Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia
Paclitaxel is a chemotherapeutic agent used to treat a wide range of malignant tumors. Although it has anti-tumoral properties, paclitaxel also shows significant adverse effects on the peripheral nervous system, causing peripheral neuropathy. Paclitaxel has previously been shown to exert direct neur...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Toxics |
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| Online Access: | https://www.mdpi.com/2305-6304/11/7/581 |
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| author | Amira Elfarnawany Faramarz Dehghani |
| author_facet | Amira Elfarnawany Faramarz Dehghani |
| author_sort | Amira Elfarnawany |
| collection | DOAJ |
| description | Paclitaxel is a chemotherapeutic agent used to treat a wide range of malignant tumors. Although it has anti-tumoral properties, paclitaxel also shows significant adverse effects on the peripheral nervous system, causing peripheral neuropathy. Paclitaxel has previously been shown to exert direct neurotoxic effects on primary DRG neurons. However, little is known about paclitaxel’s effects on non-neuronal DRG cells. They provide mechanical and metabolic support and influence neuronal signaling. In the present study, paclitaxel effects on primary DRG non-neuronal cells were analyzed and their concentration or/and time dependence investigated. DRGs of Wister rats (6–8 weeks old) were isolated, and non-neuronal cell populations were separated by the density gradient centrifugation method. Different concentrations of Paclitaxel (0.01 µM–10 µM) were tested on cell viability by MTT assay, cell death by lactate dehydrogenase (LDH) assay, and propidium iodide (PI) assay, as well as cell proliferation by Bromodeoxyuridine (BrdU) assay at 24 h, 48 h, and 72 h post-treatment. Furthermore, phenotypic effects have been investigated by using immunofluorescence techniques. Paclitaxel exhibited several toxicological effects on non-neuronal cells, including a reduction in cell viability, an increase in cell death, and an inhibition of cell proliferation. These effects were concentration- and time-dependent. Cellular and nuclear changes such as shrinkage, swelling of cell bodies, nuclear condensation, chromatin fragmentation, retraction, and a loss in processes were observed. Paclitaxel showed adverse effects on primary DRG non-neuronal cells, which might have adverse functional consequences on sensory neurons of the DRG, asking for consideration in the management of peripheral neuropathy. |
| first_indexed | 2024-03-11T00:36:28Z |
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| institution | Directory Open Access Journal |
| issn | 2305-6304 |
| language | English |
| last_indexed | 2024-03-11T00:36:28Z |
| publishDate | 2023-07-01 |
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| series | Toxics |
| spelling | doaj.art-b3709bdc8f524f3fbaba9bc45e7985da2023-11-18T21:36:53ZengMDPI AGToxics2305-63042023-07-0111758110.3390/toxics11070581Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root GangliaAmira 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), GermanyPaclitaxel is a chemotherapeutic agent used to treat a wide range of malignant tumors. Although it has anti-tumoral properties, paclitaxel also shows significant adverse effects on the peripheral nervous system, causing peripheral neuropathy. Paclitaxel has previously been shown to exert direct neurotoxic effects on primary DRG neurons. However, little is known about paclitaxel’s effects on non-neuronal DRG cells. They provide mechanical and metabolic support and influence neuronal signaling. In the present study, paclitaxel effects on primary DRG non-neuronal cells were analyzed and their concentration or/and time dependence investigated. DRGs of Wister rats (6–8 weeks old) were isolated, and non-neuronal cell populations were separated by the density gradient centrifugation method. Different concentrations of Paclitaxel (0.01 µM–10 µM) were tested on cell viability by MTT assay, cell death by lactate dehydrogenase (LDH) assay, and propidium iodide (PI) assay, as well as cell proliferation by Bromodeoxyuridine (BrdU) assay at 24 h, 48 h, and 72 h post-treatment. Furthermore, phenotypic effects have been investigated by using immunofluorescence techniques. Paclitaxel exhibited several toxicological effects on non-neuronal cells, including a reduction in cell viability, an increase in cell death, and an inhibition of cell proliferation. These effects were concentration- and time-dependent. Cellular and nuclear changes such as shrinkage, swelling of cell bodies, nuclear condensation, chromatin fragmentation, retraction, and a loss in processes were observed. Paclitaxel showed adverse effects on primary DRG non-neuronal cells, which might have adverse functional consequences on sensory neurons of the DRG, asking for consideration in the management of peripheral neuropathy.https://www.mdpi.com/2305-6304/11/7/581peripheral neuropathyDRG non-neuronal cellspaclitaxelMTT assayLDH assayBrdU assay |
| spellingShingle | Amira Elfarnawany Faramarz Dehghani Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia Toxics peripheral neuropathy DRG non-neuronal cells paclitaxel MTT assay LDH assay BrdU assay |
| title | Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia |
| title_full | Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia |
| title_fullStr | Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia |
| title_full_unstemmed | Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia |
| title_short | Time- and Concentration-Dependent Adverse Effects of Paclitaxel on Non-Neuronal Cells in Rat Primary Dorsal Root Ganglia |
| title_sort | time and concentration dependent adverse effects of paclitaxel on non neuronal cells in rat primary dorsal root ganglia |
| topic | peripheral neuropathy DRG non-neuronal cells paclitaxel MTT assay LDH assay BrdU assay |
| url | https://www.mdpi.com/2305-6304/11/7/581 |
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