The Antiepileptic and Antidepressant-Like Effects of Dexpanthenol in Female Swiss Albino Mice
Objective: Oxidative stress is one of the main mechanisms of epilepsy and depression. Based on our information, behavioral effects of dexpanthenol in animals have not yet been demonstrated. Dexpanthenol itself is a topical medicine to restore skin barrier against infections caused by microorganisms which also stimulates the peristaltic movements in the gut when administered parenterally; however since it is cheap and easy to use with minor side effects, the main idea of the current research was to evaluate whether dexpanthenol has an antiepileptic and/or antidepressant-like effects. Methods: A group of female Swiss albino mice (25-30 g) were injected with dexpanthenol (ip, N = 8) or saline (ip, N = 8), and 30 min later pentylenetetrazole (65 mg/kg, ip)-induced convulsions were determined for 30 min. In addition, another group of mice were again injected with dexpanthenol (500 mg/kg, ip, N = 8) or saline (ip, N = 8) and immobility time were evaluated in the forced swim test. Finally, mouse righting reflex test was used to assess the possible changes in motor coordination. Results: Our data showed that dexpanthenol, at the dose of 500 mg/kg displayed significant antiepileptic and antidepressant-like effects without affecting motor behavior. Conclusions: A common low-cost topical drug for various skin disorders that can also be given parenterally for motility regulation has an antiepileptic and antidepressant-like activity in mice.
___
- [1] Baron JM, Glatz M, Proksch E. Optimal Support of Wound Healing: New Insights. Dermatology 2020; 236 (6):
593–600.
- [2] Mosges R, Shah-Hosseini K, Hucke HP, Joisten MJ. Dexpanthenol: An Overview of its Contribution to
Symptom Relief in Acute Rhinitis Treated with Decongestant Nasal Sprays. Adv Ther 2017; 34 (8): 1850–1858.
- [3] Kutlu O. Dexpanthenol may be a novel treatment for male androgenetic alopecia: Analysis of nine cases.
Dermatol Ther 2020; 33 (3): e13381.
- [4] Ucar M, Aydogan MS, Vardi N, Parlakpinar H. Protective Effect of Dexpanthenol on Ischemia-Reperfusion-
Induced Liver Injury. Transpl Proc 2018; 50 (10): 3135–3143.
- [5] Li-Mei W, Jie T, Shan-He W, Dong-Mei M, Peng-Jiu Y. Anti-inflammatory and Anti-oxidative Effects of
Dexpanthenol on Lipopolysaccharide Induced Acute Lung Injury in Mice. Inflammation 2016; 39 (5): 1757–
1763.
- [6] Hanck AB, Goffin H. Dexpanthenol (Ro 01-4709) in the treatment of constipation. Acta Vitaminol Enzym 1982;
4 (1–2): 87–97.
- [7] Thijs RD, Surges R, O’Brien TJ, Sander JW. Epilepsy in adults. Lancet 2019; 393 (10172): 689–701.
- [8] Zamani M, Budde T, Bozorgi H. Intracerebroventricular administration of N-type calcium channel blocker
ziconotide displays anticonvulsant, anxiolytic, and sedative effects in rats: A preclinical and pilot study.
Epilepsy Behav 2020; 111 : 107251.
- [9] Jiang W, Du B, Chi Z, Ma L, Wang S, Zhang X, Wu W, Wang X, Xu G, Guo C. Preliminary explorations of the role
of mitochondrial proteins in refractory epilepsy: some findings from comparative proteomics. J Neurosci
Res 2007; 85 (14): 3160–3170.
- [10] Patsalos PN. Anti-epileptic drugs: newly licensed and under development. IDrugs 2000; 3 (4): 416–429.
- [11] Provini F, Plazzi G, Tinuper P, Vandi S, Lugaresi E, Montagna P. Nocturnal frontal lobe epilepsy. A clinical and
polygraphic overview of 100 consecutive cases. Brain 1999; 122 (Pt 6): 1017–1031.
- [12] Stimpson N, Agrawal N, Lewis G. Randomised controlled trials investigating pharmacological and
psychological interventions for treatment-refractory depression. Systematic review. Br J Psychiatry 2002;
181 : 284–294.
