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Investigation of the effect of paracetamol against glutamate-induced cytotoxicity in C6 glia cells

Year 2021, Volume: 42 Issue: 4, 789 - 794, 29.12.2021

Murat Doğan Kenan Yıldızhan

Abstract

Paracetamol is an active metabolite with analgesic and antipyretic properties of phenacetin, which is sold without a prescription in our country and in many countries. However, the effect of paracetamol on oxidative stress due to glutamate-induced cytotoxicity remains unclear. This study aims to investigate the effect of an appropriate dose of paracetamol on nitric oxide and increased oxidative stress as a result of glutamate-induced cytotoxicity in C6 cells. The cells were divided into 4 groups as Control group, Glutamate group, Paracetamol group, and Paracetamol+Glutamate group. Cell viability rate between groups was measured by XTT assay. Oxidative stress and antioxidant levels were measured with TOS and TAS elisa kits. Paracetamol at all concentrations significantly increased cell viability in C6 cells (p < 0.001). Paracetamol also increased TAS levels (p <0.01) while significantly decreased TOS levels (p < 0.001). In addition, paracetamol was observed to decrease TNF-α and NO levels (p <0.001). In conclusion, paracetamol has protective feature on glutamate-induced cytotoxicity in C6 glial cells by suppressing oxidative stress. The results of this study show that when the appropriate dose of paracetamol is used, it can be a crucial promoter agent in glutamate toxicity-induced neurodegeneration.

Keywords

Paracetamol Glutamate-toxicity Oxidative stress Nitric oxide C6 cell.

Thanks

The authors would like to thank the CUTFAM Research Center, Sivas Cumhuriyet University, School of Medicine, Sivas, Turkey, for providing the necessary facilities to conduct this study.

References

  • [1] Gündoğdu G., Şenol O., Demirkaya A.K., Glutamat Eksitotoksisitesi Oluşturulan Primer Kortikal Nöron Kültürlerinde Parietinin Nöroprotektif Etkisinin İncelenmesi, Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 13(2) (2018) 165-173.
  • [2] Lewerenz J., Maher P., Chronic Glutamate Toxicity in Neurodegenerative Diseases-What Is the Evidence?, Front Neurosci., 9 (2015) 469.
  • [3] Rego A.C., Oliveira C.R., Mitochondrial Dysfunction and Reactive Oxygen Species in Excitotoxicity and Apoptosis: Implications for the Pathogenesis of Neurodegenerative Diseases, Neurochem Res., 28(10) (2003) 1563-1574.
  • [4] Taşkın T., Dogan M., Yilmaz B.N., Senkardes I., Phytochemical screening and evaluation of antioxidant, enzyme inhibition, anti-proliferative and calcium oxalate anti-crystallization activities of Micromeria fruticosa spp. brachycalyx and Rhus coriaria, Biocatalysis and Agricultural Biotechnology, 27 (2020) 1-7.
  • [5] Butterfield D.A. Pocernich C.B., The Glutamatergic System and Alzheimer's Disease: Therapeutic Implications, CNS Drugs, 17(9) (2003) 641-652.
  • [6] Wang J., Wang F., Mai D., Qu S., Molecular Mechanisms of Glutamate Toxicity in Parkinson's Disease, Front Neurosci., 14 (2020) 585584.
  • [7] Yıldızhan K., Nazıroğlu M., Microglia and Its Role in Neurodegenerative Diseases, Journal of Cellular Neuroscience and Oxidative Stress, 11(2) (2019) 861-873.
  • [8] Penugonda S., Mare S., Goldstein G., Banks W.A., Ercal N., Effects of N-Acetylcysteine Amide (NACA), a Novel Thiol Antioxidant against Glutamate-Induced Cytotoxicity in Neuronal Cell Line Pc12, Brain Res., 1056(2) (2005) 132-138.
