<i>Viburnum opulus</i> protects against acetaminophen-induced splenic injury through coordinated antioxidant and anti-inflammatory responses
JOURNAL OF MOLECULAR HISTOLOGY, cilt.57, sa.5, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 57 Sayı: 5
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s10735-026-10995-w
- Dergi Adı: JOURNAL OF MOLECULAR HISTOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Bursa Uludağ Üniversitesi Adresli: Evet
Özet
Acetaminophen (APAP) overdose induces systemic oxidative and inflammatory responses, yet its effects on splenic homeostasis remain poorly characterized. We investigated whether prophylactic Viburnum opulus L. protects against APAP-induced splenic injury and the molecular pathways potentially underlying this protection. Forty female Wistar rats were allocated to control, APAP, N-acetylcysteine (NAC), V. opulus 100 (VO-100), and 300 mg/kg (VO-300) groups. NAC or V. opulus was administered orally for seven days, followed by a single oral APAP dose of 3 g/kg. Splenic histomorphology and immunohistochemical expression of cleaved Caspase-3, Ki-67, NF-kappa B, iNOS, SOD1, NRF2, and GPX4 were evaluated; network pharmacology and independent splenic transcriptomic analyses contextualized the experimental findings. APAP disrupted white- and red-pulp organization, induced lymphoid depletion, follicular disorganization, congestion, and sinusoidal dilatation, and significantly altered all seven markers, increasing cleaved Caspase-3, NF-kappa B, and iNOS immunoreactivity while reducing Ki-67, SOD1, and NRF2. GPX4 also decreased, but the control-APAP comparison lost significance after multiple-testing correction. VO-300 markedly attenuated the histomorphological alterations, reduced inflammatory and apoptosis-associated marker expression, and increased proliferative and antioxidant markers toward control levels. Network pharmacology identified 44 shared targets between major V. opulus constituents and APAP-toxicity-associated genes, with AKT1, NFKB1, PTGS2, and STAT3 as key hub proteins linked to oxidative-stress, apoptotic, and NF-kappa B-related pathways; 28 of these targets were confirmed in independent spleen transcriptomic data. Prophylactic V. opulus, particularly at 300 mg/kg, therefore, limits APAP-induced splenic injury by preserving tissue architecture, proliferative activity, and antioxidant defenses while attenuating inflammatory and apoptosis-associated responses.