ArticleAntioxidants (Basel, Switzerland)2026
Hesperetin-Loaded PLGA Nanoparticles Ameliorate Cisplatin-Induced Oxidative Stress and Testicular Dysfunction in Rats: Association with NRF2/HO-1, NF-κB, and ACSL4/GPX4/SLC7A11 Signaling Modulation.
Article in Antioxidants (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCisplatin is a widely used chemotherapeutic agent whose gonadotoxic effects, largely driven by oxidative stress and inflammation, pose a major threat to male reproductive health. This study evaluated whether hesperetin (HES) and hesperetin-loaded poly (lactic-co-glycolic acid) nanoparticles (HES-PLGA-NPs) can protect against cisplatin-induced testicular dysfunction in adult male Sprague Dawley rats.
methodsSixty rats were randomly assigned to six groups: control, HES, HES-PLGA-NPs, cisplatin (CIS), CIS + HES, and CIS + HES-PLGA-NPs. CIS (7.5 mg/kg/week, i.p.) was given intraperitoneally for four weeks, while HES and nano-HES (50 mg/kg/day, p.o.) were orally administered concurrently. Reproductive hormones, testicular weight, sperm parameters, oxidative stress and antioxidant markers, NRF2/HO-1 and NF-κB signaling, apoptotic indices, ferroptosis-related markers, histopathology, and GPX4/ACSL4 immunoexpression were assessed.
resultsCIS caused marked reproductive dysfunction, including reduced testosterone, FSH, and LH, decreased testicular weight, and impaired sperm quality. These changes were associated with severe oxidative and nitrosative stress (↑ MDA, NO, 8-OHdG), depletion of antioxidant defenses (↓ SOD, CAT, GSH), reduced NRF2/HO-1, elevated NF-κB activity and pro-inflammatory cytokines, apoptosis-related changes (↑ Bax, caspase-3; ↓ Bcl-2), and ferroptosis-associated alterations (↑ Fe
conclusionsHES-PLGA-NPs were associated with multi-mechanistic protection against cisplatin-induced oxidative, inflammatory, apoptotic, and ferroptosis-associated damage in the testes, and may represent a promising nanoantioxidant candidate warranting further investigation for preserving male reproductive function during chemotherapy.
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