Yıl 2020, Cilt 8 , Sayı 1, Sayfalar 546 - 553 2020-01-31

Sıçanlarda 2,3,7,8-Tetraklorodibenzo-P-Dioksin (TCDD) 'nin Neden Olduğu Hepatoksisite ve Nefrotoksisite Üzerine Protokateşik Asitin (PCA) Rolü
Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats

Ahmet SAVCI [1] , İlknur ÖZDEMİR [2]


En toksik dioksin bileşiklerinden biri olan TCDD'nin insan ve hayvan dokularında serbest radikal oluşturarak oksidatif hasara neden olduğu bilinmektedir. Bu çalışmada, TCDD tarafından toksisite oluşturulan sıçan karaciğeri ve böbreğinde önemli bir fenolik bileşik olan PCA’nın koruyucu etkileri araştırıldı. Bu amaçla 28 adet Wistar Albino cinsi sıçanlar (3-4 aylık ve 280-310 g ağırlığında) kullanıldı. Sıçanlar kontrol, TCDD, PCA ve TCDD + PCA olmak üzere rastgele 4 eşit gruba ayrıldı. TCDD ve PCA mısır yağı içinde çözüldü ve sırasıyla 2 µg / kg ve 100 mg / kg dozunda 45 gün boyunca gavaj yolu ile sıçanlara uygulandı. Çalışmanın sonunda TCDD'nin malondialdehit (MDA) seviyesini arttırdığı, ancak glutatyon (GSH) seviyesini ve süperoksit dismutaz (SOD), katalaz (CAT) ve glutatyon peroksidaz (GSH Px) aktivitelerini azalttığı gözlendi. PCA uygulamasının TCDD'nin aksine enzim aktivitelerini ve GSH seviyelerini arttırdığı ve MDA seviyelerini düşürdüğü tespit edildi. Sonuç olarak, PCA'nın TCDD'nin neden olduğu lipid peroksidasyonunu azalttığı ve antioksidan aktivitesini desteklediği görülmüştür. Bu nedenle PCA’nın, TCDD'nin neden olduğu toksisiteye karşı potansiyel bir indirgeyici madde olduğu öne sürülebilir.

It is known that TCDD, one of the most toxic dioxin compounds, causes oxidative damage by forming free radical in human and animal tissues. In this study, the protective effect of PCA, an important phenolic compound, was examined in rat kidney and liver tissues with TCDD-induced toxicity. For this purpose, 28 Wistar Albino rats (3-4 months old and weighing 280-310 g) were used. Rats were randomly divided into 4 equal groups (control, TCDD, PCA and TCDD+PCA). TCDD and PCA were dissolved in corn oil at doses of 2 µg/kg and 100 mg/kg, respectively. Subsequently, the substances were administered to the rats by oral gavage for 45 days. The test results showed that in both kidney and liver tissues, TCDD increased the level of malondialdehyde (MDA) but inhibited the level of glutathione (GSH) and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). PCA administration was found to increase the enzyme activities and GSH levels, whereas it decreased the TCDD and MDA levels. In conclusion, it was observed that PCA decreased the TCDD-induced lipid peroxidation, increasing the antioxidant activity. Therefore, it might be suggested that PCA is a potential reducing agent for the toxicity caused by TCDD.

