Fluvoxamine alleviates paclitaxel-induced neurotoxicity

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Paclitaxel (Px) is a vital chemotherapy drug but causes neurotoxicity, leading to chemotherapy-associated cognitive impairment (CACI), or "chemobrain".
• Endoplasmic reticulum (ER) stress is implicated in Px-induced neurotoxicity, and while BIX showed promise, it lacks clinical use.
• Fluvoxamine (Flv) has been shown to alleviate ER stress by inducing the sigma-1 receptor (Sig-1R).

Purpose of the Study:

• To investigate the potential of fluvoxamine (Flv) to mitigate paclitaxel (Px)-induced neurotoxicity in vitro.
• To explore the role of sigma-1 receptor (Sig-1R) induction in Flv's neuroprotective effects against Px.

Main Methods:

• SK-N-SH cells were pre-treated with fluvoxamine (Flv) before paclitaxel (Px) exposure.
• Neurotoxicity was assessed via MTS viability assay.
• ER stress markers (CHOP, cleaved caspase 4, cleaved caspase 3) and Sig-1R expression were evaluated. The Sig-1R antagonist NE100 was used to confirm pathway involvement.

Main Results:

• Flv pre-treatment significantly reduced Px-induced elevation of ER stress markers (CHOP, cleaved caspase 4, cleaved caspase 3).
• Flv significantly increased Sig-1R expression in SK-N-SH cells.
• Cell viability was higher in Flv-treated cells, and this effect was reversed by the Sig-1R antagonist NE100.

Conclusions:

• Fluvoxamine (Flv) demonstrates neuroprotective effects against paclitaxel (Px)-induced neurotoxicity in vitro.
• The protective mechanism involves the alleviation of ER stress and is, in part, mediated by the induction of the sigma-1 receptor (Sig-1R).
• These findings suggest Flv as a potential therapeutic strategy to mitigate Px-induced neurotoxicity and chemobrain.