Histidine, carnosine, and ergothioneine attenuate pyrazole/LPS-induced hepatotoxicity through modulation of CYP2E1, Nrf2, and NF-κB signaling in mice
Molecular Biology Reports, cilt.53, sa.1, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 53 Sayı: 1
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s11033-026-12341-5
- Dergi Adı: Molecular Biology Reports
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest)
- Anahtar Kelimeler: carnosine, CYP2E1, ergothioneine, hepatotoxicity, histidine, lipopolysaccharide, NF-κB, Nrf2, oxidative stress, Pyrazole
- İstanbul Üniversitesi Adresli: Evet
Özet
Background/Aim: Cytochrome P450 2E1 (CYP2E1) is key in liver damage from oxidative stress. The pyrazole (Pyr)- and lipopolysaccharide (LPS)- induced mouse model, which combines CYP2E1 induction with endotoxemia, is useful for studying liver protection. This study assessed how imidazole compounds (histidine, carnosine, and ergothioneine) affect Pyr + LPS-induced liver injury and the mechanisms involved. Methods: Male C57BL/6J mice received histidine (250 mg/kg, i.p.), carnosine (250 mg/kg, i.p.), histidine + carnosine (250 mg/kg each, i.p.), or ergothioneine (70 mg/kg, oral) for 10 consecutive days. Pyrazole (150 mg/kg, i.p.) was administered on days 8 and 9, followed by LPS (10 mg/kg, i.p.) on day 10. Serum ALT and AST activities, hepatic oxidative stress markers (ROS, TBARS, AOPP), antioxidant parameters (GSH, SOD, GSH-Px, FRAP), CYP2E1 protein levels, nitric oxide metabolites (NOx), and mRNA expressions of Nrf2, HO-1, NF-κB, TNF-α, and IL-6 were determined. Histopathological examination was also performed. Results: Pyr + LPS administration significantly elevated serum ALT and AST levels, hepatic CYP2E1, oxidative stress markers, and NOx, while reducing antioxidant defenses. NF-κB, TNF-α, IL-6, and HO-1 mRNA expressions were elevated. Pre-treatment with all imidazole compounds significantly attenuated these alterations, reduced CYP2E1 levels, and further upregulated HO-1 expression. The combination of histidine and carnosine also increased Nrf2 mRNA expression. Histopathological findings corroborated the biochemical results. Conclusion: Histidine, carnosine, and ergothioneine protected against Pyr + LPS-induced hepatic injury and reduced oxidative stress. These effects were accompanied by alterations in CYP2E1 protein levels and NF-κB/Nrf2/HO-1-related gene expression; however, further studies are needed to clarify the underlying mechanisms.