  • [1] T. Molcan, S. Swigonska, A. Nynca, A. Sadowska, M. Ruszkowska, K. Orlowska and R.E. Ciereszko, “Is CYP1B1 involved in the metabolism of dioxins in the pig?” BBA – Gen. Subjects, vol. 1863, pp. 291–303, 2019.
  • [2] L. Wang, M. Kumar, Q. Deng, X. Wang, M. Liu, Z. Gong, S. Zhang, X. Ma, Z.Y. Xu-Monette, M. Xiao, Q. Yi, K.H. Young, K.S. Ramos and Y. Li, “2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces peripheral blood abnormalities and plasma cell neoplasms resembling multiple myeloma in mice,” Cancer Letters, vol. 440–441, pp. 135–144, 2019.
  • [3] B.P. Slezak, G.E. Hatch, M.J. DeVito, J.J. Diliberto, R. Slade, K. Crissman, E. Hassoun and L.S. Birnbaum, “Oxidative Stress in Female B6C3F1 Mice following Acute and Subchronic Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD),” Toxicological Sciences, vol. 54, pp. 390-398, 2000.
  • [4] O. Ciftci, O.M. Disli and N. Timurkaan, “Protective effects of protocatechuic acid on TCDD-induced oxidative and histopathological damage in the heart tissue of rats,” Toxicology and Industrial Health, DOI: 10.1177/0748233712442735, 2012.
  • [5] M.S. Mohsenzadeh, B.R. Zanjani and G. Karimi, “Mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin- induced cardiovascular toxicity: An overview,” Chemico-Biological Interactions, vol. 282, pp. 1-6, 2018.
  • [6] R. Bentli, O. Ciftci, A. Cetin and A. Otlu, “Anti-inflammatory Montelukast prevents toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin: Oxidative stress, histological alterations in liver, and serum cytokine levels,” Toxicology and Industrial Health, vol. 32, no: 5, pp. 769-76, 2016.
  • [7] K.S. Pikula, A.M. Zakharenko, V. Aruoja, K.S. Golokhvast and A.M. Tsatsakis, “Oxidative stress and its biomarkers in microalgal ecotoxicology,” Current Opinion in Toxicology, vol. 13, pp. 8–15, 2019.
  • [8] P.A. Kern, R.B. Fishman, W. Song, A.D. Brown and V. Fonseca, “The effect of 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) on oxidative enzymes in adipocytes and liver,” Toxicology, vol. 171, pp. 117-125, 2002.
  • [9] C. Latchoumycandane and P.P. Mathur, “Effects of vitamin E on reactive oxygen speciesmediated 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in rat testis,” Journal of Applied Toxicology, vol. 22, pp. 345-351, 2002.
  • [10] O.A. Shaikh-Omar, “Recombinant expression of the aryl hydrocarbon receptor,” PhD Thesis, University of Nottingham, Nottingham England, 2007.
  • [11] J. Yan, J. Jung, Y. Hong, Y. Moon, H. Suh, Y. Kim, H. Yun-Choi and D. Song, “Protective effect of protocatechuic acid isopropyl ester against murine models of sepsis: inhibition of TNF-alpha and nitric oxide production and augmentation of IL-10,” Biological and Pharmaceutical Bulletin, vol. 27, pp. 2024-2027, 2004.
  • [12] A.K. Khan, R. Rashid, N. Fatıma, S. Mahmood, S. Mir, S. Khan, N. Jabeen and G. Murtaza, “Pharmacological Activities of Protocatechuic Acid,” Acta Poloniae Pharmaceutica, vol. 72, no. 4, pp. 643-650, 2015.
  • [13] I.A. Adedara, O. Omole, E.S. Okpara, O.B. Fasina, M.F. Ayeni, O.M. Ajayi, E.O. Busari and E.O. Farombi, “Impact of prepubertal exposure to dietary protocatechuic acid on the hypothalamic-pituitary-testicular axis in rats,” Chemico-Biological Interactions, vol. 290, pp. 99–109, 2018.
  • [14] K. Valentova, L. Cvak, A. Muck, J. Ulrichova and V. Simanek, “Antioxidant activity of extracts from the leaves of Smallanthus sonchifolius,” European Journal of Nutrition, vol. 42, pp. 61-66, 2003.
  • [15] M. Yoshino and K. Murakami, “Interaction of iron with polyphenolic compounds: application to antioxidant characterization,” Analytical Biochemistry, vol. 257, pp. 40-4, 1998.
  • [16] R. Masella, A. Cantafora, D. Modesti, A. Cardilli, L. Gennaro, A. Bocca and E. Coni, “Antioxidant activity of 3,4-DHPEA-EA and protocatechuic acid: a comparative assessment with other olive oil biophenols,” Redox Report, vol. 4, pp. 113-21, 1999.
  • [17] O.H. Lowry, N.J. Rosebrough, A.L. Farr and R.J. Randall, “Protein measurement with pholin phenol reagent,” Journal of Biological Chemistry, vol. 193, pp. 265-275, 1951.
  • [18] Y. Sun, L.W. Oberley and Y. Li, “A simple method for clinical assay of superoxide dismutase” Clinical Chemistry, vol. 34, pp. 497-500, 1988. [19] H. Aebi, “Catalase in vitro assay methods,” Methods in Enzymology, vol. 105, pp. 121-126, 1984.
