Liproxstatin-1 is a potent inhibitor of ferroptosis and can protect against ferroptosis-inducing agents, such as buthionine sulfoxamine (BSO), erastin, and (1S,3R)-RSL3 (RSL3). Moreover, Liproxstatin-1 does not interfere with other classical types of cell death, such as TNFα-induced apoptosis and H2O2-induced necrosis. Recently, Liproxstatin-1 has attracted the attentions as it exhibits various kinds of pharmacological activities. For example, Liproxstatin-1 can protect mouse myocardium against ischemia/reperfusion injury; Liproxstatin-1 could alleviate iron overload and attenuates morphine tolerance; Liproxstatin-1 could prevent both RSL3-induced death of primary human renal proximal TECs and GPX4 deletion-induced acute renal failure. Therefore, Liproxstatin-1 inhibits ferroptosis and promotes cell survival.[1].
The in vitro experiment demonstrated that Liproxstatin-1 could suppress ferroptosis, with an EC50 of 115.3 nM. The percentage of PI-positive cells was lower in the Liproxstatin-1 group further proving the anti-ferroptotic effect of Liproxstatin-1 (P < 0.0001). Furthermore, Liproxstatin-1 suppressed mitochondrial lipid peroxidation and increased the levels of GSH compared with the RSL-3 group (P < 0.0001). GPX4 was restored to normal levels by Liproxstatin-1 treatment.[2].
The in vivo experiment indicated that ferroptosis occurred in TECs during UUO-induced renal fibrosis and that Liproxstatin-1 was able to inhibit the ferroptosis. In addition, Liproxstatin-1 was able to prevent the morphological changes and renal function impairment that were induced by UUO in vivo.[1].
References:
[1] 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.
[2] 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.
Liproxstatin-1 是一种有效的铁死亡抑制剂，可以防止铁死亡诱导剂，例如丁硫氨酸亚砜胺 (BSO)、erastin 和 (1S,3R)-RSL3 (RSL3)。此外，Liproxstatin-1 不干扰其他经典类型的细胞死亡，例如 TNFα 诱导的细胞凋亡和 H2O2 诱导的细胞坏死。最近，Liproxstatin-1 因其表现出多种药理活性而备受关注。例如，Liproxstatin-1 可以保护小鼠心肌免受缺血/再灌注损伤； Liproxstatin-1可减轻铁过载并减弱吗啡耐受性； Liproxstatin-1 可以预防 RSL3 诱导的原发性人肾近端 TEC 死亡和 GPX4 缺失诱导的急性肾功能衰竭。因此，Liproxstatin-1抑制铁死亡，促进细胞存活。[1]。
体外实验表明，Liproxstatin-1 可以抑制铁死亡，EC50 为 115.3 nM。 Liproxstatin-1 组中 PI 阳性细胞的百分比较低，进一步证明了 Liproxstatin-1 的抗铁死亡作用 (P < 0.0001)。此外，与 RSL-3 组相比，Liproxstatin-1 抑制线粒体脂质过氧化并增加 GSH 水平 (P < 0.0001)。 GPX4通过Liproxstatin-1治疗恢复到正常水平。[2]。
体内实验表明，在 UUO 诱导的肾纤维化过程中，TEC 发生了铁死亡，而 Liproxstatin-1 能够抑制铁死亡。此外，Liproxstatin-1能够阻止UUO在体内引起的形态学改变和肾功能损害。[1]。