Effect of leukemia inhibitory factor in experimental cisplatin neuropathy in mice.
In this study, the effect of leukemia inhibitory factor (LIF) on cisplatin (CDDP)-induced neuropathy was evaluated. Mice were treated with CDDP, 2 mg/kg i.p. twice a week nine times. During the last week some of the mice were also injected with LIF, 2 mug/kg s.c. every other day for a total of four injections. Development of neuropathy was evaluated with changes in tail flick latency and sensory nerve conduction velocity (NCV). At the end of the treatment period dorsal root ganglia (DRG) were microscopically examined. Some of the DRGs were explanted into extracellular matrix, covered with culture medium and incubated for 3 days. During and at the end of the incubation, cellular migration and axonal outgrowth from the DRGs were quantified. LIF proved effective in reversing the increase in tail flick latency (p<0.05) and improving the reduction in NCV induced by CDDP. CDDP led to smaller nuclear and somatic size in neurons, while with LIF, the latter was restored to control values (p<0.01). No apoptotic nucleus was observed among DRG neurons while very few and moderate numbers detected among satellite and Schwann cells, respectively. With LIF, none of the cells had apoptosis. CDDP caused a decrease in the number of migrating cells and in the length of outgrowing axons while LIF treatment restored both capacities (p<0.05) In conclusion, in CDDP-induced neuropathy, LIF was found to be effective in correcting some functional and morphological deteriorations related with major involvement of Schwann cells.
Oztürk
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Department of Physiology, Neuroscience Research Unit, Medical School, Yüzüncü Yil University, Fizyoloji ABD, 65200 Van, Turkey. drgurkan@yyu.edu.tr
Erdoğan
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E
Anlar
O
O
Kösem
M
M
Taşpinar
M
M
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D001369:Axons / Q000378:metabolism; D002465:Cell Movement; D002945:Cisplatin / Q000009:adverse effects* / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D012583:Schwann Cells / Q000378:metabolism; D013997:Time Factors
D003432:Cross-Linking Reagents; D003470:Culture Media; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D002945:Cisplatin