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

Titiek Hidayati; Akrom Akrom; Indrayanti Indrayanti; Suny Sun

doi:10.3889/oamjms.2021.5855

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).

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

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