Investigation of the Protective Effect of Thymoquinone on the Livers of the Obese Rats Induced by a High-Fat Diet

Öz

Aim: Obesity, which reduces the quality of life and forms the basis of many diseases, is caused by the imbalance between calories consumed and calories expended. The increase in calories consumed and fat accumulation in the body also cause many health problems. Obesity-related fatty liver and liver damage are one of these diseases. Fatty liver causes deterioration of functions and, accordingly, changes in homeostasis. Thymoquinone, an antioxidant, is preferred for liver damage. This study aimed to examine the protective effect of thymoquinone on liver damage caused by obesity. Materials and Methods: In our study, 24 adult male Wistar albino rats were randomly divided into four groups (n: 6). Non-obese control (NOC) and non-obese thymoquinone (NTQ) groups were fed with standard chow; obese control (OC), obese-thymoquinone (OTQ) groups were fed with high-fat diet (40% of calories from fat) for 15 weeks. All treatment groups were given 10 mg/kg thymoquinone i. p. for six weeks. After the experimental study, the subjects were placed under intracardiac perfusion, and liver tissues were removed. Liver samples were subjected to tissue processing and cut into five μm thick sections for stereological and histopathological analyses. The obtained samples were stained with hematoxylin-eosin. The preparations were examined under a camera microscope, liver and sinusoid volumes were analyzed using the Cavalieri method, and hepatocyte counts were analyzed using the physical dissector method. Results: In the volumetric analyses, an increase was observed in both total liver and sinusoid volumes in the OC group compared to the NOC group. Again, in both volume analyses, it was observed that the volumes in the OTQ groups decreased compared to the OC groups. In the examination of the hepatocyte count, an increase was observed in the OC group compared to the NOC group, while it was observed that it decreased in the OTQ groups compared to the OC groups. In addition, it was observed that the number of hepatocytes in the NTQ group increased significantly compared to the NOC group. When histopathological analyses were examined, ballooned hepatocytes were selected in the OC group, while this ballooning was not observed in the OTQ group. Conclusion: Considering the analyses and the data obtained, thymoquinone may have a protective effect on obesity-induced liver damage. In addition, more comprehensive analyses should examine the pathways through which this effect progresses.

Anahtar Kelimeler

• thymoquinone
• liver
• obesity
• hepatoprotective effect; stereology

Kaynakça

1. 1. Erdal M, Altunkaynak BZ, Kocaman A, Alkan I, Öztas E. The role of HMGB1 in liver inflammation in obese rats. Biotechnic & Histochemistry. 2019;94(6):449–458.
2. 2. Milić S, Lulić D, Štimac D. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations. World Journal Of Gastroenterology. 2014;20(28):9330–9337.
3. 3. Kaplan JM, Nowell M, Lahni P, O’Connor M, Hake PW, Zingarelli B. Short-Term high fat feeding increases organ injury and mortality after polymicrobial sepsis. Obesity (Silver Spring). 2012;20:1995–2002.
4. 4. Mayoral LP, Andrade GM, Mayoral EP, Huerta TH, Canseco SP, Rodal Canales FJ, Cabrera-Fuentes HA, Cruz MM, Pérez Santiago AD, Alpuche JJ, Zenteno E, Ruíz HM, Cruz RM, Jeronimo JH, Perez-Campos E. Obesity subtypes, related biomarkers & heterogeneity. The Indian Journal Of Medical Research. 2020;151(1):11–21.
5. 5. Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263–73.
6. 6. Brunner KT, Henneberg CJ, Wilechansky RM, Long MT. Nonalcoholic fatty liver disease and obesity treatment. Current Obesity Reports. 2019;8(3):220–228.
7. 7. Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, Esquivel-Soto J, Morales-González A, Esquivel-Chirino C, Durante-Montiel I, Sánchez-Rivera G, Valadez-Vega C, Morales-González J. A. Inflammation, oxidative stress, and obesity. International Journal Of Molecular Sciences. 2011;12(5):3117–32.
8. 8. Abdali D, Samson SE, Grover AK. How effective are antioxidant supplements in obesity and diabetes? Medical Principles And Practice. 2015;24(3):201–15.

