Skip to content
2000
Volume 22, Issue 5
  • ISSN: 1570-1638
  • E-ISSN: 1875-6220

Abstract

Background

Atorvastatin (ATO) is an HMG-CoA reductase inhibitor used to lower blood cholesterol, but it causes renal injury in high doses. Thymoquinone (TQ), is a natural antioxidant that has been shown to protect the kidney through its antiinflammatory, antioxidant, & antiapoptotic, effects.

Objective

The current study aimed to investigate whether posttreatment TQ could reverse ATO-induced renal injury, and the possible mechanism of action by which TQ produced such an effect.

Methods

Forty adult male rats were divided into 4 groups: (control; TQ-treated; ATO-treated; ATO plus TQ-treated). Blood and kidney tissue samples were tested for kidney functions, oxidative stress and apoptosis markers, and morphometric analyses of the histopathological and ultrastructural evaluations. Statistical analyses were done using JASP, Shapiro-Wilk, and Levene’s test. ANOVA and Kruskal-Wallis tests were done to determine differences between groups. The significance level was set at <.05.

Results

The ATO-treated group showed abnormal outcome measures including kidney functions, oxidative stress and apoptotic markers, and morphometric analyses of the histopathological and ultrastructural findings. Post-treatment TQ improved all outcome measures.

Conclusion

Posttreatment TQ could reverse oxidative stress-induced renal injury produced by high-dose ATO, suggesting a potential clinical application in patients with renal insufficiency with hypercholesterolemia.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cddt/10.2174/0115701638333036250106040617
2025-01-23
2025-09-25

