05). Compared to the cobalt applied group; In the Cobalt + Silibinin applied group, partial increases in all saturated fatty acids (14:0, 15:0, 16:0, 17:0, 18:0) except 24:0 fatty acid, all monounsaturated fatty acids were increased. Significant increases in fatty acids (15:1, 16:1 n-7, 18:1 n-7, 18:1, n-9) at varying rates (p<0.05, p<0.001) detected. Compared to cobalt, polyunsaturated fatty acids are again in the Cobalt + Silibinin group; Significant increases (p<0.05, p<0.001, p<0,01) were detected in all polyunsaturated fatty acids (18:3 n-3, 20:4 n6, 22:5 n3, 22:6 n3) except 18:2 n-6c fatty acid.
In conclusion; In the study conducted to determine the lung fatty acid profile of rats administered Silibinin against cobalt toxicity; It is thought that the decrease in the amount of saturated fatty acids in the cobalt group compared to the control may be an indicator of damage. Again, fatty acid synthesis, which we think is the reason for the increase in some unsaturated fatty acids in the cobalt group.

Keywords

Cobalt, silibinin, rat, fatty acid

References

• Adam, C., Garnier-Laplace, J. 2003. Bioaccumulation of silver-110m, cobalt-60, cesium- 137, and manganese-54 by the freshwater algae Scenedesmus obliquus and Cyclotella meneghiana and by suspended matter collected during a summer bloom event. Limnol. Oceanogr. 48, 2303–2313.
• Akkuş, İ. 1995. Serbest Radikaller ve Fizyopatolojik Etkileri, Mimoza Yayınları, Konya.
• Amirsaadat, S., Pilehvar-Soltanahmadi, Y., Zarghami, F., Alipour, S., Ebrahimnezhad, Z., & Zarghami, N. (2017). Silibinin-loaded magnetic nanoparticles inhibit hTERT gene expression and proliferation of lung cancer cells. Artificial cells, nanomedicine, and biotechnology, 45(8), 1649-1656.
• Aydın S. 2012. Antioxidant Capacities Of Mulberry, Cranberry, Cherry And Walnut Fruits That Are Grown In Elazig Region, And The Examination Of Their Effects On Oxidative Stress In Some Experimental Models, dissertation PHD, Fırat University, Turkey.
• Beydilli, H., Yilmaz, N., Cetin, E. S., Topal, Y., Celik, O. I., Sahin, C., Topal, H., Cigerci, I. H., Sozen, H. Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free-radical damage in rat liver. Iranian Red Crescent medical journal.2015; 17(4): e25310.
• Biedermann, D., Vavříková, E., Cvak, L., & Křen, V. (2014). Chemistry of silybin. Natural product reports, 31(9), 1138-1157.
• Chhabra, N., Buzarbaruah, S., Singh, R., Kaur, J. (2013). Silibinin: A promising anti-neoplastic agent for the future? A critical reappraisal. International Journal of Nutrition, Pharmacology, Neurological Diseases, 3(3), 206.
• Christie WW (1990) Gas chromatography and lipids, The Oil Pres, Glaskow.
• Christie WW (1992) Preparation of fatty acid methyl esters. Inform 3: 1031–1034.
• Cristofalo R., Bannwart-Castro C.F., Magalhaes C.G., Borges V.T., Peracoli J.C., Witkin S.S., et al. (2013). Silibinin attenuates oxidative metabolism and cytokine production by monocytes from preeclamptic women, Free Radic. Res. 47, 268e275.
• Demir E, Yılmaz Ö (2014). The effects of bitter almond oil on some biochemical parameters in serum and erythrocytes of streptozotocin-induced Type-1 diabetic rats. Marmara Pharm J 18: 13-21.
• Dereń, K., Bienkiewicz, M., Styczyńska, M., Olejnik, P., & Bronkowska, M. (2021). Assessment Of The Content Of Chromıum, Nıckel And Cobalt In Chocolate Products Wıth Dıfferent Cocoa Mass Content Avaılable On The Polısh Market. Journal of Elementology, 26(3).
• De Groot, H., Rauen, U., 1998. Tissue injury by reactive oxygen species and the protective effects of flavonoids. Fundamental and Clinical Pharmacology 12, 249–255.
• Dos Reis L.L., Alho L.D.O.G., de Abreu C.B., Melao M.D.G.G. Using multiple endpoints to assess the toxicity of cadmium and cobalt for chlorophycean Raphidocelis subcapitata. Ecotoxicol. Environ. Saf. 2021;208:111628.
• Essid E., Dernawi Y., Petzinger E. (2012). Apoptosis induction by OTA and TNF-alpha in cultured primary rat hepatocytes and prevention by silibinin, Toxins 4 (2012) 1139e1156.
