Protective effect of pantothenic acid in kainic acid-induced status eilepticus and associated neurodegeneration in mice

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Abstract

Pantothenic acid (PA) is a water-soluble vitamin (Vitamin B) that has recently been investigated in various chemical-induced neurotoxicity studies. The present study was designed to explore the biological importance of PA as a neuromodulator by releasing monoamine oxidase (MAO)-A and MAO-B in kainic acid (KA)-induced status epilepticus and the associated neurodegeneration in mice. The mice were intraperitoneally administered with KA at a dose of 10 mg/kg, and the injection solution was maintained at pH 7.2 ± 0.1 before the injection. Subsequently, the mice were observed for various behavioral changes, such as grooming, rearing, hind limb scratching, urination, defecation, jaw movements, salivation, head nodding, incidence of convulsions, and their latency or any mortality, which were recorded during a 4-h period. Further, the animals were euthanized for biochemical and histopathological analysis. The oxidative stress status was determined by measuring levels of glutathione, superoxide dismutase, nitrites, and catalase enzymes. The MAO-A and MAO-B activities, which represent an indicator of brain memory function, and the level of tumor necrosis factor alpha, which is an inflammatory marker in brain tissues, were also measured. The PA pre-treated mice showed a significant increase in retention with latency, as demonstrated in the passive avoidance test, which indicate its protective effect against the KA-induced cognitive deficit. The results showed that the anti-oxidative and anti-inflammatory potential of PA is due to the change in lipid peroxidation, which may prevent mitochondrial damage in neuronal cell, thereby conferring neuroprotection.

Keywords

Epilepsy

Kainic acid

Pantothenic acid

Pharmacological activity

Biochemical analysis

Histopathology

References

[1]

Baxendale S, Heaney D, 2021, Memory complaints in the epilepsy clinic. Pract Neurology, 21(1): 25–29. https://doi.org/10.1136/practneurol-2020-002523

[2]

Packer RM, McGreevy PD, Salvin HE, et al., 2018, Cognitive dysfunction in naturally occurring canine idiopathic epilepsy. PLoS One, 13(2): e0192182. https://doi.org/10.1371/journal.pone.0192182

[3]

Garthwaite J, 2019, NO as a multimodal transmitter in the brain: Discovery and current status. Br J Pharmacol, 176(2): 197–211. https://doi.org/10.1111/bph.14532

[4]

Postnikova TY, Zubareva OE, Kovalenko AA, et al., 2017, Status epilepticus impairs synaptic plasticity in rat hippocampus and is followed by changes in expression of NMDA receptors. Biochemistry (Mosc), 82(3): 282–290. https://doi.org/10.1134/S0006297917030063

[5]

Wang X, Zhang Y, Cheng W, et al., 2021, Decreased excitatory drive onto hilar neuronal nitric oxide synthase expressing interneurons in chronic models of epilepsy. Brain Res, 1764: 147467. https://doi.org/10.1016/j.brainres.2021.147467

[6]

Gupta YK, Briyal S, Sharma M, 2009, Protective effect of curcumin against kainic acid induced seizures and oxidative stress in rats. Indian J Physiol Pharmacol, 53(1): 39–46.

[7]

Lin TK, Chen SD, Lin KJ, et al., 2020, Seizure-induced oxidative stress in status epilepticus: Is antioxidant beneficial? Antioxidants, 9(11): 1029. https://doi.org/10.3390/antiox9111029

[8]

Kim DH, Kim DW, Jung BH, et al., 2019, Ginsenoside Rb2 suppresses the glutamate-mediated oxidative stress and neuronal cell death in HT22 cells. J Ginseng Res, 43(2): 326–334.

