Protective Effects of Pentoxifylline on Methamphetamine Induced Cell Death in PC12 Cells

Authors

DOI:

https://doi.org/10.22100/jkh.v18i1.3076

Keywords:

Methamphetamine, Pentoxyphylline, Apoptosis, Cell death

Abstract

Introduction: Methamphetamine abuse has been a global concern in the last few decades. An estimated 3.5 million people have been affected by methamphetamine abuse. Methamphetamine induces apoptosis in most cell lines. Pentoxyphilline, as a phosphodiesterase inhibitor, can reduce methamphetamine-induced cell death by inflammation reduction.

Methods: PC12 cells were grown in a DMEM culture medium. Assays used in this study are listed below: MTT test for cell viability detection, LDH test for cytotoxicity measurement, caspase activity colorimetric assay kit (Bio-techne) for caspase-3 activity diagnosis, Rhodamine 123 for detection of mitochondrial membrane potential, fluorescence microscope for measurement of antioxidant enzyme activities.

Results: Pentoxyphilline increased cell viability and the Rhodamine-123 absorbance. Besides, it reduced cell cytotoxicity, caspase-3 activity, and (OH) generation in all concentrations of 1 nM to 100 µM (P<0.05) by an optimal concentration of 100 µM.

Conclusion: In conclusion, Pentoxyphilline, as a phosphodiesterase inhibitor, can significantly reduce methamphetamine-induced cell death through its anti-inflammatory effects.

References

Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. science. 2003;301(5634):805-9. Available from: https://www.science.org/doi/abs/10.1126/science.1083328.

Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E. Neurogenesis in the adult is involved in the formation of trace memories. Nature. 2001;410(6826):372-6. Available from: https://www.nature.com/articles/35066584.

Taupin P. Adult neurogenesis and neuroplasticity. Restor Neurol Neurosci. 2006;24(1):9-15. Available from: https://content.iospress.com/articles/restorative-neurology-and-neuroscience/rnn00325.

Panegyres P. The contribution of the study of neurodegenerative disorders to the understanding of human memory. Qjm. 2004;97(9):555-67. Available from: https://academic.oup.com/qjmed/article/97/9/555/1594855.

Leuner B, Mendolia-Loffredo S, Kozorovitskiy Y, Samburg D, Gould E, Shors TJ. Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J Neurosci. 2004;24(34):7477-8. Available from: https://www.jneurosci.org/content/24/34/7477.short.

Haroon E, Watari K, Thomas A, Ajilore O, Mintz J, Elderkin-Thompson V, et al. Prefrontal myo-inositol concentration and visuospatial functioning among diabetic depressed patients. Psychiatry Research: J Neuroimaging. 2009;171(1):10-9. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0925492708000498?casa_token=k0xBqiHmEa8AAAAA:ASnfeeVbZh69KPHQ-U552HxK6pB44O_PqpAZSP-T0SpXiRuH-Ag_vXFTw8S3WeznNBrWmHvwhw.

Nestler EJ. Cellular basis of memory for addiction. Dialogues Clin Neurosci. 2022. Available from:.

Sloviter RS. The neurobiology of temporal lobe epilepsy: too much information, not enough knowledge. Comptes rendus biologies. 2005;328(2):143-53. Available from: https://www.tandfonline.com/doi/full/10.31887/DCNS.2013.15.4/enestler.

Sim HI, Kim DH, Kim M. Cellular messenger molecules mediating addictive drug-induced cognitive impairment: cannabinoids, ketamine, methamphetamine, and cocaine. Future Journal of Pharmaceutical Sciences. Available from: https://link.springer.com/article/10.1186/s43094-022-00408-6. 2022;8(1):1-8.

Jones CM, Compton WM, Mustaquim D. Patterns and characteristics of methamphetamine use among adults—United States, 2015–2018. MMWR Morb Mortal Wkly Rep 2020;69(12):317. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725509/.

Steiner H, Van Waes V. Addiction-related gene regulation: Risks of exposure to cognitive enhancers vs. other psychostimulants. Prog Neurobiol. 2013;100:60-80. Available from: . https://www.sciencedirect.com/science/article/pii/S0301008212001530

Abubakar I, Tillmann T, Banerjee A. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385(9963):117-71. Available from: https://discovery.ucl.ac.uk/id/eprint/1462383/.

Miller GM. The emerging role of trace amine‐associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity. Journal of neurochemistry. 2011;116(2):164-76. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2010.07109.x.