- [13] Bian H, Wang G, Huang J, Liang L, Zheng Y, Wei Y, Wang H, Xiao L, Wang H. Dihydrolipoic acid protects
against lipopolysaccharide-induced behavioral deficits and neuroinflammation via regulation of Nrf2/HO-
1/NLRP3 signaling in rat. J Neuroinflammation 2020; 17 (1): 166.
- [14] Jackson MJ, Turkington D. Depression and anxiety in epilepsy. J Neurol Neurosurg Psychiatry 2005; 76 Suppl
1: i45-47.
- [15] Vazquez B, Devinsky O. Epilepsy and anxiety. Epilepsy Behav 2003; 4 Suppl 4: S20-5.
- [16] Inan SY, Aksu F. Influence of sex on the interaction between dizocilpine (MK-801) pretreatment and acute
cold-restraint stress in epilepsy susceptibility in an animal study. Gend Med 2008; 5 (2): 136-146.
- [17] Iqbal J, Adu-Nti F, Wang X, Qiao H, Ma XM. Sex difference in depression: Which animal models mimic it.
Behav Neurosci 2020; 134 (3): 248–266.
- [18] Rehm J, Shield KD. Global Burden of Disease and the Impact of Mental and Addictive Disorders. Curr
Psychiatry Rep 2019; 21: 10.
- [19] Dai YJ, Xu ZH, Feng B, Xu CL, Zhao HW, Wu DC, Hu WW, Chen Z. Gender difference in acquired seizure
susceptibility in adult rats after early complex febrile seizures. Neurosci Bull 2014; 30 (6): 913–922.
- [20] Medina AE, Manhaes AC, Schmidt SL. Sex differences in sensitivity to seizures elicited by pentylenetetrazol
in mice. Pharmacol Biochem Behav 2001; 68 (3): 591–596.
- [21] Rattka M, Brandt C, Bankstahl M, Broer S, Loscher W. Enhanced susceptibility to the GABA antagonist
pentylenetetrazole during the latent period following a pilocarpine-induced status epilepticus in rats.
Neuropharmacology 2011; 60 (2–3): 505–512.
- [22] Inan SY, Büyükafşar K. Antiepileptic effects of two Rho-kinase inhibitors, Y-27632 and fasudil, in mice. Br J
Pharmacol 2008; 155 (1): 44-51.
- [23] Korkmaz MF, Parlakpinar H, Erdem MN, Ceylan MF, Ediz L, Samdanci E, Kekilli E. The therapeutic efficacy of
dexpanthenol on sciatic nerve injury in a rat model. Br J Neurosurg 2020; 34(4): 397-401.
- [24] Kose A, Parlakpinar H, Ozhan O, Ermis N, Yildiz A, Vardi N, Cigremis Y. Therapeutic effects of dexpanthenol on
the cardiovascular and respiratory systems following cecal ligation and puncture-induced sepsis in rats.
Biotech Histochem 2020; 95 (6): 428–437.
- [25] Rizzi A, Vergura R, Marzola G, Ruzza C, Guerrini R, Salvadori S, Regoli D, Calo G. Neuropeptide S is a
stimulatory anxiolytic agent: a behavioural study in mice. Br J Pharmacol 2008; 154 (2): 471–479.
- [26] Castagne V, Moser P, Roux S, Porsolt RD. Rodent models of depression: forced swim and tail suspension
behavioral despair tests in rats and mice. Curr Protoc Pharmacol 2010; Chapter 5: Unit 5.8.
- [27] Inan SY, Yalcin I, Aksu F. Dual effects of nitric oxide in the mouse forced swimming test: Possible contribution
of nitric oxide mediated serotonin release and potassium channel modulation. Pharmacol Biochem Behav
2004; 77 (3): 457-464.
- [28] Keller P. Bepanthen in lupus erythematodes. Dermatol Wochenschr 1952; 125 (11): 243–246.
- [29] Heer F. Treatment of chronic bronchitis with penicillin and bepanthen. Ther Umsch 1952; 9 (1): 8.
- [30] Dworacek H. Bepanthen as a protective remedy in roentgen lesions of the skin. Strahlentherapie 1953; 91
(4): 643–646.