• Flora K., Hahn M., Rosen H., Benner K. (1998). Milk thistle (Silybum marianum) for the therapy of liver disease, Am. J. Gastroenterol. 93, 139e143
• Frutos P, Toral PG, Ramos-Morales E, Shingfield KJ, Belenguer A, Hervas G. Oral administration of cobalt acetate alters milk fatty acid composition, consistent with an inhibition of stearoyl-coenzyme A desaturase in lactating ewes. J Dairy Sci 2014;97:1036–46.
• Giorgi V.S., Peracoli M.T., Peracoli J.C., Witkin S.S., Bannwart-Castro C.F.(2012). Silibinin modulates the NF-kappab pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women, J. Reprod. Immunol. 95, 67e72.
• Grattagliano, I., Diogo, C.V., Mastrodonato, M., de Bari, O., Persichella, M., Wang, D.Q., Liquori, A., Ferri, D., Carratu, M.R., Oliveira, P.J., Portincasa, P., 2013. A silybinphospholipids complex counteracts rat fatty liver degeneration and mitochondrial oxidative changes. World J. Gastroenterol.: WJG 19, 3007–3017.
• Gutteridge, J.M.C. 1995. Lipid peroxidation and antioxidants as biomarkers of tissue damage, Clin Chem, 41, 1819-1828.
• Haddad, Y., Vallerand, D., Brault, A., Haddad, P.S., 2011. Antioxidant and hepatoprotective effects of silibinin in a rat model of nonalcoholic steatohepatitis. Evidence-based complementary and alternative medicine: eCAM 2011, nep164.
• Halliwell, B. 1996. Oxidative stress, nutrition and health. Experimental strategies for optimization of nutritional antioxidant intake in humans, Free Radic Res., 25, 57–74.
• Huseini, H.F., Larijani, B., Heshmat, R., Fakhrzadeh, H., Radjabipour, B., Toliat, T., Raza, M., 2006. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother. Res.: PTR 20, 1036–1039.
• Jomova, K. ve Valko, M. (2011). Advances in metal-induced oxidative stress and human disease, Toxicology 283 (2–3) (2011) 65–87.
• Karlengen IJ, Taugbøl O, Salbu B, Aastveit AH, Harstad OM. Effect of different levels of supplied cobalt on the fatty acid composition of bovine milk. Br J Nutr 2013;109:834–43.
• Kaur, M., Deep, G., Agarwal, R. (2009). Silibinin in skin health: efficacy and mechanism of action. Nutritional Cosmetics, Elsevier, 2009, pp. 501–528.
• Kiruthiga, P. V., Pandian, S. K., & Devi, K. P. (2010). Silymarin protects PBMC against B (a) P induced toxicity by replenishing redox status and modulating glutathione metabolizing enzymes—an in vitro study. Toxicology and applied pharmacology, 247(2), 116-128.
• Křen, V., & Walterova, D. (2005). Silybin and silymarin-new effects and applications. Biomedical Papers, 149(1), 29-41.
• Karlengen IJ, Harstad OM, Kjos NP, Salbu B, Aastveit AH, Taugbøl O. Cobalt reduces the D9-desaturase index of sow milk. J Anim Physiol Anim Nutr (Berl) 2011;95:676–84.
• Kumar, R., Deep, G., Agarwal, R. (2015). An overview of ultraviolet B radiation-induced skin cancer chemoprevention by silibinin, Curr. Pharmacol. Rep. 1 (3): 206–215.
• Jancova, P., Anzenbacherova, E., Papouskova, B., Lemr, K., Luzna, P., Veinlichova, A., Anzenbacher, P., Simanek, V. (2007). Silybin is metabolized by cytochrome P450 2C8 in vitro. Drug Metab. Dispos. 35, 2035–2039.
• Li Y., Xiong B., , Miao Y., Gao Q. (2023). Silibinin supplementation ameliorates the toxic effects of butyl benzyl phthalate on porcine oocytes by eliminating oxidative stress and autophagy. Environmental Pollution 329, 121734. Mateen S, Tyagi A, Agarwal C, Singh RP, Agarwal R. 2010. Silibinin inhibits human nonsmall cell lung cancer cell growth through cell‐cycle arrest by modulating expression and function of key cell‐cycle regulators. Mol Carcinog. 49:58–247.
• Mohammadi, M., Ariafar, S., Talebi-Ghane, E., Afzali, S., 2022. Comparative efficacy of silibinin and nano-silibinin on lead poisoning in male Wistar rats. Toxicology. 475, 153242 .
• Musazadeh, V., Karimi, A., Jafarzadeh, J., Sanaei, S., Vajdi, M., & Niazkar, H. R. (2022). The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms. Biomedicine & Pharmacotherapy, 113593.
