Effect of exenatide on oxaliplatin-induced neurite degeneration in cultured PC12 cells.

<p>Cultured PC12 cells were incubated with oxaliplatin (3 μM) for 24 h in the presence or absence of exenatide (3, 10, or 30 nM). (A) Photographs were originally magnified 800 ×. Scale bar = 100 μm. (B) Neurite length was measured using image analysis software (MetaXpress). Results are expressed as the mean ± standard error mean (<i>n</i> = 3). **<i>P</i> < 0.01 compared with control, ††<i>P</i> < 0.01 compared with oxaliplatin alone.</p

Effects of extended-release exenatide on recovery from mechanical allodynia and axonal degeneration induced by oxaliplatin.

<p>Oxaliplatin (4 mg/kg) was administered i.v. twice per week for 4 weeks (days 1, 2, 8, 9, 15, 16, 22, and 23). Extended-release exenatide (100 μg/kg) was administered s.c. once per week for 9 weeks (days 1, 8, 15, 22, 29, 36, 43, 50, and 57). Oxaliplatin treatment ceased on day 23, however exenatide treatment was continued for an additional 5 weeks. (A) The von Frey test was performed before the first drug administration (on day 0) and on days 35, 42, 49, 56, and 63. Values are expressed as the mean ± standard error mean of five to six animals. (B) On days 42 and 63, the sciatic nerve was harvested, and samples were stained with toluidine blue. Images were captured at 800× magnification. Scale bar = 60 μm. (C) The area of axon (number of axon: from 3000 to 6000/field) was measured using image analysis software (Image J 1.36). Values are expressed as the mean ± standard error mean of four animals. *<i>P</i> < 0.05, **<i>P</i> < 0.01 compared with vehicle, ††<i>P</i> < 0.01 compared with oxaliplatin alone.</p

Effects of extended-release exenatide on incidence of mechanical allodynia and axonal degeneration induced by oxaliplatin.

<p>Oxaliplatin (4 mg/kg) was administered i.v. twice per week for 4 weeks (days 1, 2, 8, 9, 15, 16, 22, and 23). Extended-release exenatide (100 μg/kg) was administered s.c. once per week for 4 weeks. (A) The von Frey test was performed before the first drug administration (on day 0) and on days 7, 14, 21, and 28. Values are expressed as the mean ± standard error mean of five to six animals. (B) On day 28, the sciatic nerve was harvested, and samples were stained with toluidine blue. Images were captured at 800× magnification. Scale bar = 60 μm. (C) The area of axon was calculated by image analysis software (Image J 1.36) from approximately 3000 to 6000 axons per group. Values are expressed as the mean ± standard error mean of four animals. **<i>P</i> < 0.01 compared with vehicle.</p

Effect of exenatide on oxaliplatin-induced tumor cytotoxicity.

<p>C-26 cells were incubated with oxaliplatin (70 μM) for 24 h in the presence or absence of exenatide (3, 10, or 30 μg/mL). Cell viability was measured using the WST-8 assay. Values are expressed as a percentage of the control (<i>n</i> = 4). **<i>P</i> < 0.01 compared with control.</p

Effect of exenatide on oxaliplatin-induced cell viability in cultured PC12 cells.

<p>Cultured PC12 cells were incubated with oxaliplatin (3 μM) for 24 h in the presence or absence of exenatide (3, 10, or 30 nM). Cell viability was measured using the WST-8 assay. Results are expressed as the mean ± standard error mean (<i>n</i> = 4). **<i>P</i> < 0.01 compared with control.</p

Effect of extended-release exenatide on oxaliplatin-induced anti-tumor activity in tumor cell-implanted mice.

<p>C-26 cell-implanted mice were treated with oxaliplatin (6 mg/kg, i.p. days 1, 2, 8, and 9) and extended-release exenatide (150 μg/kg, s.c. days 1 and 8). Tumor volumes were measured on days 0, 4, 7, and 11. Values are expressed as the mean ± standard error mean of 8–12 animals on days 0, 4, 7, and 11. *<i>P</i> < 0.05, **<i>P</i> < 0.01 compared with vehicle.</p