Erythropoietin Against Cisplatin-induced Peripheral Neurotoxicity in Rats

Overview

Journal Med Oncol

Publisher Springer

Specialty Oncology

Date 2004 Aug 10

PMID 15299192

Citations 5

Authors

Bulent Orhan

Suayib Yalcin

Gulay Nurlu

Dilara Zeybek

Sevda Muftuoglu

Affiliations

Soon will be listed here.

Abstract

Cisplatin (CDDP) is a potent anticancer drug, and neurotoxicity is one of its most important dose-limiting toxicities. In this study we investigated the role of recombinant human erythropoietin (rhuEPO) for protection against CDDP-induced neurotoxicity. All experiments were conducted on female Wistar-albino rats. Animals were randomly assigned to three groups. Group A received only CDDP, group B received CDDP plus rhuEPO, and group C received only rhuEPO. Electroneurography (ENG) was done in the beginning and at the end of 7 wk, then the rats were sacrificed and the sciatic nerve was removed for histopathological examination. The mean initial latency was 2.7438 ms in group A, 2.4875 ms in group B, and 2.62 ms in group C. After 7 wk of treatment, the latency was 2.4938, 2.6313, and 2.3900 ms, respectively. The difference in latencies was not statistically significant. The amplitude of compound muscle action potential (CMAP) was 12.8125 mV, 14.3875 mV, and 14.5600 mV before the treatment and 8.4875, 12.8250, and, 13.0800 mV after treatment, respectively. Amplitude of CMAP was significantly greater in rhuEPO-treated groups (groups B and C) compared to cisplatin only Group A. The mean area of CMAP was 12.2625, 12.3500, and, 12.2800 mV s before the treatment and 5.7125, 10.6463, and 9.1600 mV s after the treatment, respectively. The area of CMAP was significantly larger in rhuEPO-treated groups. In histopathological studies thick, thin, and total number of nerve fibers were 4053, 5050, and 9103, in group A, 5100, 8231, and 13331, in group B, and 5264, 6010, and 11274, in group C respectively. In the microscopic examination active myelinization process was observed in rhuEPO-treated groups. We concluded that at the given dose and schedule CDDP-induced motor neuropathy and rhuEPO prevented this neuropathy by sparing the number of normal nerve fibers and by protecting the amplitude and area of CMAP. We concluded that rhuEPO may also play a role in active myelinization and it is an active agent in protection against CDDP-induced peripheral neuropathy, warranting further clinical studies.

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References

Aggarwal S . A histochemical approach to the mechanism of action of cisplatin and its analogues. J Histochem Cytochem. 1993; 41(7):1053-73. DOI: 10.1177/41.7.8515048. View

Yalcin S, Orhan B . Recombinant human erythropoietin in the treatment of chronic anemia of cancer. Acta Haematol. 1998; 100(2):115. DOI: 10.1159/000040883. View

Beguin Y, Baron F, Fillet G . Influence of marrow erythropoietic activity on serum erythropoietin levels after autologous hematopoietic stem cell transplantation. Haematologica. 1999; 83(12):1076-81. View

Cece R, Petruccioli M, Cavaletti G, Barajon I, Tredici G . An ultrastructural study of neuronal changes in dorsal root ganglia (DRG) of rats after chronic cisplatin administrations. Histol Histopathol. 1995; 10(4):837-45. View

Tredici G, Braga M, Nicolini G, Miloso M, Marmiroli P, Schenone A . Effect of recombinant human nerve growth factor on cisplatin neurotoxicity in rats. Exp Neurol. 1999; 159(2):551-8. DOI: 10.1006/exnr.1999.7174. View

Maxwell P, Ferguson D, Nicholls L, Iredale J, Pugh C, Johnson M . Sites of erythropoietin production. Kidney Int. 1997; 51(2):393-401. DOI: 10.1038/ki.1997.52. View