[9]

Chen J, Quan QY, Yang F, et al., 2010, Effects of lamotrigine and topiramate on hippocampal neurogenesis in experimental temporal-lobe epilepsy. Brain Res, 1313: 270–282. https://doi.org/10.1016/j.brainres.2009.12.024

[10]

Golechha M, Chaudhry U, Bhatia J, et al., 2011, Naringin protects against kainic acid-induced status epilepticus in rats: Evidence for an antioxidant, anti-inflammatory and neuroprotective intervention. Biol Pharm Bull, 34(3): 360–365. https://doi.org/10.1248/bpb.34.360

[11]

Milatovic D, Gupta RC, 2019, Antioxidants in prevention and treatment of diseases and toxicity. In: Nutraceuticals in Veterinary Medicine. Berlin: Springer, Cham. pp. 205–213.

[12]

Silva B, Oliveira PJ, Dias A, et al., 2008, Quercetin, kaempferol and biapigenin from Hypericum perforatum are neuroprotective against excitotoxic insults. Neurotox Res, 13(3-4): 265–279. https://doi.org/10.1007/BF03033510

[13]

Patassini S, Begley P, Xu J, et al., 2019, Cerebral vitamin B5 (D-pantothenic acid) deficiency as a potential cause of metabolic perturbation and neurodegeneration in Huntington’s disease. Metabolites, 9(6): 113. https://doi.org/10.3390/metabo9060113

[14]

Wu Z, Xu Q, Zhang L, et al., 2009, Protective effect of resveratrol against kainate-induced temporal lobe epilepsy in rats. Neurochem Res, 34(8): 1393–1400. https://doi.org/10.1007/s11064-009-9920-0

[15]

Binvignat O, Olloquequi J, 2020, Excitotoxicity as a target against neurodegenerative processes. Curr Pharm Des, 26(12): 1251–1262. https://doi.org/10.2174/1381612826666200113162641

[16]

Paudel YN, Shaikh MF, Shah S, et al., 2018, Role of inflammation in epilepsy and neurobehavioral comorbidities: Implication for therapy. Eur J Pharmacol, 837: 145–155. https://doi.org/10.1016/j.ejphar.2018.08.020

[17]

Rana A, Musto AE, 2018, The role of inflammation in the development of epilepsy. J Neuroinflammation, 15(1): 144. https://doi.org/10.1186/s12974-018-1192-7

[18]

Stubley-Weatherly L, Harding JW, Wright JW, 1996, Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats. Brain Res, 716(1-2): 29–38.

[19]

Nugroho A, Park JH, Choi JS, et al., 2019, Structure determination and quantification of a new flavone glycoside with anti-acetylcholinesterase activity from the herbs of Elsholtzia ciliata. Nat Prod Res, 33(6): 814–821. https://doi.org/10.1080/14786419.2017.1413556

[20]

Hessen E, Lossius MI, Reinvang I, et al., 2006, Predictors of neuropsychological impairment in seizure‐free epilepsy patients. Epilepsia, 47(11): 1870–1878. https://doi.org/10.1111/j.1528-1167.2006.00830.x

[21]

Giustarini D, Colombo G, Garavaglia ML, et al., 2017, Assessment of glutathione/glutathione disulphide ratio and S-glutathionylated proteins in human blood, solid tissues, and cultured cells. Free Radic Biol Med, 112: 360–375. https://doi.org/10.1016/j.freeradbiomed.2017.08.008

[22]

Emre KA, Yilmaz S, Çeribaşi AO, et al., 2018, Protective effect of lycopene on diethylnitrosamine-induced oxidative stress and catalase expression in rats. Ankara Üniv Vet Fak Derg, 66(1): 43–52.

[23]

Ghani MA, Barril C, Bedgood DR Jr., et al., 2017, Measurement of antioxidant activity with the thiobarbituric acid reactive substances assay. Food Chem, 230: 195–207.

[24]

De Leon JA, Borges CR, 2020, Evaluation of oxidative stress in biological samples using the thiobarbituric acid reactive substances assay. J Vis Exp, 159: e61122.

[25]

Huang G, Zhu F, Chen Y, et al., 2016, Spectrophotometric assay for monoamine oxidase activity with 2, 4-dinitrophenylhydrazine as a derivatized reagent. Anal Biochem, 512: 18–25.