  • [20] W.P. De Valentine, “Studies on the quantitative and qualitative characterisation of erytrocyte glutathione peroxidase,” Journal of Laboratory and Clinical Medicine, vol. 70, pp. 158-159, 1967.
  • [21] J. Sedlak and R.H. Lindsay, “Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent,” Analytical Biochemistry, vol. 24, no. 25, pp. 192-205, 1968.
  • [22] K. Yagi, “Assay of lipid peroxidation in blood plasma or serum” Methods in Enzymology, vol. 105, pp. 328-331, 1984.
  • [23] H.J. Zhang, Y.N. Liu, P. Xian, J. Ma, Y.W. Sun, J.S. Chen, X. Chen, N.J. Tang, “Maternal exposure to TCDD during gestation advanced sensory-motor development, but induced impairments of spatial learning and memory in adult male rat offspring” Chemosphere, vol. 212, pp. 678-686, 2018.
  • [24] O. Ciftci, I. Ozdemir, N. Vardi, A. Beytur and F. Oguz, “Ameliorating effects of quercetin and chrysin on 2,3,7,8- tetrachlorodibenzo- p-dioxin-induced nephrotoxicity in rats,” Toxicology and Industrial Health, vol. 28, no. 10, pp. 947-54, 2012.
  • [25] H. Türkez, F. Geyikoğlu and I.Y. Mokhtar, “Beneficial effect of astaxanthin on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced liver injury in rats,” Toxicology and Industrial Health, vol. 29, no. 7, pp. 591-9, 2013.
  • [26] A. Nowak, J. Kochan, W. Niżański, A. Partyka, R. Kozdrowski, O. Rodak, M. Tarnowska, W. Mlodawska, A. Migdal and M. Witkowski, “Influence of Dioxin (TCDD) on the In Vitro Characteristics of Equine Gametes,” Journal of Equine Veterinary Science, vol. 61, pp. 88-94, 2017.
  • [27] E.A. Hassoun, J. Vodhanel, B. Holden and A. Abushaban, “The Effects of Ellagic Acid and Vitamin E Succinate on Antioxidant Enzymes Activities and Glutathione Levels in Different Brain Regions of Rats After Subchronic Exposure to TCDD,” Journal of Toxicology and Environmental Health, vol. 69, pp. 381–393, 2006.
  • [28] A.A. Hamdy, A. Rasha and M. Khafagy, “2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced cytotoxicity accompanied by oxidative stress in rat Sertoli cells: Possible role of mitochondrial fractions of Sertoli cells,” Toxicology and Applied Pharmacology, vol. 252, pp. 273–280, 2011. [29] O. Ciftçi, İ. Özdemir, S. Tanyıldızı, S. Yildiz and H. Oguzturk, “Antioxidative effects of curcumin, β-myrcene and 1,8-cineole against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced oxidative stress in rats liver” Toxicology and Industrial Health, vol. 27, no. 5, pp. 447-53, 2011.
  • [30] H. Türkez, F. Geyikoglu and I.Y. Mokhtar, “Ameliorative effect of docosahexaenoic acid on 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced histological changes, oxidative stress, and DNA damage in rat liver,” Toxicology and Industrial Health, vol. 28, no. 8, pp. 687-96, 2011.
  • [31] G. Shi, L. An, B. Jiang, S. Guan and Y.M. Bao, “Alpinia protocatechuic acid protects against oxidative damage in vitro and reduces oxidative stress in vivo,” Neuroscience Letters, vol. 403, pp. 206–210, 2006.
  • [32] A. Beytur, O. Ciftci, M. Aydin, O. Cakir, N. Timurkaan and F. Yılmaz, “Protocatechuic acid prevents reproductive damage caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in male rats” Andrologia, vol. 44, pp. 454-461, 2012.
  • [33] O. Coskun, M. Kanter, F. Armutcu, K. Cetin, B. Kaybolmaz and O. Yazgan, “Protective effects of quercetin, a flavonoid antioxidant, in absolute ethanol-induced acut gastric ulcer,” European Journal of General Medicine, vol. 1, pp. 37-42, 2004.
  • [34] A. Mansouri, P.M. Dimitris and K. Panagiotis, “Determination of hydrogen peroxide scavenging activity of cinnamic and benzoic acids employing a highly sensitive peroxyoxalate chemiluminescence-based assay: Structure–activity relationships,” Journal of Pharmaceutical and Biomedical Analysis, vol. 39, pp. 22–26, 2005.
  • [35] C. Liua, J. Wang, C. Chu, M.T. Cheng and T.H. Tseng, “In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity,” Food and Chemical Toxicology, vol. 40, pp. 635–641, 2002.
  • [36] S. Adefegha, O. Omojokun and G. Oboh, “Modulatory effect of protocatechuic acid on cadmium induced nephrotoxicity and hepatoxicity in rats in vivo,” SpringerPlus, vol. 4, pp. 619, 2015.
  • [37] L. Safaeian, R. Emami, V. Hajhashemi and Z. Haghighatian, “Antihypertensive and antioxidant effects of protocatechuic acid in deoxycorticosterone acetate-salt hypertensive rats,” Biomedicine & Pharmacotherapy, vol. 100, pp. 147–155, 2018.
Birincil Dil en
Konular Mühendislik
Bölüm Makaleler
Yazarlar

