Molecular insights into the protective role of nano-naringin in mancozeb-induced testicular damage and infertility

Chitosan-wrapped naringin protected rat testes from pesticide damage better than the plain compound did

Journal: Biological Research | Published: 2026-07-06 | Type: Journal Article | PMID: 42410491 Authors: Hassanen Eman I, Elbagwry Sara S, Eldin Zienab E, Azouz Rehab A, Ibrahim Marwa A, Doghaim Rawhia (Cairo University and Egyptian Chinese University, Faculty of Veterinary Medicine, Egypt) Funding/COI: Funding source not listed. Authors declare no competing interests.

Summary

This is a rodent toxicology study, not a human trial. Researchers exposed male Wistar rats to the fungicide mancozeb and tested whether naringin, a citrus flavonoid, could protect the testes from damage, either in its plain form or packaged into chitosan nanoparticles. Both forms helped, but the nanoparticle version outperformed plain naringin on hormone levels, sperm parameters, gene expression, and tissue structure.

Claims

• 42 adult male Wistar rats were split into 6 groups of 7: control, naringin (NAR) alone, nano-naringin (NARNPs) alone, mancozeb (MZ) alone, NAR+MZ, and NARNPs+MZ
• MZ (250 mg/kg) caused reduced body weight gain, lower sperm viability/motility/concentration, higher sperm abnormalities, lower testosterone, and increased lipid peroxidation in testicular tissue
• MZ suppressed testicular expression of steroidogenic genes (CYP19A1, StAR, HSD-3β) and cell proliferation markers
• Co-administering NAR (20 mg/kg) with MZ partially restored sperm quality, testosterone, and antioxidant enzyme activity
• NARNPs (20 mg/kg) with MZ produced larger improvements than NAR alone across hormone levels, gene expression, sperm parameters, and testicular histology
• The nanoparticle formulation itself: 147 ± 1.2 nm hydrodynamic diameter, +40 ± 1.4 mV zeta potential, 11.58% loading capacity, 93.87% entrapment efficiency
• NAR, NARNPs, and control groups showed no significant differences in sperm parameters when MZ wasn't present, suggesting neither compound is toxic on its own at these doses

Study Quality

The design includes appropriate controls, separate groups for NAR alone and NARNPs alone confirm the compounds aren't independently harming the animals, which strengthens the causal read on the protective effect. The study also stacks multiple outcome types (serum hormones, oxidative stress markers, gene expression, histopathology, immunohistochemistry) rather than relying on one endpoint, and the nanoparticle characterization (XRD, dynamic light scattering, zeta potential, TEM) is unusually thorough for a toxicology paper.

That said, this is a standard small-animal toxicology design with real limits. Seven animals per group is a small sample for six-way comparisons across many outcome measures, which raises the risk of both false positives and underpowered null findings. Only a single dose of each compound was tested, so there's no dose-response curve to establish whether 20 mg/kg is optimal or arbitrary. The paper reports fertility-adjacent surrogates (sperm counts, hormone levels, histology) but not actual fertility outcomes like pregnancy rates or litter size.

Red Flags

• Small group size (n=7) for a six-arm study with many outcome measures
• No dose-response testing for NAR or NARNPs, single fixed dose only
• No mention of randomization or blinding procedures in the methods
• No power calculation reported
• Funding source not disclosed, which limits assessment of independence
• Surrogate reproductive endpoints only, no actual fertility/litter outcomes measured
• Novel nanoparticle formulation has no reported pharmacokinetic or long-term toxicity data beyond this single study

Strengths

• Proper untreated-compound control arms (NAR alone, NARNPs alone) rule out the antioxidants themselves causing harm
• Multi-domain outcome assessment: hormones, oxidative stress markers, gene expression, histopathology, immunohistochemistry
• Detailed physicochemical characterization of the nanoparticle formulation
• Institutional ethics approval obtained

Verdict

A competently designed rat toxicology study with good internal controls and thorough nanoparticle characterization, but it's early-stage preclinical work with a small sample, one dose tested, and no fertility outcomes, undisclosed funding, and it says nothing about whether this translates to humans. Worth a skim if you track nanomedicine delivery systems or pesticide reproductive toxicology, not a reason to think about supplements.