Thymoquinone Increased Expression of CD4CD25Treg in Sprague-Dawley Rats Induced Dimethylbenzanthracene

Authors

  • Titiek Hidayati Department of Family Medicine and Public Health, Medicine and Health Science Faculty, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Indonesia
  • Akrom Akrom Department of Pathology Anatomy, Medicine and Health Science Faculty, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Indonesia
  • Indrayanti Indrayanti Department of Pathology Anatomy, Medicine and Health Science Faculty, Universitas Muhammadiyah Yogyakarta, Yogyakarta, Indonesia
  • Suny Sun Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan City, Taiwan

DOI:

https://doi.org/10.3889/oamjms.2021.5855

Keywords:

Thymoquinone, Tamoxifen, DMBA, CD4CD25Treg, anti-inflammation

Abstract

BACKGROUND: The carcinogen dimethylbenzanthracene (DMBA) is immunotoxic. Thymoquinone, meanwhile, is known to have antioxidant and anti-inflammatory effects.

AIM: This study aims to determine the effect of thymoquinone and tamoxifen on the CD4CD25Treg count in Sprague-Dawley (SD) rats induced by DMBA.

METHODS: The 50 SD rats were divided into five groups. Group I (normal control) was given standard drinking and food. Group II was given thymoquinone, Group III was given tamoxifen, Group IV was given DMBA, and Group V was given solvent control. Thymoquinone, tamoxifen, and solvent control administration started 2 weeks before DMBA administration and continued during DMBA induction. In the 3rd week, except for the normal group, all groups were created to be induced with 10 × 20 mg/kg body weight of DMBA for 5 weeks. In the 21st week, surgery and data collection were performed. The hematology profile and CD4CD25Treg number were carried out employing a flow cytometer. The difference in the average number of CD4CD25Treg and blood cells between groups was analyzed with one-way analysis of variance

RESULTS: The results revealed that DMBA induction reduced the number of erythrocytes, HB levels, platelet counts, and leukocyte counts (p < 0.05). The administration of thymoquinone and tamoxifen reduced the hematopoiesis effect of DMBA. The thymoquinone and tamoxifen group had a higher number of CD4CD25Treg and leukocytes than the DMBA group (p < 0.05).

CONCLUSION: There was no difference in the average CD4CD25Treg, leukocyte count, lymphocyte count, and monocyte count between the thymoquinone and the tamoxifen groups (p > 0.05).

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References

Vatner RE, Janssen EM. STING, DCs and the link between innate and adaptive tumor immunity. Mol Immunol. 2019;110:13- 23. https://doi.org/10.1016/j.molimm.2017.12.001 PMid:29273394

Xue Q, Guo ZY, Li W, Wen WX, Meng YL, Jia LT, et al. Human activated CD4+ T lymphocytes increase IL-2 expression by downregulating microRNA-181c. Mol Immunol. 2011;48(4):592- 9. https://doi.org/10.1016/j.molimm.2010.10.021 PMid:21112091

Hidayati T, Akrom A. Black cumin seed oil increase leucocyte and CD4Thelper number in sprague-dawley rats induced with dimethylbenzanthracene. Int J Public Health Sci. 2019;8(2):238- 45. https://doi.org/10.11591/ijphs.v8i2.17930

Lança T, Silva-Santos B. The split nature of tumor-infiltrating leukocytes: Implications for cancer surveillance and immunotherapy. Oncoimmunology. 2012;1(5):717-25. https://doi.org/10.4161/onci.20068 PMid:22934263

Hassannia H, Abediankenari S, Ghaffari J. FOXP3 and TGF-β gene polymorphisms in allergic rhinitis. Iran J Immunol. 2011;8(4):218-25. PMid:22201619

Long SA, Buckner JH. CD4 + FOXP3 + T regulatory cells in human autoimmunity: More than a numbers game. J Immunol. 2011;187(5):2061-6. https://doi.org/10.4049/jimmunol.1003224 PMid:21856944

Lim AK, Tesch GH. Inflammation in diabetic nephropathy. Mediators Inflamm. 2012;2012:146154.