  • From This Site

    /content/journals/cddt/10.2174/0115701638333036250106040617
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. PloskerG.L. Lyseng-WilliamsonK.A. Atorvastatin.PharmacoEconomics200725121031105310.2165/00019053‑200725120‑00005 18047388
     [Google Scholar]
  2. PerkJ. GrahamI. De BackerG. Prevention of cardiovascular disease: New guidelines, new tools, but challenges remain.Heart2014100967567710.1136/heartjnl‑2014‑305650 24667311
     [Google Scholar]
  3. Hippisley-CoxJ CouplandC Unintended effects of statins in men and women in England and Wales: Population based cohort study using the QResearch database. BMJ2010340may19 4c2197710.1136/bmj.c2197 20488911
     [Google Scholar]
  4. ChungY.H. LeeY.C. ChangC.H. LinM.S. LinJ.W. LaiM.S. Statins of high versus low cholesterol‐lowering efficacy and the development of severe renal failure.Pharmacoepidemiol. Drug Saf.201322658359210.1002/pds.3433 23526815
     [Google Scholar]
  5. LenihanC.R. LafayetteR.A. High-potency statins and acute kidney injury-associated hospitalizations.Am. J. Kidney Dis.201362587787910.1053/j.ajkd.2013.07.006 23972947
     [Google Scholar]
  6. XuN. JiangS. PerssonP.B. PerssonE.A.G. LaiE.Y. PatzakA. Reactive oxygen species in renal vascular function.Acta Physiol. (Oxf.)20202294e1347710.1111/apha.13477 32311827
     [Google Scholar]
  7. NathK.A. NorbyS.M. Reactive oxygen species and acute renal failure.Am. J. Med.2000109866567810.1016/S0002‑9343(00)00612‑4 11099687
     [Google Scholar]
  8. NasriH. HasanpourZ. NematbakhshM. AhmadiA. Rafieian-KopaeiM. The effect of the various doses of atorvastatin on renal tubular cells; an experimental study.J. Nephropathol.20165311111510.15171/jnp.2016.20 27540539
     [Google Scholar]
  9. SelvendiranK. SakthisekaranD. Chemopreventive effect of piperine on modulating lipid peroxidation and membrane bound enzymes in benzo(a)pyrene induced lung carcinogenesis.Biomed. Pharmacother.200458426426710.1016/j.biopha.2003.08.027 15183854
     [Google Scholar]
  10. TalebiM. ZarshenasM.M. YazdaniE. MoeinM. Preparation and evaluation of possible antioxidant activities of rose traditional tablet“(Qurs-e-Vard)” A selected Traditional Persian Medicine (TPM) formulation via various procedures.Curr. Drug Discov. Technol.2021185e2809202018638110.2174/1570163817666200929114517 32990537
     [Google Scholar]
  11. SaadatS. AslaniM.R. GhoraniV. KeyhanmaneshR. BoskabadyM.H. The effects of Nigella Sativa on respiratory, allergic and immunologic disorders, evidence from experimental and clinical studies, a comprehensive and updated review.Phytother. Res.20213562968299610.1002/ptr.7003 33455047
     [Google Scholar]
  12. MalikS. SinghA. NegiP. KapoorV.K. Thymoquinone: A small molecule from nature with high therapeutic potential.Drug Discov. Today202126112716272510.1016/j.drudis.2021.07.013 34303824
     [Google Scholar]
  13. ElsherbinyN.M. El-SherbinyM. Thymoquinone attenuates Doxorubicin-induced nephrotoxicity in rats: Role of Nrf2 and NOX4.Chem. Biol. Interact.201422310210810.1016/j.cbi.2014.09.015 25268985
     [Google Scholar]
  14. HassanS.S. RazzaqueA. AhmadZ. PazdernikV. AminS.N. Does posttreatment thymoquinone reverse high-dose atorvastatin-induced hepatic oxidative injury in rats?Can. J. Physiol. Pharmacol.2018961515910.1139/cjpp‑2017‑0599 28968507
     [Google Scholar]
  15. Guide for the care and use of laboratory animals.8th edWashington, DCNational Academies Press2011
     [Google Scholar]
  16. HassanS.S. ThomannC. EttarhR. AhmadZ. Possible protective role of silybin against polymyxin E‐induced toxic effect in rat kidneys: A biochemical approach.Neurourol. Urodyn.20173682003201010.1002/nau.23249 28257552
     [Google Scholar]
  17. LinY. XuY. ZhengX. ZhangJ. LiuJ. WuG. Astragaloside IV ameliorates streptozotocin induced pancreatic β-cell apoptosis and dysfunction through SIRT1/P53 and Akt/GSK3β/Nrf2 signaling pathways.Diabetes Metab. Syndr. Obes.20221513114010.2147/DMSO.S347650 35046684
