Effect of the SOD mimetic MnL4 on in vitro and in vivo oxaliplatin toxicity: Possible aid in chemotherapy induced neuropathy

Mannelli, Lorenzo Di Cesare; Zanardelli, Matteo; Landini, Ida; Pacini, Alessandra; Ghelardini, Carla; Mini, Enrico; Bencini, Andrea; Valtancoli, Barbara; Failli, Paola

doi:10.1016/j.freeradbiomed.2016.01.023

Cited by 34 publications

(26 citation statements)

References 60 publications

(86 reference statements)

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“…29) Meanwhile, many previous studies have indicated that oxidative stress is one of the causes of oxaliplatin-induced peripheral neuropathy. [30][31][32][33] Our previous study indicated that DMF and MMF ameliorate neurite degenerations, which caused by oxaliplatin, cisplatin and bortezomib, via activation of Nrf2 pathway in cultured cell. 17) Thus, in this study, it is possible that the co-administration of DMF ameliorated axonopathy and mechanical allodynia by relieving oxidative stress caused by oxaliplatin treatment in the nerve cells.…”

Section: Discussionmentioning

confidence: 97%

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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Section: Discussionmentioning

confidence: 97%

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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“…Moreover, DPP-4 inhibitors have also been reported to have antioxidant effects 25,26 . Many studies have shown that oxidative stress plays a role in oxaliplatin-induced neuropathy [27][28][29] . Taken together, the neuroprotective peptides and antioxidant effect, aside from GLP-1, might play a role in the neuroprotective effect of alogliptin on oxaliplatin-induced neuropathy.…”

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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“…105 Another SOD mimetic, MnL4, inhibited oxaliplatin-induced mechanical and cold hypersensitivities. 108 Peroxynitrite decomposition catalysts have been shown to reverse established paclitaxel-induced mechanical hypersensitivity 109 and to also prevent the development of mechanical hypersensitivity induced by paclitaxel, oxaliplatin and bortezomib. 88 109 Novel mitochondria-targeted antio xidants have also been evaluated.…”

Section: Role Of Oxidative Stress In Cipnmentioning

confidence: 99%

Clinical and preclinical perspectives on Chemotherapy-Induced Peripheral Neuropathy (CIPN): a narrative review

Flatters

Dougherty

Colvin

2017

British Journal of Anaesthesia

262

239

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This review provides an update on the current clinical and preclinical understanding of chemotherapy induced peripheral neuropathy (CIPN). The overview of the clinical syndrome includes a review of its assessment, diagnosis and treatment. CIPN is caused by several widely-used chemotherapeutics including paclitaxel, oxaliplatin, bortezomib. Severe CIPN may require dose reduction, or cessation, of chemotherapy, impacting on patient survival. While CIPN often resolves after chemotherapy, around 30% of patients will have persistent problems, impacting on function and quality of life. Early assessment and diagnosis is important, and we discuss tools developed for this purpose. There are no effective strategies to prevent CIPN, with limited evidence of effective drugs for treating established CIPN. Duloxetine has moderate evidence, with extrapolation from other neuropathic pain states generally being used to direct treatment options for CIPN. The preclinical perspective includes a discussion on the development of clinically-relevant rodent models of CIPN and some of the potentially modifiable mechanisms that have been identified using these models. We focus on the role of mitochondrial dysfunction, oxidative stress, immune cells and changes in ion channels from summary of the latest literature in these areas. Many causal mechanisms of CIPN occur simultaneously and/or can reinforce each other. Thus, combination therapies may well be required for most effective management. More effective treatment of CIPN will require closer links between oncology and pain management clinical teams to ensure CIPN patients are effectively monitored. Furthermore, continued close collaboration between clinical and preclinical research will facilitate the development of novel treatments for CIPN.

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Effect of the SOD mimetic MnL4 on in vitro and in vivo oxaliplatin toxicity: Possible aid in chemotherapy induced neuropathy

Cited by 34 publications

References 60 publications

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

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

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

Clinical and preclinical perspectives on Chemotherapy-Induced Peripheral Neuropathy (CIPN): a narrative review

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