  • [9] Yildizhan K., Naziroglu M., Glutathione Depletion and Parkinsonian Neurotoxin Mpp(+)-Induced Trpm2 Channel Activation Play Central Roles in Oxidative Cytotoxicity and Inflammation in Microglia, Mol. Neurobiol., 57(8) (2020) 3508-3525.
  • [10] Wen X., Huang A., Hu J., Zhong Z., Liu Y., Li Z., Neuroprotective Effect of Astaxanthin against Glutamate-Induced Cytotoxicity in HT22 Cells: Involvement of the Akt/Gsk-3beta Pathway, Neuroscience, 303 (2015) 558-568.
  • [11] Kato S., Negishi K., Mawatari K., Kuo C.H., A Mechanism for Glutamate Toxicity in the C6 Glioma Cells Involving Inhibition of Cystine Uptake Leading to Glutathione Depletion, Neuroscience, 48(4) (1992) 903-914.
  • [12] Das A., Belagodu A., Reiter R.J., Ray S.K., Banik N.L., Cytoprotective Effects of Melatonin on C6 Astroglial Cells Exposed to Glutamate Excitotoxicity and Oxidative Stress, J. Pineal Res., 45(2) (2008) 117-24.
  • [13] Clissold S.P., Paracetamol and Phenacetin, Drugs, 32 Suppl. 4. (1986) 46-59.
  • [14] Botting R., Cox-1 and Cox-3 Inhibitors, Thrombosis research, 110(5-6) (2003) 269-272.
  • [15] Graham G.G., Scott K.F., Mechanism of Action of Paracetamol, American Journal of Therapeutics, 12(1) (2005) 46-55.
  • [16] Graham G.G., Davies M.J., Day R.O., Mohamudally A., Scott K.F., The Modern Pharmacology of Paracetamol: Therapeutic Actions, Mechanism of Action, Metabolism, Toxicity and Recent Pharmacological Findings, Inflammopharmacology, 21(3) (2013) 201-232.
  • [17] Toussaint K., Yang X.C., Zielinski M.A., Reigle K.E., Sacavage S.D., Nagar S., Raffa R.B., What Do We (Not) Know About How Paracetamol (Acetaminophen) Works?, Journal of Clinical Pharmacy and Therapeutics, 35(6) (2010) 617-638.
  • [18] Taskiran A.S., Ergul M., The Effect of Salmon Calcitonin against Glutamate-Induced Cytotoxicity in the C6 Cell Line and the Roles the Inflammatory and Nitric Oxide Pathways Play, Metab Brain Dis., 36(7) (2021) 1985-1993.
  • [19] Kritis A.A., Stamoula E.G., Paniskaki P.A., Vavilis T.D., Researching Glutamate - Induced Cytotoxicity in Different Cell Lines: A Comparative/Collective Analysis/Study, Front Cell Neurosci., 9 (2015) 91.
  • [20] Ergul M., Taskiran A.S., Thiamine Protects Glioblastoma Cells against Glutamate Toxicity by Suppressing Oxidative/Endoplasmic Reticulum Stress, Chem. Pharm. Bull. (Tokyo), 69(9) (2021) 832-839.
  • [21] Park E., Gim J., Kim D.K., Kim C.S., Chun H.S., Protective Effects of Alpha-Lipoic Acid on Glutamate-Induced Cytotoxicity in C6 Glioma Cells, Biol. Pharm. Bull., 42(1). (2019) 94-102.
  • [22] Neniskyte U., Vilalta A., Brown G.C., Tumour Necrosis Factor Alpha-Induced Neuronal Loss Is Mediated by Microglial Phagocytosis, FEBS Lett., 588(17) (2014) 2952-2956.
  • [23] Marchetti L., Tumor Necrosis Factor (Tnf)-Mediated Neuroprotection against Glutamate-Induced Excitotoxicity Is Enhanced by N-Methyl-D-Aspartate Receptor Activation. Essential Role of a Tnf Receptor 2-Mediated Phosphatidylinositol 3-Kinase-Dependent Nf-Kappa B Pathway, J. Biol. Chem., 279(31) (2004) 32869-32881.
  • [24] Lesage A.S., Peeters L., Leysen J.E., Lubeluzole, a Novel Long-Term Neuroprotectant, Inhibits the Glutamate-Activated Nitric Oxide Synthase Pathway, Journal of Pharmacology and Experimental Therapeutics, 279(2) (1996) 759-766.