Gopalakrishnan T, Ganapathy S, Veeran V, Namasivayam N. Preventive effect of D-carvone during DMBA induced mouse skin tumorigenesis by modulating xenobiotic metabolism and induction of apoptotic events. Biomed Pharmacother. 2019;111:178-87. https://doi.org/10.1016/j.biopha.2018.12.071 PMid:30583225

Pugalendhi P, Manoharan S, Panjamurthy K, Balakrishnan S, Nirmal MR. Antigenotoxic effect of genistein against 7, 12-dimethylbenz[a]anthracene induced genotoxicity in bone marrow cells of female Wistar rats. Pharmacol Rep. 2009;61(2):296-303. https://doi.org/10.1016/s1734-1140(09)70035-0 PMid:19443942

Wibowo AE, Sriningsih S, Wuyung PE, Ranasasmita R. The influence of DMBA (7,12-dimethylbenz-[a]anthracene) regimen in the development of mammae carcinogénesis on sprague dawley female rat. Indones J Cancer Chemoprev. 2010;1(1):60. https://doi.org/10.14499/indonesianjcanchemoprev1iss1pp60-66

Siregar C, Wasito EB, Sudiana IK. Effect of butyric acid on p53 expression and apoptosis in colon epithelial cells in mice after treated with 9, 10-dimethyl-1, 2-benz(a)anthracene. Procedia Chem. 2016;18:141-6. https://doi.org/10.1016/j.proche.2016.01.022

Hong CH, Lee CH, Yu HS, Huang SK. Benzopyrene, a major polyaromatic hydrocarbon in smoke fume, mobilizes langerhans cells and polarizes Th2/17 responses in epicutaneous protein sensitization through the aryl hydrocarbon receptor. Int Immunopharmacol. 2016;36:111-7. https://doi.org/10.1016/j.intimp.2016.04.017 PMid:27129092

Miyata M, Furukawa M, Takahashi K, Gonzalez FJ, Yamazoe Y. Mechanism of 7,12-dimethylbenz [a] anthracene-induced immunotoxicity: Role of metabolic activation at the target organ. Jpn J Pharmacol. 2001;86(3):302-9. https://doi.org/10.1254/jjp.86.302 PMid:11488430

Chai YS, Chen YQ, Lin SH, Xie K, Wang CJ, Yang YZ, et al. Curcumin regulates the differentiation of naïve CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice. Biomed Pharmacother. 2020;125:109946. https://doi.org/10.1016/j.biopha.2020.109946 PMid:32004976

Ghasemi HA, Kasani N, Taherpour K. Effects of black cumin seed (Nigella sativa L.), a probiotic, a prebiotic and a synbiotic on growth performance, immune response and blood characteristics of male broilers. Livest Sci. 2014;164(1):128-34. https://doi.org/10.1016/j.livsci.2014.03.014

Majdalawieh AF, Hmaidan R, Carr RI. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol. 2010;131(2):268-75. https://doi.org/10.1016/j.jep.2010.06.030 PMid:20600757

Hidayati T, Akrom, Indrayanti, Sagiran. Chemopreventive effect of black cumin seed oil (BCSO) by increasing p53 expression in dimethylbenzanthracene (DMBA)-induced Sprague Dawley rats. Res J Chem Environ. 2019;23(8):24-32. https://doi.org/10.11591/ijphs.v8i2.17930

Adam GO, Rahman MM, Lee SJ, Kim GB, Kang HS, Kim JS, et al. Hepatoprotective effects of Nigella sativa seed extract against acetaminophen-induced oxidative stress. Asian Pac J Trop Med. 2016;9(3):221-7. https://doi.org/10.1016/j.apjtm.2016.01.039 PMid:26972391

