# Modulation of VEGF and IL-2 in radiation-induced brain injury: neuroprotective effects of melatonin and ascorbic acid in rats

**Authors:** Gulhan Guler Avci, Fikret Gevrek, Sefa Colak, Asiye Yanci

PMC · DOI: 10.1007/s11060-026-05484-9 · Journal of Neuro-Oncology · 2026-02-27

## TL;DR

This study shows that melatonin and ascorbic acid can protect rat brains from radiation damage by preserving blood vessels and balancing immune responses.

## Contribution

The study reveals that melatonin and ascorbic acid reduce radiation-induced brain injury by modulating VEGF and IL-2, without synergistic benefit from combining them.

## Key findings

- Radiation increased vasocongestion and neuronal damage while suppressing VEGF and elevating IL-2.
- Melatonin and ascorbic acid reduced injury and balanced VEGF and IL-2 levels compared to radiation alone.
- Combining melatonin and ascorbic acid did not provide additional benefits over using either alone.

## Abstract

This study investigates the neuroprotective effects of melatonin and ascorbic acid, alone and in combination, on radiation-induced brain injury, specifically focusing on vascular and immunological modulations.

Thirty-three male Wistar-Albino rats were assigned to five groups: Control (G1), Radiotherapy (RT) only (single dose 20 Gy) (G2), RT + Melatonin (20 mg/kg) (G3), RT + vitamin C (100 mg/kg) (G4), and RT + Melatonin + Vitamin C (G5). The treatments were administered intraperitoneally the day after RT. Brain tissues were evaluated 28 days post-irradiation for histopathological neural damage, vasocongestion, and immunohistochemical expression of vascular endothelial growth factor (VEGF) and interleukin-2 (IL-2).

High-dose RT significantly increased vasocongestion and neuronal damage while suppressing VEGF expression and elevating IL-2 levels (p < 0.001). Both melatonin and ascorbic acid effectively reduced histopathological injury, maintained VEGF levels, and balanced IL-2 expression compared to the RT-only group (p < 0.05). However, combining both agents provided no significant synergistic advantage over monotherapies. Notably, single-fraction high-dose RT resulted in a marked suppression of VEGF expression, suggesting an impaired vascular synthetic capacity rather than a compensatory angiogenic response.

Melatonin and ascorbic acid provide substantial neuroprotection against radiation-induced brain injury by preserving vascular integrity and modulating local immune responses. These antioxidants represent potential therapeutic strategies for minimizing RT-induced neurotoxicity.

## Linked entities

- **Proteins:** VEGFA (vascular endothelial growth factor A), IL2 (interleukin 2)
- **Chemicals:** melatonin (PubChem CID 896), ascorbic acid (PubChem CID 9888239), vitamin C (PubChem CID 54670067)

## Full-text entities

- **Genes:** Ang2 (angiogenin, ribonuclease A family, member 2) [NCBI Gene 497229] {aka Ang, Raa2}, Ang (angiogenin) [NCBI Gene 305843] {aka Ang1}, Pecam1 (platelet and endothelial cell adhesion molecule 1) [NCBI Gene 29583] {aka CD31, Pecam}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Hif1a (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 29560] {aka HIF1-alpha, MOP1}, Tek (TEK receptor tyrosine kinase) [NCBI Gene 89804] {aka Tie-2, Tie2}, Il2 (interleukin 2) [NCBI Gene 116562], Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}
- **Diseases:** brain tumors (MESH:D001932), radiation damage (MESH:D011832), bladder tumor (MESH:D001749), neuronal apoptosis (MESH:D065703), glioblastoma (MESH:D005909), intestinal damage (MESH:D007410), Neuronal damage (MESH:D009410), vascular damage (MESH:D057772), cytotoxic (MESH:D064420), brain damage (MESH:D001925), neurological damage (MESH:D020196), brain toxicity (MESH:D001927), brain injury (MESH:D001930), Hypoxia (MESH:D000860), histopathological damage (MESH:D020263), hypoxic (MESH:D002534), brain edema (MESH:D001929), edema (MESH:D004487), endothelial dysfunction (MESH:D014652), tumor (MESH:D009369), neurotoxicity (MESH:D020258), neural damage (MESH:D015441), histopathological injury (MESH:D014947), inflammation (MESH:D007249)
- **Chemicals:** reactive oxygen species (MESH:D017382), formalin (MESH:D005557), alcohol (MESH:D000438), eosin (MESH:D004801), citric acid (MESH:D019343), ketamine HCl (MESH:D007649), AA2G (MESH:C065378), temozolomide (MESH:D000077204), Hematoxylin (MESH:D006416), Melatonin (MESH:D008550), hydrogen peroxide (MESH:D006861), Aquose Mount Reagent (-), bevacizumab (MESH:D000068258), Ascorbic acid (MESH:D001205), water (MESH:D014867), xylazine (MESH:D014991), hesperidin (MESH:D006569), xylenes (MESH:D014992), oxygen (MESH:D010100), paraffin (MESH:D010232)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12948915/full.md

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Source: https://tomesphere.com/paper/PMC12948915