9. 9. Ohishi T, Goto S, Monira P, Isemura M, Nakamura Y. Antiinflammatory action of green tea. Anti-Inflammatory & Anti- Allergy Agents in Medicinal Chemistry. 2016;15(2):74–90.
10. 10. Al Asoom L. Is nigella sativa an effective bodyweight lowering agent and a mitigator of obesity risk? A Literature Review. Vascular Health And Risk Management. 2016;18:495–505.
11. 11. Asgharzadeh F, Bargi R, Beheshti F, Hosseini M, Farzadnia M, Khazaei M. Thymoquinone restores liver fibrosis and improves oxidative stress status in a lipopolysaccharideinduced inflammation model in rats. Avicenna Journal Of Phytomedicine. 2017;7(6):502–510.
12. 12. Vanamala J, Kester AC, Heuberger AL, Reddivari L. Mitigation of obesity-promoted diseases by Nigella sativa and thymoquinone. Plant Foods For Human Nutrition. 2012;67(2):111–119.
13. 13. Harphoush S, Wu G, Qiuli G, Zaitoun M, Ghanem M, Shi Y, Le G. Thymoquinone ameliorates obesity-induced metabolic dysfunction, improves reproductive efficiency exhibiting a doseorgan relationship. Systems Biology in Reproductive Medicine. 2019;65(5):367–382.
14. 14. Suddek GM. Protective role of thymoquinone against liver damage induced by tamoxifen in female rats. Canadian Journal of Physiology and Pharmacology. 2014;92(8):640–644.
15. 15. Altunkaynak BZ, Ozbek E. Overweight and structural alterations of the liver in female rats fed a high-fat diet: a stereological and histological study. Turkish Journal of Gastroenterology. 2009;20(2):93–103.
16. 16. Engin A. The definition and prevalence of obesity and metabolic syndrome. Advances in Experimental Medicine and Biology. 2017;960:1–17.
17. 17. Du J, Zhu A, Song D, Mi X, Jiang H. Morphological changes of liver in obese rats induced by high fat diet and its significance. Chinese Journal of Endocrine Surgery. 2019;6:463–465.
18. 18. Polyzos SA, Kountouras J, Mantzoros CS. Obesity and nonalcoholic fatty liver disease: from pathophysiology to therapeutics. Metabolism Clinical and Experimental. 2019;92:82–97.
19. 19. Marchesini G, Moscatiello S, Di Domizio S, Forlani G. Obesityassociated liver disease. J Clin Endocrinol Metab. 2008;93(11 Suppl 1):S74–80.
20. 20. André J Scheen, Françoise H Luyckx, Obesity and liver disease, Best Practice & Research Clinical Endocrinology & Metabolism, Volume 16, Issue 4, 2002, 703–716.
21. 21. Kayıhan Karaçor, Meryem Çam, Nuri Orhan, Erdal Coşgun, Hilmi Demirin. High Fatty Diet Effects on Rat Liver. Eur J Gen Med. 2014;11(2):99–108.
22. 22. Lei Zhang, Peipei Xu, Yi Cheng, Peili Wang, Xinrun Ma, Mingyao Liu, Xin Wang, Feng Xu, Diet-induced obese alters the expression and function of hepatic drug-metabolizing enzymes and transporters in rats, Biochemical Pharmacology, Volume 164, 2019, 368–376.
23. 23. Silahtaroğlu S. Nigella stellaris boiss bitkisi üzerinde farmakognozik araştırmalar. Yüksek Lisans Tezi. Mersin Üniversitesi, Sağlık Bilimleri Enstitüsü, 2009.
24. 24. Geng W, Li C, Zhan Y, Zhang R, Zheng J. Thymoquinone alleviates liver fibrosis via miR-30a-mediated epithelialmesenchymal transition. Journal of Cellular Physiolgy, 2020.
25. 25. Almatroodi SA, Alnuqaydan AM, Alsahli MA, Khan AA, Rahmani AH. Thymoquinone, the most prominent constituent of nigella sativa, attenuates liver damage in streptozotocininduced diabetic rats via regulation of oxidative stress, inflammation and cyclooxygenase-2 protein expression. Applied Sciences. 2021;11(7):3223.
26. 26. Ayuob NN, Abdel-Hamid AAHM, Helal GMM, Mubarak WA. Thymoquinone reverses nonalcoholic fatty liver disease (NAFLD) associated with experimental hypothyroidism. Romanian Journal Of Morphology And Embryology. 2019;60(2):479–486.
27. 27. Danaei GH, Amali A, Karami M, Khorrami MB, Riahi-Zanjani B, Sadeghi M. The significance of thymoquinone administration on liver toxicity of diazinon and cholinesterase activity;a recommendation for prophylaxis among individuals at risk. BMC Complementary Medicine and Therapies. 2022;22:321.
28. 28. Azzubaidi MS, Noor NM, Noriah M, Mizher AH. Antihypertensive and antihyperlipidemic activities of thymoquinone in l-name hypertensive rats. Journal of Hypertension. 2015;33:7–8.