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2026-07-21 PubMed

Nano-Rosmarinic Acid outperforms crude RA, protecting against pesticide-induced testicular toxicity in rats.

Nano-Rosmarinic Acid Protects Against Chlorfenapyr-Induced Testicular Toxicity Through Modulation of NRF2/HO-1 and NF-κB/NLRP3 Signaling Pathways.

Background

Exposure to environmental toxins like pesticides can severely impact male reproductive health, leading to testicular toxicity and infertility. The widely used pesticide chlorfenapyr (CFP) is known for its reproductive toxicity, often inducing oxidative stress and inflammation. Current interventions are often limited by poor bioavailability or side effects. Rosmarinic acid (RA), a natural compound, shows promise with its antioxidant and anti-inflammatory properties, but its therapeutic potential is hindered by poor absorption. Nano-encapsulation aims to overcome these physicochemical limitations, enhancing RA's delivery and efficacy against toxin-induced damage.

Study Design

Researchers investigated the protective effects of nano-encapsulated Rosmarinic acid (RA-CHNPs) against chlorfenapyr (CFP)-induced testicular toxicity in 60 adult male Wistar rats (n=10/group). Animals received oral CFP (180 mg/kg/day) and/or RA (75 mg/kg/day, crude or nano-encapsulated) for 30 consecutive days. Primary endpoints included testicular weight, sperm parameters, reproductive hormone levels (LH, FSH, testosterone), oxidative stress markers, pro-inflammatory cytokine production, apoptosis, and activation of NF-κB/NLRP3 signaling, assessed via immunohistochemistry and other biochemical assays.

Results

Chlorfenapyr (CFP) exposure significantly reduced testicular weight, sperm count, sperm motility, and reproductive hormone levels (LH, FSH, testosterone). These adverse effects were accompanied by marked oxidative stress, increased pro-inflammatory cytokine production, and activation of the NF-κB/NLRP3 signaling pathway. Immunohistochemical analysis confirmed strong NF-κB expression in spermatogenic and Leydig cells, alongside robust NLRP3 expression within seminiferous tubules in the CFP group. Co-administration of RA-CHNPs led to a marked attenuation of these adverse effects, demonstrating greater protective efficacy than crude RA. RA-CHNPs reduced NF-κB and NLRP3 expression, which correlated with improved testicular architecture, restored spermatogenic activity, and normalized reproductive hormone levels. These protective effects were associated with activation of the NRF2/HO-1 antioxidant pathway, suppression of inflammatory responses, and regulation of apoptosis-related genes.

Nano-encapsulated Rosmarinic acid provided superior protection against CFP-induced testicular toxicity compared to crude Rosmarinic acid.

Key Findings

  • Chlorfenapyr (CFP) significantly reduced testicular weight, sperm count, sperm motility, and reproductive hormone levels.
  • CFP exposure activated NF-κB/NLRP3 signaling and increased oxidative stress and inflammation.
  • Nano-encapsulated Rosmarinic acid (RA-CHNPs) markedly attenuated CFP-induced adverse effects.
  • RA-CHNPs reduced NF-κB and NLRP3 expression, improving testicular architecture and hormone levels.
  • The protective effects of RA-CHNPs were linked to NRF2/HO-1 pathway activation and apoptosis regulation.

Why It Matters

This study highlights the significant potential of nanoformulation strategies to enhance the therapeutic efficacy of natural compounds like Rosmarinic acid. For individuals concerned about environmental toxin exposure or seeking adjunctive support for reproductive health, this suggests that optimized delivery methods could unlock greater benefits. While preclinical, the findings indicate that nano-RA could offer a more potent intervention than crude RA for mitigating chemically-induced testicular damage. This could inform future research into novel protocols for protecting male fertility, potentially influencing how antioxidants and anti-inflammatories are formulated and combined in a stack to maximize bioavailability and target specific pathways like NRF2/HO-1 and NF-κB/NLRP3 for superior outcomes.


rosmarinic-acid nanoformulation testicular-toxicity chlorfenapyr nrf2-ho-1 nf-kb-nlrp3
Source: pubmed:42478942 · Ingested 2026-07-21 · Digest: gemini-2.5-flash