Abstract
Background
There is limited data regarding the hazardous effect of gentamicin (GM) on the uterus and whether or not vinpocetine (Vinpo) ameliorates it. The present study aimed to identify the possible protective effect of Vinpo in GM-induced uterine injury in rats.
Methods
Female rats were assorted in control-group, Vinpo-group, GM-group, and Vinpo plus GM group. Serum and uterine GM concentration were measured. Uterine oxidative stress parameters besides inflammatory and apoptotic biomarkers were evaluated. Uterine histopathological examination and interlukin-1beta (IL-1β) immune-histochemical study were detected.
Results
GM significantly increased uterine oxidative stress, inflammatory and apoptotic biomarkers. Histopathological picture of uterine damage and increased IL-1β immunoexpression were detected. Vinpo significantly ameliorated the distributed GM concentration, oxidative stress, inflammatory and apoptotic biomarkers with a prompt improvement in histopathological picture and a decrease in IL-1β immunoexpression.
Conclusion
Vinpo protective effect against GM-induced uterine injury involves modulation of inflammasome/caspase-1/IL-1β signaling pathway.
Similar content being viewed by others
Data availability
All data are available in Prism files as supplementary material on request.
References
Abdeen A, Amir Samir A, Elkomy A, Aboubaker M, Habotta OA et al (2021) The potential antioxidant bioactivity of date palm fruit against gentamicin-mediated hepato-renal injury in male albino rats. Biomed Pharmacother 143:112154. https://doi.org/10.1016/j.biopha.2021.112154
Abdelzaher WY, El-Tahawy NFG, Ali ASA, Mohamed HA, Welson LDAA (2023) Rivastigmine ameliorates gentamicin experimentally induced acute renal toxicity. Int Immunopharmacol 114:109492
Nadeem RI, Aboutaleb AS, Younis NS, Ahmed HI (2023) Diosmin mitigates gentamicin-induced nephrotoxicity in rats: insights on miR-21 and -155 expression, Nrf2/HO-1 and p38-MAPK/NF-_B pathways. Toxics 11:48. https://doi.org/10.3390/toxics11010048
Aly H (2019) Testicular toxicity of gentamicin in adult rats: ameliorative effect of lycopene. Hum Exp Toxicol 38(11):1302–1313. https://doi.org/10.1177/0960327119864160
Taha M, Elazab ST, Saati AA, Ahmed GS, Baokbah TAS, Fathy K, El-Shenbaby I, Abdelbagi O, Hassan MAE, Ibrahim MM, Badawy AM (2022) Zamzam water ameliorates gentamicin-induced testicular toxicity in a rat model via targeting sperm parameters, testicular tissue oxidative insult, inflammation, apoptosis, and pituitary-gonadal axis. Toxics 11(1):2. https://doi.org/10.3390/toxics11010002
Samy M, Ahmed RSI, Shanab O et al (2023) Protective and ameliorative effects of curcumin and/or quercetin against gentamicin induced testicular damage in rats. SVU-IJVS 6(1):63–73
Paradelis AG, Tarlatzis BC, Triantaphyllidis CJ, El-Messidi MM, Papaloucas AC (1982) Effect of aminoglycoside antibiotics on the contractility of the uterus. Methods Find Exp Clin Pharmacol 4(5):337–341
Chen C, Chen Y, Wu P, Chen B (2014) Update on new medicinal applications of gentamicin: evidence-based review. J Formos Med Assoc 113(2):72–82. https://doi.org/10.1016/j.jfma.2013.10.002
Al-Kuraishy HM, Alexiou A, Papadakis M, Elhussieny O, Saad HM, Batiha GE (2023) New insights on the potential effect of vinpocetine in Parkinson’s disease: one of the neglected warden and baffling topics. Metab Brain Dis 38(6):1831–1840. https://doi.org/10.1007/s11011-023-01254-y
Deshmukh R, Sharma V, Mehan S, Sharma N, Bedi KL (2009) Amelioration of intracerebroventricular streptozotocin induced cognitive dysfunction and oxidative stress by vinpocetine—a PDE1 inhibitor. Eur J Pharmacol 620(1–3):49–56
Ishola IO, Awogbindin IO, Olubodun-Obadun TG, Olajiga AE, Adeyemi OO (2023) Vinpocetine prevents rotenone-induced Parkinson disease motor and non-motor symptoms through attenuation of oxidative stress, neuroinflammation and α-synuclein expressions in rats. Neurotoxicology 96:37–52
Lee JY, Komatsu K, Lee BC, Miyata M, Bohn AO et al (2015) Vinpocetine inhibits streptococcus pneumoniae–induced upregulation of mucin MUC5AC expression via induction of MKP-1 phosphatase in the pathogenesis of otitis media. J Immunol 194:5990–5998
Ali AA, El-Zaitony AS, Al-Haleem ENA (2017) Evaluation of therapeutic efficacy of Vinpocetine in adjuvant induced arthritis model in rats. J Pain Manage Med 2:3. https://doi.org/10.4172/jpmme.1000115
Sonkar AB, Kumar P, Kumar A et al (2023) Vinpocetine mitigates DMH-induce pre-neoplastic colon damage in rats through inhibition of pro-inflammatory cytokines. Int Immunopharmacol 119:110236
Bagoly E, Fehér G, Szapáry L (2017) The role of vinpocetine in the treatment of cerebrovascular diseases based in human studies. Orv Hetil 148:1353–1358
Mohammed AS, Al-Hassani AN, Alrawi RA, Tawfeeq RD (2023) The protective effect of taurine, piracetam and vinpocetine on etoposide-induced inflammation and brain injury in the serum of female albino rats. Ecancermedicalscience 17:1499. https://doi.org/10.3332/ecancer.2023.1499