Year 2021, Volume: 42 Issue: 4, 789 - 794, 29.12.2021

Murat Doğan Kenan Yıldızhan

Abstract

References

  • [1] Gündoğdu G., Şenol O., Demirkaya A.K., Glutamat Eksitotoksisitesi Oluşturulan Primer Kortikal Nöron Kültürlerinde Parietinin Nöroprotektif Etkisinin İncelenmesi, Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 13(2) (2018) 165-173.
  • [2] Lewerenz J., Maher P., Chronic Glutamate Toxicity in Neurodegenerative Diseases-What Is the Evidence?, Front Neurosci., 9 (2015) 469.
  • [3] Rego A.C., Oliveira C.R., Mitochondrial Dysfunction and Reactive Oxygen Species in Excitotoxicity and Apoptosis: Implications for the Pathogenesis of Neurodegenerative Diseases, Neurochem Res., 28(10) (2003) 1563-1574.
  • [4] Taşkın T., Dogan M., Yilmaz B.N., Senkardes I., Phytochemical screening and evaluation of antioxidant, enzyme inhibition, anti-proliferative and calcium oxalate anti-crystallization activities of Micromeria fruticosa spp. brachycalyx and Rhus coriaria, Biocatalysis and Agricultural Biotechnology, 27 (2020) 1-7.
  • [5] Butterfield D.A. Pocernich C.B., The Glutamatergic System and Alzheimer's Disease: Therapeutic Implications, CNS Drugs, 17(9) (2003) 641-652.
  • [6] Wang J., Wang F., Mai D., Qu S., Molecular Mechanisms of Glutamate Toxicity in Parkinson's Disease, Front Neurosci., 14 (2020) 585584.
  • [7] Yıldızhan K., Nazıroğlu M., Microglia and Its Role in Neurodegenerative Diseases, Journal of Cellular Neuroscience and Oxidative Stress, 11(2) (2019) 861-873.
  • [8] Penugonda S., Mare S., Goldstein G., Banks W.A., Ercal N., Effects of N-Acetylcysteine Amide (NACA), a Novel Thiol Antioxidant against Glutamate-Induced Cytotoxicity in Neuronal Cell Line Pc12, Brain Res., 1056(2) (2005) 132-138.
  • [9] Yildizhan K., Naziroglu M., Glutathione Depletion and Parkinsonian Neurotoxin Mpp(+)-Induced Trpm2 Channel Activation Play Central Roles in Oxidative Cytotoxicity and Inflammation in Microglia, Mol. Neurobiol., 57(8) (2020) 3508-3525.
  • [10] Wen X., Huang A., Hu J., Zhong Z., Liu Y., Li Z., Neuroprotective Effect of Astaxanthin against Glutamate-Induced Cytotoxicity in HT22 Cells: Involvement of the Akt/Gsk-3beta Pathway, Neuroscience, 303 (2015) 558-568.
  • [11] Kato S., Negishi K., Mawatari K., Kuo C.H., A Mechanism for Glutamate Toxicity in the C6 Glioma Cells Involving Inhibition of Cystine Uptake Leading to Glutathione Depletion, Neuroscience, 48(4) (1992) 903-914.
  • [12] Das A., Belagodu A., Reiter R.J., Ray S.K., Banik N.L., Cytoprotective Effects of Melatonin on C6 Astroglial Cells Exposed to Glutamate Excitotoxicity and Oxidative Stress, J. Pineal Res., 45(2) (2008) 117-24.
  • [13] Clissold S.P., Paracetamol and Phenacetin, Drugs, 32 Suppl. 4. (1986) 46-59.
  • [14] Botting R., Cox-1 and Cox-3 Inhibitors, Thrombosis research, 110(5-6) (2003) 269-272.
  • [15] Graham G.G., Scott K.F., Mechanism of Action of Paracetamol, American Journal of Therapeutics, 12(1) (2005) 46-55.
  • [16] Graham G.G., Davies M.J., Day R.O., Mohamudally A., Scott K.F., The Modern Pharmacology of Paracetamol: Therapeutic Actions, Mechanism of Action, Metabolism, Toxicity and Recent Pharmacological Findings, Inflammopharmacology, 21(3) (2013) 201-232.
  • [17] Toussaint K., Yang X.C., Zielinski M.A., Reigle K.E., Sacavage S.D., Nagar S., Raffa R.B., What Do We (Not) Know About How Paracetamol (Acetaminophen) Works?, Journal of Clinical Pharmacy and Therapeutics, 35(6) (2010) 617-638.
  • [18] Taskiran A.S., Ergul M., The Effect of Salmon Calcitonin against Glutamate-Induced Cytotoxicity in the C6 Cell Line and the Roles the Inflammatory and Nitric Oxide Pathways Play, Metab Brain Dis., 36(7) (2021) 1985-1993.
  • [19] Kritis A.A., Stamoula E.G., Paniskaki P.A., Vavilis T.D., Researching Glutamate - Induced Cytotoxicity in Different Cell Lines: A Comparative/Collective Analysis/Study, Front Cell Neurosci., 9 (2015) 91.
  • [20] Ergul M., Taskiran A.S., Thiamine Protects Glioblastoma Cells against Glutamate Toxicity by Suppressing Oxidative/Endoplasmic Reticulum Stress, Chem. Pharm. Bull. (Tokyo), 69(9) (2021) 832-839.
  • [21] Park E., Gim J., Kim D.K., Kim C.S., Chun H.S., Protective Effects of Alpha-Lipoic Acid on Glutamate-Induced Cytotoxicity in C6 Glioma Cells, Biol. Pharm. Bull., 42(1). (2019) 94-102.
  • [22] Neniskyte U., Vilalta A., Brown G.C., Tumour Necrosis Factor Alpha-Induced Neuronal Loss Is Mediated by Microglial Phagocytosis, FEBS Lett., 588(17) (2014) 2952-2956.
  • [23] Marchetti L., Tumor Necrosis Factor (Tnf)-Mediated Neuroprotection against Glutamate-Induced Excitotoxicity Is Enhanced by N-Methyl-D-Aspartate Receptor Activation. Essential Role of a Tnf Receptor 2-Mediated Phosphatidylinositol 3-Kinase-Dependent Nf-Kappa B Pathway, J. Biol. Chem., 279(31) (2004) 32869-32881.
  • [24] Lesage A.S., Peeters L., Leysen J.E., Lubeluzole, a Novel Long-Term Neuroprotectant, Inhibits the Glutamate-Activated Nitric Oxide Synthase Pathway, Journal of Pharmacology and Experimental Therapeutics, 279(2) (1996) 759-766.
There are 24 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Natural Sciences
Authors

Murat Doğan 0000-0003-2794-0177

Kenan Yıldızhan 0000-0002-6585-4010

Publication Date December 29, 2021
Submission Date September 23, 2021
Acceptance Date December 4, 2021
Published in Issue Year 2021Volume: 42 Issue: 4

Cite

APA Doğan, M., & Yıldızhan, K. (2021). Investigation of the effect of paracetamol against glutamate-induced cytotoxicity in C6 glia cells. Cumhuriyet Science Journal, 42(4), 789-794.