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image of Investigation of the Effect of Rose Oxide in Animal Models of Paclitaxel-induced Neuropathic Pain in Rats

Abstract

Introduction

Neuropathy caused by chemotherapy, a dose-limiting neurotoxic side effect, often leads to treatment discontinuation. About 30 to 70% of patients treated with paclitaxel experience peripheral neuropathy due to the drug combination and dosage. Given the significant prevalence of neuropathy in individuals who have undergone chemotherapy treatments and the growing need for new therapeutic approaches, including those based on natural resources, it is imperative to investigate substances capable of mitigating this adverse effect.

Methods

Natural plant compounds are often used to treat various pathological conditions due to superior treatment options and minimal side effects. Rose oxide (RO), monoterpenes present in several essential oils, have demonstrated anti-inflammatory activity by inhibiting IL-1β production and leukocyte migration. Therefore, the present study aimed to investigate the effect of rose oxide in its free form on animal models of neuropathic pain induced by antineoplastics in rats. Neuropathic pain was induced by paclitaxel at a dose of 20 mg/kg i.p. for four consecutive days and treated with rose oxide at doses of 12.5, 25, and 50 mg/kg and after this period, behavioral analyzes (von Frey mechanical allodynia, acetone test and open field), biochemical, hematological and assessment of oxidative stress (malondialdehyde levels). The results suggested that rose oxide has antinociceptive activity in animal models of antineoplastic-induced neuropathic pain in rats.

Results

Furthermore, treatment with RO did not show significant adverse effects on biochemical and hematological parameters, with the exception of the 12.5 mg/kg dose of RO affected creatinine levels and all doses of TGP, while the highest dose (50 mg/kg) caused changes in total proteins and albumin, suggesting a more binding strong with plasma proteins. Finally, treatment with RO 25 mg/kg significantly altered malondialdehyde (MDA) levels.

Conclusion

These results suggest that the use of RO in its free form may be a promising option for the treatment of antineoplastic-induced neuropathic pain in humans. However, further studies are needed to confirm these findings and evaluate safety and efficacy.

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2025-02-28
2025-05-24
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References

