Role of Protocatechuic Acid (PCA) on Hepatoxicity and Nephrotoxicity Induced by 2, 3, 7, 8-Tetracholorodibenzo-P-Dioxin (TCDD) in Rats

Year 2020, Volume: 8 Issue: 1, 546 - 553, 31.01.2020

Ahmet Savcı , İlknur Özdemir

https://doi.org/10.29130/dubited.538712

Cited By: 1

Abstract

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.

Keywords

Antioxidant, TCDD, protocatechuic acid, oxidative damage, rat

Supporting Institution

İnönü University

Project Number

2011/A-15.

Thanks

This research was supported by IUBAP (Scientific Research Fund of İnönü University) under grant 2011/A-15.

Sıçanlarda 2,3,7,8-Tetraklorodibenzo-P-Dioksin (TCDD) 'nin Neden Olduğu Hepatoksisite ve Nefrotoksisite Üzerine Protokateşik Asitin (PCA) Rolü

Abstract

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.

Keywords

Antioksidan, Oksidatif hasar, Protokateşik asit, TCDD, Sıçan

Project Number

2011/A-15.

References

• [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.