Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy
<p>Abstract</p> <p>Background</p> <p>Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root g...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-07-01
|
| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/10/77 |
| _version_ | 1818472259783753728 |
|---|---|
| author | Egensperger Rupert Kribben Andreas Dzagnidze Anna Liedert Bernd Schäfers Maria Obermann Mark Katsarava Zaza Yoon Min-Suk Limmroth Volker Diener Hans-Christoph Thomale Juergen |
| author_facet | Egensperger Rupert Kribben Andreas Dzagnidze Anna Liedert Bernd Schäfers Maria Obermann Mark Katsarava Zaza Yoon Min-Suk Limmroth Volker Diener Hans-Christoph Thomale Juergen |
| author_sort | Egensperger Rupert |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG) cells leading to sensory polyneuropathy (PNP). We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO) protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden.</p> <p>Results</p> <p>A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s ± 1,68 m/s; cisplatin + rhEPO 49,66 m/s ± 1,26 m/s; control 55,01 m/s ± 1,88 m/s; p < 0,001). The co-application of rhEPO, however, did not alter the level of unrepaired cisplatin-DNA lesions accumulating in DRG target cells. Micro-morphological analyses of the sciatic nerve from cisplatin-exposed mice showed damaged myelin sheaths and mitochondria. Co-administered rhEPO inhibited myelin sheaths from structural injuries and resulted in an increased number of intact mitochondria.</p> <p>Conclusion</p> <p>The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.</p> |
| first_indexed | 2024-04-14T04:04:25Z |
| format | Article |
| id | doaj.art-0f3cab2e44c24f228db24b933e7a660d |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-04-14T04:04:25Z |
| publishDate | 2009-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-0f3cab2e44c24f228db24b933e7a660d2022-12-22T02:13:24ZengBMCBMC Neuroscience1471-22022009-07-011017710.1186/1471-2202-10-77Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathyEgensperger RupertKribben AndreasDzagnidze AnnaLiedert BerndSchäfers MariaObermann MarkKatsarava ZazaYoon Min-SukLimmroth VolkerDiener Hans-ChristophThomale Juergen<p>Abstract</p> <p>Background</p> <p>Cisplatin mediates its antineoplastic activity by formation of distinct DNA intrastrand cross links. The clinical efficacy and desirable dose escalations of cisplatin are restricted by the accumulation of DNA lesions in dorsal root ganglion (DRG) cells leading to sensory polyneuropathy (PNP). We investigated in a mouse model by which mechanism recombinant erythropoietin (rhEPO) protects the peripheral nervous system from structural and functional damage caused by cisplatin treatment with special emphasis on DNA damage burden.</p> <p>Results</p> <p>A cumulative dose of 16 mg cisplatin/kg resulted in clear electrophysiological signs of neuropathy, which were significantly attenuated by concomitant erythropoietin (cisplatin 32,48 m/s ± 1,68 m/s; cisplatin + rhEPO 49,66 m/s ± 1,26 m/s; control 55,01 m/s ± 1,88 m/s; p < 0,001). The co-application of rhEPO, however, did not alter the level of unrepaired cisplatin-DNA lesions accumulating in DRG target cells. Micro-morphological analyses of the sciatic nerve from cisplatin-exposed mice showed damaged myelin sheaths and mitochondria. Co-administered rhEPO inhibited myelin sheaths from structural injuries and resulted in an increased number of intact mitochondria.</p> <p>Conclusion</p> <p>The protective effect of recombinant erythropoietin is not mediated by reducing the burden of DNA platination in the target cells, but it is likely to be due to a higher resistance of the target cells to the adverse effect of DNA damage. The increased frequency of intact mitochondria might also contribute to this protective role.</p>http://www.biomedcentral.com/1471-2202/10/77 |
| spellingShingle | Egensperger Rupert Kribben Andreas Dzagnidze Anna Liedert Bernd Schäfers Maria Obermann Mark Katsarava Zaza Yoon Min-Suk Limmroth Volker Diener Hans-Christoph Thomale Juergen Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy BMC Neuroscience |
| title | Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy |
| title_full | Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy |
| title_fullStr | Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy |
| title_full_unstemmed | Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy |
| title_short | Erythropoietin overrides the triggering effect of DNA platination products in a mouse model of Cisplatin-induced neuropathy |
| title_sort | erythropoietin overrides the triggering effect of dna platination products in a mouse model of cisplatin induced neuropathy |
| url | http://www.biomedcentral.com/1471-2202/10/77 |
| work_keys_str_mv | AT egenspergerrupert erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT kribbenandreas erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT dzagnidzeanna erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT liedertbernd erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT schafersmaria erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT obermannmark erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT katsaravazaza erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT yoonminsuk erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT limmrothvolker erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT dienerhanschristoph erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy AT thomalejuergen erythropoietinoverridesthetriggeringeffectofdnaplatinationproductsinamousemodelofcisplatininducedneuropathy |