Observation: In my RSL3-induced ferroptosis mouse model, no significant reduction in GPX4 protein levels was observed under certain treatment conditions.
Experimental Details:
- RSL3 Administration: Vehicle: 10% DMSO + 90% corn oil (freshly prepared before each injection). Dosage & Schedule: Chronic treatment: Daily intraperitoneal (i.p.) injection for 3 or 6 consecutive days. Acute treatment: A single i.p. injection (30 mg/kg) at model induction, followed by sacrifice 24 hours later.
Notable Finding: Only the acute treatment (single high-dose RSL3, 24-hour endpoint) resulted in a modest decrease in GPX4 expression, whereas prolonged administration (3–6 days) did not significantly alter GPX4 levels.
Question: What could explain the absence of GPX4 suppression in the chronic RSL3 treatment group despite its established role in ferroptosis induction?
Typically, protein expression is assessed using cell-based experiments, while phenotypic outcomes (such as tumor size, body weight, etc.) are evaluated in animal studies. According to the literature, the doses of RSL3 used in animal experiments are generally quite high, often around 100 mg/kg. A dose of 30 mg/kg would be considered relatively low (see reference [3]).
Although RSL3 can inhibit ferroptosis, it is essential to first confirm that your animal model of induced ferroptosis has been successfully established. Alternatively, you may consider combining RSL3 with a ferroptosis inducer, which can result in more pronounced experimental effects.
References: [1] https://www.hindawi.com/journals/omcl/2022/4930643/ [2] https://www.aging-us.com/article/202774/text [3] https://www.pnas.org/doi/10.1073/pnas.2009201117
Finally, I recommend first optimizing your experiments in cell models. You may refer to the following articles: https://pubmed.ncbi.nlm.nih.gov/32679060/ (Published by one of our MedChemExpress (MCE) customers) https://www.frontiersin.org/articles/10.3389/fphar.2018.01371/full
The answer to this question comes from MedChemExpress (MCE) Technical Support.
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