# New Insight into Potential Otoprotective Effects of Lactoferrin: Is It Paradoxically Ototoxic? An Experimental Investigation

**Authors:** Ahmet Mutlu, Ayse Yasemin Gunduz, Burcu Bakici, Murat Erinc, Erdogan Bulut, Onur Ersoy, Serdal Celik, Dogan Cakan, Mahmut Tayyar Kalcioglu

PMC · DOI: 10.3390/audiolres16020040 · 2026-03-06

## TL;DR

This study investigates whether lactoferrin, known for its protective properties, might paradoxically cause hearing damage in the inner ear.

## Contribution

The study experimentally evaluates lactoferrin's potential ototoxic effects using electrophysiological and histological methods in rats.

## Key findings

- Lactoferrin showed partial recovery at lower frequencies but worsening thresholds at higher frequencies.
- Cochlear structures in lactoferrin-treated rats remained largely intact with no significant structural damage.
- VEGF immunoreactivity was severe in lactoferrin and control groups but weaker in the antiseptic group.

## Abstract

To evaluate the potential ototoxic effects of lactoferrin on the inner ear using electrophysiological and histological methods. Methods: Thirty-two Sprague-Dawley rats (64 ears) were divided into four groups: control, saline, antiseptic solution (70% isopropyl alcohol + 2% chlorhexidine), and lactoferrin. Groups II–IV received three intratympanic injections. Auditory brainstem response (ABR) tests were performed at baseline, day 7, and day 21. Cochlear histology and VEGF immunoreactivity were assessed. Results: Baseline hearing was similar across groups. Post-treatment, Groups II and IV showed partial recovery at 8, 16, and 24 kHz, while Groups III and IV had worsening thresholds at higher frequencies. Histologically, Group IV’s cochlear structures remained largely intact. VEGF immunoreactivity was severe to moderate in Groups I, II, and IV, and weaker in Group III. Conclusions: Lactoferrin showed relative safety at lower frequencies but possible ototoxicity at higher frequencies. However, no significant structural damage was observed in cochlear tissues.

## Linked entities

- **Proteins:** tf.S (transferrin S homeolog), VEGFA (vascular endothelial growth factor A)
- **Chemicals:** isopropyl alcohol (PubChem CID 3776), chlorhexidine (PubChem CID 9552079)

## Full-text entities

- **Genes:** Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Ltf (lactotransferrin) [NCBI Gene 301034]
- **Diseases:** cancer (MESH:D009369), tissue injury (MESH:D017695), effusion (MESH:D000080324), deterioration (MESH:D000075902), atrophy (MESH:D001284), functional loss (MESH:D006315), infection (MESH:D007239), dehydration (MESH:D003681), injury to (MESH:D014947), infective otitis media (MESH:D010033), dislocation (MESH:D004204), inflammation (MESH:D007249), vascular impairment (MESH:D020141), perforation (MESH:D057112), Ototoxic (MESH:D006311), hearing impairment (MESH:D034381), necrosis (MESH:D009336), cochlear damage (MESH:D015834), otologic disorders (MESH:D004427), hypothermia (MESH:D007035), pain (MESH:D010146), complication (MESH:D008107), toxicities (MESH:D064420), age-related hearing loss (MESH:D010024)
- **Chemicals:** toluene (MESH:D014050), aminoglycosides (MESH:D000617), H2O2 (MESH:D006861), ketamine (MESH:D007649), ROS (MESH:D017382), xylazine (MESH:D014991), Eosin solution (-), Paraffin (MESH:D010232), citrate (MESH:D019343), furosemide (MESH:D005665), formalin (MESH:D005557), chlorhexidine (MESH:D002710), Saline (MESH:D012965), xylene (MESH:D014992), cisplatin (MESH:D002945), water (MESH:D014867), isopropyl alcohol (MESH:D019840), Hematoxylin (MESH:D006416), DAB (MESH:C000469), Eosin (MESH:D004801), alcohol (MESH:D000438), iron (MESH:D007501)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Bos taurus (bovine, species) [taxon 9913], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** 608A-C, 346A-C, 136A-C

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13010596/full.md

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Source: https://tomesphere.com/paper/PMC13010596