[26]

Mira L, Fernandez MT, Santos M, et al., 2002, Interactions of flavonoids with iron and copper ions: A mechanism for their antioxidant activity. Free Radic Res, 36(11): 1199–1208. https://doi.org/10.1080/1071576021000016463

[27]

Celli R, Santolini I, Van Luijtelaar G, et al., 2019, Targeting metabotropic glutamate receptors in the treatment of epilepsy: Rationale and current status. Expert Opin Ther Targets, 23(4): 341–351. https://doi.org/10.1080/14728222.2019.1586885

[28]

Mattson MP, 2019, Excitotoxicity. In: Stress: Physiology, Biochemistry, and Pathology. Cambridge: Academic Press. pp. 125–134.

[29]

Lu CW, Lin TY, Chiu KM, et al., 2020, Silymarin inhibits glutamate release and prevents against kainic acid-induced excitotoxic injury in rats. Biomedicines, 8(11): 486. https://doi.org/10.3390/biomedicines8110486

[30]

Jang S, Dilger RN, Johnson RW, 2010, Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice. J Nutr, 140(10): 1892–1898. https://doi.org/10.3945/jn.110.123273

[31]

JK, Lee JK, Won JS, et al., 2008, Statin inhibits kainic acid-induced seizure and associated inflammation and hippocampal cell death. Neurosci Lett, 440(3): 260–264. https://doi.org/10.1016/j.neulet.2008.05.112

[32]

Vanamala J, Leonardi T, Patil BS, et al., 2006, Suppression of colon carcinogenesis by bioactive compounds in grapefruit. Carcinogenesis, 27(6): 1257–1265. https://doi.org/10.1093/carcin/bgi318

[33]

Bauer B, Hartz AM, Pekcec A, et al., 2008, Seizure-induced up-regulation of P-glycoprotein at the blood–brain barrier through glutamate and cyclooxygenase-2 signaling. Mol Pharmacol, 73(5): 1444–1453. https://doi.org/10.1124/mol.107.041210

[34]

Bais S, Kumari R, Prashar Y, 2018, Ameliorative effect of trans-sinapic acid and its protective role in cerebral hypoxia in aluminium chloride induced dementia of Alzheimer’s Type. CNS Neurol Disord Drug Targets, 17(2): 144–154. https://doi.org/10.2174/1871527317666180309130912

[35]

Kangtao, Yangqian, Bais S, 2018, Neuroprotective effect of protocatechuic acid through MAO-B inhibition in aluminium chloride induced dementia of Alzheimer’s Type in rats. Int J Pharmacol, 14(6): 879–888. https://doi.org/10.3923/ijp.2018.879.888

[36]

Bais S, Gill NS, Rana N, 2014, Effect of Juniperus communis extract on reserpine induced catalepsy. Invent Rapid Ethnopharmacol, 2014(4): 117–120.

[37]

Wang S, Wu S, Bais S, et al., 2018, Ameliorative potential of Lagenaria sicereria extract as anti-anxiety drug in various models of anxiety in rats. Int J Pharmacol, 14(8): 1179–1187. https://doi.org/10.3923/ijp.2018.1179.1187

[38]

Zhu Y, Li X, Yang W, et al., 2018, Anti-depressant activity of standardized Macrotyloma uniflorum extract in experimental models of depression in rats. Int J Pharmacol, 14(6):848–855. https://doi.org/10.3923/ijp.2018.848.855

[39]

Chen Q, Chen X, Fu Z, et al., 2019, Anti-amnesic effect of Leea indica extract in scopolamine-induced amnesia of Alzheimer’s Type in rats. Int J Pharmacol, 15(1): 116-123.

[40]

Zhao Y, Wang D, Bais S, et al., 2019, Modulation of pro-inflammatory mediators by eugenol in AlCl3 induced dementia in rats. Int J Pharmacol, 15(4): 457–64. https://doi.org/10.3923/ijp.2019.457.464

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The authors have no conflict of interest to declare.

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