Statins ameliorate oxaliplatin- and paclitaxel-induced peripheral neuropathy via glutathione S-transferase

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect inadequately managed by current treatments.
• Statins, primarily used for cholesterol reduction, have shown potential in mitigating neuropathy, but the underlying mechanisms are not fully understood.

Purpose of the Study:

• To investigate the novel effects of statins on chemotherapy-induced peripheral neuropathy in a mouse model.
• To elucidate the molecular pathways involved in statin-mediated amelioration of CIPN.

Main Methods:

• Mice were treated with chemotherapy agents (oxaliplatin or paclitaxel) and statins.
• Neuropathic pain was assessed using mechanical stimuli and cold sensation tests.
• The role of the glutathione S-transferase (GST) pathway was investigated using a GST inhibitor.
• Artificial intelligence was employed to identify GST-associated molecules and pathways.

Main Results:

• Statin administration did not alter cold sensation deficits induced by chemotherapy.
• Concurrent statin treatment significantly mitigated mechanical allodynia caused by oxaliplatin and paclitaxel.
• Inhibition of GST abolished the protective effect of statins against mechanical hypersensitivity.
• GST inhibition did not impact normal sensory perception or the anti-tumor efficacy of chemotherapy agents.

Conclusions:

• Statins exhibit a class effect in ameliorating chemotherapy-induced mechanical allodynia.
• The ameliorative effect of statins is mediated through the activation of the glutathione S-transferase (GST) pathway.
• Targeting the GST pathway represents a potential therapeutic strategy for managing CIPN.