Protective Effect of HMG-CoA Reductase Inhibitor Rosuvastatin on Doxorubicin-Induced Cognitive Impairment, Oxidative Stress and Neuroinflammation: Possible Role of CREB, ERK1/2, and BDNF

Abd El-Aal SA, AbdElrahman M, Reda AM, Afify H, Ragab GM, El-Gazar AA, Ibrahim SSA (2022) Galangin mitigates DOX-induced cognitive impairment in rats: Implication of NOX-1/Nrf-2/HMGB1/TLR4 and TNF-α/MAPKs/RIPK/MLKL/BDNF. NeuroToxicology 92:77–90

Abdallah HM, El Sayed NS, Sirwi A, Ibrahim SRM, Mohamed GA, Abdel Rasheed NO (2021) Mangostanaxanthone IV ameliorates Streptozotocin-Induced Neuro-Inflammation, amyloid deposition, and Tau hyperphosphorylation via modulating PI3K/Akt/GSK-3β pathway. Biology (Basel) 10(12):1298

CAS  PubMed  Google Scholar 

Abdel-Aziz AK, Mantawy EM, Said RS, Helwa R (2016) The tyrosine kinase inhibitor, Sunitinib malate, induces cognitive impairment in vivo via dysregulating VEGFR signaling, apoptotic and autophagic machineries. Exp Neurol 283(Pt A):129–141

Article  CAS  PubMed  Google Scholar 

Abdelaziz HA, Hamed MF, Ghoniem HA, Nader MA, Suddek GM (2025) Empagliflozin mitigates PTZ-Induced seizures in rats: modulating Npas4 and CREB-BDNF signaling pathway. J Neuroimmune Pharmacol 20(1):5

Article  PubMed Central  PubMed  Google Scholar 

Alhowail AH, Eggert M, Bloemer J, Pinky PD, Woodie L, Bhattacharya S, Bhattacharya D, Buabeid MA, Smith B, Dhanasekaran M, Piazza G, Reed MN, Escobar M, Arnold RD, Suppiramaniam V (2023) Phenyl-2-aminoethyl Selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment. PLoS ONE 18(11):e0294280

Article  PubMed Central  PubMed  Google Scholar 

Ali MA, Menze ET, Tadros MG, Tolba MF (2020) Caffeic acid phenethyl ester counteracts doxorubicin-induced chemobrain in Sprague-Dawley rats: emphasis on the modulation of oxidative stress and neuroinflammation. Neuropharmacology 181:108334

Article  CAS  PubMed  Google Scholar 

Ali AE, Elsherbiny DM, Azab SS, El-Demerdash E (2022) The diuretic Amiloride attenuates doxorubicin-induced chemobrain in rats: behavioral and mechanistic study. Neurotoxicology 88:1–13

Article  CAS  PubMed  Google Scholar 

Alsaud MM, Alhowail AH, Aldubayan MA, Almami IS (2023) The ameliorative effect of Pioglitazone against neuroinflammation caused by doxorubicin in rats. Molecules 28(12):4775

Article  PubMed Central  CAS  PubMed  Google Scholar 

Amidfar M, de Oliveira J, Kucharska E, Budni J, Kim YK (2020) The role of CREB and BDNF in neurobiology and treatment of Alzheimer’s disease. Life Sci 15(257):118020

Article  Google Scholar 

Aski ML, Rezvani ME, Khaksari M, Hafizi Z, Pirmoradi Z, Niknazar S, Mehrjerdi FZ (2018) Neuroprotective effect of Berberine chloride on cognitive impairment and hippocampal damage in experimental model of vascular dementia. Iran J Basic Med Sci 21(1):53–58

PubMed Central  PubMed  Google Scholar 

Cicek B, Genc S, Yeni Y, Kuzucu M, Cetin A, Yildirim S, Bolat I, Kantarci M, Hacimuftuoglu A, Lazopoulos G, Tsatsakis A, Tsarouhas K, Taghizadehghalehjoughi A (2022) Artichoke (Cynara Scolymus) methanolic leaf extract alleviates Diethylnitrosamine-Induced toxicity in BALB/c mouse brain: involvement of oxidative stress and apoptotically related Klotho/PPARγ signaling. J Pers Med 12(12):2012

Article  PubMed Central  PubMed  Google Scholar 

Domoki F, Kis B, Gáspár T, Snipes JA, Bari F, Busija DW (2010) Rosuvastatin induces delayed preconditioning against L-glutamate excitotoxicity in cultured cortical neurons. Neurochem Int 56(3):404–409

Article  CAS  PubMed  Google Scholar 

Ebrahim NA, Elnagar MR, El-Gamal R, Habotta OA, Albadawi EA, Albadrani M, Bahashwan AS, Hassan HM (2024) Melatonin mitigates doxorubicin induced chemo brain in a rat model in a NRF2/p53-SIRT1 dependent pathway. Heliyon 10(19):e38081

Article  PubMed Central  CAS  PubMed  Google Scholar 

Ekici M, Güneş H, Gezer A (2024) Sinapic acid reduces Pentylenetetrazol induced seizures in rats. Indian J Exp Biol 62:379–392