Orcid: 0000-0002-9609-785X
Yazar: Ahmet SAVCI (Sorumlu Yazar)
Kurum: MUS ALPARSLAN UNIVERSITY
Ülke: Turkey


Orcid: 0000-0002-8566-8979
Yazar: İlknur ÖZDEMİR
Kurum: INONU UNIVERSITY
Ülke: Turkey


Destekleyen Kurum İnönü University
Proje Numarası 2011/A-15.
Teşekkür This research was supported by IUBAP (Scientific Research Fund of İnönü University) under grant 2011/A-15.
Tarihler

Yayımlanma Tarihi : 31 Ocak 2020

Bibtex @araştırma makalesi { dubited538712, journal = {Düzce Üniversitesi Bilim ve Teknoloji Dergisi}, issn = {}, eissn = {2148-2446}, address = {}, publisher = {Düzce Üniversitesi}, year = {2020}, volume = {8}, pages = {546 - 553}, doi = {10.29130/dubited.538712}, title = {Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats}, key = {cite}, author = {SAVCI, Ahmet and ÖZDEMİR, İlknur} }
APA SAVCI, A , ÖZDEMİR, İ . (2020). Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats. Düzce Üniversitesi Bilim ve Teknoloji Dergisi , 8 (1) , 546-553 . DOI: 10.29130/dubited.538712
MLA SAVCI, A , ÖZDEMİR, İ . "Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats". Düzce Üniversitesi Bilim ve Teknoloji Dergisi 8 (2020 ): 546-553 <https://dergipark.org.tr/tr/pub/dubited/issue/49725/538712>
Chicago SAVCI, A , ÖZDEMİR, İ . "Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats". Düzce Üniversitesi Bilim ve Teknoloji Dergisi 8 (2020 ): 546-553
RIS TY - JOUR T1 - Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats AU - Ahmet SAVCI , İlknur ÖZDEMİR Y1 - 2020 PY - 2020 N1 - doi: 10.29130/dubited.538712 DO - 10.29130/dubited.538712 T2 - Düzce Üniversitesi Bilim ve Teknoloji Dergisi JF - Journal JO - JOR SP - 546 EP - 553 VL - 8 IS - 1 SN - -2148-2446 M3 - doi: 10.29130/dubited.538712 UR - https://doi.org/10.29130/dubited.538712 Y2 - 2019 ER -
EndNote %0 Düzce Üniversitesi Bilim ve Teknoloji Dergisi Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats %A Ahmet SAVCI , İlknur ÖZDEMİR %T Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats %D 2020 %J Düzce Üniversitesi Bilim ve Teknoloji Dergisi %P -2148-2446 %V 8 %N 1 %R doi: 10.29130/dubited.538712 %U 10.29130/dubited.538712
ISNAD SAVCI, Ahmet , ÖZDEMİR, İlknur . "Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats". Düzce Üniversitesi Bilim ve Teknoloji Dergisi 8 / 1 (Ocak 2020): 546-553 . https://doi.org/10.29130/dubited.538712
AMA SAVCI A , ÖZDEMİR İ . Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats. DÜBİTED. 2020; 8(1): 546-553.
Vancouver SAVCI A , ÖZDEMİR İ . Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats. Düzce Üniversitesi Bilim ve Teknoloji Dergisi. 2020; 8(1): 553-546.