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Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats.

Fujita S, Ushio S, Ozawa N, Masuguchi K, Kawashiri T, Oishi R, Egashira N - PLoS ONE (2015)

Bottom Line: GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems.Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells.Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.

ABSTRACT

Background: Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells.

Methods: Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves.

Results: Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice.

Conclusion: These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus

Effect of exenatide on oxaliplatin-induced tumor cytotoxicity.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 (n = 4). **P < 0.01 compared with control.
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pone.0141921.g005: Effect of exenatide on oxaliplatin-induced tumor cytotoxicity.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 (n = 4). **P < 0.01 compared with control.

Mentions: Exposure of cultured C-26 cells to oxaliplatin (70 μM) for 24 h significantly decreased tumor cell viability (P < 0.01 by the Tukey-Kramer test, Fig 5). Exenatide (3, 10 or 30 nM) had no effect on the oxaliplatin-induced decrease in cell viability.


Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats.

Fujita S, Ushio S, Ozawa N, Masuguchi K, Kawashiri T, Oishi R, Egashira N - PLoS ONE (2015)

Effect of exenatide on oxaliplatin-induced tumor cytotoxicity.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 (n = 4). **P < 0.01 compared with control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4633148&req=5

pone.0141921.g005: Effect of exenatide on oxaliplatin-induced tumor cytotoxicity.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 (n = 4). **P < 0.01 compared with control.
Mentions: Exposure of cultured C-26 cells to oxaliplatin (70 μM) for 24 h significantly decreased tumor cell viability (P < 0.01 by the Tukey-Kramer test, Fig 5). Exenatide (3, 10 or 30 nM) had no effect on the oxaliplatin-induced decrease in cell viability.

Bottom Line: GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems.Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells.Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.

ABSTRACT

Background: Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells.

Methods: Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves.

Results: Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice.

Conclusion: These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus