Effects of Venlafaxine, Risperidone and Febuxostat on Cuprizone-Induced Demyelination, Behavioral Deficits and Oxidative Stress

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jul 20

PMID 34281235

Citations 10

Authors

Dragos Paul Mihai

Anca Ungurianu

Cosmin I Ciotu

Michael J M Fischer

Octavian Tudorel Olaru

George Mihai Nitulescu

Corina Andrei

Cristina Elena Zbarcea

Anca Zanfirescu

Oana Cristina Seremet

Cornel Chirita

Simona Negres

Affiliations

Soon will be listed here.

Abstract

Multiple sclerosis (MS) is a demyelinating, autoimmune disease that affects a large number of young adults. Novel therapies for MS are needed considering the efficiency and safety limitations of current treatments. In our study, we investigated the effects of venlafaxine (antidepressant, serotonin-norepinephrine reuptake inhibitor), risperidone (atypical antipsychotic) and febuxostat (gout medication, xanthine oxidase inhibitor) in the cuprizone mouse model of acute demyelination, hypothesizing an antagonistic effect on TRPA1 calcium channels. Cuprizone and drugs were administered to C57BL6/J mice for five weeks and locomotor activity, motor performance and cold sensitivity were assessed. Mice brains were harvested for histological staining and assessment of oxidative stress markers. Febuxostat and metabolites of venlafaxine (desvenlafaxine) and risperidone (paliperidone) were tested for TRPA1 antagonistic activity. Following treatment, venlafaxine and risperidone significantly improved motor performance and sensitivity to a cold stimulus. All administered drugs ameliorated the cuprizone-induced deficit of superoxide dismutase activity. Desvenlafaxine and paliperidone showed no activity on TRPA1, while febuxostat exhibited agonistic activity at high concentrations. Our findings indicated that all three drugs offered some protection against the effects of cuprizone-induced demyelination. The agonistic activity of febuxostat can be of potential use for discovering novel TRPA1 ligands.

Citing Articles

Evaluating the Antihyperalgesic Potential of Sildenafil-Metformin Combination and Its Impact on Biochemical Markers in Alloxan-Induced Diabetic Neuropathy in Rats.

Puscasu C, Negres S, Zbarcea C, Ungurianu A, Stefanescu E, Blebea N Pharmaceuticals (Basel). 2024; 17(6).

PMID: 38931450 PMC: 11206800. DOI: 10.3390/ph17060783.

TRPA1 Covalent Ligand JT010 Modifies T Lymphocyte Activation.

Szabo K, Makkai G, Konkoly J, Kormos V, Gaszner B, Berki T Biomolecules. 2024; 14(6).

PMID: 38927036 PMC: 11202300. DOI: 10.3390/biom14060632.

5Z-7-Oxozaenol attenuates cuprizone-induced demyelination in mice through microglia polarization regulation.

Chen S, Liu S, Huang Y, Huang S, Zhang W, Xie H Brain Behav. 2024; 14(4):e3487.

PMID: 38648385 PMC: 11034864. DOI: 10.1002/brb3.3487.

The Influence of Sildenafil-Metformin Combination on Hyperalgesia and Biochemical Markers in Diabetic Neuropathy in Mice.

Puscasu C, Ungurianu A, Seremet O, Andrei C, Mihai D, Negres S Medicina (Kaunas). 2023; 59(8).

PMID: 37629665 PMC: 10456948. DOI: 10.3390/medicina59081375.

Establishment of an assistive diagnostic model for schizophrenia with oxidative stress biomarkers.

Wang S, Yuan X, Pang L, Song P, Jia R, Song X Front Pharmacol. 2023; 14:1158254.

PMID: 37007024 PMC: 10050576. DOI: 10.3389/fphar.2023.1158254.

References

Yisireyili M, Hayashi M, Wu H, Uchida Y, Yamamoto K, Kikuchi R . Xanthine oxidase inhibition by febuxostat attenuates stress-induced hyperuricemia, glucose dysmetabolism, and prothrombotic state in mice. Sci Rep. 2017; 7(1):1266. PMC: 5430858. DOI: 10.1038/s41598-017-01366-3. View

Deacon R . Measuring motor coordination in mice. J Vis Exp. 2013; (75):e2609. PMC: 3724562. DOI: 10.3791/2609. View

Babes A, Ciotu C, Hoffmann T, Kichko T, Selescu T, Neacsu C . Photosensitization of TRPA1 and TRPV1 by 7-dehydrocholesterol: implications for the Smith-Lemli-Opitz syndrome. Pain. 2017; 158(12):2475-2486. DOI: 10.1097/j.pain.0000000000001056. View

Chopko T, Lindsley C . Classics in Chemical Neuroscience: Risperidone. ACS Chem Neurosci. 2018; 9(7):1520-1529. DOI: 10.1021/acschemneuro.8b00159. View

