Semaglutide Shows Neuroprotective Effects Against Chemotherapy Damage in Animal Study

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and debilitating side effect of many cancer treatments, leading to chronic pain, numbness, and functional impairment. Current therapeutic options for CIPN are limited and often insufficient, highlighting a critical unmet medical need. This study aimed to investigate semaglutide's potential to mitigate nerve damage induced by the chemotherapeutic agent cyclophosphamide and elucidate the underlying molecular mechanisms.

Treatment with semaglutide significantly attenuated markers of neuropathy and oxidative stress. The 0.1 mg/kg dose of semaglutide led to a remarkable 43% reduction in oxidative stress markers, such as malondialdehyde (MDA), and a 2.5-fold increase in the activity of crucial antioxidant enzymes like superoxide dismutase (SOD) and catalase, compared to the cyclophosphamide-only group. > Semaglutide treatment significantly preserved neuronal integrity and function, with the 0.1 mg/kg dose restoring nerve conduction velocity by 35% and reducing neuronal apoptosis (programmed cell death) by 55% compared to untreated controls (p<0.001). Furthermore, semaglutide upregulated key neuroprotective pathways, demonstrating a 1.8-fold increase in SIRT1 and AMPK protein expression and a 2.1-fold increase in PI3K/AKT/mTOR pathway activation, all vital for cell survival, metabolism, and growth. These molecular improvements correlated with significant behavioral benefits, including a 60% reduction in mechanical allodynia (pain sensitivity to light touch).