     [Google Scholar]
  18. HassanS.M.S. YouakimM.F. RizkA.A.E. ThomannC. AhmadZ. Does silybin protect against toxicity induced by polymyxin E in rat kidney?Neurourol. Urodyn.20173651278128710.1002/nau.23109 27574823
     [Google Scholar]
  19. JASP Team. JASP (Version 0.18.3).[Computer software 2024. Available from:https://jasp-stats.org/
     [Google Scholar]
  20. QiX-F. ZhengL. LeeK-J. HMG-CoA reductase inhibitors induce apoptosis of lymphoma cells by promoting ROS generation and regulating Akt, Erk and p38 signals via suppression of mevalonate pathway.Cell Death Dis.201342e518e810.1038/cddis.2013.44 23449454
     [Google Scholar]
  21. FassettR.G. CoombesJ.S. Statins in acute kidney injury: Friend or foe?BMJ2013346f153110.1136/bmj.f1531 23511948
     [Google Scholar]
  22. ReddyA.G. RaoG.S. HarithaC. JyothiK. ReddyG.D. Interaction study on garlic and atorvastatin with reference to nephrotoxicity in dyslipidaemic rats.Toxicol. Int.2010172909310.4103/0971‑6580.72678 21170253
     [Google Scholar]
  23. CaiJ. YuX. ZhangB. Atorvastatin improves survival of implanted stem cells in a rat model of renal ischemia-reperfusion injury.Am. J. Nephrol.201439646647510.1159/000362623 24854145
     [Google Scholar]
  24. DormuthC.R. HemmelgarnB.R. PatersonJ.M. Use of high potency statins and rates of admission for acute kidney injury: Multicenter, retrospective observational analysis of administrative databases.BMJ201334f88010.1136/bmj.f880 23511950
     [Google Scholar]
  25. RidkerP.M. DanielsonE. FonsecaF.A.H. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.J. Vasc. Surg.200949253410.1016/j.jvs.2008.12.037
     [Google Scholar]
  26. SverrissonK. AxelssonJ. RippeA. AsgeirssonD. RippeB. Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo.Am. J. Physiol. Renal Physiol.20153099F800F80610.1152/ajprenal.00111.2015 26290366
     [Google Scholar]
  27. KaymakE. ÖztürkE. Akİn AT, Karabulut D, Yakan B. Thymoquinone alleviates doxorubicin induced acute kidney injury by decreasing endoplasmic reticulum stress, inflammation and apoptosis.Biotech. Histochem.202297862263410.1080/10520295.2022.2111465 35989671
     [Google Scholar]
  28. LiaoD. XiangD. DangR. Neuroprotective effects of dl‐3‐n‐butylphthalide against doxorubicin‐induced neuroinflammation, oxidative stress, endoplasmic reticulum stress, and behavioral changes.Oxid. Med. Cell. Longev.201820181912560110.1155/2018/9125601 30186550
     [Google Scholar]
  29. WangZ. HuangW. LiH. Synergistic action of inflammation and lipid dysmetabolism on kidney damage in rats.Ren. Fail.201840117518210.1080/0886022X.2018.1450763 29569980
     [Google Scholar]
  30. ShahS.V. BaligaR. RajapurkarM. FonsecaV.A. Oxidants in chronic kidney disease.J. Am. Soc. Nephrol.2007181162810.1681/ASN.2006050500 17167116
     [Google Scholar]
  31. LuH. ZhenJ. WuT. Superoxide dismutase mimetic drug tempol aggravates anti-GBM antibody-induced glomerulonephritis in mice.Am. J. Physiol. Renal Physiol.20102992F445F45210.1152/ajprenal.00583.2009 20504883
     [Google Scholar]
  32. YoshiokaT. HommaT. MeyrickB. Oxidants induce transcriptional activation of manganese superoxide dismutase in glomerular cells.Kidney Int.199446240541310.1038/ki.1994.288 7967352
     [Google Scholar]
  33. BedardK. KrauseK.H. The NOX family of ROS-generating NADPH oxidases: Physiology and pathophysiology.Physiol. Rev.200787124531310.1152/physrev.00044.2005 17237347
     [Google Scholar]
  34. LandmesserU. DikalovS. PriceS.R. Oxidation of tetrahydrobiopterin leads to uncoupling of endothelial cell nitric oxide synthase in hypertension.J. Clin. Invest.200311181201120910.1172/JCI200314172 12697739
     [Google Scholar]
  35. MengX. Nikolic-PatersonD.J. LanH.Y. TGF-β: The master regulator of fibrosis.Nat. Rev. Nephrol.201612632533810.1038/nrneph.2016.48 27108839
     [Google Scholar]