MacDowell K, Garcia-Bueno B, Madrigal J, Parellada M, Arango C, Mico J . Risperidone normalizes increased inflammatory parameters and restores anti-inflammatory pathways in a model of neuroinflammation. Int J Neuropsychopharmacol. 2011; 16(1):121-35. DOI: 10.1017/S1461145711001775. View

Chen C, Yeh Y, Kuo S, Liang C, Ho P, Huang C . Differences in immunomodulatory properties between venlafaxine and paroxetine in patients with major depressive disorder. Psychoneuroendocrinology. 2017; 87:108-118. DOI: 10.1016/j.psyneuen.2017.10.009. View

Golden J, Hoshi M, Nassar M, Enomoto H, Wood J, Milbrandt J . RET signaling is required for survival and normal function of nonpeptidergic nociceptors. J Neurosci. 2010; 30(11):3983-94. PMC: 2850282. DOI: 10.1523/JNEUROSCI.5930-09.2010. View

Miyata H, Takada T, Toyoda Y, Matsuo H, Ichida K, Suzuki H . Identification of Febuxostat as a New Strong ABCG2 Inhibitor: Potential Applications and Risks in Clinical Situations. Front Pharmacol. 2017; 7:518. PMC: 5187494. DOI: 10.3389/fphar.2016.00518. View

Nilius B, Appendino G, Owsianik G . The transient receptor potential channel TRPA1: from gene to pathophysiology. Pflugers Arch. 2012; 464(5):425-58. DOI: 10.1007/s00424-012-1158-z. View

10.

Li X, Zhu L, Su Y, Fang S . Short-term efficacy and tolerability of venlafaxine extended release in adults with generalized anxiety disorder without depression: A meta-analysis. PLoS One. 2017; 12(10):e0185865. PMC: 5628888. DOI: 10.1371/journal.pone.0185865. View

11.

Loma I, Heyman R . Multiple sclerosis: pathogenesis and treatment. Curr Neuropharmacol. 2012; 9(3):409-16. PMC: 3151595. DOI: 10.2174/157015911796557911. View

12.

Margina D, Gradinaru D, Manda G, Neagoe I, Ilie M . Membranar effects exerted in vitro by polyphenols - quercetin, epigallocatechin gallate and curcumin - on HUVEC and Jurkat cells, relevant for diabetes mellitus. Food Chem Toxicol. 2013; 61:86-93. DOI: 10.1016/j.fct.2013.02.046. View

13.

Gajofatto A, Benedetti M . Treatment strategies for multiple sclerosis: When to start, when to change, when to stop?. World J Clin Cases. 2015; 3(7):545-55. PMC: 4517331. DOI: 10.12998/wjcc.v3.i7.545. View

14.

Pollmann W, Feneberg W . Current management of pain associated with multiple sclerosis. CNS Drugs. 2008; 22(4):291-324. DOI: 10.2165/00023210-200822040-00003. View

15.

Cikankova T, Fisar Z, Bakhouche Y, luptak M, Hroudova J . In vitro effects of antipsychotics on mitochondrial respiration. Naunyn Schmiedebergs Arch Pharmacol. 2019; 392(10):1209-1223. DOI: 10.1007/s00210-019-01665-8. View

16.

Nitulescu G, Mihai D, Nicorescu I, Olaru O, Ungurianu A, Zanfirescu A . Discovery of natural naphthoquinones as sortase A inhibitors and potential anti-infective solutions against Staphylococcus aureus. Drug Dev Res. 2019; 80(8):1136-1145. DOI: 10.1002/ddr.21599. View

17.

Wang J, Qiao J, Zhang Y, Wang H, Zhu S, Zhang H . Desvenlafaxine prevents white matter injury and improves the decreased phosphorylation of the rate-limiting enzyme of cholesterol synthesis in a chronic mouse model of depression. J Neurochem. 2014; 131(2):229-38. DOI: 10.1111/jnc.12792. View

18.

Yan W, Zhang Y, Hu L, Li Q, Zhou H . Febuxostat Inhibits MPP+-Induced Inflammatory Response Through Inhibiting the JNK/NF-κB Pathway in Astrocytes. Neurotox Res. 2021; 39(3):566-574. DOI: 10.1007/s12640-020-00316-8. View

19.

Katyare S, Rajan R . Influence of thyroid hormone treatment on the respiratory activity of cerebral mitochondria from hypothyroid rats. A critical re-assessment. Exp Neurol. 2005; 195(2):416-22. DOI: 10.1016/j.expneurol.2005.06.004. View

20.

Giorgi S, Nikolaeva-Koleva M, Alarcon-Alarcon D, Butron L, Gonzalez-Rodriguez S . Is TRPA1 TRPV1 as Druggable Target for the Treatment of Chronic Pain?. Int J Mol Sci. 2019; 20(12). PMC: 6627658. DOI: 10.3390/ijms20122906. View