Achat-Mendes C, Lynch LJ, Sullivan KA, Vallender EJ, Miller GM. Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1. Pharmacol Biochem Behav. 2012;101(2):201-7. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0091305711003546.

Rogge G, Jones D, Hubert G, Lin Y, Kuhar M. CART peptides: regulators of body weight, reward and other functions. Nat Rev Neurol. 2008;9(10):747-58. Available from: https://www.nature.com/articles/nrn2493.

Vaughan RA, Foster JD. Mechanisms of dopamine transporter regulation in normal and disease states. Trends Pharmacol Sci 2013;34(9):489-96. Available from: https://www.sciencedirect.com/science/article/abs/pii/S016561471300134X.

Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG. Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons. Neuron. 2014;83(2):404-16. Available from: https://www.sciencedirect.com/science/article/pii/S0896627314004875.

Guo L-H, Schluesener H. The innate immunity of the central nervous system in chronic pain: the role of Toll-like receptors. Cell Mol Life Sci. 2007;64(9):1128-36. Available from: https://link.springer.com/article/10.1007/s00018-007-6494-3.

Dugue R, Nath M, Dugue A, Barone FC. Roles of pro-and anti-inflammatory cytokines in traumatic brain injury and acute ischemic stroke. Mech Neuroinflamm. 2017;211:4901. Available from: https://books.google.com/books?hl=en&lr=&id=_vyPDwAAQBAJ&oi=fnd&pg=PA211&dq=Dugue+R,+Nath+M,+Dugue+A,+Barone+FC.+Roles+of+pro-and+anti-inflammatory+cytokines+in+traumatic+brain+injury+and+acute+ischemic+stroke.+Mech+Neuroinflamm.+2017%3B211:4901.&ots=hPe_-iMTRU&sig=K1UNhXX4b4_C4FF5ILK5kyL6X2c#v=onepage&q&f=false.

Seo MH, Eo MY, Myoung H, Kim SM, Lee JH. The effects of pentoxifylline and tocopherol in jaw osteomyelitis. Journal of the Korean Association of Oral and Maxillofacial Surgeons. 2020;46(1):19. Available from: https://synapse.koreamed.org/upload/synapsedata/pdfdata/3070jkaoms/jkaoms-46-19.pdf.

Peterson TC, Peterson MR, Raoul JM. The effect of pentoxifylline and its metabolite-1 on inflammation and fibrosis in the TNBS model of colitis. Eur J Pharmacol. 2011;662(1-3):47-54. Available from: https://www.sciencedirect.com/science/article/pii/S0014299911004390?casa_token=yCBDuVoEdWwAAAAA:YwJWTiAEI8Y2-6ZLa_nD3X9wtjZdBuligJD6a8DeleujpPKWcr7TqQeuXa3WCOnOVF_OTRVV7g.

Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, et al. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009;27(19):3117-25. Available from: https://www.researchgate.net/profile/Gyoergy-Bodoky/publication/24436241_Randomized_Phase_III_Trial_Comparing_Biweekly_Infusional_FluorouracilLeucovorin_Alone_or_With_Irinotecan_in_the_Adjuvant_Treatment_of_Stage_III_Colon_Cancer_PETACC-3/links/568641a408ae197583971f18/Randomized-Phase-III-Trial-Comparing-Biweekly-Infusional-Fluorouracil-Leucovorin-Alone-or-With-Irinotecan-in-the-Adjuvant-Treatment-of-Stage-III-Colon-Cancer-PETACC-3.pdf.

Vukanić ZS, Čolić M, Dimitrijević M. Effect of pentoxifylline on differentiation and maturation of human monocyte-derived dendritic cells in vitro. Int Immunopharmacol. 2007;7(2):167-74. Available from: https://www.sciencedirect.com/science/article/pii/S1567576906002827?casa_token=r2iS-Axaif8AAAAA:EbkxIh1LZmmsds3b_3Q-gfbXyU2HSskywx93yWctMxJ9nl1_7TJLGwGZq64Vdmy7y9cNblwrrw.

Kuznetsova M, Shevchenko J, Khantakova J, Khristin A, Obleukhova I, Silkov A, et al. PENTOXIFYLLINE ENHANCES IN VITRO T-CELL ANTITUMOR RESPONSE IN BREAST CANCER PATIENTS. Медицинская иммунология. 2021;23(4):785-90. Available from: https://cyberleninka.ru/article/n/pentoxifylline-enhances-in-vitro-t-cell-antitumor-response-in-breast-cancer-patients.