- [31] Ebner F, Heller A, Rippke F, Tausch I. Topical use of dexpanthenol in skin disorders. Am J Clin Dermatol 2002;
3 (6): 427–433.
- [32] Portella A. Treatment of the chronic constipation of age with pantothenol. Rass Int Clin Ter 1956; 36 (21):
641–652.
- [33] Watne AL, Mendoza C, Rosen R, Nadler S, Case R. The role of dexpanthenol in postoperative ileus. JAMA
1962; 181 : 827–830.
- [34] Etensel B, Ozkisacik S, Ozkara E, Serbest YA, Oztan O, Yazici M, Gürsoy H. The protective effect of
dexpanthenol on testicular atrophy at 60th day following experimental testicular torsion. Pediatr Surg Int
2007; 23 (3): 271–275.
[35] Proksch E, de Bony R, Trapp S, Boudon S. Topical use of dexpanthenol: a 70th anniversary article. J
Dermatolog Treat 2017; 28 (8): 766–773.
- [36] Bilgic Y, Akbulut S, Aksungur Z, Erdemli ME, Ozhan O, Parlakpinar H, Vardi N, Turkoz Y. Protective effect of
dexpanthenol against cisplatin-induced hepatotoxicity. Exp Ther Med 2018; 16 (5): 4049–4057.
- [37] Toplu Y, Sapmaz E, Parlakpinar H, Kelles M, Kalcioglu MT, Tanbek K, Kizilay A. The Effect of Dexpanthenol on
Ototoxicity Induced by Cisplatin. Clin Exp Otorhinolaryngol 2016; 9 (1): 14–20.
- [38] Slyshenkov VS, Dymkowska D, Wojtczak L. Pantothenic acid and pantothenol increase biosynthesis of
glutathione by boosting cell energetics. FEBS Lett 2004; 569 (1–3): 169–172.
- [39] Bondy SC. The relation of oxidative stress and hyperexcitation to neurological disease. Proc Soc Exp Biol
Med 1995; 208 (4): 337–345.
- [40] Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: evidence base and therapeutic
implications. Int J Neuropsychopharmacol 2008; 11 (6): 851–876.
- [41] Lazzarotto L, Pfluger P, Regner GG, Santos FM, Aguirre DG, Brito VB, Moura DJ, Dos Santos NM, Nascimento
Picada J, Parmeggiani B, Frusciante MR, Leipnitz G, Pereira P. Lacosamide improves biochemical, genotoxic,
and mitochondrial parameters after PTZ-kindling model in mice. Fundam Clin Pharmacol 2020; DOI:
10.1111/fcp.12598.
- [42] Wu Y, Wang Y, Wu Y, Li T, Wang W. Salidroside shows anticonvulsant and neuroprotective effects by
activating the Nrf2-ARE pathway in a pentylenetetrazol-kindling epileptic model. Brain Res Bull 2020; 164:
14–20.
- [43] Pedreanez A, Arcaya JL, Carrizo E, Rincon J, Viera N, Pena C, Vargas R, Mosquera J. Experimental depression
induces renal oxidative stress in rats. Physiol Behav 2011; 104 (5): 1002–1009.
- [44] Ozdemir R, Demirtas G, Parlakpinar H, Polat A, Tanbag K, Taslidere E, Karadag A. Dexpanthenol therapy
reduces lung damage in a hyperoxic lung injury in neonatal rats. J Matern Fetal Neonatal Med 2016; 29 (11):
1801–1807.
- [45] Ichiseki T, Matsumoto T. Oxidative stress may underlie the sex differences seen in steroid-induced
osteonecrosis models. Med Hypotheses 2006; 66 (6): 1256.
- [46] Verma Y, Rana S V. Sex differences in oxidative stress induced by benzene in rats. Indian J Exp Biol 2004; 42
(1): 117–120.
- [47] Mendoza-Nunez VM, Beristain-Perez A, Perez-Vera SP, Altamirano-Lozano MA. Age-related sex differences
in glutathione peroxidase and oxidative DNA damage in a healthy Mexican population. J Womens Heal
2010; 19 (5): 919–926.