Reversal of Bortezomib-Induced Neurotoxicity by Suvecaltamide, a Selective T-Type Ca-Channel Modulator, in Preclinical Models.

ABSTRACT: This study evaluated suvecaltamide, a selective T-type calcium channel modulator, on chemotherapy-induced peripheral neurotoxicity (CIPN) and anti-cancer activity associated with bortezomib (BTZ). Rats received BTZ (0.2 mg/kg thrice weekly) for 4 weeks, then BTZ alone (n = 8) or BTZ+suvecaltamide (3, 10, or 30 mg/kg once daily; each n = 12) for 4 weeks. Nerve conduction velocity (NCV), mechanical threshold, β-tubulin polymerization, and intraepidermal nerve fiber (IENF) density were assessed. Proteasome inhibition was evaluated in peripheral blood mononuclear cells. Cytotoxicity was assessed in human multiple myeloma cell lines (MCLs) exposed to BTZ alone (IC50 concentration), BTZ+suvecaltamide (10, 30, 100, 300, or 1000 nM), suvecaltamide alone, or vehicle. Tumor volume was estimated in a

SUBMITTER: Meregalli C 

PROVIDER: S-EPMC8507761 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature