# Protective effects of morin and propolis against cytarabine-induced neurotoxicity: a multi-biomarker approach

**Authors:** Hakan Bağ, Seval Yılmaz, Songül Çeribaşı

PMC · DOI: 10.1515/biol-2025-1289 · Open Life Sciences · 2026-02-20

## TL;DR

This study shows that morin and propolis can protect against brain damage caused by the chemotherapy drug cytarabine in rats.

## Contribution

The study introduces morin and propolis as potential neuroprotective agents against cytarabine-induced toxicity.

## Key findings

- Cytarabine increased oxidative stress and apoptosis markers in rat brain tissue.
- Morin and propolis reduced oxidative damage and restored antioxidant enzyme activity.
- Histopathological brain damage from cytarabine was significantly reduced by both compounds.

## Abstract

Cytarabine (Cyt) is a cornerstone chemotherapeutic agent for acute myeloid leukemia (AML) and various hematological malignancies. This study sought to investigate the neuroprotective potential of morin and propolis against Cyt-induced neurotoxicity. Forty-two Sprague Dawley rats were randomly assigned to six groups: control, morin (200 mg/kg/day), propolis (100 mg/kg/day), Cyt (100 mg/kg/day), morin + Cyt, and propolis + Cyt. Biochemical analysis of brain tissue revealed that Cyt administration significantly elevated malondialdehyde (MDA) levels and glutathione-S-transferase (GST) activity, while depleting catalase (CAT) and glutathione peroxidase (GSH-Px) activities. Immunohistochemical findings showed that Cyt increased 8-hydroxydeoxyguanosine (8-OHdG) and B-cell lymphoma/leukemia-2-associated X protein (Bax) expression, whereas it downregulated Glutathione peroxidase 4 (GPX4) and B-cell lymphoma/leukemia-2 (Bcl-2). Treatment with morin or propolis effectively reversed these oxidative and apoptotic markers, as evidenced by decreased MDA and Bax levels, alongside increased activities of antioxidant enzymes. Furthermore, the histopathological alterations induced by Cyt were markedly ameliorated by both antioxidants. These results suggest that Cyt-induced neuronal degeneration is driven by oxidative stress and apoptosis, processes that can be mitigated by morin and propolis supplementation.

## Linked entities

- **Genes:** BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], GPX4 (glutathione peroxidase 4) [NCBI Gene 2879], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596]
- **Proteins:** GSTU5 (glutathione S-transferase tau 5), Cat (Catalase), GPX2 (glutathione peroxidase 2)
- **Chemicals:** morin (PubChem CID 5281670), cytarabine (PubChem CID 6253)
- **Diseases:** acute myeloid leukemia (MONDO:0015667)

## Full-text entities

- **Genes:** Bax (BCL2 associated X, apoptosis regulator) [NCBI Gene 24887], CDA (cytidine deaminase) [NCBI Gene 978] {aka CDD}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, Hmox1 (heme oxygenase 1) [NCBI Gene 24451] {aka HEOXG, Heox, Hmox, Ho-1, Ho1, hsp32}, Gpx4 (glutathione peroxidase 4) [NCBI Gene 29328] {aka Gshpx-4, Phgpx, gpx-4, snGpx}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, p53-ps (Wistar clone pR53P1 p53 pseudogene) [NCBI Gene 301300], GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, Bcl2 (BCL2, apoptosis regulator) [NCBI Gene 24224] {aka Bcl-2}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, Gpx1 (glutathione peroxidase 1) [NCBI Gene 24404] {aka GSHPx, GSHPx-1}, Hpgds (hematopoietic prostaglandin D synthase) [NCBI Gene 58962] {aka Ptgds2}, Lpo (lactoperoxidase) [NCBI Gene 287610]
- **Diseases:** acute cerebellar syndrome (MESH:D000071072), gait disturbances (MESH:D020233), nystagmus (MESH:D009759), motor coordination disorders (MESH:D019957), dysarthria (MESH:D004401), hematological malignancies (MESH:D019337), Cerebellar dysfunction (MESH:D002526), seizures (MESH:D012640), AML (MESH:D015470), squamous cell carcinoma (MESH:D002294), cerebral dysfunction (MESH:D002547), inflammation (MESH:D007249), neurodegenerative disorders (MESH:D019636), mitochondrial dysfunction (MESH:D028361), keratoconjunctivitis (MESH:D007637), cancer (MESH:D009369), Neurotoxicity (MESH:D020258), neuroinflammation (MESH:D000090862), cortex (MESH:D000303), breast cancer (MESH:D001943), degeneration (MESH:D009410), impairments in working memory (MESH:D008569), chronic diseases (MESH:D002908), cognitive impairment (MESH:D003072), leukemia (MESH:D007938), colorectal cancer (MESH:D015179), death (MESH:D003643), ataxia (MESH:D001259), gastrointestinal mucosal damage (MESH:D005767), acute lymphocytic leukemia (MESH:D054198), cardiovascular diseases (MESH:D002318), cytotoxic damage (MESH:D064420)
- **Chemicals:** free radicals (MESH:D005609), water (MESH:D014867), terpenes (MESH:D013729), TBA (MESH:C029684), essential oils (MESH:D009822), phenolic acids (MESH:C017616), gentamicin (MESH:D005839), cyt (MESH:D003520), 8-Hydroxydeoxyguanosine (MESH:D000080242), flavonol (MESH:C041477), ethanol (MESH:D000431), methyl alcohol (MESH:D000432), paraffin (MESH:D010232), oxygen (MESH:D010100), ammonium chloride (MESH:D000643), xylene (MESH:D014992), guanine (MESH:D006147), Cyt (MESH:D003561), steroids (MESH:D013256), GSH (MESH:D005978), polyphenols (MESH:D059808), lipid (MESH:D008055), Morin (MESH:C008548), 1,2-dichloro-4-nitrobenzene (MESH:C028328), beeswax (MESH:C038228), DAB (MESH:C000469), alcohol (MESH:D000438), caffeic acid (MESH:C040048), PBS (MESH:D007854), coumarins (MESH:D003374), 3,3'-Diaminobenzidine (MESH:D015100), pyrimidine nucleoside (MESH:D011741), eosin (MESH:D004801), ROS (MESH:D017382), flavonoids (MESH:D005419), dimethyl sulfoxide (MESH:D004121), formalin (MESH:D005557), 3,5,7,2',4'-pentahydroxyflavone (-), H2O2 (MESH:D006861), Hematoxylin (MESH:D006416), polyunsaturated fatty acids (MESH:D005231), sodium citrate (MESH:D000077559), amino acids (MESH:D000596), NADP (MESH:D009249), Propolis (MESH:D011429), selenium (MESH:D012643), MDA (MESH:D008315), 8-hydroxyguanine (MESH:C024829)
- **Species:** Meleagris gallopavo (common turkey, species) [taxon 9103], Apis mellifera (bee, species) [taxon 7460], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

129 references — full list in the complete paper: https://tomesphere.com/paper/PMC12918924/full.md

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Source: https://tomesphere.com/paper/PMC12918924