Liproxstatin-1

Cell lines

ONL-93 oligodendrocytes

Preparation Method

Cells were cultured and expanded in DMEM/nutrient mixture F-12, supplemented with 10% FBS and 1% penicillin-streptomycin at 37°C and 5% CO2. The culture medium was changed every 2 days. The oligodendrocyte (OLN-93 cell line) model of ferroptosis was established using RSL-3 (7.89 μM).

Reaction Conditions

The cell viability after the treatment with 0, 0.5, 1.5, 2.0, 2.5, 3.0 nM Liproxstatin-1 and the treatment with 0, 0.5, 1.0, 1.5, 2.0 μM were used for the determination of EC50.

Applications

Liproxstatin-1 could suppress ferroptosis, with an EC50 of 115.3 nM. Liproxstatin-1 displayed the lowest EC50 among these compounds.

Animal models

Specific-pathogen-free 8-week-old male C57BL/6 mice

Preparation Method

To establish the animal model, first, the left ureter of mice was exposed and ligated with 4-0 silk sutures, and the ligatures were dissected to prevent retrograde urinary tract infections. The sham operation was executed in a similar manner, but without ureter ligation. Twenty-four C57BL/6 mice were randomly divided into four groups: (1) sham group, (2) Liproxstatin-1 group, (3) UUO group, and (4) UUO + Liproxstatin-1 group. The mice in the Liproxstatin-1 and UUO + Liproxstatin-1 groups were intraperitoneally injected with Liproxstatin-1 for 14 consecutive days after surgery. The mice in the sham and UUO groups were intraperitoneally injected with equal volumes of 0.9% NaCl solution.

Dosage form

200 μL Liproxstatin-1 (10 mg/kg/d, dissolved in DMSO and then diluted with 0.9% NaCl)

Applications

Liproxstatin-1 could reduce the levels of renal iron in the UUO mice. In addition, Liproxstatin-1 treatment could significantly reduce the number of iron-positive cells in the UUO + Liproxstatin-1 group compared with the UUO group. Liproxstatin-1 treatment significantly decreased the GSSG/ GSH ratio in the UUO group.

References:
[1]. Fan BY, et al. Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4. Neural Regen Res. 2021 Mar;16(3):561-566.
[2]. Zhang B, et al. Liproxstatin-1 attenuates unilateral ureteral obstruction-induced renal fibrosis by inhibiting renal tubular epithelial cells ferroptosis. Cell Death Dis. 2021 Sep 11;12(9):843.