Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several chemotherapeutic agents, such as Paclitaxel. The main symptoms of CIPN are pain and numbness in the hands and feet. Paclitaxel is believed to accumulate in the dorsal root ganglia and free nerve endings. Novel thera...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/12/1873 |
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| author | Amira Elfarnawany Faramarz Dehghani |
| author_facet | Amira Elfarnawany Faramarz Dehghani |
| author_sort | Amira Elfarnawany |
| collection | DOAJ |
| description | Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several chemotherapeutic agents, such as Paclitaxel. The main symptoms of CIPN are pain and numbness in the hands and feet. Paclitaxel is believed to accumulate in the dorsal root ganglia and free nerve endings. Novel therapeutic agents might help to mitigate or prevent Paclitaxel toxicity on dorsal root ganglion (DRG) neurons. Thus, we used primary DRG neurons as a model to investigate the potential neuroprotective effects of the endocannabinoid-like substance, palmitoylethanolamide (PEA). DRG neurons were isolated from cervical to sacral segments of spinal nerves of Wister rats (6–8 weeks old). After isolation and purification of neuronal cell populations, different concentrations of Paclitaxel (0.01–10 µM) or PEA (0.1–10 µM) or their combination were tested on cell viability by MTT assay at 24 h, 48, and 72 h post-treatment. Furthermore, morphometric analyses of neurite length and soma size for DRG neurons were performed. Adverse Paclitaxel effects on cell viability were apparent at 72 h post-treatment whereas Paclitaxel significantly reduced the neurite length in a concentration-dependent manner nearly at all investigated time points. However, Paclitaxel significantly increased the size of neuronal cell bodies at all time windows. These phenotypic effects were significantly reduced in neurons additionally treated with PEA, indicating the neuroprotective effect of PEA. PEA alone led to a significant increase in neuron viability regardless of PEA concentrations, apparent improvements in neurite outgrowth as well as a significant decrease in soma size of neurons at different investigated time points. Taken together, PEA showed promising protective effects against Paclitaxel-related toxicity on DRG neurons. |
| first_indexed | 2024-03-09T17:16:27Z |
| format | Article |
| id | doaj.art-a37ac985e9c44b7da2683efb9c74727a |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T17:16:27Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-a37ac985e9c44b7da2683efb9c74727a2023-11-24T13:34:52ZengMDPI AGBiomolecules2218-273X2022-12-011212187310.3390/biom12121873Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion NeuronsAmira Elfarnawany0Faramarz Dehghani1Department of Anatomy and Cell Biology, Medical Faculty, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), GermanyDepartment of Anatomy and Cell Biology, Medical Faculty, Martin Luther University Halle-Wittenberg, Grosse Steinstrasse 52, 06108 Halle (Saale), GermanyChemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several chemotherapeutic agents, such as Paclitaxel. The main symptoms of CIPN are pain and numbness in the hands and feet. Paclitaxel is believed to accumulate in the dorsal root ganglia and free nerve endings. Novel therapeutic agents might help to mitigate or prevent Paclitaxel toxicity on dorsal root ganglion (DRG) neurons. Thus, we used primary DRG neurons as a model to investigate the potential neuroprotective effects of the endocannabinoid-like substance, palmitoylethanolamide (PEA). DRG neurons were isolated from cervical to sacral segments of spinal nerves of Wister rats (6–8 weeks old). After isolation and purification of neuronal cell populations, different concentrations of Paclitaxel (0.01–10 µM) or PEA (0.1–10 µM) or their combination were tested on cell viability by MTT assay at 24 h, 48, and 72 h post-treatment. Furthermore, morphometric analyses of neurite length and soma size for DRG neurons were performed. Adverse Paclitaxel effects on cell viability were apparent at 72 h post-treatment whereas Paclitaxel significantly reduced the neurite length in a concentration-dependent manner nearly at all investigated time points. However, Paclitaxel significantly increased the size of neuronal cell bodies at all time windows. These phenotypic effects were significantly reduced in neurons additionally treated with PEA, indicating the neuroprotective effect of PEA. PEA alone led to a significant increase in neuron viability regardless of PEA concentrations, apparent improvements in neurite outgrowth as well as a significant decrease in soma size of neurons at different investigated time points. Taken together, PEA showed promising protective effects against Paclitaxel-related toxicity on DRG neurons.https://www.mdpi.com/2218-273X/12/12/1873peripheral neuropathic painneurotoxicitydorsal root ganglion neuronspalmitoylethanolamidepaclitaxelneurite length |
| spellingShingle | Amira Elfarnawany Faramarz Dehghani Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons Biomolecules peripheral neuropathic pain neurotoxicity dorsal root ganglion neurons palmitoylethanolamide paclitaxel neurite length |
| title | Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons |
| title_full | Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons |
| title_fullStr | Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons |
| title_full_unstemmed | Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons |
| title_short | Palmitoylethanolamide Mitigates Paclitaxel Toxicity in Primary Dorsal Root Ganglion Neurons |
| title_sort | palmitoylethanolamide mitigates paclitaxel toxicity in primary dorsal root ganglion neurons |
| topic | peripheral neuropathic pain neurotoxicity dorsal root ganglion neurons palmitoylethanolamide paclitaxel neurite length |
| url | https://www.mdpi.com/2218-273X/12/12/1873 |
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