• Nejati-Koshki K, Zarghami N, Pourhassan-Moghaddam M, Rahmati Yamchi M, Mollazade M, Nasiri M, et al. 2012. Inhibition of leptin gene expression and secretion by silibinin: possible role of estrogen receptors. Cytotechnology. 64:719–726.
• Salcan I, Dilber M, Bayram R, Suleyman E, Erhan E, Karahan Yilmaz S, Yazici G.N, Coban A, Suleyman H. Effect of Taxifolin on Cobalt-induced Ototoxicity in Rats: A Biochemical and Histopathological Study. International Journal of Pharmacology,2000; 16: 522-528.
• Salimi-Sabour E., Tahri R.A., Asgari A., Ghorbani M. (2023). The novel hepatoprotective effects of silibinin-loaded nanostructured lipid carriers against diazinon-induced liver injuries in male mice. Pesticide Biochemistry and Physiology 197 (2023) 105643
• Saxena, N., Dhaked, R.K., Nagar, D.P., 2022. Silibinin ameliorates abrin induced hepatotoxicity by attenuating oxidative stress, inflammation and inhibiting Fas pathway. Environ. Toxicol. Pharmacol. 93, 103868 .
• Shingfield KJ,A¨ ro¨ la¨ A, Ahvenja¨ rvi S, Vanhatalo A, Toivonen V, Griinari JM, Huhtanen P. Ruminal infusions of cobalt-EDTA reduce mammary D9-desaturase index and alter milk fatty acid composition in lactating cows. J Nutr 2008;138:710–7.
• Singh, R.P., Agarwal, R. (2005). Mechanisms and preclinical efficacy of silibinin in preventing skin cancer. Eur. J. Cancer 41, 1969–1979.
• Song, X.Y., Liu, P.C., Liu, W.W., Zhou, J., Hayashi, T., Mizuno, K., Hattori, S., Fujisaki, H., Ikejima, T., 2022. Silibinin inhibits ethanol- or acetaldehyde-induced ferroptosis in liver cell lines. Toxicol. in Vitro 82, 105388.
• Surai PF 2015. Silymarin as a natural antioxidant: an overview of the current evidence and perspectives. Antioxidants (Basel). 4:204–247.
• Taugbøl O, Karlengen IJ, Bolstad T, Aastveit AH, Harstad OM. Cobalt supplied per os reduces the mammary D9-desaturase index of bovine milk. J Anim Sci 2008;86:3062–8.
• Taugbøl O, Karlengen IJ, Salbu B, Aastveit AH, Harstad OM. Intravenous injections of cobalt reduce fatty acid desaturation products in milk and blood of lactating cows. J Anim Physiol Anim Nutr (Berl) 2010;94:635–40.
• Taylor A., Marks V. (1978). Cobalt: A review. Journal of Human Nutrition, 32, 165-177.
• Triantafyllou, A., Liakos, P., Tsakalof, A., Georgatsou, E., Simos, G., Bonanou, S. (2006) Cobalt induces hypoxia-inducible factor-1α (HIF-1α) in HeLa cells by an iron-independent, but ROS-, PI-3K-and MAPK-dependent mechanism, Free Radic. Res. 40 (8) (2006) 847–856.
• Tvrzicka E, Vecka M, Stankova Zak A (2002) Analysis of fatty acids inplasma lipoproteins by gas chromatography flame ionisation detection Quantative aspects. Anal Chim Acta 465: 337-350.
• Watanabe, C. H., Monteiro, A. S. C., Gontijo, E. S. J., Lira, V. S., de Castro Bueno, C., Kumar, N. T., Rosa, A. H. (2017). Toxicity assessment of arsenic and cobalt in the presence of aquatic humic substances of different molecular sizes. Ecotoxicology and environmental safety, 139, 1-8.
• Victorrajmohan, C., Pradeep, K., Karthikeyan, S., 2005. Influence of silymarin administration on hepatic glutathione-conjugating enzyme system in rats treated with antitubercular drugs. Drugs in R&D 6, 395–400.
• Yan, Y., Wang, Y., Tan, Q., Lubet, R. A., You, M. (2005). Efficacy of deguelin and silibinin on benzo (a) pyrene-induced lung tumorigenesis in A/J mice. Neoplasia, 7(12), 1053-1057.
• Yao, J., Zhi, M., Minhu, C., 2011. Effect of silybin on high-fat-induced fatty liver in rats. Braz. J. Med. Biol. Res. 44, 652–659.
• Yao, J., Zhi, M., Gao, X., Hu, P., Li, C., Yang, X., 2013. Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with nonalcoholic fatty liver. Braz. J. Med. Biol. Res. 46, 270–277.
• Zhao, G., Ye, S., Yuan, H., Ding, X., Wang, J., 2017. Surface sediment properties and heavy metal pollution assessment in the Pearl River Estuary, China. Environ. Sci. Pollut. Res. 24, 2966–2979.