Chinta SJ, Andersen JK. Redox imbalance in Parkinson's disease. Biochim Biophys Acta. 2008;1780(11):1362-7. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0304416508000470?casa_token=ieyVr04n44kAAAAA:BiUSkad3_wZ5Aiz6qL2Om2AgrE7w9BJ7Kh6_jm3BO2q5A-j8qMaLh_rk0Thkx23UvvRy--Zidg.

Tuppo EE, Arias HR. The role of inflammation in Alzheimer's disease. Int J Biochem. 2005;37(2):289-305. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1357272504002699?casa_token=aflUhTMUAvUAAAAA:GvljZf8lwj84eCi8OYDE6JO4LlTUl4lUpAfuLHLdlzpKcLmLQ4b4ic5S43n7VmZxGotW1NPA3w.

Block ML, Hong J-S. Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. Prog Neurobiol. 2005;76(2):77-98. Available from:. https://www.sciencedirect.com/science/article/pii/S0301008205000675?casa_token=seIvITjEUNMAAAAA:XN1u2oV38Qdjgsi3pyA5Q4k3V8RrGdtxyjksuIN_0geXMg3GNMKi4qJSPRkXdPJo5nJxz91N0Q

Simpson DS, Oliver PL. ROS generation in microglia: understanding oxidative stress and inflammation in neurodegenerative disease. Antioxidants. 2020;9(8):743. Available from: https://www.mdpi.com/2076-3921/9/8/743.

Guilarte TR. Is methamphetamine abuse a risk factor in parkinsonism? Neurotoxicology. 2001.;22(6):725-31 Available from:https://www.sciencedirect.com/science/article/abs/pii/S0161813X01000468?casa_token=SYkBEl5ETjUAAAAA:InQk1rUDBkWWjRrd1yRNGxAJSDXx9N44dSSpw_EsZU221E7iZqDm7W67-S7fTcLrC6VL8U8-Ow.

Tocharus J, Khonthun C, Chongthammakun S, Govitrapong P. Melatonin attenuates methamphetamine‐induced overexpression of pro‐inflammatory cytokines in microglial cell lines. Journal of pineal research. 2010;48(4):347-52. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-079X.2010.00761.x?casa_token=XSB6smmOVfQAAAAA%3A9wY_fVFQWpraB-lyq2dGNrlKAzvaXk3V5dl6iBBe3X05YQZH0FPdH5zNFgCbel6C_cu2r88kHHMONI0.

Lewis D, Kenneally M, van denHeuvel C, Byard RW. Methamphetamine deaths: changing trends and diagnostic issues. Medicine, Science and the Law. 2021;61(2):130-7. Available from: https://journals.sagepub.com/doi/abs/10.1177/0025802420986707.

Wang B, Chen T, Wang J, Jia Y, Ren H, Wu F, et al. Methamphetamine modulates the production of interleukin-6 and tumor necrosis factor-alpha via the cAMP/PKA/CREB signaling pathway in lipopolysaccharide-activated microglia. Int Immunopharmacol. 2018;56:168-78. Available from: https://www.sciencedirect.com/science/article/pii/S1567576918300249?casa_token=I9hq95b9nxMAAAAA:0icB36hRUxJsv9OrD46r80-t7PpV9TfBIIcdX-otpXw9a6Fx_6yk9BJGvHC5fO8ekUMU4EwpaQ.

Baratz R, Tweedie D, Wang J-Y, Rubovitch V, Luo W, Hoffer BJ, et al. Transiently lowering tumor necrosis factor-α synthesis ameliorates neuronal cell loss and cognitive impairments induced by minimal traumatic brain injury in mice. Journal of Neuroinflammation. 2015;12(1):1-14. Available from: https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015-0237-4.

Neves KRT, Nobre HV, Leal LKA, de Andrade GM, Brito GAdC, Viana GSdB. Pentoxifylline neuroprotective effects are possibly related to its anti-inflammatory and TNF-alpha inhibitory properties, in the 6-OHDA model of Parkinson’s disease. Parkinson’s Disease. 2015;2015. Available from: https://www.hindawi.com/journals/pd/2015/108179/.

Nouri M, Movassaghi S, Soleimani M, Sharifi ZN. Protective effect of pentoxifylline on male Wistar rat testicular germ cell apoptosis induced by 3, 4-methylenedioxymeth amphetamine. Iran J Basic Med Sci. 2016;19(6):646. Available from:.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951604/.

Tian C, Murrin LC, Zheng JC. Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells. PloS one. 2009;4(5):e5546. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0005546.

Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 2016;1863(12):2977-92. Available from: https://www.sciencedirect.com/science/article/pii/S0167488916302324.

Su L-J, Zhang J-H, Gomez H, Murugan R, Hong X, Xu D, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev. 2019;2019. Available from https://www.hindawi.com/journals/omcl/2019/5080843/.

Kim SJ, Kim HS, Seo YR. Understanding of ROS-inducing strategy in anticancer therapy. Oxid Med Cell Longev. 2019;2019. Available from: https://www.hindawi.com/journals/omcl/2019/5381692/.

Park JH, Kim SE, Jin JJ, Choi HS, Kim CJ, Ko IG. Pentoxifylline alleviates perinatal hypoxic-ischemia-induced short-term memory impairment by suppressing apoptosis in the hippocampus of rat pups. International Neurourology Journal. 2016;20(2):107. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4932643/.

Movassaghi S, Sharifi ZN, Mohammadzadeh F, Soleimani M. Pentoxifylline protects the rat liver against fibrosis and apoptosis induced by acute administration of 3, 4-methylenedioxymethamphetamine (MDMA or ecstasy). Iranian journal of basic medical sciences. 2013;16(8):922-7. Available from: http://eprints.mums.ac.ir/8112/.

Keller N, Ozmadenci D, Ichim G, Stupack D, editors. Caspase-8 function, and phosphorylation, in cell migration. Seminars in Cell & Developmental Biology; 2018: Elsevier. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1084952117305293.

Mohr A, Deedigan L, Jencz S, Mehrabadi Y, Houlden L, Albarenque S-M, et al. Caspase-10: A molecular switch from cell-autonomous apoptosis to communal cell death in response to chemotherapeutic drug treatment. Cell Death & Differentiation. 2018;25(2):340-52. Available from: https://www.nature.com/articles/cdd2017164.

de la Cadena SG, Massieu L. Caspases and their role in inflammation and ischemic neuronal death. Focus on caspase-12. Apoptosis: An International Journal on Programmed Cell Death. 2016;21(7):763. Available from: https://www.proquest.com/openview/dc245bc7dd750fcf64e0dfd95e8a81cc/1?pq-origsite=gscholar&cbl=55375.

Shalini S, Dorstyn L, Dawar S, Kumar S. Old, new and emerging functions of caspases. Cell Death & Differentiation. 2015;22(4):526-39. Available from: https://www.nature.com/articles/cdd2014216.

Baracca A, Sgarbi G, Solaini G, Lenaz G. Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of proton flux through F0 during ATP synthesis. Biochim Biophys Acta. 2003;1606(1-3):137-46. Available from https://www.sciencedirect.com/science/article/pii/S0005272803001105.

Esteras N, Adjobo-Hermans MJ, Abramov AY, Koopman WJ. Visualization of mitochondrial membrane potential in mammalian cells. Methods Mol Biol. 155: Elsevier; 2020. p. 221-45. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0091679X19301207

Rashedinia M, Saberzadeh J, Khodaei F, Mashayekhi Sardoei N, Alimohammadi M, Arabsolghar R. Effect of sodium benzoate on apoptosis and mitochondrial membrane potential after aluminum toxicity in PC-12 cell line. Iranian Journal of Toxicology. 2020;14(4):237-44. Available from: http://ijt.arakmu.ac.ir/browse.php?a_code=A-10-677-1&slc_lang=en&sid=1.

Seo T-B, Kim T-W, Shin M-S, Ji E-S, Cho H-S, Lee J-M, et al. Aerobic exercise alleviates ischemia-induced memory impairment by enhancing cell proliferation and suppressing neuronal apoptosis in hippocampus. International Neurourology Journal. 2014;18(4):187. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280438/

Kim M, Shin MS, Lee JM, Cho HS, Kim CJ, Kim YJ, et al. Inhibitory effects of isoquinoline alkaloid berberine on ischemia-induced apoptosis via activation of phosphoinositide 3-kinase/protein kinase B signaling pathway. International neurourology journal. 2014;18(3):115. Available from: https://www.sciencedirect.com/science/article/pii/B9781483227344500176

Downloads

Additional Files

Published

2023-11-27

Issue

Section

Original Article(s)

How to Cite

Protective Effects of Pentoxifylline on Methamphetamine Induced Cell Death in PC12 Cells. (2023). Knowledge and Health in Basic Medical Sciences, 18(1), Page:60-67. https://doi.org/10.22100/jkh.v18i1.3076

Most read articles by the same author(s)

<< < 59 60 61 62 63 64 65 > >>