Class effects of proton pump inhibitors in preventing oxaliplatin-induced peripheral neurotoxicity

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Oxaliplatin-induced peripheral neuropathy (OIPN) is a significant dose-limiting side effect of oxaliplatin chemotherapy.
• Current countermeasures for OIPN are limited, necessitating the exploration of novel therapeutic strategies.
• Prior research indicated that omeprazole, a proton pump inhibitor (PPI), may offer protection against OIPN.

Purpose of the Study:

• To investigate whether other proton pump inhibitors (PPIs) share omeprazole's protective effects against oxaliplatin-induced peripheral neuropathy (OIPN).
• To evaluate the efficacy of different PPIs in both in vitro and in vivo models of OIPN.

Main Methods:

• In vitro experiments using cultured F11 neuronal cells exposed to oxaliplatin.
• In vivo experiments involving repeated administration of PPIs to rats followed by assessment of mechanical allodynia.
• Comparison of PPIs (esomeprazole, lansoprazole, rabeprazole) with vonoprazan, a potassium-ion competitive acid blocker.

Main Results:

• Esomeprazole, lansoprazole, and rabeprazole demonstrated significant protection against oxaliplatin-induced neuronal cell damage in vitro.
• Repeated administration of these PPIs effectively prevented the development of mechanical allodynia in rats.
• Vonoprazan, a different class of acid-reducing agent, did not exhibit protective effects against OIPN in this study.

Conclusions:

• Proton pump inhibitors (PPIs) exhibit a class effect in preventing oxaliplatin-induced peripheral neuropathy (OIPN).
• These findings suggest that PPIs could serve as a potential therapeutic strategy to mitigate OIPN.
• Further research into PPIs as countermeasures for chemotherapy-induced neurotoxicity is warranted.