Thymoquinone played a protective role against tartrazine-induced hepatotoxicity

Document Type : Original Article

Authors

1 Department of Medical Biochemistry, Medical Faculty, İnönü University, Malatya, Turkey

2 Department of Histology and Embryology, Medical Faculty, İnönü University, Malatya, Turkey

3 Department of Histology and Embryology, Medical Faculty, Turgut Ozal University, Malatya, Turkey

4 Department of Biostatistics, Medical Faculty, Inonu University, Malatya, Turkey

Abstract

Objective(s): The current study, the first of its kind in the literature, aimed to observe the toxic effects of Tartrazine, a commonly used dyestuff in industries and foods, on the liver, and investigate whether this toxicity could be eliminated with thymoquinone coadministration. 
Materials and Methods: 32 male Wistar albino rats were procured from İnönü University Experimental Animals Breeding and Research Center. The rats were randomly assigned to 4 equal groups: Control group, Thymoquinone group, Tartrazine group, and Thymoquinone + Tartrazine group. Rat liver tissue and blood samples were obtained and biochemical and histopathological examinations were conducted on the samples.
Results: Tartrazine administration increased the oxidant (malondialdehyde and superoxide dismutase) and oxidative stress index parameters (total oxidant status) in the liver tissue and decreased the antioxidant parameters (glutathione, glutathione peroxidase, catalase, and total antioxidant status) leading to histopathological problems (hematoxylin-eosin staining and Caspase-3 immunoreactivity) and inflammation (tumor necrosis factor-α and interleukin-6) in the serum samples. Thymoquinone, on the other hand, improved antioxidant and anti-inflammatory effects. 
Conclusion: At this time and dose, thymoquinone has a protective effect against tartrazine hepatotoxicity. Thymoquinone can be used as a protective agent against tartrazine toxicity. 

