Oxaliplatin induces hypomyelination and reduced neuregulin 1 expression in the rat sciatic nerve

Tsutsumi, Kuniaki; Yamashita, Yuji; Ushio, Soichiro; Kawashiri, Takehiro; Kaname, Takanori; Fujita, Shunsuke; Oishi, Ryozo; Egashira, Nobuaki

doi:10.1016/j.neures.2014.02.004

Cited by 25 publications

(18 citation statements)

References 24 publications

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“…It is conceivable that neurodegeneration, such as axonopathy, neuronopathy, or myelinopathy, are responsible for oxaliplatin-dependent chronic neuropathy [7][8][9] . In the present study, we examined the protective property of alogliptin on oxaliplatin-induced peripheral neuropathy focused on axonopathy.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of alogliptin on oxaliplatin-induced peripheral neuropathy in vivo and in vitro

Shigematsu

Kawashiri

Kobayashi

et al. 2020

Sci Rep

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Oxaliplatin is a platinum-based antineoplastic drug commonly used for treating colorectal, gastric, and pancreatic cancer. However, it frequently causes peripheral neuropathy as dose-limiting toxicity and is lacking a strategy for prevention. Alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, is an oral antidiabetic drug. Previous studies have shown that DPP-4 inhibitors have pleiotropic effects, including neuroprotection. In this study, we investigated the effects of alogliptin on oxaliplatin-induced peripheral neuropathy using in vitro and in vivo models. In PC12 cells, alogliptin attenuated neurite disorders induced by oxaliplatin and cisplatin. The repeated injection of oxaliplatin caused mechanical allodynia and axonal degeneration of the sciatic nerve in rats. These neuropathies were ameliorated by co-administration of alogliptin. Moreover, alogliptin did not attenuate tumor cytotoxicity of oxaliplatin in the cultured colon, gastric, or pancreatic cancer cell lines and tumor-bearing mice. These findings suggest that alogliptin may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.Oxaliplatin is a platinum-based chemotherapeutic agent used for the standard treatment of colorectal, gastric, and pancreatic cancer. However, it has a particularly high risk of acute and chronic neuropathies. Acute neuropathy occurs in nearly all patients within hours to days after oxaliplatin infusion. Paranesthesia in the hands, feet, and the perioral region is manifested by exposure to cold temperature but is transient and reversible in most cases 1,2 .It is believed that voltage-gated ion channels and transient receptor potential channels are involved in oxaliplatin-induced acute neurotoxicity 3-5 . Chronic neuropathy results from the repeated treatment of oxaliplatin, which is dose-limiting toxicity. Sensory and motor dysfunction occurs similar to cisplatin-induced neuropathy and may last for several months or years 2,6 . Chronic neurotoxicity is considered to be caused by morphological changes in neurons, such as axon degeneration, neuronal cell body damage, and myelin disorder 7-9 . These neuropathies remain a significant clinical problem in chemotherapy with oxaliplatin as they impact the quality of life and can lead to drug reduction or discontinuation.Although many researches have been conducted to prevent chemotherapy-induced peripheral neuropathy, an effective treatment has yet to be found 10 . According to the clinical practice guideline established by the American Society of Clinical Oncology in 2014, no agents have yet to be recommended for the prevention of chemotherapy-induced peripheral neuropathy 11 .Alogliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, is clinically used for the treatment of type 2 diabetes mellitus. It lowers the blood glucose level mainly by preventing the inactivation of glucagon-like peptide-1 (GLP-1). Recently, it has received considerable attention as DPP-4 inhibitors have pleiotropic effects in addition to hypoglycemic action 12,13 . It has been reported that ...

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of alogliptin on oxaliplatin-induced peripheral neuropathy in vivo and in vitro

Shigematsu

Kawashiri

Kobayashi

et al. 2020

Sci Rep

Self Cite

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“…Although a detailed mechanism of neuropathy development due to chemotherapy has not been identified, it is reported that oxaliplatin causes morphological degeneration, including axonal disorder, neuronal cell damage and myelin alternation. [9][10][11][12][13] It has recently reported that the knockout of nuclear factor-erythroid-2-related factor 2 (Nrf2) aggravates oxaliplatin-induced mechanical allodynia and that the activation of the Nrf2 signaling pathway ameliorates oxaliplatin-induced neuropathy in mice. 14) Dimethyl fumarate (DMF) is a drug for treating multiple sclerosis.…”

Section: Introductionmentioning

confidence: 99%

Dimethyl Fumarate Attenuates Oxaliplatin-Induced Peripheral Neuropathy without Affecting the Anti-tumor Activity of Oxaliplatin in Rodents

Miyagi

Kawashiri

Shimizu

et al. 2019

Biological & Pharmaceutical Bulletin

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Oxaliplatin has been used as a first choice for colorectal, gastric and pancreatic cancer, but it induces peripheral neuropathies. Dimethyl fumarate (DMF) is an oral drug for multiple sclerosis with neuroprotective effects on oxidative stress. Using both in vivo and in vitro models, we investigated the effects of DMF on oxaliplatin-induced peripheral neuropathy and other side effects, as well as on the anti-tumor activity of oxaliplatin. Repeated intraperitoneal injection of 4 mg/kg oxaliplatin (twice per week for 4 weeks) caused mechanical allodynia (as revealed by the von Frey tests), cold hyperalgesia (as revealed by the acetone tests), and axonal degeneration in the sciatic nerve of rats. Co-administration of oral DMF (200 mg/kg, five times per week for 4 weeks) relieved oxaliplatin-induced mechanical allodynia but not cold hyperalgesia, and ameliorated axonal degeneration. In addition, DMF did not exacerbate oxaliplatin-induced body weight loss or bone marrow suppression, such as reduction in red blood cells, white blood cells, neutrophils and lymphocytes. Furthermore, DMF did not inhibit the anti-tumor activity of oxaliplatin in any cultured cancer cell line (C26, mouse colon carcinoma; HCT116, human colon carcinoma; MKN45, human gastric adenocarcinoma; MIA PaCa-2, human pancreatic carcinoma) or C26-bearing mice. These results suggest that DMF prevents oxaliplatin-induced mechanical allodynia and axonal degeneration without affecting the anti-tumor activity of oxaliplatin. Therefore, DMF may be useful for managing oxaliplatin-induced chronic peripheral neuropathy.

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“…BACE1‐mediated processing of NRG1 leads to its interaction with neighbouring ErbB family receptors, which are expressed in Schwann cells. Interestingly, oxaliplatin was reported to reduce NRG1 expression in the sciatic nerve (Tsutsumi et al, ). Reduced axonal NRG1 causes a decrease in the nerve conduction velocity that is associated with hypomyelination in sciatic nerves (Michailov et al, ).…”

Section: Discussionmentioning

confidence: 99%

miR‐15b mediates oxaliplatin‐induced chronic neuropathic pain through BACE1 down‐regulation

Ito

Sakai

Miyake

et al. 2017

British J Pharmacology

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Oxaliplatin induces hypomyelination and reduced neuregulin 1 expression in the rat sciatic nerve

Cited by 25 publications

References 24 publications

Neuroprotective effect of alogliptin on oxaliplatin-induced peripheral neuropathy in vivo and in vitro

Neuroprotective effect of alogliptin on oxaliplatin-induced peripheral neuropathy in vivo and in vitro

Dimethyl Fumarate Attenuates Oxaliplatin-Induced Peripheral Neuropathy without Affecting the Anti-tumor Activity of Oxaliplatin in Rodents

miR‐15b mediates oxaliplatin‐induced chronic neuropathic pain through BACE1 down‐regulation

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