Uric Acid Lowering Effect of Thymoquinone in Potassium Oxonate-Induced Hyperuricemic Rats
DOI:
https://doi.org/10.47489/szmc.v40i2.854Keywords:
Hyperuricemia, Thymoquinone, Potassium Oxonate, AllopurinolAbstract
Background: High serum uric acid levels lead to hyperuricemia, which, if left untreated, can result in gout, metabolic syndrome and can also be an aggravating factor in renal and cardiovascular conditions. Nowadays xanthine oxidase inhibitors and uricosuric drugs are used to treat hyperuricemia. Thymoquinone, derived from Nigella Sativa Linn, can be explored for its potential uric acid lowering effects.
Objective: To evaluate the effect of Thymoquinone on serum and urinary uric acid in potassium oxonate induced hyper-uricemic rats.
Method: This experimental study was conducted at the Post Graduate Medical Institute, Lahore from January 2021 -January 2022. Twenty-four rats were randomly divided into four groups (A-D). Group A and B were taken as normal and disease control respectively. Groups B- D were injected intraperitoneal potassium oxonate on days 1, 3 and 7 to induce hyperuricemia. Group C was given oral Allopurinol (5mg/kg) whereas Group D was treated with Thymoquinone at 20 mg/kg orally for seven consecutive days. Serum and urine samples were taken on days 0, 1, 3 and 7, while serum and urinary creatinine levels on day 0 and 7 were obtained to estimate fractional excretion of uric acid. Data was analyzed and processed by SPSS version 24. (p value ? 0.05 was considered significant)
Results: A significant reduction in serum uric acid levels (p-value <0.001) was seen from day 1 to 7 in Thymoquinone treated group when compared to the disease control, whereas this difference was insignificant when compared to Allopurinol treated group. Thymoquinone treated group also showed significantly increased urinary uric acid levels on day 7 (p-value <0.001).
Conclusion: Thymoquinone effectively lowers serum uric acid levels and shows an increase in urinary uric acid levels. It also enhances urine volume and fractional excretion of uric acid (FEUA %). These effects suggest its potential in preventing or treating hyperuricemia.
References
Song P, Wang H, Xia W, Chang X, Wang M, An L. Prevalence and correlates of hyperuricemia in the middle-aged and older adults in China. Sci Rep. 2018;8(1):4314. https://www.nature.com/articles/s41598-018-22570-9
Qudwai W, Jawaid M. Frequency of uric acid levels symptomatic and asymptomatic hyperuricemia among the Pakistani population. Mid East J Fam Med. 2017;15:52-7. http://www.mejfm.com/September2017/Hyperuricemia.pdf
Raja S, Kumar A, Aahooja RD, Thakuria U, Ochani S, Shaukat F. Frequency of hyperuricemia and its risk factors in the adult population. Cureus. 2019;11(3). https://doi.org/10.7759/cureus.4198
Shaikh AA, Altaf A. Prevalence of hyperuricemia in Sukkur; Pakistan: A cross sectional survey. Prof Med J. 2019;26(09):1567-9. https://doi.org/10.29309/TPMJ/2019.26.09.4027
Muzzammil M, Qadir A, Mughal A, Effendi J, Minhas MS, Jahanzeb S. The prevalence of hyperuricemia and its associated risk factors in patients presenting with joint pain in Karachi. Int J Res Orthop. 2020;6(6):1151. https://dx.doi.org/10.18203/issn.2455-4510.IntJResOrthop20204579
Shaikhomar O, Header E. Dietary Etiological Factors Contributing to the Prevalence of Hyperuricemia in Makkah Region. Prensa Med Argent S. 2020;2:2-7. https://www.researchgate.net/profile/Osama-Shaikhomar/publication/348975708_Dietary_Etiological_Factors_Contributing_to_the_Prevalence_of_Hyperuricemia_in_Makkah_Region/links/6019a669a6fdcc37a8fc06b1/Dietary-Etiological-Factors-Contributing-to-the-Prevalence-of-Hyperuricemia-in-Makkah-Region.pdf.