Liu RT, Wang A, To E, Gao J, Cao S et al (2014) Vinpocetine inhibits amyloid-beta induced activation of NF-κB, NLRP3 inflammasome and cytokine production in retinal pigment epithelial cells. Exp Eye Res 127:49–58
Wei S, Ma W, Zhang B, Li W (2021) NLRP3 inflammasome: a promising therapeutic target drug-induced toxicity. Front Cell Dev Biol 9:634607. https://doi.org/10.3389/fcell.2021.634607
Omar ME, Salam A, Hamdy SM (2016) Effect of piracetam, vincamine, vinpocetine, and donepezil on oxidative stress and neurodegeneration induced by aluminum chloride in rats. Comp Clin Pathol 25:305–318. https://doi.org/10.1007/s00580-015-2182-0
Botros SR, Matouk AI, Anter A, Khalifa MM, Heeba GH (2022) Protective effect of empagliflozin on gentamicin-induced acute renal injury via regulation of SIRT1/NF-κB signaling pathway. Environ Toxicol Pharmacol 1(94):103907
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310
Ridnour LA, Sim JE, Hayward MA, Wink DA, Martin SM, Buettner GR, Spitz DR (2000) A spectrophotometric method for the direct detection and quantitation of nitric oxide, nitrite, and nitrate in cell culture media. Anal Biochem 281(2):223–229. https://doi.org/10.1006/abio.2000.4583
Soria G, Ofri-Shahak M, Haas I, Yaal-Hahoshen N et al (2011) Inflammatory mediators in breast cancer: coordinated expression of TNFα & IL-1β with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition. BMC Cancer 11:1–20
Refaie MM, El-Hussieny M (2017) The role of interleukin-1b and its antagonist (diacerein) in estradiol benzoate-induced endometrial hyperplasia and atypia in female rats. Fundam Clin Pharmacol 31(4):438–446
Hasan HF, Hamzah AM, Zghair ZR (2013) Study the comparative effect between Cyperus esculentus seeds extract and gentamicin on induced endometritis in mice. JPCS 7:40–47
Ahmadvand H, Nouryazdan N, Nasri M, Adibhesami G, Babaeenezhad E (2020) Renoprotective effects of gallic acid against gentamicin nephrotoxicity through amelioration of oxidative stress in rats. Braz Arch Biol Technol 63:e20200131
Ali DM, Mahmoud MH, Rifaai RA, Fawzy MA, Atta M, Welson NN, Batiha GS, Alexiou A, Papadakis M, Abdelzaher WY (2023) Diacerein modulates TLR4/ NF-κB/ IL-1β and TRPC1/CHOP signalling pathways in gentamicin-induced parotid toxicity in rats. J Cell Mol Med 27:1735–1744
Rao AM, Anand U, Anand CV (2011) Myeloperoxidase in chronic kidney disease. Ind J Clin Biochem 26(1):28–31
Refaie MM, El-Hussieny M, Bayoumi AM, Shehata S, Welson NN, Abdelzaher WY (2022) Simvastatin cardioprotection in cyclophosphamide-induced toxicity via the modulation of inflammasome/caspase1/interleukin1β pathway. Hum Exp Toxicol 41:1–11. https://doi.org/10.1177/09603271221111440
Yang Y, Wang H, Kouadir M et al (2019) Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis 10:128
Li R, Yang X, Yu Y et al (2016) C1q/tumor necrosis factor related protein 6 (CTRP6) is involved in gentamicin-induced acute kidney injury in rats. Chin J Cell Mol Immunol 32:1458–1461
Ruiz-Miyazawa KW, Zarpelon AC, Pinho-Ribeiro FA et al (2015) Vinpocetine reduces carrageenan-induced inflammatory hyperalgesia in mice by inhibiting oxidative stress, cytokine production and NF-Κb activation in the paw and spinal cord. PLoS ONE 10:e0118942
Al-Kuraishy HM, Al-Gareeb AI, Al-Nami MS (2019) Vinpocetine improves oxidative stress and pro-inflammatory mediators in acute kidney injury. Int J Prev Med 10:142
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Author information
Authors and Affiliations
Contributions
AG and WYA contributed in selecting the point of research, data analysis, drafting, revising the article, give final approval of the version to be published, and agree to be accountable for all aspects of the work. MEA performed and wrote the part of histopathology, and immunohistochemistry. MA participated in data analysis and methodology. MAF performed Western blotting measurements. AH, MKA and FFA participated in writing and editing the manuscript. All authors revised the final copy of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
All authors declare they have no conflict of interest.
Ethics statement
The handling and treatment of rats adhered to the guidelines outlined by the Institutional Ethical Committee (Faculty of Medicine, Minia University, Egypt) of experimental animals and also followed the National Institutes of Health’s (NIH) Guide for the care and utilization of laboratory animals (Approval No: 397:2022; the approval date: 13/12/2022), Faculty of Medicine, Minia University, Egypt.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Geddawy, A., Attya, M.E., Hegazy, A. et al. The ameliorative effect of vinpocetine against gentamicin-induced uterine-injury in rats involves the inflammasome/caspase-1/IL-1β pathway. Mol Biol Rep 51, 655 (2024). https://doi.org/10.1007/s11033-024-09556-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11033-024-09556-9