Keywords


1. Mehedi N,  Ainad-Tabet S,  Mokrane N,  Addou S,  Zaoui C,  Kheroua O,  et al.  Reproductive toxicology of tartrazine (FD and C Yellow No. 5) in Swiss Albino mice. Am J Pharmacol Toxicol 2009; 4: 130–135.
2. Mittal A, Kurup L,  Mittal J. Freundlich and Langmuir adsorption isotherms and kinetics for the removal of tartrazine from aqueous solutions using hen feathers. J Hazard Mater 2007; 146: 243–248.
3.Walton J. Strategic Human Resource Development; Prentice Hall: Upper Saddle River, NJ, USA, 1999.  
4. Mpountoukas P,   Pantazaki A,  Kostareli E,  Christodoulou P,  Kareli D, Poliliou S,  et al.  Cytogenetic evaluation and DNA interaction studies of the food colorants amaranth, erythrosine and tartrazine. Food Chem Toxicol 2010; 48: 2934–2944.
5. Chung KT, Stevens SE,  Cerniglia CE. The reduction of azo dyes by the intestinal microflora. Crit Rev Microbiol 1992; 18: 175–190.
6. Jones R, Ryan AJ,  Wright SE. The metabolism and excretion of tartrazine in the rat, rabbit and man. Food Cosmet Toxicol 1964; 2: 447–452.
7. Soares BM, Araujo TMT, Ramos JAB, Pinto LC,   Khayat BM, Bahia MDO, et al. Effects on DNA repair in human lymphocytes exposed to the food dye tartrazine yellow. Anticancer Res 2015; 35:1465–1474.
8. Amin KA, Abdel Hameid H, Abd Elsttar AH. Effect of food azo dyes tartrazine and carmoisine on biochemical parameters related to renal, hepatic function and oxidative stress biomarkers in young male rats. Food Chem Toxicol 2010; 48: 2994–2999. 
9. Velioglu C, Erdemli ME,  Gul M,  Erdemli Z,  Zayman E,  Bag HG, et al.  Protective effect of crocin on food azo dye tartrazine-induced hepatic damage by improving biochemical parameters and oxidative stress biomarkers in rats. Gen Physiol Biophys 2019; 38: 73–82.
10. Erdemli Z, Altinoz E, Erdemli ME,  Gul M, Gozukara Bag H, Gul S. Ameliorative effects of crocin on tartrazine dye–induced pancreatic adverse effects: a biochemical and histological study. Environ Sci Pollut Res 2021; 28: 2209–2218.
11. Ghoshehi OA, Houdi AA, Crooks PA.  High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J Pharm Biomed 1999; 19: 757–62.
12. Danaei GH,  Memar B,  Ataee R,  Karami M. Protective effect of thymoquinone, the main component of Nigella sativa, against diazinon cardio-toxicity in rats. Drug Chem Toxicol 2019; 42: 585–591.
13. Abdel-Daim MM, Abo El-Ela FI,  Alshahrani FK, Bin-Jumah M,  Al-Zharani M, Almutairi B,  et al. Protective effects of thymoquinone against acrylamide-induced liver, kidney and brain oxidative damage in rats. Environ Sci Pollut Res Int 2020; 27: 37709–37717.
14. Abd Al Haleem EN, Hasan WYS, Arafa HMM. Therapeutic effects of thymoquinone or capsaicin on acrylamide-induced reproductive toxicity in rats mediated by their effect on oxidative stress, inflammation, and tight junction integrity. Drug Chem Toxicol 202; 45: 2328-2340.
15. Hashem KS, Abdelazem AZ, Mohammed MA, Nagi AM,  Aboulhoda BE, Mohammed ET, et al. Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions. Environ Sci Pollut Res 2021; 28:10100–10113.
16. Erdemli ME, Yigitcan B, Erdemli Z, Gul M, Gozukara Bag H,  Gul S. Thymoquinone protection against 2,3,7,8-tetrachlorodibenzo-p-dioxin induced nephrotoxicity in rats.  Biotech Histochem 2020; 95:567–574.
17. Balta I, Sevastre B, Mireşan V, Taulescu M, Raducu C, Longodor AL, et al. Protective effect of blackthorn fruits (Prunus spinosa) against tartrazine toxicity development in albino Wistar rats. BMC Chem 2019; 13: 1–11.
18. Kong LY, Li GP, Yang P, Xi Z.  Protective effect of thymoquinone on cholestatic rats with liver injury. Genet Mol Res 2015); 14: 12247–12253.
19. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351–358.
20. Ellman GL.   Tissue sulphydryl groups. Arch Biochem Biophys 1959; 82: 70–77. 
21. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497–500.
22. Aebi H, Bergmeyer HU. Methods of Enzymatic Analysis. Verlag Chemie/Academic Press Inc., Weinheim/NewYork 1974; 673-680.
23. Paglia D, Valentine WN. Studies on the quantitative and qualitative charecterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70:158-169.
24. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265–275.
25. Erel O. A novel automated direct measurement method for total anti-oxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004; 37: 277–285.
26. Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005; 38: 1103–1111.
27. Bancroft JD,  Gamble M. Theory and Practice of Histological Techniques. 5th ed. London: Churchill Livingstone; p, 2002; 173–185.
28. Budwit-Novotny DA, McCarty KS, Cox EB,  Soper JT, Mutch DG, Creasman WT, et al. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res 1986; 46: 5419–5425.
29. Sadek KM, Lebda MA,  Abouzed TK,  Nasr SM,  EL-Sayed Y. The molecular and biochemical insight view of lycopene in ameliorating tramadol-induced liver toxicity in a rat model: implication of oxidative stress, apoptosis, and MAPK signaling pathways. Environ Sci Pollut Res Int 2018; 25:33119–33130.
30. Sadek K,  Beltagy D,  Saleh E, Abouelkhair R. Camel milk and bee honey regulate profibrotic cytokine gene transcripts in liver cirrhosis induced by carbon tetrachloride. Can J Physiol Pharmacol 2016; 94: 1–10.
31. Zeweil MM,  Sadek KM, Elsadek MF,  Mahmoud SF,  Ahmed BM,   Khafaga AF. Sidr honey abrogates the oxidative stress and downregulates the hyaluronic acid concentration and gene expression of TGF-β1 and COL1a1 in rat model of thioacetamide-induced hepatic fibrosis. Anim Sci J 2020;91:e13434.
32. Sadek KM,  Saleh EA, Nasr SM. Molecular hepatoprotective effects of lipoic acid against carbon tetrachloride-induced liver fibrosis in rats: Hepatoprotection at molecular level. Hum Exp Toxicol 2018; 37: 142–154.
33. Hımrı I, Bellahcen S,  Souna F,  Belmekki F,   Aziz M,  Bnouham M,  et al. A 90-day oral toxıcıty study of tartrazine, a synthetic food dye, ın wistar rats. Int J Clin Pharm 2011; 3: 159-69.
34. El-Desoky GE, Abdel-Ghaffar A, Al-Othman ZA, Habila MA,  Al-Sheikh YA, Ghneim HK, et al.  Curcumin protects against tartrazine-mediated oxidative stress and hepatotoxicity in male rats. Eur Rev Med Pharmacol Sci 2017; 21: 635–645.
35. Abd-Elhakim YM, Moustafa GG,  Hashem MM, Ali HA,  Abo-ELSooud K, El-Metwally AE. Influence of the long-term exposure to tartrazine and chlorophyll on the fibrogenic signalling pathway in liver and kidney of rats: the expression patterns of collagen 1-α, TGFβ-1, fibronectin, and caspase-3 genes. Environ Sci Pollut Res Int 2019; 26: 12368–12378. 
36. Shahid F,  Farooqui Z,  Alam T,  Abidi S,  Parwez I,  Khan F. Thymoquinone supplementation ameliorates cisplatin-induced hepatic pathophysiology. Hum Exp Toxicol 2021; 40: 1673–1684.
37. Erdemli ME, Yigitcan B, Gul M,  Bag HG,  Gul S,  Aksungur Z. Thymoquinone is protective against 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hepatotoxicity. Biotech Histochem 2018; 93 :453–462. 
38. Al Aboud D,  Baty RS, Alsharif KF, Hassan KE, Zhery AS, Habotta OA, et al. Protective efficacy of thymoquinone or ebselen separately against arsenic-induced hepatotoxicity in rat. Environ Sci Pollut Res Int 2021; 28: 6195–2206. 
39. Mabrouk  A, Salah IBH,  Chaieb W, Cheikh HB. Protective effect of thymoquinone against lead-induced hepatic toxicity in rats. Environ Sci Pollut Res 2016; 23: 12206–12215.
40. El-Sheikh AAK, Morsy MA, Abdalla AM, Hamouda AH, Alhaider IA. Mechanisms of thymoquinone hepatorenal protection in methotrexate-induced toxicity in rats. Mediat Inflamm 2015; http://dx.doi.org/10.1155/2015/859383.