Mitigation of Cisplatin-Induced Neurotoxicity via Nrf2/HO-1 Signaling and Autophagy: The Protective Role of Vitamin D
Journal of Biochemical and Molecular Toxicology, cilt.40, sa.6, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 40 Sayı: 6
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/jbt.70941
- Dergi Adı: Journal of Biochemical and Molecular Toxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, Zoological Record, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: autophagy, cerebral cortex, cisplatin, heme oxygenase-1, NF-E2-related factor 2, oxidative stress, vitamin D
- İnönü Üniversitesi Adresli: Evet
Özet
This study examined the impact of vitamin D (Vit D) treatment on oxidative stress in the brain caused by cisplatin (CP). A total of 21 Wistar Albino rats were allocated into three groups: control; CP, which received a single dose of 7 mg/kg CP on the first day; and VitD + CP (administered a single dose of 7 mg/kg CP on the first day followed by 1000 IU/mL Vit D for 7 days). The brain was removed immediately after the experiment. Biochemical oxidative stress (OSI), total antioxidant status (TAS), and total oxidant status (TOS) were calculated in left hemisphere tissue samples. In addition, measurements of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were also performed in this tissue. We examined tissue samples from the right hemisphere using histological and immunohistochemical methods to detect Nrf2, HO-1, BEC-1, and LC3 proteins. Biochemical analyses revealed a slight increase in TOS and a slight decrease in TAS in the CP group, while in the VitD + CP group, TOS decreased slightly and TAS increased significantly. The differences between the groups were not statistically significant. Furthermore, the OSI value increased statistically significantly in the CP group, while it decreased statistically significantly in the VitD + CP group. In the cerebral cortex of the CP group, widespread degenerate neurons were observed, characterized by dark pyknotic nuclei. Furthermore, the results indicated that CP administration induced a significant increase in HO-1 immunoreactivity, reflecting a compensatory activation of the Nrf2-mediated antioxidant response. Moreover, Nrf2, HO-1, and LC3 immunoreactivity were found to be significantly lower in the VitD + CP group compared to the CP group. Overall, VitD shows potential as an adjunctive agent against CP neurotoxicity, pending further mechanistic validation.