Dirican A, Sahin OS, Tasli S, Coban E, Sogut E, Kucukzeybek Y, et al. Thymoquinone enhances cisplatin-induced neprotoxicity in high dose. J Oncol Sci. 2016;1:17-24. https://doi.org/10.1016/j.jons.2015.11.005

Ismail N, Abdel-Mottaleb Y, Ahmed AA, El-Maraghy NN. Novel combination of thymoquinone and resveratrol enhances anticancer effect on hepatocellular carcinoma cell line. Future J Pharm Sci. 2018;4(1):41-6. https://doi.org/10.1016/j.fjps.2017.08.001

Ahmad A, Husain A, Mujeeb M, Khan SA, Najmi AK, Siddique NA, et al. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed. 2013;3(5):337- 52. https://doi.org/10.1016/s2221-1691(13)60075-1 PMid:23646296

Randhawa MA, Alghamdi MS. Anticancer activity of Nigella sativa (Black Seed)-a review. Am J Chin Med. 2011;39(6):1075- 91. https://doi.org/10.1142/s0192415x1100941x PMid:22083982

Mahmoud YK, Abdelrazek HM. Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy. Biomed Pharmacother. 2019;115:108783. https://doi.org/10.1016/j.biopha.2019.108783 PMid:31060003

Akrom A, Nurfadjrin R, Darmawan E, Hidayati T. Black cumin seed oil antidiabetogenic by increasing pancreatic P53 expression. Int J Public Health Sci. 2018;7(3):207. https://doi. org/10.11591/ijphs.v7i3.13694

Arafa ES, Zhu Q, Shah ZI, Wani G, Barakat BM, Racoma I, et al. Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells. Mutat Res. 2011;706(1-2):28-35. https://doi.org/10.1016/j.mrfmmm.2010.10.007 PMid:21040738

Alenzi FQ, El-Bolkiny YE, Salem ML. Protective effects of Nigella sativa oil and thymoquinone against toxicity induced by the anticancer drug cyclophosphamide. Br J Biomed Sci. 2010;67(1):20- 8. https://doi.org/10.1080/09674845.2010.11730285 PMid:20373678

Akrom A, Mustofa M. Black cumin seed oil increases phagocytic activity and secretion of IL-12 by macrophages. Biomed Res. 2017;28(12):1-11.

Shiizaki K, Kawanishi M, Yagi T. Modulation of benzo [a] pyrene-DNA adduct formation by CYP1 inducer and inhibitor. Genes Environ. 2017;39(1):1-8. https://doi.org/10.1186/ s41021-017-0076-x

El-Kaream SA. Biochemical and biophysical study of chemopreventive and chemotherapeutic anti-tumor potential of some Egyptian plant extracts. Biochem Biophys Rep. 2019;18:100637. https://doi.org/10.1016/j.bbrep.2019.100637 PMid:31016248

Majdalawieh AF, Fayyad MW. Immunomodulatory and anti-inflammatory action of Nigella sativa and thymoquinone: A comprehensive review. Int Immunopharmacol. 2015;28(1):295- 304. https://doi.org/10.1016/j.intimp.2015.06.023 PMid:26117430

Ahmad A, Mishra RK, Vyawahare A, Kumar A, Rehman MU, Qamar W, et al. Thymoquinone (2-Isoprpyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects. Saudi Pharm J. 2019;27(8):1113-26. https://doi.org/10.1016/j.jsps.2019.09.008 PMid:31885471

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Published

2021-03-04

How to Cite

1.
Hidayati T, Akrom A, Indrayanti I, Sun S. Thymoquinone Increased Expression of CD4CD25Treg in Sprague-Dawley Rats Induced Dimethylbenzanthracene. Open Access Maced J Med Sci [Internet]. 2021 Mar. 4 [cited 2021 Apr. 16];9(T4):87-91. Available from: https://oamjms.eu/index.php/mjms/article/view/5855