Oxaliplatin is an essential drug in the chemotherapy of colorectal, gastric, and pancreatic cancers, but it frequently causes peripheral neuropathy as a dose-limiting factor. So far, animal models of oxaliplatin-induced peripheral neuropathy have been established. The mechanisms of development of neuropathy induced by oxaliplatin have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory effects on neuropathy. In this review, we summarize the basic and clinical evidence for the therapeutic effects of oxaliplatin. In basic research, there are many reports of neuropathy inhibitors that target oxidative stress, inflammatory response, sodium channel, transient receptor potential (TRP) channel, glutamate nervous system, and monoamine nervous system. Alternatively, very few drugs have clearly demonstrated the efficacy for oxaliplatin-induced peripheral neuropathy in clinical trials. It is important to activate translational research in order to translate basic research into clinical research.

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 ...

Thiopeptin is a new antibiotic, produced by Streptomyces tateyamensis and developed solely for animal use as a feed additive. The antibiotic content in animal tissue and feed was assayed in terms of the antimicrobial activity against Mycoplasma laidlawii A. This antibiotic was found to be relatively nontoxic in rats and mice. In chickens, this antibiotic is excreted into feces within 48 hr of administration and is not absorbed in tissue. It is well tolerated in both broilers and swine and is highly stable in animal feed. Thiopeptin-supplemented feed contributes to the improvement of weight gain, feed efficiency in chickens and swine, and the egg performance in layers. Thus, thiopeptin, when used as a feed additive, is quite suitable for supplementing animal nutrition.

Paclitaxel is an essential drug in the chemotherapy of ovarian, non-small cell lung, breast, gastric, endometrial, and pancreatic cancers. However, it frequently causes peripheral neuropathy as a dose-limiting factor. Animal models of paclitaxel-induced peripheral neuropathy (PIPN) have been established. The mechanisms of PIPN development have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory PIPN effects. This review summarizes the basic and clinical evidence for therapeutic or prophylactic effects for PIPN. In pre-clinical research, many reports exist of neuropathy inhibitors that target oxidative stress, inflammatory response, ion channels, transient receptor potential (TRP) channels, cannabinoid receptors, and the monoamine nervous system. Alternatively, very few drugs have demonstrated PIPN efficacy in clinical trials. Thus, enhancing translational research to translate pre-clinical research into clinical research is important.

No abstract