CAS  Google Scholar 

Ekladious ST, El Sayed NS (2019) Effect of Pioglitazone and Simvastatin in lipopolysaccharide-induced amyloidogenesis and cognitive impairment in mice: possible role of glutamatergic pathway and oxidative stress. Behav Pharmacol 30(1):5–15

Article  CAS  PubMed  Google Scholar 

Fang L, Song Y, Jin H, Liu Y, Gou S (2024) An approach to apply BDNF targeting Fe3O4-Based nanoparticles as multifunctional Anti-Alzheimer agents. Small 20(48):e2403625

Article  PubMed  Google Scholar 

Gamal NK, El-Naga RN, Ayoub IM, George MY (2025) Neuromodulatory effect of Troxerutin against doxorubicin and cyclophosphamide-induced cognitive impairment in rats: potential crosstalk between gut-brain and NLRP3 inflammasome axes. Int Immunopharmacol 149:114216

Article  CAS  PubMed  Google Scholar 

Gao L, Zhang Y, Sterling K, Song W (2022) Brain-derived neurotrophic factor in Alzheimer’s disease and its pharmaceutical potential. Transl Neurodegener 11(1):4

Article  PubMed Central  CAS  PubMed  Google Scholar 

Guo Y, Zou G, Qi K, Jin J, Yao L, Pan Y, Xiong W (2021) Simvastatin impairs hippocampal synaptic plasticity and cognitive function in mice. Mol Brain 14(1):41

Article  PubMed Central  CAS  PubMed  Google Scholar 

Guo T, Wang Y, Hayat MA, Si Y, Ni Y, Zhang J, Qiu Y, Zeng Y, Cao Y, Hong Y, Chen B, Hu J (2025) Recombinant human heavy-chain ferritin nanoparticles loaded with Rosuvastatin attenuates secondary brain injury in intracerebral hemorrhage. Int J Biol Macromol 302:140542

Article  CAS  PubMed  Google Scholar 

Husain I, Akhtar M, Vohora D, Abdin MZ, Islamuddin M, Akhtar MJ, Najmi AK (2017) Rosuvastatin attenuates high-salt and cholesterol diet ınduced neuroinflammation and cognitive ımpairment via preventing nuclear factor kappab pathway. Neurochem Res 42:2404–2416

Article  CAS  PubMed  Google Scholar 

Lal R, Dharavath RN, Chopra K (2024) Nrf2 signaling pathway: a potential therapeutic target in combating oxidative stress and neurotoxicity in chemotherapy-ınduced cognitive ımpairment. Mol Neurobiol 61(2):593–608

Article  CAS  PubMed  Google Scholar 

Lamb YN (2020) Rosuvastatin/ezetimibe: a review in hypercholesterolemia. Am J Cardiovasc Drugs 20:381–392

Article  CAS  PubMed  Google Scholar 

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(T)(-Delta Delta C) method. Methods 25:402–408

Article  CAS  PubMed  Google Scholar 

Ludka FK, Cunha MP, Dal-Cim T, Binder LB, Constantino LC, Massari CM, Martins WC, Rodrigues ALS, Tasca CI (2017) Atorvastatin protects from Aβ 1–40-induced cell damage and depressive-like behavior via ProBDNF cleavage. Mol Neurobiol 54:6163–6173

Article  CAS  PubMed  Google Scholar 

Mani V, Alshammeri BS (2023) Quetiapine moderates Doxorubicin-Induced cognitive deficits: influence of oxidative stress, neuroinflammation, and cellular apoptosis. Int J Mol Sci 24(14):11525

Article  PubMed Central  CAS  PubMed  Google Scholar 

Mani V, Arfeen M, Rabbani SI, Shariq A, Amirthalingam P (2022) Levetiracetam ameliorates doxorubicin-induced chemobrain by enhancing cholinergic transmission and reducing neuroinflammation using an experimental rat model and molecular Docking study. Molecules 27(21):7364

Article  PubMed Central  CAS  PubMed  Google Scholar 

Mounier NM, Wahdan SA, Gad AM, Azab SS (2021) Role of inflammatory, oxidative, and ER stress signaling in the neuroprotective effect of Atorvastatin against doxorubicin-induced cognitive impairment in rats. Naunyn Schmiedebergs Arch Pharmacol 394(7):1537–1551

Article  CAS  PubMed  Google Scholar 

Muneeb M, Mansou SM, Saleh S, Mohammed RA (2022) Vitamin D and Rosuvastatin alleviate type-II diabetes-induced cognitive dysfunction by modulating neuroinflammation and Canonical/noncanonical Wnt/β-catenin signaling. PLoS ONE 17(11):e0277457

Article  PubMed Central  CAS  PubMed  Google Scholar 

Murthy SB, Zhang C, Shah S, Schwamm LH, Fonarow GC, Smith EE, Bhatt DL, Ziai WC, Kamel H, Sheth KN (2023) Antithrombotic and Statin prescription after intracerebral hemorrhage in the get with the Guidelines-Stroke registry. Stroke 54(12):2972–2980

Article  PubMed Central  CAS  PubMed  Google Scholar 

Comments (0)

No login
gif