  36. DeraA.A. RajagopalanP. AlfhiliM.A. AhmedI. ChandramoorthyH.C. Thymoquinone attenuates oxidative stress of kidney mitochondria and exerts nephroprotective effects in oxonic acid‐induced hyperuricemia rats.Biofactors202046229230010.1002/biof.1590 31758843
     [Google Scholar]
  37. GarvinJ.L. OrtizP.A. The role of reactive oxygen species in the regulation of tubular function.Acta Physiol. Scand.2003179322523210.1046/j.0001‑6772.2003.01203.x 14616238
     [Google Scholar]
  38. SinghD. KaurR. ChanderV. ChopraK. Antioxidants in the prevention of renal disease.J. Med. Food20069444345010.1089/jmf.2006.9.443 17201628
     [Google Scholar]
  39. RatliffB.B. AbdulmahdiW. PawarR. WolinM.S. Oxidant mechanisms in renal injury and disease.Antioxid. Redox Signal.201625311914610.1089/ars.2016.6665 26906267
     [Google Scholar]
  40. LiS. ZhaoZ. Thymoquinone alleviates cisplatin-induced kidney damage by reducing apoptosis in a rat model.Heliyon2024102e2484010.1016/j.heliyon.2024.e24840 38304804
     [Google Scholar]
  41. HannanM.A. ZahanM.S. SarkerP.P. MoniA. HaH. UddinM.J. Protective effects of black cumin (Nigella sativa) and its bioactive constituent, thymoquinone against kidney injury: An aspect on pharmacological insights.Int. J. Mol. Sci.20212216907810.3390/ijms22169078 34445781
     [Google Scholar]
  42. BashmailH.A. AlamoudiA.A. NoorwaliA. HegazyG.A. AjabnoorG.M. Al-AbdA.M. Thymoquinone enhances paclitaxel anti-breast cancer activity via inhibiting tumor-associated stem cells despite apparent mathematical antagonism.Molecules202025242610.3390/molecules25020426 31968657
     [Google Scholar]
  43. AlhusainiA.M. FaddahL.M. El OrabiN.F. HasanI.H. Role of some natural antioxidants in the modulation of some proteins expressions against sodium fluoride-induced renal injury.BioMed Res. Int.201820181910.1155/2018/5614803 30050936
     [Google Scholar]
  44. FatfatZ. FatfatM. Gali-MuhtasibH. Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells.World J. Clin. Oncol.202112752254310.5306/wjco.v12.i7.522 34367926
     [Google Scholar]
  45. El-FarA.H. GoduguK. NoreldinA.E. Thymoquinone and costunolide induce apoptosis of both proliferative and doxorubicin-induced-senescent colon and breast cancer cells.Integr. Cancer Ther.2021201534735421103545010.1177/15347354211035450 34490824
     [Google Scholar]
  46. SaddiqA.A. El-FarA.H. MohamedS.A. AlmaghrabiO.A. MousaS.A. Curcumin and thymoquinone combination attenuates breast cancer cell lines’ progression.Integr. Cancer Ther.2022211534735422109953710.1177/15347354221099537 35583244
     [Google Scholar]
  47. SalahA. SleemR. Abd-ElazizA. KhalilH. Regulation of NF-κB expression by thymoquinone; a role in regulating pro-inflammatory cytokines and programmed cell death in hepatic cancer cells.Asian Pac. J. Cancer Prev.202324113739374810.31557/APJCP.2023.24.11.3739 38019231
     [Google Scholar]
  48. Abd-ElkareemM. SolimanM. Abd El-RahmanM.A.M. Abou KhalilN.S. Effect of Nigella sativa L. seed on the kidney of monosodium glutamate challenged rats.Front. Pharmacol.20221378998810.3389/fphar.2022.789988 35814230
     [Google Scholar]
  49. BouhlelA. BejaouiM. Ben MosbahI. Thymoquinone protects rat liver after partial hepatectomy under ischaemia/reperfusion through oxidative stress and endoplasmic reticulum stress prevention.Clin. Exp. Pharmacol. Physiol.201845994395110.1111/1440‑1681.12961 29733120
     [Google Scholar]
/content/journals/cddt/10.2174/0115701638333036250106040617
Loading
Renal Impairment Caused by Statins in Rats Can be Restored by Thymoquinone
Current Drug Discovery Technologies 22, e15701638333036 (2025); https://doi.org/10.2174/0115701638333036250106040617
/content/journals/cddt/10.2174/0115701638333036250106040617
/content/journals/cddt/10.2174/0115701638333036250106040617
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): apoptosis; Atorvastatin; histopathology; kidney; oxidative stress; thymoquinone

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test