  1. Jordan M.A. Wilson L. Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 2004 4 4 253 265 10.1038/nrc1317 15057285
    [Google Scholar]
  2. Dranitsaris G. King J. Kaura S. Yu B. Zhang A. Nab-paclitaxel, docetaxel, or solvent-based paclitaxel in metastatic breast cancer: A cost-utility analysis from a Chinese health care perspective. Clinicoecon. Outcomes Res. 2015 7 249 256 10.2147/CEOR.S82194 25999749
    [Google Scholar]
  3. Park S.B. Lin C.S.Y. Krishnan A.V. Friedlander M.L. Lewis C.R. Kiernan M.C. Early, progressive, and sustained dysfunction of sensory axons underlies paclitaxel‐induced neuropathy. Muscle Nerve 2011 43 3 367 374 10.1002/mus.21874 21321953
    [Google Scholar]
  4. Lees J.G. Makker P.G.S. Tonkin R.S. Abdulla M. Park S.B. Goldstein D. Moalem-Taylor G. Immune-mediated processes implicated in chemotherapy-induced peripheral neuropathy. Eur. J. Cancer 2017 73 22 29 10.1016/j.ejca.2016.12.006 28104535
    [Google Scholar]
  5. Makker P.G.S. Duffy S.S. Lees J.G. Perera C.J. Tonkin R.S. Butovsky O. Park S.B. Goldstein D. Moalem-Taylor G. Characterisation of immune and neuroinflammatory changes associated with chemotherapy-induced peripheral neuropathy. PLoS One 2017 12 1 e0170814 10.1371/journal.pone.0170814 28125674
    [Google Scholar]
  6. Meyer R.A. Ringkamp M. Raja S.N. Campbell J.N. Peripheral mechanisms of cutaneous nociception. Wall and Melzack’s Textbook of Pain 6th ed. Elsevier 3 34 10.1016/B0‑443‑07287‑6/50006‑0
    [Google Scholar]
  7. Janes K. Little J.W. Li C. Bryant L. Chen C. Chen Z. Kamocki K. Doyle T. Snider A. Esposito E. Cuzzocrea S. Bieberich E. Obeid L. Petrache I. Nicol G. Neumann W.L. Salvemini D. The development and maintenance of paclitaxel-induced neuropathic pain require activation of the sphingosine 1-phosphate receptor subtype 1. J. Biol. Chem. 2014 289 30 21082 21097 10.1074/jbc.M114.569574 24876379
    [Google Scholar]
  8. Chaudhry V. Rowinsky E.K. Sartorius S.E. Donehower R.C. Cornblath D.R. Peripheral neuropathy from taxol and cisplatin combination chemotherapy: Clinical and electrophysiological studies. Ann. Neurol. 1994 35 3 304 311 10.1002/ana.410350310 7907208
    [Google Scholar]
  9. Rao R.D. Michalak J.C. Sloan J.A. Loprinzi C.L. Soori G.S. Nikcevich D.A. Warner D.O. Novotny P. Kutteh L.A. Wong G.Y. North Central Cancer Treatment Group Efficacy of gabapentin in the management of chemotherapy‐induced peripheral neuropathy. Cancer 2007 110 9 2110 2118 10.1002/cncr.23008 17853395
    [Google Scholar]
  10. Kautio A.L. Haanpää M. Saarto T. Kalso E. Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms. J. Pain Symptom Manage. 2008 35 1 31 39 10.1016/j.jpainsymman.2007.02.043 17980550
    [Google Scholar]
  11. Newman D.J. Cragg G.M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 2020 83 3 770 803 10.1021/acs.jnatprod.9b01285 32162523
    [Google Scholar]
  12. Yuan C. Zhang W. Wang J. Chinese medicine phenomics (Chinmedphenomics): Personalized, precise and promising. Phenomics 2022 2 6 383 388 10.1007/s43657‑022‑00074‑x
    [Google Scholar]
  13. Wang X. Liu X. Shi K. Meng Q. Yu Y. Wang S. Wang J. Qu C. Lei C. Yu X. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J. Integr. Med. 2023 21 6 528 536 10.1016/j.joim.2023.10.003 37957088
    [Google Scholar]
  14. Kumar G.P. Khanum F. Neuroprotective potential of phytochemicals. Pharmacogn. Rev. 2012 6 12 81 90 10.4103/0973‑7847.99898 23055633
    [Google Scholar]
  15. Onken J. Berger R.G. Biotransformation of citronellol by the basidiomycete Cystoderma carcharias in an aerated-membrane bioreactor. Appl. Microbiol. Biotechnol. 1999 51 2 158 163 10.1007/s002530051376 10091320
    [Google Scholar]
  16. Wüst M. Fuchs S. Rexroth A. Beck T. Mosandl A. Fragmentation mechanism of rose oxide in electron impact mass spectrometry. Eur. J. Mass Spectrom. (Chichester, Eng.) 1998 4 1 163 166 10.1255/ejms.204
    [Google Scholar]
  17. Nonato F.R. Santana D.G. de Melo F.M. dos Santos G.G.L. Brustolim D. Camargo E.A. de Sousa D.P. Soares M.B.P. Villarreal C.F. Anti-inflammatory properties of rose oxide. Int. Immunopharmacol. 2012 14 4 779 784 10.1016/j.intimp.2012.10.015 23122727
    [Google Scholar]
  18. Ohtsubo S. Fujita T. Matsushita A. Kumamoto E. Inhibition of thecompound action potentials of frog sciatic nerves by aroma oil compounds having various chemical structures. Pharmacol. Res. Perspect 2015 3 2 1 13
    [Google Scholar]
  19. Maia W.M.N. De Andrade F.D.C.P. Filgueiras L.A. Mendes A.N. Assunção A.F.C. Rodrigues N.D.S. Lopes L.D. Antidepressant activity of rose oxide essential oil: Possible involvement of serotonergic transmission. Heliyon 2021 7 4
    [Google Scholar]