Cerami A, Brines M, Ghezzi P, Cerami C . Effects of epoetin alfa on the central nervous system. Semin Oncol. 2001; 28(2 Suppl 8):66-70. DOI: 10.1016/s0093-7754(01)90216-7. View

Tredici G, Cavaletti G, Petruccioli M, Fabbrica D, Tedeschi M, Venturino P . Low-dose glutathione administration in the prevention of cisplatin-induced peripheral neuropathy in rats. Neurotoxicology. 1994; 15(3):701-4. View

Morishita E, Masuda S, Nagao M, Yasuda Y, Sasaki R . Erythropoietin receptor is expressed in rat hippocampal and cerebral cortical neurons, and erythropoietin prevents in vitro glutamate-induced neuronal death. Neuroscience. 1997; 76(1):105-16. DOI: 10.1016/s0306-4522(96)00306-5. View

10.

Junk A, Mammis A, Savitz S, Singh M, Roth S, Malhotra S . Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. Proc Natl Acad Sci U S A. 2002; 99(16):10659-64. PMC: 125005. DOI: 10.1073/pnas.152321399. View

11.

Yalcin S, Nurlu G, Orhan B, Zeybek D, Muftuoglu S, Sarer B . Protective effect of amifostine against cisplatin-induced motor neuropathy in rat. Med Oncol. 2003; 20(2):175-80. DOI: 10.1385/MO:20:2:175. View

12.

Koshimura K, Murakami Y, Sohmiya M, Tanaka J, Kato Y . Effects of erythropoietin on neuronal activity. J Neurochem. 1999; 72(6):2565-72. DOI: 10.1046/j.1471-4159.1999.0722565.x. View

13.

Cavaletti G, Tredici G, Marmiroli P, Petruccioli M, Barajon I, Fabbrica D . Morphometric study of the sensory neuron and peripheral nerve changes induced by chronic cisplatin (DDP) administration in rats. Acta Neuropathol. 1992; 84(4):364-71. DOI: 10.1007/BF00227662. View

14.

Digicaylioglu M, Bichet S, Marti H, Wenger R, Rivas L, Bauer C . Localization of specific erythropoietin binding sites in defined areas of the mouse brain. Proc Natl Acad Sci U S A. 1995; 92(9):3717-20. PMC: 42032. DOI: 10.1073/pnas.92.9.3717. View

15.

Vaziri N, Zhou X, Liao S . Erythropoietin enhances recovery from cisplatin-induced acute renal failure. Am J Physiol. 1994; 266(3 Pt 2):F360-6. DOI: 10.1152/ajprenal.1994.266.3.F360. View

16.

Orhan B, Yalcin S, Evrensel T, Kurt E, Manavoglu O, Erbas T . Does cisplatin stimulate erythropoietin secretion from the peritubular cells of the kidney?. Clin Nephrol. 1998; 50(3):202-3. View

17.

Cavaletti G, Minoia C, Schieppati M, Tredici G . Protective effects of glutathione on cisplatin neurotoxicity in rats. Int J Radiat Oncol Biol Phys. 1994; 29(4):771-6. DOI: 10.1016/0360-3016(94)90565-7. View

18.

de Koning P, Neijt J, Jennekens F, Gispen W . Evaluation of cis-diamminedichloroplatinum (II) (cisplatin) neurotoxicity in rats. Toxicol Appl Pharmacol. 1987; 89(1):81-7. DOI: 10.1016/0041-008x(87)90178-5. View

19.

Birgegard G, Wide L, Simonsson B . Marked erythropoietin increase before fall in Hb after treatment with cytostatic drugs suggests mechanism other than anaemia for stimulation. Br J Haematol. 1989; 72(3):462-6. DOI: 10.1111/j.1365-2141.1989.tb07733.x. View

20.

Anand A, Bashey B . Newer insights into cisplatin nephrotoxicity. Ann Pharmacother. 1993; 27(12):1519-25. DOI: 10.1177/106002809302701219. View