Ferroptosis Inhibitor Liproxstatin-1 Alleviates Triptolide-Induced Blood Testis-Barrier Disruption and Testicular...

Area of Science:

• Reproductive Toxicology
• Cellular Biology
• Pharmacology

Background:

• Triptolide (TP) from Tripterygium wilfordii has potent bioactivity but causes severe male reproductive toxicity.
• Effective interventions for TP-induced reproductive toxicity are limited.
• The role of ferroptosis in TP-induced testicular damage requires further elucidation.

Purpose of the Study:

• To characterize TP-induced ferroptosis in mouse testes and Sertoli cells.
• To evaluate liproxstatin-1 (Lip-1) as a potential therapeutic agent against TP-induced testicular injury by inhibiting ferroptosis.

Main Methods:

• TP exposure in vivo (mice) and in vitro (Sertoli cells).
• Histopathological analysis, sperm analysis, and assessment of blood-testis barrier (BTB) integrity.
• Evaluation of ferroptosis markers (redox regulators, iron homeostasis proteins) and lipid peroxidation.
• Co-treatment with Lip-1 to assess protective effects.

Main Results:

• TP induced significant testicular damage, including BTB disruption, reduced sperm quality, and increased deformity.
• TP exposure downregulated key ferroptosis regulators (NRF2, HO-1, SLC7A11, GPX4) and iron proteins (FTH1, FTL, FPN).
• Lip-1 treatment effectively protected against TP-induced testicular injury and BTB disruption by reducing lipid peroxidation and restoring the NRF2 pathway.

Conclusions:

• TP-induced male reproductive toxicity is mediated by ferroptosis.
• Pharmacological inhibition of ferroptosis using Lip-1 is a promising strategy to mitigate TP-induced testicular damage and BTB disruption.