  20. Aghili M. Zare M. Mousavi N. Ghalehtaki R. Sotoudeh S. Kalaghchi B. Akrami S. Esmati E. Efficacy of gabapentin for the prevention of paclitaxel induced peripheral neuropathy: A randomized placebo controlled clinical trial. Breast J. 2019 25 2 226 231 10.1111/tbj.13196 30773731
    [Google Scholar]
  21. Rahman M. Son M. Kim H. Lee I. Jeon H. Kim M. Kwon H. Park S. Jang J. Kim S. DHP107, a novel oral paclitaxel formulation induces less peripheral neuropathic pain and pain-related molecular alteration than intravenous paclitaxel preparation in rat. J. adv. biotechnol. exp ther 2019 2 2 1 10.5455/jabet.2019.d26
    [Google Scholar]
  22. Ohkawa H. Ohishi N. Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 1979 95 2 351 358 10.1016/0003‑2697(79)90738‑3 36810
    [Google Scholar]
  23. Stage T.B. Bergmann T.K. Kroetz D.L. Clinical pharmacokinetics of paclitaxel monotherapy: An updated literature review. Clin. Pharmacokinet. 2018 57 1 7 19 10.1007/s40262‑017‑0563‑z 28612269
    [Google Scholar]
  24. Colvin L.A. Chemotherapy-induced peripheral neuropathy: Where are we now? Pain 2019 160 1 Suppl. 1 S1 S10 10.1097/j.pain.0000000000001540 31008843
    [Google Scholar]
  25. Xu Y. Jiang Z. Chen X. Mechanisms underlying paclitaxel-induced neuropathic pain: Channels, inflammation and immune regulations. Eur. J. Pharmacol. 2022 933 175288 10.1016/j.ejphar.2022.175288 36122757
    [Google Scholar]
  26. Duggett N.A. Griffiths L.A. Flatters S.J.L. Paclitaxel-induced painful neuropathy is associated with changes in mitochondrial bioenergetics, glycolysis, and an energy deficit in dorsal root ganglia neurons. Pain 2017 158 8 1499 1508 10.1097/j.pain.0000000000000939 28541258
    [Google Scholar]
  27. Staff N.P. Fehrenbacher J.C. Caillaud M. Damaj M.I. Segal R.A. Rieger S. Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems. Exp. Neurol. 2020 324 113121 10.1016/j.expneurol.2019.113121 31758983
    [Google Scholar]
  28. Klein I. Lehmann H. Pathomechanisms of paclitaxel-induced peripheral neuropathy. Toxics 2021 9 10 229 10.3390/toxics9100229 34678925
    [Google Scholar]
  29. Seibenhener M.L. Wooten M.C. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J. Vis. Exp. 2015 6 96 e52434 25742564
    [Google Scholar]
  30. Lippoldt E.K. Ongun S. Kusaka G.K. McKemy D.D. Inflammatory and neuropathic cold allodynia are selectively mediated by the neurotrophic factor receptor GFRα3. Proc. Natl. Acad. Sci. USA 2016 113 16 4506 4511 10.1073/pnas.1603294113 27051069
    [Google Scholar]
  31. Vincent J-L. Annual update in intensive care and emergency medicine 2012. Springer Berlin Heidelberg 1st ed.Berlin, Heidelberg 2012 2012
    [Google Scholar]
  32. Jagieła J. Bartnicki P. Rysz J. Nephrotoxicity as a complication of chemotherapy and immunotherapy in the treatment of colorectal cancer, melanoma and non-small cell lung cancer. Int. J. Mol. Sci. 2021 22 9 4618 10.3390/ijms22094618 33924827
    [Google Scholar]
  33. Costa M.L. Rodrigues J.A. Azevedo J. Vasconcelos V. Eiras E. Campos M.G. Hepatotoxicity induced by paclitaxel interaction with turmeric in association with a microcystin from a contaminated dietary supplement. Toxicon 2018 150 207 211 10.1016/j.toxicon.2018.05.022
    [Google Scholar]
  34. Pieniążek A. Czepas J. Piasecka-Zelga J. Gwoździński K. Koceva-Chyła A. Oxidative stress induced in rat liver by anticancer drugs doxorubicin, paclitaxel and docetaxel. Adv. Med. Sci. 2013 58 1 104 111 10.2478/v10039‑012‑0063‑1 23612702
    [Google Scholar]
  35. Nyarota K. Zhou D.T. Albumin and total protein in cancer patients at radiotherapy clinic,Zimbabwe Saudi J Med Pharm Sci 2017 3 10 1071 6
    [Google Scholar]
  36. Yin W. Ming Z. Liu Q. Resistance distance and kirchhoff index for a class of graphs. Math. Probl. Eng. 2018 2018 1 8, 26 10.1155/2018/1028614
    [Google Scholar]
  37. Wang J. Fregoso G. Wang A. Tseng K. Transition from acute to chronic pain: Evaluating risk for chronic postsurgical pain Pain Physician 2019 22 5 479 488 31561647
    [Google Scholar]
  38. Valent P. Pathogenesis, classification, and therapy of eosinophilia and eosinophil disorders. Blood Rev. 2009 23 4 157 165 10.1016/j.blre.2009.01.001 19246139
    [Google Scholar]
  39. Araújo D.F.B. Cavalcanti I.D.L. Larrazabal-Hadj-Idris B.R. Peres A.L. Hematological and biochemical toxicity analysis of chemotherapy in women diagnosed with cervical cancer. J. Bras. Patol. Med. Lab. 2020 10.5935/1676‑2444.20200038
    [Google Scholar]
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  • Article Type:
    Research Article
Keywords: antineoplastic ; paclitaxel ; Biochemical analyses ; monoterpene ; rose oxide ; adverse effect
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