Bardin T, Richette P. Definition of hyperuricemia and gouty conditions. Curr Opin Rheumatol. 2014;26(2):186-91. https://doi.org/10.1097/BOR.0000000000000028
Singh JA, Gaffo A, editors. Gout epidemiology and comorbidities. Semin Arthritis Rheum. 2020;50(3S):S11-S16. https://doi.org/10.1016/j.semarthrit.2020.04.008
Hou Z, Ma A, Mao J, Song D, Zhao X. Overview of the pharmacokinetics and pharmacodynamics of URAT1 inhibitors for the treatment of hyperuricemia and gout. Expert Opin Drug Metab Toxicol. 2023;19(12):895-909. https://doi.org/10.1080/17425255.2023.2287477
Cicero AF, Fogacci F, Kuwabara M, Borghi C. Therapeutic strategies for the treatment of chronic hyperuricemia: an evidence-based update. Medicina. 2021;57(1):58. https://doi.org/10.3390/medicina57010058
Alhmied F, Alammar A, Alsultan B, Alshehri M, Pottoo FH. Molecular mechanisms of thymoquinone as anticancer agent. Comb Chem High Throughput Screen.2021;24(10):1644-53. https://doi.org/10.2174/1386207323999201027225305
Chatterjee G, Saha AK, Khurshid S, Saha A. A Comprehensive Review of the Antioxidant, Antimicrobial, and Therapeutic Efficacies of Black Cumin (Nigella sativa L.) Seed Oil and Its Thymoquinone. J Med Food. 2025;28(4):325-39. https://doi.org/10.1089/jmf.2024.k.0149
Wang F, Yao W, Yu D, Hao Y, Wu Y, Zhang X. Protective role of thymoquinone in hyperlipidemia-induced liver injury in LDL-R?/? mice. BMC Gastroenterol. 2023;23(1):276. https://doi.org/10.1186/s12876-023-02895-0
Mahomoodally MF, Aumeeruddy MZ, Legoabe LJ, Montesano D, Zengin G. Nigella sativa L. and its active compound thymoquinone in the clinical management of diabetes: A systematic review. Int J Mol Sci. 2022;23(20):12111. https://doi.org/10.3390/ijms232012111
Chen Y, Li C, Duan S, Yuan X, Liang J, Hou S. Curcumin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation in mice. Biomed Pharmacother. 2019;118:109195. https://doi.org/10.1016/j.biopha.2019.109195
Haidari F, Rashidi MR, Keshavarz SA, Mahboob SA, Eshraghian MR, Shahi MM. Effects of onion on serum uric acid levels and hepatic xanthine dehydrogenase/xanthine oxidase activities in hyperuricemic rats. Pak J Biol Sci.2008;11(14):1779-84. https://doi.org/10.3923/pjbs.2008.1779.1784
Zaj?czkowski S, Zió?kowski W, Badtke P, Zaj?czkowski MA, Flis DJ, Figarski A, et al. Promising effects of xanthine oxidase inhibition by allopurinol on autonomic heart regulation estimated by heart rate variability (HRV) analysis in rats exposed to hypoxia and hyperoxia. PLoS One. 2018;13(2):e0192781. https://doi.org/10.1371/journal.pone.0192781
Hosseinzadeh H, Parvardeh S, Masoudi A, Moghimi M, Mahboobifard F. Attenuation of morphine tolerance and dependence by thymoquinone in mice. Avicenna J Phytomed. 2016;6(1):55. https://pmc.ncbi.nlm.nih.gov/articles/PMC4884218/
Che Sulaiman I, Chieng B, Osman M, Ong K, Rashid J, Wan Yunus W, et al. A review on colorimetric methods for determination of organophosphate pesticides using gold and silver nanoparticles. Microchim Acta. 2020;187(2):131. https://doi.org/10.1007/s00604-019-3893-8
Toora B, Rajagopal G. Measurement of creatinine by Jaffe's reaction--determination of concentration of sodium hydroxide required for maximum color development in standard, urine and protein free filtrate of serum. Indian J Exp Biol. 2002;40(3):352-4. https://europepmc.org/article/med/12635710
Yang C-Y, Chen C-H, Deng S-T, Huang C-S, Lin Y-J, Chen Y-J, et al. Allopurinol use and risk of fatal hypersensitivity reactions: a nationwide population-based study in Taiwan. JAMA Intern Med.2015;175(9):1550-7. https://doi.org/10.1001/jamainternmed.2015.3536
Goyal SN, Prajapati CP, Gore PR, Patil CR, Mahajan UB, Sharma C, et al. Therapeutic potential and pharmaceutical development of thymoquinone: a multitargeted molecule of natural origin. Front Pharmacol.2017;8:656. https://doi.org/10.3389/fphar.2017.00656
Ahjel SW, Humadi SS, Awad SM, El-Shehry MF, Mansour YE, Elkader El-Rashedy AA. Novel pyrimidine derivatives and black cumin as xanthine oxidase inhibitors: Synthesis, docking study and formulation. Pak J Pharm Sci. 2024;37(5). http://doi.org/10.36721/PJPS.2024.37.5.REG.1151-1161.1
Hafeez A, Rehan AM, Hakim Z, Munir A, Khan RN, Khokhar A, editors. Nigella sativa Seeds Protective Ability in Pyrazinamide Induced Hyperuricemia in Mice. Proc. 2022. https://doi.org/10.47489/PSZMC-825361-44-48
Dera AA, Rajagopalan P, Alfhili MA, Ahmed I, Chandramoorthy HC. Thymoquinone attenuates oxidative stress of kidney mitochondria and exerts nephroprotective effects in oxonic acid?induced hyperuricemia rats. Biofactors. 2020;46(2):292-300. https://doi.org/10.1002/biof.1590
This work is licensed under a 